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COLLECTED PAPERS

ON

— CIRCULATION AND RESPIRATION.

FIRST SERIES,

CHIEFLY CONTAINING

LABORATORY RESEARCHES.

BY

Sir LAUDER BRUNTON,
M.D., D.Sc., LL.D. (EpIn. AND ABERD.), F.R.S., F.R.C.P.

Foreign Honorary Member of the American Academy of Arts and Sciences ;
Correspondent of the Academy of Natural Sciences of Philadelphia ;
Associate Fellow of the College of Physicians of Philadelphia; Honorary
Member of the Imperial Military Academy of Medicine of St. Petersburg ;
Correspondant Etranger de la Société de Therapeutique, Paris; Honorary
Member of the American Therapeutic Society; Honorary Member of the
Pharmaceutical Society, etc.; Consulting Physician and late Lecturer on
Pharmacology and Therapeutics to St. Bartholomew’s Hospital.

LONDON:
MACMILLAN anp Co., LIMITED,
New York: THE MAcMILLAN COMPANY.

1907.
[The Right of Translation is Reserved. ]

ne

A
a:

is

Author’s Medication,

TO
DAVID FERRIER, M.A., M.D., LL.D., F.RS.,

MY CHUM FOR THREE YEARS,
AND MY FRIEND FOR MORE THAN THIRTY

I DEDICATE THIS BOOK,

NOT ONLY AS A MARK OF LONG AND UNBROKEN FRIENDSHIP, -
BUT ALSO IN RECOGNITION
OF THE MARVELLOUS ABILITY
WHICH HAS ENABLED HIM TO DO FOR THE BRAIN
WHAT HARVEY DID FOR THE CIRCULATION
AND BRING ORDER OUT OF CHAOS.

PREFACE.

SEVERAL of my friends have complained to me that my
writings are so scattered that they have been unable to refer to
them when they wished todo so. I have therefore collected
and reprinted them. At first, I intended to publish them
in two volumes, but I found that they naturally fell into two
series, the first containing chiefly the results of experimental
research in the laboratory, and the second those of clinical
work. It is unsatisfactory to possess only one volume of a
work, but one reader may be more interested in experimental,
and another in clinical work, and so each might wish to possess
the series dealing with the subject he desires. In some
instances, the same paper appears in two languages, for I found
on one occasion, at least, that the work described in an English
paper had been ignored on the pretext that the writer had not
access to the German original. One of the first things to
strike a reader will be the number of papers with a joint
authorship. One reason of this is that I lke working with
others who are interested in the same subject as myself, and
thus have written conjointly with Dr. A. B. Meyer (now
Director of the Royal Zoological Museum at Dresden), Sir
Joseph Fayrer, Mr. Henry Power, and Mr. D’Arcy Power.

Two or three years after beginning to lecture on Materia
Medica and Therapeutics at St. Bartholomew’s Hospital, I tried
to institute a pharmacological laboratory there. The place
which I got for this purpose was about 12 feet by 6, and
formerly had been used only for washing dishes aid jars in
the museum, but a table on one side served to hold the
apparatus, and I got some students to work there with me.
One research was that of Mr. Walter Pye, on Casca, and the
other that of Mr. Tait, on Nitro-glycerine. The pulling down of
this laboratory on account of the rebuilding of the Medical
School prevented me from pursuing my plan of getting a number

vi PREFACE,

of students to work, and before the new buildings were finished
the claims of practice began to interfere with my experimental
work. I soon found that when a great part of three days is
taken up with hospital work, a very few consultations outside
will interfere seriously with laboratory work, for just when
one has everything prepared for an experiment, one may have
to fix a consultation, and all the preparations, which required
many hours to make, are rendered useless for the time, and
have to be done over again. In consequence of this difficulty I
soon determined to follow the plan of working at practice so as to
obtain the money which would allow me to pay such a salary to
a younger man as would enable him to devote his whole time to
laboratory work. JI planned the research and experiments,
provided the apparatus and material, defrayed all laboratory
expenses, and paid my assistant the salary which I was able to
earn by my practice, and which at that period of his career he
could not earn for himself. We then published the research
under our joint names. This arrangement I considered a fair
one for us both, as each gave what the other had not got, and
we were then able to do the work which neither alone could
have done. I have been exceedingly fortunate in getting such
able assistants as the late Mr. Pye, Professor Weymouth Reid,
now of Dundee, Professor Cash, of Aberdeen, Dr. Allen
Macfadyen, of the Jenner Institute, Mr. T. J. Bokenham,
Dr. Rayner Batten, and Professor Tunnicliffe, now of King’s
College.

I began to reprint these papers ten years ago, Messrs.
Harrison having sent me the first proofs in 1896. The work
has been interrupted by other occupations, and also by a
serious illness lasting from the summer of 1902 to the
autumn of 1903. In consequence of these interruptions
and the irregular way in which the work proceeded, various
errata have occurred, perhaps the most notable of which is the
absence of the fifth lecture, “ On the Experimental Investigation
of the Action of Medicines,” from its proper place, page 322,
and its relegation to the Appendix. With this exception, and that
of the Harveian Oration, most of the papers are printed in the
chronological order of the experiments they record, though not

PREFACE. Vil

always of their actual appearance in print. The Harveian
Oration has been placed first because the short history which
it gives of the physiology and pharmacology of the circulation
serves to some extent as an introduction to the other papers.

The period over which the researches described in these
papers extends (1865 to 1883) is an important one in the
history of the pharmacology of the circulation, for its beginning
coincides with the first employment in this country of
registering apparatus for the investigation of the action of
drugs on the circulation, and before its end this method was
in regular use. After Blake’s experiments with a simple
mercurial column in 1844, little or no work was done on the
action of drugs until Traube, in 1851,* investigated the action
of digitalis with one of Ludwig’s kymographs, and in 1865 to
1866, Von Bezold did his classical researches on the action
of atropine and veratrine.

When I began my experiments on digitalis in 1865, I
believe there was no recording physiological instrument of any
kind in use in this country, with the exception of one or two
of Marey’s sphygmographs, one of which was kindly lent to
me by Dr. Arthur Gamgee, and one kymograph which Burdon
Sa: derson completed in May, 1865, but which was not
described until 1867. Under the guidance of Dr. Gamgee
I made experiments on the blood pressure in animals under
the influence of digitalis with a simple mercurial column, and
on myself with the sphygmograph. The facility which I thus
acquired in using the instrument enabled me while acting as
house physician to utilize it in ascertaining the rise in blood
pressure which occurred in angina pectoris in a_ hospital
patient, and by correlating the pathological data thus acquired
with the knowledge of the pharmacological action of nitrite
of amyl which Gamgee had obtained, I succeeded in discovering
a remedy for angina pectoris.

This discovery may, I think, be fairly regarded as the first

* Traube, Charité Annalen 2ter Jahrg. und Gesammte Beitrdge, vol. i,
pp. 190 and 274.

+ Von Bezold, Wiirzburger physiol. Untersuchungen, I and II.

t Burdvun Sanderson, PAil. Trans., 1867, p. 576.

Vili PREFACE.

complete example of rational therapeutics based on experi-
mental pathological and pharmacological data. Magendie’s
application of strychnine in paralysis and Fraser and Argyll-
Robertson’s use of Calabar bean for ophthalmological purposes
preceded it, but, in both instances, whilst the action of the drug
employed was ascertained by experiment it was used to combat
a symptom and not a definite pathological condition which had
also been ascertained by experiment.

After a year in hospital I went to Vienna and worked for
some months in Professor Briicke’s laboratory on the action of
digitalis upon muscle and nerve, but the experiments I made
were never published. I then went to Berlin for a short time
and took the opportunity of working with what I believe to
have been the identical instrument employed by Traube in his
researches. In my work on digitalis I felt deeply the want
of a registering hemodynamometer (vide p. 52), but in spite
of the want I obtained proofs that digitalis both increases the
force of the heart (p. 52) and causes contraction of the
capillaries (pp. 55 and 56). Traube* ascribed the rise in blood
pressure produced by digitalis entirely to changes in the action
of the heart, and he left alterations im peripheral resistance
altogether out of account, while they appeared to me to be
a most important factor. L was very anxious to obtain
confirmatory evidence of my view that digitalis contracts the
peripheral vessels, and by means of the kymographion I
succeeded, in conjunction with A. B. Meyer, in obtaining this
evidence and thus establishing the view of the action of
digitalis (p. 145) which is now almost universally accepted.

From Berlin I went for a tour to Egypt, Syria, and the
South of Europe, and the next winter (1868 to 1869) I spent
in Amsterdam, studying physiological chemistry with Professor
Kiihne, a man of marvellous ability and far in advance of his
time. The knowledge which I gained from him enabled me to
write the section on Digestion and Secretion for Burdon
Sanderson’s Handbook for the Physiological Laboratory.

I then went to Leipzig, and was fortunate enough to be
admitted by my beloved and venerated Master, Carl Ludwig, as

* Traube, op. cit.

PREFACE. ix

one of the first students in his new Institute, in which he
delivered his first lecture shortly after I went. At that time
he was busy furnishing his new laboratories and devising new
instruments for artificial respiration, for measuring blood
pressure and the speed of circulation, for artificial circulation
in excised organs and for interchange of gases. He started
me on a research, having for its subject the independent
contraction of arterioles and capillaries when separated from
nerve centres. He liked to be present himself, and indeed to
perform most of the experiments on this subject, but in the
intervals when he was otherwise engaged I made some ex-
periments on the effect of nitrite of amyl and nitrite of soda.
These were only intended as by-play, but the research on
contractility took so long that Ludwig thought it better to
publish a paper on nitrite of amyl with only a general mention
of the work on contractility in order to secure priority. I
intended to continue it after leaving his laboratory, but when
I came to London my time was so much taken up with other
things that it became impossible.

In 1871 I began to write the Experimental Investigation
of Medicines, with the intention of expanding it into a complete
text-book on “Experimental Pharmacology.” Before the part
dealing with the circulation, however, had been finished, I
accepted the late Sir John Burdon Sanderson’s invitation
to join him in writing a Handbook for the Physiological
Laboratory to which I was to contribute the section on
Digestion and Secretion. As I performed every experiment
mentioned in it and repeated several of them many times, the
writing of this short section involved incessant work in the
laboratory for more than two years. As an example of this
I may mention that the statement at page 84 of the text-book
“that pepsine, if absolutely pure, gives no xanthoprotein
re-action,’ cost wwe many weeks’ work. In 1873 and 1874
I was engaged with Sir Joseph (then Dr.) Fayrer in examining
the action of snake venom and with Dr. Pye Smith on a report
to the British Association on Intestinal Secretion. The
re-building of the school at St. Bartholomew’s Hospital caused
an interruption in my laboratory work of nearly four years,

x PREFACE.

from 1876 to 1880, when I again resumed it with the aid of
assistance from Dr. Cash and others in the manner I have
already mentioned. From this time onward the pressure of
other engagements has only permitted me to do most of my
laboratory work by means of assistants in the manner I have
mentioned at the beginning of the preface.

I am aware that for the majority of readers this preface is
too long and too personal, but they can easily pass it over, and
some of those friends (whose desire to read some of my old papers
has led me to republish them) may be interested to know why
my experimental work on the circulation has apparently been
so fitful and so intermittent.

TABLE OF CONTENTS.

Article. Place and Date. _| Page.
1. Harveian Oration a ws es i <3 Oct. 18, 1894 1
2. On Digitalis, with Some Observations on the Urine} London (Churchill), | 29
(Thesis presented to Edinburgh University, 1866, 1868
and awarded a Gold Medal).

“3. On the Use of Nitrite of Amyl in Angina Pectoris..| Lancet, ee July 27, | 187
4, Action of Digitalis on the Blood-Vessels (Brunton | J. Anat. and Physiol.,| 141
and Meyer, 1868). 1873, vol. 7, p. 1385
5. On the Chemical Composition of the Nuclei of | Jdid., vol. 4, Nov., | 147

Blood Corpuscles. 1869, p. 91
6. Ueber die Wirkung des salpetrig-sauren Amyl-| Ber. d. Math.-Phys. | 154
oxyds auf den Blutstrom. Classe der Kénigl..
Sdchs. Gesell. d, Wiss.,
8. 285, and Ludwig’s
Arbeiten 4ter Jahrg.,
1869, s. 101
v7. On the Action of Nitrite of Amyl on the Circula- | J. Anat. and Physiol.,| 174
tion. (A translation of No. 6.) 1871, vol. 5, p. 92
8. Nitrite of Amyl in Angina Pectoris (1867) .. «.| Clin. Soc. Reps., | 185
vol. 3, 1870
9. Effect of Warmth in Preventing Death from | J. Anat.and Physiol.,| 197
Chloral (1870). May, 1874, vol. 8,
p..332
10. Influence of Temperature on the Pulsation of the | S¢.Bart.’s Hosp. Reps.,| 205
Mammalian Heart and on the Action of the| vol. 7, p. 216, 1871
Vagus.
11. Experimental Investigation of the Action of
Medicines—
I. The Standard of Health .. Lf os ..| Brit. Med. Jour., | 220
April 22 and 29, 1871,
_ pp. 418, 439
II. Action of Drugs on Protoplasm: General Direc- | 22id., May 13 and 20, | 241
tions for Experimental Investigation. 1871, pp. 495, 521
III. Artificial Circulation: Investigation of Blood | Jdid., June 3, 1871, | 266
Pressure. p- 581
IV. Determination of the Exact Structures through | Zbid., Dec. 9, 16, 30, | 290
which Drugs affect the Heart and Vessels. 1871, pp. 659, 687, 749
V. Respiration .. os es a4 i Lbid., Jan. 2, 1875, | App.
pel 643
322

ee ee ee ee ee

VI. Respiration ..

Ibid., Feb. 15, 1875,
p- 201

Xil

TABLE OF CONTENTS.

petency of the Tricuspid and Mitral Valves.

1878, vol. 15, p. 283

Article. Place and Date. | Page
12. Physiological Action of Condurango (1871) .. ..| J. Anat. and Physiol., | 340
April, 1876, p. 486
vis. On the Employment of Nitrite of Amyl in the Br. Med. Jour., 359
Collapse of Cholera. Jan. 13, 1872, p. 42
14. On the Use of Artificial Respiration and Transfusion | Idid., May 17, 1873, | 374
as a Means of Preserving Life. p- 555
15. Veranderte Wirkung zweier Arzneimittel wenn sie | Centralb.d.med.Wiss.,| 388
Gleichzeitig in den Organismus eingefiihrt werden. | Sept. 27, 1873, p. 689
16. On the Apparent Production of a New Effect by the | J. Anat. and Physiol., 390.
Joint Action of Drugs within the Animal Organism. | Nov., 1873, vol. 8, p. 94
17. On the Pathology and Treatment of Shock and! Practitioner, vol.11, | 392
Syncope. Oct., 1873, p. 246
18. Diuretische Wirkung der Digitalis (Brunton and | Centrald.f.med.Wiss.,| 410
Power). July 4, 1874, p. 497
19. On the Diuretic Action of Digitalis (Brunton and | Proc. Roy. Soc., vol. | 412
Power). 22, 1874, No. 153,
p. 240
20. Cases of Exophthalmic Goitre.. oe ee ..| St. Bart.’s Hosp.Reps.,| 414
1874, vol. 10, p. 253
21. One of the Causes of Death during the Extraction | Br. Med. Jour., Dec. 4,| 427
of Teeth under Chloroform. 1875, p. 695
22. On Irritants and Counter-irritants, with Remarks on | St. Bart.’s Hosp. Reps.,| 488
the Use of Blisters in Rheumatism. 1874, vol. 11, p. 167
23. A Simple Method of Demonstrating the Effect of | J. Anat. and Physiol.,| 455
Heat and Poisons upon the Heart of the Frog. April, 1876, vol. 10,
p. 602
24. Physiological Action of Erythrophleum Guinense | Proc. Roy. Soc., June,| 458
(Casca, Cassa, or Sassy Bark) (Brunton and Pye).| 1876, vol. 25, p. 172
25. On the Physiological Action of Casca Bark (Brunton | St.Bart.’s Hosp. Reps.,| 462
and Pye). 1876, vol. 12, p. 125
\ 26. Preliminary Notes on the Physiological Action of Ibid., p. 140 ATS
r Nitro-glycerine (Brunton and Tait).
27. On the Physiological Action of the Bark of Erythro- | Phil. Trans. Roy. Soc.,| 481
phleum Guinense, generally called Casca, Cassa, or| June 15, 1876, vol.
Sassy Bark (Brunton and Pye). 167, Part 2, p. 12
28. Note on Independent Pulsation of the Pulmonary | Proc. Roy. Soc., June,| 528
Veins and Vena Cava (Brunton and Fayrer). 1876, vol. 25, p. 172
29. On the Science of Easy Chairs oe ee --| Nature, Oct. 17,1878, | 531
p-. 637
30. On a Simple Instrument for Examining the Com- | St. Bart.’s Hosp. Reps.,| 537

TABLE OF CONTENTS.

Article. Place and Date. | Page
31. On Pulsation in the Jugular and other Veins .. | Med. Press and Cire.,| 589
July 2, 1879, p. 1

32. On the Pathology of Night Sweating in Phthisis, | St.Bart.’s Hosp. Reps.,| 545
and the Mode of Action of Strychnia and other} 1879, vol. 15, p. 119
Remedies in it.

33. On the Explanation of Stannius’s Experiment and| JZdid., 1880, vol. 16, | 557
on the Action of Strychnia on the Heart (Brunton p. 230
and Cash).

34. On the Actions and Use of Certain Remedies em-| ZLancef, Jan. 1, 1881, | 562
ployed in Bronchitis and Phthisis: p- 4

35. Note regarding the Effect of Electrical Stimulation os 572
of the Frog’s Heart, &c.

36. On the Effect of Electrical Stimulation of the Frog’s Proc. Roy. Soc., 574
Heart, and its Modification by Cold, Heat, and | June 16, 1881, vol. 32,
the Action of Drugs (Brunton and Cash). No. 214, p. 383

37. On the Effect of Electrical Stimulation of the Frog’s | Tbid., revised June 13, | 576
Heart, and its Modification by Cold, Heat, and | 1883, vol. 35, No. 227,
the Action of Drugs (Brunton and Cash). p. 455

38. The Valvular Action of the Larynx (Brunton andj J. Anat. and Physiol.,| 624
Cash). 1882-3, vol. 17,

pp. 111, 363
Appendix (being Part V (Respiration) of Article II) ..| Br. Med. Jour., Jan.2,| 643

1875, p. 1

THE HARVEIAN ORATION, 1894.
(Delivered before the Royal College of Physicians on October 18, 1894.)

Mr. PRESIDENT, FELLOWS, AND GENTLEMEN,

THIs annual meeting in memory of Harvey is usually associated
with feelings of pleasure and happiness, for it was intended by
its immortal founder to commemorate the benefactors of the
College and to encourage good fellowship amongst us.

Such commemoration of those who have benefited the College
in the past, although it necessarily recalls many who have
passed away, is, notwithstanding, on ordinary occasions pleasant
instead ef painful, because the feeling of loss through their
death is completely overpowered by the recollection of the good
they have done in their lifetime. To-day the case is very diffe-
rent, for the first thought that must needs occur to every one
present here is that on this occasion last year our late President
showed for the first time what seemed to be imperfect fulfilment
of his duty to the College by being late in his attendance at the
meeting. Perhaps nothing else could have shown more clearly
his deep concern for the welfare of the College, and his thorough
devotion of every faculty of mind and body to its interests, than
the fact that no duty, no pleasure, and no press of occupation
could tempt him to leave one iota of his work in the College
undone. The only thing that did keep him back was the hand
of Death, which, although at the last meeting he and we knew
it not, was already laid upon him. Though his death was less
happy than that of the great Harvey, inasmuch as he lingered
on for days instead of hours after he was first struck down, yet
their deaths were alike in this respect that, up to the time of
the fatal attack, each was in the full possession of his facul-
ties, each was in the enjoyment of his life. Like Radcliffe and
Mead, like Halford and Baillie, and like many other dis-

B

2 THE HARVEIAN ORATION, 1894.

tinguished Fellows of this College, the greatness of Clark is to
be estimated not by the published works which he has left be-
hind, but by the influence he exerted on his contemporaries.
For the very estimation in which his professional skill was held
led to his whole time being taken up in giving advice, and pre-
vented him from having the leisure to work out or record the
results of the pathological and clinical observations which both
his useful publications and his later career showed him to be
specially fitted to make. I might say very much more about
lim, but it has already been said much better than I could
possibly do it by yourself, Mr. President, in your annual ad-
dress, and in the eloquent and heart-stirring words which you
addressed to the College on the occasion of your taking the
presidential chair rendered vacant by the death of Sir Andrew
Clark.

But whiie we are saddened by the death of our late Presi-
dent, we hope to be gladdened by the presence amongst us
again of one whom we all reverence not only as a former Presi-
dent of this Coilege, but as one of the greatest leaders of clinical
medicine in this century, Sir William Jenner. Like Harvey,
Sir William Jenner is honoured by his College, by his country,
by his Sovereign, and by the world at large. In time of trial
and danger the lives of the Royal children were committed to
the keeping of Harvey by his King; and to-day the care not
only of her own life, but of that of her nearest and dearest, is
committed to Sir William Jenner by his Sovereign, in the full
and well-crounded assurance that in no other hands could they
be more safe. The great clinician, Graves, wished to have as
his epitaph, “ He fed fevers”; but Jenner has advanced much
beyond Graves, and, by showing us how to feed the different kinds
of fevers, has saved thousands of valuable lives. To-day this
College is acknowledging his right to rank with Sydenkam,
Heberden, Bright and Garrod, by bestowing upon him the
Moxon medal for clinical research. In numbering Sir William
amongst its medallists, the College honours itself as well as him,
and in acknowledging the great services he has rendered, it is,
on this occasion, acting as the mouthpiece of the medical pro-
fession, not only in this country but in the world at large.

“A MOTION AS IT WERE IN A CIRCLE.” 3

It was with the wish to keep green the memory of the bene-
factors of the Callege that this oration was instituted by Harvey,
and not at all with the intention that it should be devoted to
his own praise. But Harvey stands out so high above all others,
that it is only natural that in the numerous orations which have
been yearly given before the College of Physicians, the subject-
matter should have been to a great extent confined to a con-
sideration of Harveyand hisworks. On looking over many of these
orations, I find that everything that I could say about Harvey,
his person, his circumstances, his character, and his works, has
already been said so fully and eloquently that I could not add
to it any further, nor could I hope to express it even so well. I
purpose, therefure, to consider to-day some of the modern de-
velopments of Harvey’s work, more especially in relation to the
treatment of diseases of the heart and circulation. There is, I
think, a certain advantage in this also, inasmuch as one is apt,
by considering Harvey’s work only as he left it, to overlook the.
enormous extent to which it now influences our thoughts and
actions and thus to comprehend its value very imperfectly.

As he himself says, “ From a small seed springs a mighty
tree ; from the minute gemmule or apex of the acorn, how wide
does the gnarled oak at length extend his arms, how loftily does
he lift his branches to the sky, how deeply do his roots strike
down into the ground !”* :

How very minute is the gemmule from which has sprung
everything that is definite in medical science, for this gemmule
is no other than the idea which Harvey records in these
simple words: “I began to think whether there might not be
A MOTION AS IT WERE IN A CIRCLE.”

Out of this idea has grown all our knowledge of the processes
of human life in health and disease, of the signs and symptoms
which indicate disease, of the mode of action of the drugs and
appliances which we use, and the proper means of employing
them in the cure of disease. In the works that have come down
to us we find that Harvey developed his idea physiologically in
several directions. He discussed its application to the absorp-

* The Works of William Harvey, Sydenham Society’s edition, p. 320.
{ Idid., p. 46.
B «a

4 TIIE HARVEIAN ORATION, 1894.

tion and distribution of nourishment through the body, the
mixing of blood from various parts, the maintenance and distri-
bution of animal heat, and excretion through the kidneys. How
far he developed it in the direction of pathology and therapeu-
tics we do not know, as the results of his labours on these sub-
jects have, unfortunately, been lost to us by the destruction of
his manuscripts during the Civil War.

We are proud to reckon Harvey as an Englishman by birth,
but he is far too great to belong exclusively to any country;
men of various nations, and scattered all over the face of the
earth, acknowledgs him as their teacher, and have played, or
are playing, a part in developing his discovery in its various
branches of physiology, pathology, pharmacology, semeiology, and
therapeutics. Americans, Austrians, Danes, Dutchmen, French,
Germans, Italians, Norwegians, Russians and Swedes have all
shared in the work, and so numerous are they that it would be
impossible for me to name them all. Stephen Hales, however,
deserves special mention, for he was the first to measure the
pressure of blood in the arteries, and the resistance offered to
‘the circulation of the blood by the capillaries was investigated
‘by Thomas Young, a Fellow of this College, who ranks with
Harvey, Newton, and Darwin as one of the greatest scientific
men that England has ever produced, and whose undulatory
‘theory has been as fertile of results in physics as Harvey’s idea
-of circulation has been in physiology and medicine.

Harvey’s desire that those who had done good work should
not be forgotten was founded upon his knowledge of mankind,
-and of the tendency there is to forget what has already been
done by those who have gone before us. The opposite condi-
tion often prevails, and the past is glorified at the expense of
the present. But sometimes the present is wrongly glorified at
the expense of the past, and past work or past benefits are for-
gotten.

Good examples of this are afforded by physiological views
regarding the action of the vena cava and pulmonary veins and
the causation of the cardiac sounds. Harvey appears to have
tnought that the vena cava and pulmonary veins were simply
dilated passively by the passage of blood into them: but the

SOUNDS OF THE HEART. 5

fact that they possess a power of independent pulsation was
known to Haller,* and was brought prominently forward ky
Senac,f who regards the vena cava as the starting point of the
whole circulation. He says: “The vena cava is therefore the
first motor cause which dilates the cavities of the heart ; it fills
the auricles, and extends their walls in every direction.”

These observations appear to have been almost forgotten
until they were again made independently a few years ago,t
and in one of the latest and most accurate physiological treatises
which now exist, the description of the cardiac cycle is nearly
the same as that given by Senac. “A complete beat of the
whole heart, or cardiac cycle, may be observed to take place as
follows :—

“The great veins, inferior and superior ven cavee and pul-
monary veins are seen, while full of blood, to contract in the
neighbourhood of the heart ; the contraction runs in a peri-
staltic wave towards the auricles, increasing in intensity as it
goes.”

The pulsation of these veins, however, cannot be a constant
phenomenon, or it would have been noticed by such a keen
observer as Harvey.

The sounds of the heart were discovered by Harvey, or at
least were known to him, for he speaks of the sound caused in
the cescphagus of the horse by drinking, and says: “In the
same way it is with each motion of the heart, when there is a
delivery of blood from the veins of the arteries that a pulse
takes place, and can be heard within the chest.” ||

This observation remained, as far as we know, without any
further development until the time of Laennec, who introduced
the practice of auscultation ; but it was a Fellow of this College,
Dr. Wollaston,{ who first discovered that muscles during con-
traction give out a sound. Although many observations were
made regarding cardiac murmurs by Corrigan, Bouillaud and

* Haller, Elementa Physiologie, 1757, tome 1, pp. 410 and 399.

+ Senac, De la Structure du Ceur, livre iv, ch. ili, p. 24.

t Proc. Roy. Soc., 1876, No. 172.

§ M. Foster, Text-book of Physiology, 6th edition, part i, ch. iv, p. 231.

|| The Works of William Harvey, Sydenham Society’s edition, p. 32.
{ Wollaston, Phil. Trans., 1810, p. 2.

’

6 THE HARVEIAN ORATION, 1894.

Piorry, it was chiefly by Fellows of this College, Dr. Clendin-
ning, Dr. C. J. B. Williams, and Dr. Todd, that the question
was finally settled, and the conclusions at which they arrived
are those now accepted as correct, viz., that “the first or systolic
sound is essentially caused by the sudden and forcible tightening
of the muscular fibres of the ventricle when they contract; and
that the second sound which accompanies the diastole of the
ventricle depends solely on the reaction of the arterial columns
of blood in the semilunar valves at the arterial orifices.”*

Yet in recent discussions regarding the origin of cardiac
sounds, little mention has been made of the work of this com-
mittee; and, indeed, I first learned of its value from a German
source, viz.: Wagner’s Hundwérterbuch der Physiologie.

The importance of these observations in the diagnosis of
heart disease it would be hard to over-estimate. But diagnosis
‘alone is not the aim of the physician, whose object must be to
prevent, to cure, or to control disease. A knowledge of physi-
ology may greatly help us to prevent disease, not only of the
heart and vessels, but of every member of the body. The con-
trol and cure of disease may also be effected by diet and
regimen, but it is undoubtedly in many cases greatly assisted
by the use of drugs, and is sometimes impossible without them.
Harvey knew that drugs applied externally are absorbed and
act on the body,f so that colocynth thus applied will purge,
and cantharides will excite the urine; but the action of drugs
when injected into the blood appears to have been tried
first by Christopher Wren, better known as the architect- of
St. Paul’s than as a pharmacologist. According to Bishop
Spratt, “he was the first author of the noble experiment of in-
jecting liquors into the veins of animals, an experiment now
vulgarly known, but long since exhibited to the meetings at
Oxford, and thence carried by some Germans, and published
abroad. By this operation divers creatures were immediately
purged, vomited, intoxicated, killed, or revived, according to
the quality of the liquor injected. Hence arose many new

* Report of Committee consisting of C. J. B. Williams, R. B. Todd, and

John Clendinning, Brit. Assoc. Rep. for 1836, p. 155.
t The Works of William Harvey, Sydenbam Society’s edition, p. 72.

ACTION OF DRUGS ON THE CIRCULATION. 7

experiments, and chiefly that of transfusine blood, which the
Society has presented in sundry instances, that will probab?y
end in extraordinary success.”*

The method originated by Wren, of injecting drugs intc the
circulation, was skilfully utilised by Magendie for the purpose
of localising the particular part of the body upon which the
drugs exerted their action, and he thus conclusively proved
that the symptoms produced by strychnine were due to its
effect on the spinal cord. His experiments showed that the
rate of absorption from various parts of the body varied
enormously, and, through the teaching of Christison, led to the
introduction into practice by Dr. Alexander Wood of that most
useful aid to modern therapeutics, the hypodermic syringe.

The first quantitative experiments on the effect of drugs
upon the circulation were made, to the best of my knowledge,
by James Blake in 1844, in the laboratory of University
College, at the suggestion of the late Professor Sharpey, with the
hemadynamometer of Poiseuille, which had then been recently
introduced.

In speaking about the work of Blake and Sharney, who are
both dead, cne requires to use the greatest care not to unduly
detract from the merit of one by ascribing more to the other;
but those who knew Prof. Sharpey’s enormous range of know-
ledge, his readiness to put it all at-the disposal of others, and
the influence he exerted over all who came in contact with
him, as well as his unselfishness in making no claim whatever
to what was justly his due, will at once recognise how greatly
Blake was indebted to Sharpey. More especially is this tue
case when we consider that, although the credit for the olbserva-
tions themselves belongs to Blake, yet after the impetus which
Sharpey gave him had passed away, he did very little more
during the course of a long life. It seems all the more neces-
sary to commemorate Sharpey on this occasion, because he has
left comparatively few writings beliind him, and anyone who
should judge by them alone of his influence upon physiological
progress in this country would grievously under-estimate. it.

* The History of the Royal Society of London for the Improving of Natural
Knowledge, by ‘I’. Spratt, late Lord Bishop of Rochester.

8 THE HARVEIAN ORATION, 1894.

For Sharpey was above ali a teacher, and his work was
written not with pen and ink on paper or parchment, but was
engraved upon the hearts and minds of his pupils and his
friends. Upon two of these, especially, has Sharpey’s mantle
fallen, and to Burdon Sanderson and Michael Foster we owe a
revival of experimental physiology in this country, a revival of
the method which Harvey not only used in making his great
discovery, but also employed to demonstrate the truth of it to
the rulers of this land. By their writings, by their lectures, by
their original experiments, by their demonstrations, and by the
pupils they have trained, Burdon Sanderson and Michael Foster,
under the auspices of Acland and Humphry, have diffused
amongst the medical men of this country a knowledge of
physiology so extensive and exact as could only be found, before
_ their time, amongst those who had made a special study of the
subject. Yet more than to them, more than to anyone else
since the time of Harvey, do we owe our present knowledge of
the circulation to Carl Ludwig. Heit is who first enabled the
pressure of blood in the arteries to record its own variations
automatically, so that alterations could be noticed and measured
which were too rapid or too slight to be detected by the eye.
To him, also, we owe the plan of artificial circulation by which
the changes in the functions of the organs and in the vessels
which supply them can be observed, quite apart from the heart,
lungs, or from the nervous system.

_ Like Sharpey, Ludwig is a great teacher, and, like the great
architects of the Middle Ages, who built the wonderful
cathedrals which all admire, but whose builder’s name no man
knows, Ludwig has been content to sink his own name in his
anxiety for the progress of his work, and in his desire to aid
his pupils. The researches which have appeared under these
pupils’ names have been in many instances, perhaps in most,
not only suggested by Ludwig, but carried out experimentally
with his own hands, and the paper which recorded the
results finally written by himself. In the papers which have ~
appeared under his pupils’ names we find their obligation
to the master recorded in such terms as “unter Mitwirkung.”

LUDWIG’S GRAPHIC. METHOD—-EFFECTS OF EMOTION. 9

But no one, except those who have worked with him, can
understand what such “ co-operation ” meant.

The graphic method introduced by Ludwig for the purpose
of measuring the blood pressure, was adapted by Volkman to
the registration of the pulse in man, and the same method has
been modified and rendered more easily applicable at the bed-
side by Marey and Chauveau, to whom we chiefly owe our know-
ledge of the modifications in the form of the apex-beat and of
the pulse curve. It is to Ludwig and his scholars, however,
that we owe the greater part of our knowledge of the mechanism
of the circulation and of the varying distribution of the blood
in various parts of the body.

The effect of emotion upon the heart was carefully noted by
Harvey, who says: “For every affection of mind which is
attended with pain or pleasure, hope or fear is the cause of an
agitation whose influence extends to the heart.*

Not only was Harvey well acquainted with the fact that the
beats of the heart vary very much in strergth and rate, but he
also knew that the circulation in various parts of the body may
be very different at one and the same time. He says: “It is
manifest that the blood in its course does not.everywhere pass
with the same celerity, neither with the same force in all
places, and at all times, but that it varies greatly according to
age, sex, temperament, habit of body, and other contingent.
circumstances, external as well as internal, natural, or non-
natural. For it does not course through intricate and obstructed
passages with the same readiness that it does through straight,
unimpeded, and pervious channels. Neither does it run
through close, hard aud crowded parts with the same velocity
as through spongy, soft and permeable tissues. Neither
does it flow with such swiftness when the impulse (of the
heart) is slow and weak, as when this is forcible and frequent,
in which case the blood is driven onwards with vigour, and in
large quantity.”

“ And what, indeed, is more deserving of attention than the
fact that in almost every affection, appetite, hope, or fear, our

* The Works of William Harvey, Sydenham Society’s edition, p. 70.

10 THE HARVEIAN ORATION, 1894,

body suffers, the countenance changes, and the blood appears to
course hither and thither. In anger the eyes are fiery and the
pupils contracted ; in modesty the cheeks are suffused with
blushes; in fear, and under a sense of infamy and of shame,
the face is pale, but the ears burn as if for the evil they heard
or were to hear; in lust, how quickly is the member distended
with blood and erected.”*

Harvey’s great contemporary, Milton, though so violently
opposed to him in politics, would certainly not remain in
ignorance of Harvey’s work, and he has noted the changes in
the colour of the face produced by emotions. In describing the
behaviour of Satan on his journey from Hell to Paradise, he
says :—

“ Thus while he spake, each passion dimm’d his face,
Thrice changed with pale, ire, envy, and despair ;
Which marr’d his borrow’d visage.” ¢

But although these facts were known to Harvey so long ago,
it is only in comparatively recent years that the mechanism by
which they are brought about has been investigated, and it is
only within the last decade that physiologists have begun
regularly to believe that the cardiac muscle has a power of
rhythmic pulsation independent of its nerves, although Harvey
had noted that when the heart was cut into small pieces the
fragments would stiil continue to pulsate~ We may fairly,
indeed, compare the movements of the heart, as regarded by
physiologists of the present day, to those of a horse which is
capable of going independently, although its pace may be slowed
or accelerated by the reins or spur of the rider. The power of
the vagus to act as a rein to the heart, and slow its movements
or stop them altogether, was first noted by Edward and Ernest
Heinrich Weber, while the effect that it sometimes has of
accelerating instead of slowing, like the effect of shaking the
reins of the horse, was observed by Schiff, Moleschott and
Lister, and the transmission of excitation from one chamber to
another was experimented on by Paget.

* The Works of William ILarvey, Sydenham Society’s edition, pp, 128—
129.

+ Paradise Lost, by John Milton, book iv.
t The Works of William Harvey, Sydenham Society’s edition, p. 28.

CONTRACTILITY OF VESSELS. 11:

The accelerating nerves of the heart, and the position of the
nerve-centre from which they spring, were more thoroughly in-
vestigated by von Bezold,* while the power of the vagus to
weaken as well as slow the heart was observed by Gaskell. The
position of the cardiac centre, which, like the rider, regulates
- the movements of the heart, was located in the medulla
. oblongata chiefly by Ludwig and his scholars. Like the heart,
the vessels are regulated in diameter by the nervous system in
accordance with the wants of the body generally ; and the effect
upon the vaso-motor nerves which, when cut, allow them to

ulate, and, when stimulated, canse them to contract, was dis-
covered by Bernard, Brown-Séquard and by our countryman,
Waller; while the power of other nerves to cause immediate
dilatation was discovered by Bernard, Eckhardt, and Ludwig in
the submaxillary glands, penis and peripheral vessels respec-
tively.

The heart, when cut out of the body, still continues to beat,
although removed completely from the influence of the central
nervous system, and the vessels have a somewhat similar power
of independent contractility. The alterations produced in the
circulation, generally and locally, by the contractile power of
the vessels, and the changes caused in the vessels by the central
nervous system, by peripheral stimulation of the nerves, or by
variations in the quality of the blood, have formed the subject
of a series of researches extending over many years; and
though originated, and in many cases entirely conducted by
Ludwig, have appeared to a great extent under the names of his
pupils. The starting-point of these investigations was an exami-
nation of the changes in blood as it flowed through isolated
organs, with the view of ascertaining in what manner the com-
bustion by which the animal heat is maintained, is effected in
the body. While keeping up the circulation of blood through
the vessels of miuscles severed from the body, Ludwig and
Sezelkow{t observed variations in the flow which appeared to

* Von Bezold, Untersuchungen iiber die Innervation des Herzens, 1863.
Leipzig : Engelmann.

+ Ludwig and Brunton, Ludwig’s Arbeiten. Vierter Jahrgang, 1869, p. 106.

{~ Ludwig and Sczelkow, Henle and Pyeuffers Zeitschrift, 1863, vol. 17,
p- 106, and vide p. 122.

12 THE HARVEIAN ORATION, 1894.

indicate contractile power in the vessels themselves. This
research was carried on under Ludwig’s direction by various
of his scholars in succession, Alexander Schmidt, Dogiel,
Sadler, myself, Hafiz, Lépine, A. Mosso, von Frey, and Gaskell.
Their observations, as well as those of Cohnheim and Gunning,
have shown that the muscular fibres of the arterioles, not only
in the muscles but throughout the body generally, have a power
of independent, and sometimes rhythmical, contraction and
relaxation. Their contractility is, however, controlled by the
central nervous system in accordance with the wants of the
body generally. For the amount of blood contained in the
body is insufficient to fill the whole of the vascular system at
once ; and when the vessels are fully dilated, as they are after
death, we find that nearly the whole of the blood of the body
may be contained in the veins alone. It is, therefore, neces-
sary that when one part of the body is receiving a larger supply
of blood, another should be receiving a smaller supply; and
the functions of the vaso-motor centres have been well com-
pared by Ludwig to the turncocks in a great city, who cut off
the water supply from one district at the same time they turn
it on to another. Thus it is that when the brain is active the
feet may get cold, and Mosso has shown this in an exceedingly
neat manner by placing a man on a large board delicately
balanced at its centre, and demonstrating that whenever the
man begins to think, the increased supply of blood to his
brain causes the head to go down and the heels to rise up. A
similar condition was indicated by Mayow, who gave a different
explanation. He said that the “ vital spirits” were not able to be
in more than one place at once, and therefore it happens that if
a man eats a heavy meal he is apt to become drowsy, because the
“vital spirits” descend from the brain to the stomach in order
to carry on digestion ; and, on the other hand, if a man thinks
vigorously after dinner, the “vital spirits” have to leave the
stomach to go to the brain, and consequently digestion is im-
perfectly performed. If we substitute the word blood for
“vital spirits,’ we have an exact expression of present physio-
logical ideas.

VESSELS IN MUSCLES. 13

Ubi stimulus ibi afluxus is an old doctrine and expresses a
great truth. Wherever the need for increased nourishment or
increased supply of oxygen exists in the healthy body, thither
does the blood flow in larger quantities than usual. If the
glands are active, their blood supply is greatly increased, as was
shown by Bernard,and a similar occurrence takes place in the con-
tracting muscle, as has been shown by Ludwig and his scholars.
The vessels of the intestines and skin, as well as their numerous
glands, have their calibre regulated by the vaso-motor nerves
which proceed from the centre in the medulla oblongata. This
centre acts most readily upon the vessels of the intestine, and
rather less readily on those of the skin. In consequence of
this, when the centre is irritated, the vessels of the intestine
contract and drive the blood through the skin, so that it is
warmer than before, and it is only when the stimulation is very
great that the vessels of both contract, so that the skin receives
less blood than normal, and becomes colder than before. But
if the vessels of the skin and intestine are both contracted,
where does the blood go? This question was put by Ludwig,
and answered by the experiments which he made with Hafiz.
It is evident that if the heart be stopped while the blood
pressure is being measured in the artery of an animal, the
pressure will fall regularly and steadily, because the blood is
flowing out all the time through the arterioles and capillaries
into the veins. One would naturally expect that if the arterioles
were contracted by irritation of the vaso-motor centre in the
medulla, the fall of blood pressure would either not take place
at all, or would be very much slower than before ; but on trying
the experiment, Ludwig and Hafiz found, to their surprise, that
the blood pressure fell almost as quickly as when the vaso-
motor centre was left alone, and the vessels of the skin and
intestine therefore remained uncontracted. In other words, the
vessels which supply the muscles of the body and limbs are
capable of such extension that when fully dilated they will
allow the arterial blood to pour through them alone nearly as
quickly as it usually does through the vessels of the skin, intes-
tine and muscles together. This observation, it seems to me,

14 THE HARVEIAN ORATION, 1894.

is one of the greatest importance, and one that has hardly
received, as yet, the attention which it merits. One consequence
of it is obvious—viz., that contraction of the cutaneous vessels,
such as occurs upon exposure to cold, will drive more blood
through the muscles, and as oxidation goes on more rapidly
in them the result will be increased production of heat.

‘The experiments I have just mentioned show that the vessels
of the muscles are not controlled by the vasu-motor centre in
the medulla oblongata in the same way as those of the intestine
and skin. How far their vascular centres may be associated
with those for voluntary movements, which have been so
admirably localised by Ferrier in the cerebral cortex, stil
remains to be made out. The circulation through the muscles
_ is indeed a complex phenomenon, and it was shown by Ludwig
and Sadler to depend upon at least two factors having an
antagonistic action. When a muscle is thrown into action, it
mechanically compresses the blood vessels within it, and thus
tends to lessen the circulation through it, but at the same time
the stimulus which is sent down through the motor nerve and
ealls it into action, brings about a dilatation of the vascular
walls, and thus increases the circulation through the muscle.

When the amount of blood is measured before, during and
after stimulation of the motor nerve, it is sometimes found
that the flow is diminished, at others that it is increased. This
difference depends upon the comparative effect of the mechani-
cal compression of the vessels of the muscles just mentioned,
and upon the increase of their lumen by the dilatation of
their walls. It invariably happens, however, that after the
muscle has ceased to act, the flow of blood through the muscle
is increased. This increase is quite independent of any altera-
tion in the general pressure of blood in the arteries, and it
occurs when an artificial stream of blood, under constant pres-
sure, is sent through the muscle. The dilatation in the muscular
vessels, as indicated by the increased flow of blood, and con-
sequent change of colour in the frog’s tongue, was observed by
Lépine after stimulation of the peripheral ends of the hypo-
glossal and glossopharyngeal nerves,* and the actual changes

* Lépine, Ludwig’s Arbeiten, 5ter Jahrg., 1870, p. 114.

RELATION OF MUSCLES TO THE HEART. ‘15

in the vessels themselves were observed microscopically by von
_ Frey and Gaskell.*

The dilatation of muscular vessels on irritation of peripheral
nerves was thus brought into a line with the dilatation noticed
in the vessels of the submaxillary gland by Bernard, and in the .
eorpora cavernosa by Eckhardt. It is evident that alteration in
the size of such a huge vascular tract as the muscular arteries
must influence, to a great extent, the blood pressure in the
arteries generally. It is equally evident that the changes
induced in the condition of the blood pressure by muscular
action may be of two kinds, either a rise or a fall. If the arte-
rioles are compressed by the muscles so that the flow through
them is impeded, the general blood pressure will rise. When
this effect is more than counteracted by the dilatation of the
arterioles themselves under nervous influence, the general blood
pressure will fall, for the blood will find an easy passage from
the arteries into the veins through the muscles. We can thus
see how readily a rise or fall in the general blood pressure may
be induced by exercise of the muscles. If they contract suddenly
or violently they will tend to compress the arterioles, and raise
the blood pressure, whilst if they contract gently their contrac-
tion will have little effect in compressing the arterioles, and
these, becoming dilated, will allow the blood pressure to fall.

But there is still another factor which may tend to increase
the blood pressure during severe muscular exertion, viz., a
quickened pulse, for stimulation of the nerve fibres passing
from the muscles to the central nervous system greatly accele-
rates the beats of the heart.. In this respect stimulation of the
muscular nerves differs from that of the cutaneous and visceral
nerves, inasmuch as the latter tend rather to slow than to
quicken the pulse. This peculiar effect of the muscular nerves
upon the heart would, indeed, appear to be a provision of nature
for the purpose of maintaining an exceedingly active circula-
tion during the active calls upon nutrition which violent exer-
tions entail. Muscular exercise, therefore, has a special tendency
to raise the blood pressure in the arterial system, and conse-

* Von Frey, Ludwig’s Arbeiten, 1lter Jahrg., 1876, p. 106; and Gaskell,
ibid., p. 79; and Centraldb. f. die Med. Wiss., 1876, p. 557.

16 THE HARVEIAN ORATION, 1894.

quently to increase the resistance which the left ventricle has
to overcome. Moreover, in the case of the intestinal vessels,
there is a special provision made for preventing their contrac-
tion from causing too great a rise of arterial pressure. This
consists in the depressor nerve, which passes from the heart and
tends to produce dilatation of the abdominal vessels, and thus
to prevent any undue pressure occurring within the heart from
their excessive contraction. But in the case of the muscles, we
have no such nerve. Its place seems to be taken by the dilating
fibres which occur in the motor nerves. As I have already said,
however, their power to dilate the muscular vessels may be at
first more than counteracted by mechanical compression at the
commencement of exertion. Thus the blood pressure in the —
arteries, and the resistance which it opposes to the contraction
and emptying of the ventricle, may be unduly increased at first
by any effort, especially if it be sudden or severe.

As a general rule, the distension of any hollow muscular
organ is attended with great pain. How great is the suffering
when obstruction of the bowel prevents evacuation of its con-
tents ; or when calculi, in their passage down the gall duct or
ureters, forcibly distend their walls. One of the severest tor-
tures of the middle ages was to distend the stomach with water,
and the Emperor Tiberius could imagine no more awful punish-
ment for those whom he hated than to make them drink wine,
and, at the same time, by means of a ligature, to prevent the
distended bladder from emptying itself. The heart is no
exception to this rule, and distension of its cavities brings on
most acute physical suffering. Its inability to empty itself is a
question of relative, and not of absolute power; for a strong
heart may be‘unable to work only against enormously increased
resistance in the peripheral arterioles, while a heart, weakened
by degeneration, may be unable to empty itself in face of
pressure little, if at all, above the normal.

When the contractile power of the heart is not, as it is in
health, considerably in excess of the resistance opposed to it in
the vessels, but is only nearly equal to it, a slight increase in the
resistance may greatly interfere with the power of the heart to
empty itself, and bring on pain varying in amount from slight

CARDIAC PAIN—BREATULESSNESS. L7

uneasiness to the most intense agony in angina pectoris. This
is, indeed, what we find, for a heart whose nutrition has been
weakened by disease of its arteries, and consequent imperfect
supply of blood to the cardiac muscle, is unable to meet any
increased resistance if this should be offered to it, and pain is at
once felt. In such cases, unless they be far advanced, we find,
precisely as we might expect, that walking on the level usually
causes no pain, but the attempt to ascend even a slight rise, by
which the muscles are brought into more active exertion, brings
on pain at once. Yet here again we find, as we should expect,
that if the patient is able to continue walking, the pain passes
off and does not return. These phenomena would be inexplic-
able were it not for Ludwig’s observations on circulation through
the muscles, but in the light of these observations everything
is made perfecily intelligible. Walking on the flat, by causing
no violent exertion of the muscles, produces no mechanical con-
striction of the vessels, and thus does not increase the blood
pressure. The greater exertion of walking up a bill has this
effect, but if the patient is able to continue his exertions, the
increased dilatation of the vessels—a consequence of muscular
activity—allows the pressure again to fall and relieves the pain.

As muscular exertion continues and the vessels of the muscles
become dilated, the flow of blood from the arteries into the veins
will tend to become much more rapid thanusual. The pressure
in the arterial system will consequently fall, but that in the
veins will become increased, and unless a corresponding dilata-
tion occurs in the pulmonary circulation, blood will tend to
accumulate in the right side of the heart, the right ventricle
will be unable to empty itself completely, shortness of breath
will arise, and even death may occur. At first the right side of
the heart is affected, and the apex beat disappears from its
normal place and is felt in the epigastrium. But the left
ventricle also becomes dilated, though whether this is simply
through nervous influence tending to make it act concordantly
with the right, or for some other reason, it is at present
impossible to say. Severe exertions, even for a few minutes,
may produce this conditiun in healthy persons,* and when the

* Schott, Verhandl, de ix. Congresses in“Med. zu Wien, 1806.
; ;

18 THE HARVEIAN ORATION, 1894.

exertion is over-continued it may lead to permanent mischief.
More especially is this the case in young growing boys, and it
is not merely foolish, it is wicked to insist upon boys engaging
in games or contests which demand a long-continued over-
exertion of the heart, such as enforced races and paper-chases
extending uver several miles. Intermittent exertion, either of
a single muscle or of a group of muscles, or of the whole body,
appears to lead to better nutrition and increased strength and
hypertrophy, but over-exertion, especially if continuous, leads to
impaired nutrition, weakness and atrophy. If we watch the
movements of young animals, we find that they are often rapid,
but fitful, irregular and varied in character, instead of being
steady, regular and uniform. They are the movements of the
butterfly, and not of the bee. The varied plays of childhood,
the gambols of the lamb, and the frisking of the colt, are all
well adapted to increase the strength of the body without doing
it any injury ; butif the colt, instead of being allowed to frisk
at its own free will, is put in harness, or ridden in races, the
energy which ought to have gone to growth is used up by the
work, its nutrition is affected, its powers diminished, and its life
is shortened. The rules which have been arrived at by the
breeders of horses ought to be carefully considered by the
teachers of schools, and by the medical Pas wei who super-
intend the pupils.

In youth and middle age every organ of the body is adapted
for doing more work than it is usually called upon to do.
Every organ can, as it if usually termed, “make a spurt” if
required ; but as old age comes on this capacity disappears, the
tissues become less elastic, the arteries become more rigid and
less capable of dilating and allowing a freer flow of blood to any
part, whether it be the intestine, the skin, the brain, the
muscles, or the heart itself. Mere rigidity of the arteries
supplying the muscles of the heart will lessen the power of”
extra exertion, but if the vessels be not only rigid, but diminished
in calibre, the muscles of the limbs and the heart itself will be
unfit even for their ordinary work, and will tend to fail on the
slightest over-exertion. This fact was noticed by Sir Benjamiti
Brodie, who, when speaking of patients with degenerating and

OSSIFICATION OF ARTERIES. 19

contracted arteries, such as lead to senile gangrene, said:
“Such patients walk a short distance very well, but when they
attempt more than this, the muscles seem to be unequal to the
task, and they can walk no further. The muscles are not
absolutely paralysed, but in a stage approaching to it. The
cause of all this is sutticiently obvious. The lower limbs require
sometimes a larger and sometimes a smaller supply of blood:
During exercise a larger supply is wanted on account of the
increased action of the muscles; but the arteries being ossified
or obliterated, and thus incapable of dilatation, the increased
supply cannot be obtained. This state of things is not peculiar
to the lower limbs. Wherever muscular structures exist the
same cause will produce the same effect. Dr. Jenner first, and
Dr. Parry of Bath afterward, published observations which were
Supposed to prove that the disease which is usually called
‘angina pectoris’ depends on ossification of the coronary
arteries. . . . When the coronary arteries are in this condi-
tion they may be capable of admitting a moderate supply of
blood to the muscular structure of the heart; and as long as the
patient makes no abnormal exertion, the circulation goes on well
enough; when, however, the heart is excited to increased action,
whether it be during a fit of passion, or in running, or walking
upstairs, or lifting weights, then the ossified arteries being
incapable of expanding so as to let in the additional quantity of
blood, which, under these circumstances, is required, its action.
stops and syncope ensues; and I say that this exactly corre-
spouds to the seuse of weakness and want of muscular power
Which exists in persons who have the arteries of the legs
obstructed or ossified.”*

But the syncope and stoppage of the heart mentioned by
Brodie are not the only consequences of impaired cardiac
nutrition. The heart may be still able to carry on the circula-
tion, but the patient may suffer intense pain in the process.
The outside of the heart was found by Harvey to be insensible
to light touches, but the inside of the heart appears to be much
more sensitive either to touch or pressure, and the internal pres-

* Lectures on Pathology and Surgery, by Sir Benjamin Brodie, London,
1846, p. 360.

C2

20 THE ITARVEIAN ORATION, 1894.

sure caused by inability to empty itself produces, as I have
already said, intense pain.

A knowledge of the mode of the circulation of blood through
the muscles enables us to understand not only the pathology of
angina pectoris, but the rationale of various methods of treating
patients suffering from angina pectoris or other forms of heart
disease. In most cases our object is a two-fold one—to increase
the power of the heart, and to lessen the resistance it has to
overcome. Insome cases we require also to aid the elimination
of water, which has so accumulated as to give rise to cedema of
the cellular tissue, or dropsy of the serous cavities. In our
endeavours to produce these beneficial changes in our patients,
- we employ regimen diet, and drugs, and it is evident that as in
one case the condition of a patient’s heart may be very different
indeed from that in another, the regimen which may be useful
to one may be fatal to the other. We have already seen that
sudden and violent exertion may raise the blood pressure, and
so lead to intense cardiac pain or to stoppage of the heart and
instant death; while more gentle exercise, by increasing the
circulatior: of the muscles, may lessen the pressure and give
relief to the heart.

The methods of increasing the muscular circulation may be
roughly divided into three, according as the patient lies, stands,
and walks. ‘First, absolute rest in bed with massage*; second,
graduated movements of the muscles of the limbs and body
while the patient stands still; third, graduated exercises in
walking and climbing.

The second of these methods has been specially worked out
by the brothers Schott, of Nauheim, and the third is generally
connected with the name of Oertel.

It is obvious that in cases of heart disease where the failure
is great and the patient is unable even to stand, much less walk,
where breathlessness is extreme and dropsy is present, the
second and third methods of treatment are inapplicable. It is
in such cases that the method of absolute rest in bed, not allow-
ing the patient to rise for any purpose whatever, hardly allowing
him to feed himself or turn himself in bed, proves advantageous.

* Lauder Brunton, Practitioner, vol. li, p. 190.

EFFECT OF MASSAGE. 21

The appetite is usually small, the digesticn imperfect, and
flatulence troublesome ; and here an absolute milk diet, like
that usually employed in typhoid fever, is often most service-
able, being easily taken and easily digested, while the milk
sugar itself has a diuretic action, and tends to reduce dcropsy.
But while simple rest prevents the risk of increased arterial
tension and consequent opposition to the cardiac contractions
which might arise from muscular exertion, the benefit which
would accrue from continuous muscular exertions and increased
circulation would be lost were it not that they can be supplied
artificially by massage. This plan of treatment, although it has
only recently been revived, was known to Harvey, “who
narrates the case of a man who, in consequence of an injury—
of an affront which he could not revenge—was so overcome
with hatred, spite, and passion that he fell into a strange dis-
order, suffering from extreme compression and pain in the heart
and breast, from which he only received some little relief at last
when the whole of his chest was pummelled by a strong man, as
the baker kneads dough.”*

This was a very rough form of massage, but the same knead-
ing movements which Harvey described have been elaborated
into a complete system, more especially by Ling in Sweden, and
made widely known in America and this country by Weir-
Mitchell and Playfair. One might naturally expect that knead-
ing the muscles would increase the circulation through them in
somewhat the same way as active exercise, but, to the best of
my knowledge, no actual experiments existed to prove this, and
I accordingly requested my friend and assistant, Dr. Tunnicliffe,
to test the matter experimentally. The method employed was,
in the main, the same as that devised by Ludwig, and employed
by Sadler and Gaskell under his direction. The results were
that, during the kneading of a muscle, the amount of venous
blood which issued from it was sometimes diminished and some-
times increased; that just after the kneading was over the flow
was diminished (apparently from the blood accumulating in the
muscle), and this diminution was again succeeded by a. greatly
increased flow exactly corresponding to that observed by Ludwig

* The Works of William Harvey, Sydenl:am Society's edition p. 128.

22 TUE HARVEIAN ORATION. 1894.

and his scholars. The clinical results are precisely what one
would expect from increased circulation in the muscles, and
cases apparently hopeless sometimes recover most wonderfully
under this treatment.

For patients who are stronger, so that confinement to bed is
unnecessary, and who yet are unable to take walking exercise,
Schott’s treatment is most useful, and it may be used as:an ad-
junct to the later stages of the treatment just described, or as a
sequel to it. Here the patient is made to go through various
exercises of the arms, legs, and trunk with a vertain amount of
resistance, which is applied either by the patient himself setting
in action the opposing muscles, or by an attendant, who gently
resists every movement made by the patient, but graduates his
resistance so as not to cause the least hurry in breathing, or the
least oppression of the heart. Perhaps the easiest.way of em-
ploying graduated resistance is by the ergostat of Giéirtner,
which is simply an adaptation of the labour crank of prisons,
where the number of turns of a wheel can be regulated in each
minute, and the resistance, which is applied by a brake, may be
eraduated to an ounce. The objection to it is the uniformity of
movement and its wearisome monotony.

Oertel’s plan of gradually walking day by day up a steeper
and steeper incline, and thus training the cardiac muscle, is well
adapted for strong persons, but when applied injudiciously, may
lead, just like hasty or excessive exertion, to serious or fatal
results. In Schott’s method stimulation of the skin by baths is
used as an aajunct, and this may tend to slow the pulse as
already mentioned. But in all these plans the essence of treat-
ment is the derivation of blood through a new channel, that of
ihe muscular vessels; and the results in relieving cardiac dis-
tress'and pain may be described in the same words which

~Harvey employs in reference to diseases of the circulation :
“ How speedily some of these diseases that are even reputed in-
curable are remedied and dispelled as if by enchantment.”*

There is’ yet another consequence of the circulation to which
Harvey has called attention, although only very briefly, which
has now become of the utmost importance, and that is the ad-

“* The Works of Witliam Harvey, Sydenham Society’s edition, p. 141.

HARVEY'S CHEMISTRY: ‘23

-mixture of blood from various parts of the body. After describ-
-ing the intestinal veins, Harvey says: “The blood returning by
these veins and bringing the eruder juices along with it, on
the one hand from the stomach, where they are thin, watery,
and not yet perfectly chylified ; on the other, thick and more
earthy, as derived from the feeces, but all pouring into this
splenic branch, are duly tempered by the: admixture of con-
traries.”*

Harvey’s chemical expressions are crude, for chemistry:as a
science only began to exist about a century and a half after
-Harvey’s death, yet the general idea which he expresses in: the
words which I have just quoted is wonderfully near the truth.

Two of the most important constituents of the blood are
chloride of sodium and water. Chioride*of sodium is a neutral
salt, but during digestion both it and water are decomposed in
the gastric glands, and hydrochloric acid is poured into the
stomach, while a corrésponding amount of soda is returned into
the blood, whose alkalinity increases pari passu with the acidity
of the stomach. . Part of this alkali is excreted in the urine, so
that the urine during digestion is often neutral or alkaline.
Possibly some of it, passes out through the liver.in the bile, and
through the pancreas and intestinal glands into the intestine,
where, again mixing with the acid: chyle from the stomach,
neutralisation takes place, so that neutral and comparatively
inactive chloride of sodium is again formed frem the union: of
active alkali and acid. But it is most probable that what occurs
in the stomach occurs also in the other glands, and that ‘the
liver, pancreas and intestine do not. merely pour out the excess
of alkali resulting from gastric digestion, but: that these glands
also decompose: neutral salts, pouring the alkali out through
their ducts, and returning the acid into the blood.

_ We are now leaving the region of definite fact and passing

into that of fancy, but the fancies are not entirely baseless, and

may show in what directions we’ may obey Harvey’s behést to

search out and study the secrets of nature by way of experi-

ment. For what is apparently certain in regard to the decom-

position of chloride of sodium:in the steamach, and probably in
* The Works of William Harvey, Ssienhain' Society's edition, p. 75.

24 TUE HARVEIAN ORATION, 189-4,

the case of neutral salts in the pancreas and intestine, is also
probable in that important, though as yet very imperfectly
known, class of bodies which are known as zymogens. Just as
we have in the stomach an inactive salt, so we have also an
inactive _pepsinogen, which, like the salt, is split up in the
gastric glands, and active pepsine is poured into the stomach.
But is pepsine the cnly active substance produced? Has no
other body, resulting from the decomposition of pepsinogen,
been poured into the blood while the pepsine passed into the
stomach? Has the inactive pepsinogen not been split up into
two bodies active when apart, inactive when combined? May
it not be fitly compared, as I have said elsewhere, to a cup or
«lass, harmless while whole, but yielding sharp and even dan-
gerous splinters when broken, although these may again be
united into a harmless whole ?*

This question at present we cannot answer, but in the pan-
creas there is an indication that something of the kind takes
place, for Lépine has discovered that while this gland pours into
the intestine a ferment which converts starch into sugar, it
pours through the lymphatics into the blood another ferment
which destroys sugar. Whether a similar occurrence takes
place in regard to its other ferments in the pancreas, or in the
glands of the intestine, we do not know. Nor do we yet know
whether the same process goes on in the skin, and whether the
secretion of sweat, which is usually looked upon as its sole
function, bears reaily a relationship to cutaneous activity similar
to'that which the secretion of bile bears to the functions of the
liver. There are indications that such is the case, for when the
skin is varnished, not only does the temperature of the animal
rapidly sink, but congestion occurs. in internal organs, and
dropsy takes place in serous cavities, while in extensive burns
of the skin rapid disintegration of the blood corpuscles occurs.
It is obvious that if this idea be at all correct, a complete revo-
lution will be required in the views we have been accustemed
to entertain regarding the action of many medicines. In the
case of purgatives and diaphoreties, for example, we have looked
mainly at the secretions poured out after their administration

* Practitioner, vol. xxxv, August, 1885. .

FERMENTS FROM GLANDS AND ORGANS. 25

for an explanation of their usefulness, whereas it may be that
the main part of the benefit that they produce is not due to the
substances liberated through the secretions which they cause to
be poured out; but to those which are returned from the intestine
and skin into the circulating blood.

ilow important an effect the excessive admixture of juices
from one part of the animal body with the circulating blood
may have, was shown in the most striking way by Wooldridge.
The juice of the thyroid gland is harmless so long as it remains
in the gland, and is probably useful when it enters the blood in
smail quantities in the ordinary course of life. Yet he found
that if this juice be injecied directly into the vessels it will
cause the blood to coagulate almost instantaneously and kill the
animal as quickly as a rifle bullet. But what is powerful for
harm is, likewise, powerful for good, and’ the administration of
thyroid juice in cases of myxcedema is one of the most remark-
able therapeutic discoveries of modern times.

Since the introduction by Corvisart of pepsine as a remedy in
dyspepsia, digestive ferments have been largely employed to
assist the stomach and intestine in the performance of their
functions, but very little has been done until lately in the way
of modifying tissue changes in the body by the introduction of
ferments derived from solid organs.

For ages back, savages have eaten raw hearts and other organs
of the animals which they have killed, or the enemies they have
conquered, under the belief that they would thereby obtain in-
creased vigour or courage; but the first definite attempt to cure
a disease by supplying a ferment from a solid non-glandular
organ of the body was, I believe, made in Harvey’s own hospital
by the use of raw meat in diabetes.*

It was not, however, until Brown-Séquard recommended the
use of testicular extract that the attention of the profession be-
came attracted to the use of extracts of solid organs. Since
then extract of thyroid, extract of kidney, extract of supra renal
capsule have been employed; but even yet they are only upon
their trial, and the limits of their utility have not yet been
definitely ascertained.

* Lauder Brunton, Brit. Med. Jour., February 21, 1874, pp. 221 e¢ seq.

26 THE HARVEIAN ORATION, 1894.

Another therapeutic method has been recently introduced
which bids fair to be of the utmost importance—viz., the treat-
ment of disease by antitoxins. The discovery by Pasteur of the
dependence of many diseases upon the presence: of minute or-
ganisms may be ranked with that of Harvey, in regard both to
the far-reaching benefits which it has conferred upon mankind
and to the simplicity of its origin. The germ of all his dis-
coveries was the attempt to answer the apparently useless ques-
tion, “ Why does a crystal of tartaric acid sometimes crystallise
in one form and sometimes in another?” From this germ
sprang his discovery of the nature of yeast, and of those microbes
which originate fermentation, putrefaction and disease.

These minute organisms, far removed from man as they are
in their structure and place in nature, appear in some respects
to resemble him in the processes of their growth and nutrition.
They seem, indeed, to have the power of splitting up inactive
bodies into substances having a great physiological or chemical
activity. From grape sugar, which is comparatively inert, they
produce carbonic acid and alcohol, both of which have a power-
ful physiological action. From inert albumen they produce
albumoses having a most powerful toxic action, and: to the
poisonous properties of these substances attention was for a
while alone directed. But it would appear that at the same
time as they produce poisons they also form antidotes, and when
introduced into the living organism they give rise to the pro-
duction of these antidotes. in still greater quantity than. when
cultivated without the body.

The plan of protection from infective diseases, which was first
employed by. Jenner in small-pox, is now being extended to
many other diseases, and the. protective substances which are
formed in the body, and’ their mode of action, are being care-
fully investigated. .The introduction of either pathogenic
«microbes or of toxic products appears to. excite in the body a
process of tissue-change by which antitoxins are produced, and
these may be employed either for the purpose of protection or
eure: Dy the use of-antitoxins tetanus and waa appear
to be deprived of their terrible power.

But it,seems. probable, that a similar result ‘may us ohnisen

ANTITOXIC ACTION OF EXERCISE. 27

by the introduction of certain tissue-juices into the general cir-
culation, for it was shown by Wooldridge that thyroid juice has
the power of destroying anthrax poison. Increase of the circu-
lation in certain organs will almost certainly increase their
tissue-change, will throw their juices or the products of their
functional activity into the general circulation, and thus influ-
ence the invasion or progress of disease. As I have already
mentioned, we are able to influence the circulation in. muscles
both by voluntary exertion and by massage, and we. should
expect that both of these measures would influence the con-
stituents of the blood generally. Such, indeed, appears to be
the case, for J. K. Mitchell* has found: that after massage the
number of blood corpuscles in the circulation is very consider-
ably increased. We can thus understand why exercise either
of the hody or its parts may increase its power to resist infective
diseases.

Had time allowed it, I had intended to discuss the modifica-
tions of the heart and vessels by the introduction of remedies
into the circulation, the power of drugs to slow or strengthen,
to quicken or weaken the power of the heart, to contract or
relax the arterioles, to raise or lower the blood pressure, to
relieve pain or to remove dropsy; but to do this would require
time far exceeding that of a single hour. Moreover, the
methods and res:lts of such research were admirably expounded
to the College by Dr. Leech in his Croonian lecture, and I have
therefore thought I should be better fulfilling the wish of
Harvey that the orator of the year should exhort the Fellows
and Membcrs of the College to search out the secrets of nature
by way of experiment by directing their attention to some fields
of research which have received at present little attention, but
promise results of great practical value.

Lastly, I have to exhort you to continue in mutual love and
affection amongst yourselves; and it seems to me that the best
way of doing this is to direct your attention to the examples of
Harvey and of our late President, whose death we deplore to-
day. They were beloved by their feilows while they lived,
their loss was lamented when they died, and they have left

* American Journal of Medical Science, Vay, 1894.

28 THE HARVEIAN ORATION, 1894.

behind them an example not only of goodness, but of courage.
Harvey, seated speechless in his chair, distributing rings and
parting gifts to his friends while awaiting the approach of death ;
and Andrew Clark, steadfastly determining to continue at work
and die in harness, in spite of the hemoptysis which seemed to
threaten a speedy death, afford us noble examples which ought
to encourage us to follow the directions of the venerable Long-
fellow, who, taking the organ Harvey studied to symbolise such
courage as Harvey and Clark showed, says :—-
‘“* Let us then he up and doing
With a heart for auy fate,

Still achieving, still pursuinz,
Learn to labour and to wait,”

ON DIGITALIS, WITH SOME OBSERVATIONS
ON THE URINE.

(THESIS PRESENTED TO THE UNIVERSITY OF EDINBURGH, 1856, AND To
WHICH A GoLD Mrpat was AWARDED.)

Published in Book Form, Churchill, London, 1868.

PREFACE,

ENCOURAGED by the distinction awarded to this Thesis by
the Medical Faculty of the Edinburgh University, and
believing that it contains some facts not altogether without
interest or importance, I have been induced to publish it,
though fully conscious of its very imperfect condition.
Though my time was not only short, but much broken up,
the omissions would probably not have been so numerous,
and the amount of new material greater, were it not that,
fearing lest I should see, not what was actually before me,
but what others had seen, and I thought I ought to see, I
left myself, during the greater part of the time, purposely
ignorant of the literature of Digitalis, only reading it up
after most of my experiments had been already performed,
and then learning that many of my observations had been
already made by various experimenters, whose results they
only confirmed.

Here I gladly take the opportunity of acknowledging my
great obligation to Dr. Maclagan, who first suggested this
subject to me, and by kindly allowing me the use of his labora-
tory, has enabled me to make experiments I would otherwise
have been obliged to leave untried; to Dr. Gamgee, for the
great, indeed, essential aid he has afforded me by advice,
instruments, and personal assistance; to Dr. Christison, for
help given me by books and specimens; to several of my
fellow-students, especially to Messrs. Downie, Maclean, anc
Nicolson, for the assistance they rendered me in the per-
formance of my experiments; and to Mr. Salom, Optician,
for the use of his Weather Tables.

March, 1868.

ON DIGITALIS. |

AS we review the rapid progress made within late years by
physiology, pathology, and other departments of medical science,
and compare it with the slow advance of therapeutics, we
experience a growing dissatisfaction with our present empirical
method of treatment, which, consisting, as it does, in the mere
tentative administration of drugs without a definite knowledge
of their action, must necessarily retard progress, the same
medicine being tried time after time by different physicians,
and the panacea of one generation being discarded by the next,
only to be again resorted to and trusted in by a third.

Turning from this unsatisfactory method, we begin anxiously
to look for one of a more rational character, which shall be
based not only on a knowledge of the changes induced by
disease, but on a minute and accurate acquaintance with the
action of the remedies which we prescribe for its cure. |

At present, however, our knowledge of their action is ex-
tremely vague and superficial, consisting, in the majority of
eases, chiefly of the external symptoms manifested by animals
under the influence of poisonous doses, and of the changes
observed after their administration in disease, when it is often
extremely difficult, and sometimes impossible, to say hew much
is owing to the drug, and how much to the natural course
of the malady. |

Perhaps no better example of the imperfection of our know-
ledge can be given than the views entertained respecting
digitalis, for although it is in daily and hourly use, and, for _
several years back, hardly a month has passed without an
article upon it in one or other of the medical journals, it is
regarded by some as weakening the heart’s action, by others as
strengthening it, some placing it at the head of the list of
diuretics, others denying that it possesses this property at all;

HISTORY. : 31

and even when two authorities agree as to the results produced
by it, their views as to its modus operandi are of the most dis-
similar nature. Such being the state of our knowledge of this
valuable medicine, I have been induced to make the following
investigations with the view of deciding some at least of the
disputed points; and if I have not done so much as I would
wish, I trust that my labour may not be entirely in vain, but
prove, at least, a stepping-stone towards the desired end.

HISTORY.

So striking is the appearance of this elegant plant, with its
tall stem rising from the midst of a thick bunch of downy
leaves, and gracefully bending at the top under the weight of
its beautiful purple bells, that it is imposible to believe the
ancient herbalist would have passed it over in silence. As no
notice of it is found in their works, we are led to believe that
they were unacquainted with it. Its popular name of Foxglove*
occurs in Saxon writings of the 11th century; but it seems to
have been unknown to the learned till near the middle of the
16th, as it had no Latin name till 1535, when Fuchsius, pro-
fessor of medicine at Tiibingen, gave it that of Digitalis, which
it still retains. It seems formerly to have enjoyed a great
reputation as an external applicationf for the cure of wounds
and scrofulous ulcers,f and for causing the absorption of scro-
fulous glandular enlargements.$

The internal administration of ‘its juice has been orieot
as a remedy for scrofula by Van Helmont,| Haller, Fourcroy,**
and Merz.tT

According to Lobel, digitalis was employed on account of its

* Pereira’s Mat. Med.

+ Ferrein, Matitre Med., tomeiii, 1770, p.67. Vide Homolle and Quevenne,
p. 189.

~ Geoffrey, Trait. de Mat. Med., 1743, tome vi, p. 202 (H. and Q., p. 140).

§ Ferrein, op. cit.

| aaaroias Medicarium, i1776—1794 (H. and Q., p. 188).

{| Hist. Stirpium Indig. Helvetie, 1768 (H. and Q.).

** Encyclopedie Methodique, tome v, p. 456 (H. and Q.),

tt Dissert. Inaugural, Jena, 1790 (H. and Q.).

32 ON DIGITALIS, WITH SOME OBSERVATIONS ON THE URINE.

emetic and cathartic properties by the peasantry of Somerset-
shire as a cure for fevers. Ferrein* alludes to these properties,
and observes that it was reckoned a cure for inveterate
apoplexy, but ought only to be administered to robust persons. —
It occurs in the list of simples of the London Pharmacopceias

for 1650, 1678, 1682, and 1721, is excluded from that of 1746,
but appears again in 1788, and in that of 1809 it is not men-
tioned merely, but the preparation of its tincture and infusion
are described, and in all subsequent editions it has held a promi-
nent place. At an early period it seems to have been less used
on the continent than in England, as it is absent from the
Pharmacopoeia of Leyden for 1718. Drake affirms that its
action as a diuretic was unknown till 1770, and in 1775,
Withering wrote the first monograph on its action as such,
noticing also its power of lowering the pulse. From this
latter property it began to be used in hemorrhages, and
Ferriar,} giving it for heemoptyses in the early stages of phthisis
thought that it also prevented the farther formation of tubercle—
Beddoes,t Drake,§ Fowler,| Mosman,{ Barr,** Maclean,tt and
Darwin,*t have all recommended its use in phthisis, and Brin-
-ton§§ says that it is the best remedy for hemorrhage from
cavities in its advanced stages. Ferriar||| thought it useful in in-
flammatory fever, and Currie, Thomas,*** Rasori,ttt Hirtz,ttt

* Ferrein, op. cit.
' + Ferriar, On Digitalis,

t Beddoes, On Consumption, Digitalis, and Scrofula, 1801 (H. and Q.),

§ Drake, Letter to Beddoes (H. and Q.).

|| Fowler, Letter (H. and Q..).

{ Mosman, Lssay on Scrofula, Glandular Consumption, and Observations on
Digitalis (H. and Q.).

** Barr, Letter to Beddoes (H. and Q.).

++ Maclean, Med. and Pays. Journ., lxv, p. 180-201 (H. and Q.).

tt Darwin, vide H. and Q., p. 323.

§§ Brinton, quoted by Handfield Jones in Clinical Remarks on Functional
Nervous Disorders.

\|\| Ferriar, op. cié.

{4 Currie, Medical Reports.

*** Thomas, Practice of Physic.

att Rasori, Annales de Therapeutizyue de Rognetia, 1845 (H. and Q.).

tt} Bulletin de Therapeutique, February 28 and March 15 (vide Year Book

of Sedesham Society, 1862, P- 110).

USES OF DIGITALIS IN DISEASE. 33

Millet,* Oppolzer,t Schneider, and Traube,§ all hold the
same opinion. In continued fever, it has been recommended
by Clutterbuck, and in bad cases of typhoid fever by Wun-
derlich.{ It has been proposed as an antiperiodic in ague by
Davy,** Graffeneuer,ff and Gerard,{{ and Bouillaud§§ has treated
between 40 and 50 cases successfully by it. It has been recom-
mended in hemicrania by Debouti|| and Serre, and it was
found to be highly efficacious in neuralgia by Boison***: and
Hardwicke.t{f According to Thomas,fft it effects a permanent
cure in epilepsy, and Parkinson,§§§ Moll,|||| Corrigan,{71 Cramp-
ton,17% Sharkey,{9797 Neligan,174 and Duclos**** have em-
ployed it with success. Dr. C. L. Robertsonffff finds it extremely
useful in the second stage of general pareses of the insane.
Mr. G. M. Jones,tHt of Jersey, employed it in large doses in

* Millet, Bullet. de Therap. Ann. par Jamain, 1360, p. 55 (Sydenham
Society Year Book, 1860, p. 221).

t+ Oppolzer, Canst. Jahrb. vol. iii, p. 273 (vide Sydenham Society Year
Book, 1860, p. 219).

ft Schneider, Annuaire de Thérapeutique, 1859, pp. 82-88 (Sydenham
Society Year Book, 1859).

§ Traube, Deutsche Klinik, No. 47,1859, Canst. Jahrb., vol. iii, p. 273 (vide
Sydenham Society Year Book, 1860, p. 219).

| Clutterbuck, Inquiry on the Nature and Seat of Fever, 1807 (H. and Q.).

§ Wunderlich, Med. Times and Gaz., ane p. 2040.

**® Davy, vide H. and Q., p. 324.

tt Graffeneuer, Merat and Delen’s Dict. de Mat. Med., tome ii, p. 645-47
(H. and Q., p. 324).

tt Gerard, Thesis Montpellier (H. and Q.).

§§ Bouillaud, Traité de Nosographie Médicale, 1846, tome iii, p. 471, and
Clinique Medicale de la Charité, tome iii, p. 236 (H. and Q.).

\||| Debout, vide Sydenham Society Year Book, 1861, p. 161.
_ ¥VT Serre, Bullet. de Ther., Apri! 15, 1861, and Canst. Jahrb., vol. iii, p. 29
(vide Sydenham Society Year Book, 1861, p. 164).

*** Boison, Bul. de la Soc. Med. de Gent, May and June, 1861 (vide Syden-
ham Society Year Book, 1861, p. 164).

ttt Hardwicke, quoted by Handfield Jones, op. cit.

{tit Thomas, op. cit.

§§§ Parkinson, Theatre of Plants, p. 654 (H. and Q.).

\||||| Moll, Hpilepsia Digitali Sanata, Dissert. Bonn, 1823 (H. and Q.).

799 H. and Q., p. 144.

**** Duclos, Bul. de Ther., lix, 1860, Sydenham Society Year Book, 1861,
p. 161.

+++t+ Robertson, Brit. Med. Journ., Oct. 3, 1863.

~{it Jones, Med. Times and Gaz., Sept. 29, 1860.

34 ON DIGITALIS, WITH SOME OBSERVATIONS ON THE URINE.

delirium tremens; and Peacock,* Carev,t and Reidt record sue-
cessful cases. It has long been recognised as an excellent
diuretic in dropsy depending on disease of the heart, but its
administration. was sometimes thought. dangerous when there
was much weakness of that organ. Drs. Handfield Jones,§
Fuller, Germaine, and Wilks§ believe, however, that it
strengthens rather than enfeebles the heart, and is, therefore,
most useful when that organ is weak, and dangerous only in
hypertrophy. Mr. W. H. Dickinson has found it an excellent
remedy in menorrhagia, and a powerful oxytoxic. The general
poisonous action of <ligitalis has been examined by Orfila,
Bouley and Reynal, Dupuy and Delafond, Bouchardat and
Sandras, Stannius, and others. Its action on the arterial ten-
sion and the heart has been studied by Blake, Traube, Wivo-
gradoff, Briquet, Kolliker, Dybkowsky and Pelikan, Euienberg
and Ehrenhaus, Handfield Jones, Fagge and Stevenson. Its
influence on the temperature has been examined by Traube,
Dumeril, Demarquay, and Leconte, &c.; on the metamorphosis
of tissue by Winogradoff and Stadion.

CHEMICAL HISTORY.

Up to the year 1841, when Messrs. Homolle and Quevenne
succeeded in obtaining from digitalis a neutral principle in the
form of a yellowish powder, presenting the bitterness and
possessing the physiological action of the plant, the active
principle had been sought for in vain, though several chemists
believed they had obtained it in the shape of brownish or
yellowish extracts, to which they had accordingly given the
name of digitaline, a name afterwards applied to the sub-
stance obtained by Homolle and Quevenne.

The results of the analyses given by these gentlemen of
digitalis, and their -description of the characters of its consti-
tuents, are as follows :— |

Digitaline—-In scales or masses—pale yellow — easily

* Peacock, Med. Times and Gaz., Aug. 3, 1861.
+ Carey, Med. Times and Gaz., Aug. 24, 1861.

t Reid, Edin. Med. Journ., 1864-65, p. 112.
§ H. Jones, Assoc. Med. Journ., 1802, 2, p. 181.

CHEMICAL COMPOSITION OF DIGITALIS. 35

powdered, and the powder of a ycllowish colour, intensely
bitter, with a peculiar faint odour, and causing sneezing if it
be carelessly moved, heavier than water, and doubtfully
erystallisable. It is unalterable in air, fuses at 100°, and
above this becomes coloured and loses its bitterness, which is
replaced by an astringent taste. It is neutral to test-paper, ©
but gives off acid fumes when burnt. It contains no nitrogen.
It is soluble in nearly 2,000 parts of cold and 1,000 of hot
water It is easily soluble in alcohol and wood _ spirit, in
about 100 parts of pure ether, in a considerably larger pro-
portion if the ether contain water, and more especially
alcohol, completely soluble in chloroform, partly in almond
oil and oleic acid, and insoluble in sulphide of carbon. It
forms no compounds with acids. Concentrated sulphuric acid
forms a brownish solution, becoming somewhat purple, and*
depositing olive-coloured flakes on the addition of water.
With hydrochloric acid it forms a light green liquid, becoming
darker as it stands, and lessene but not changed by the
addition of water. Its aqueous solution is not precipitated by
bichloride of mercury, acetate, or subacetate of lead, nitrate of
silver, perchloride of iron, chloride of gold or platinum, or
acetate of copper.

Migitalose—This has a white crystalline—almost micaceous
—aspect. Its point of fusion is 206°, and it is soluble in con-
centrated sulphuric acid, giving it a pale yellow colour, but
forming with dilute acid a rose-coloured solution. It is neu-
tral, tasteless, soluble in alcohol and ether, insoluble in water.

Digitalin.—This is a white neutral powder, soluble in alcohol,
insoluble in water, insipid or faintly bitter; furnishing to water
a transparent material in which this bitterness resides. Its
alcoholic solution is precipitated by caustic potash.

Digitalide.—This occurs in pale, gummy-looking scales, is
neutral, soluble in water and feeble alcohol, slightly in strong
alcohol, insoluble in ether. Its taste is sweetish, with a bitter
after-taste. Is perhaps the bitter part of digitalis, which is
soluble in water, along with colouring matter. It is also
precipitated by caustic potash, and distinguished from digitalin
by its form,

D 2

36 ON DIGITALIS, WITH SOME OBSERVATIONS ON THE URINE.

Digitalic Acid—White, crystallisable, and of an acid taste
and peculiar odour, becoming suffucating under heat, soluble in
water and alcohol, slightly in ether, decomposes in air, and
becomes brown with extreme facility: the decomposition being
favoured by light and alkalis.

Antirrlinic Acid.—This is volatile and oily in appearance.
Besides these, there are Digitaloic Acid, Tannie Acid, Sugar,
Pectin, an albuminoid azotised matter, a crystallisable orange-
red colouring matter, chlorophyll, a volatile oil, and ligneous
fibre.

The process they employed for the extraction of digitaline,
was to precipitate a watery infusion of digitalis by subacetate
of lead, to remove the excess of lead by a mixture of carbonate
and phosphate of soda, and the lime by oxalate of ammonia.
To the filtrate they added tannin, and the product of this was
mixed with litharge, dried, powdered, and treated by alcohol.
This was then evaporated, and the residue was treated with
concentrated ether, which dissolved the other principles and left
the digitaline. This process, as modified by O. Henry, and
adopted in the British Pharmacopeeia, consists in treating the
syrupy alcoholic extract with acetic acid, decolorising by animal
charcoal, precipitating by tannin, decomposing by litharge, and
thus freeing the digitaline which is decolorised by animal
charcoal and purified by ether.

The composition of digitalis has been examined by many
other chemists, especially Radig, Morin, Buchner, Kossman,
and Walz.

Walz* has obtained as volatile principles digitalosmin and
digitalissic acid (valeric acid), and as non-volatile principles
digitalin, digitasolin, digitalacrin, digitaloin, and digitaloic acid.
Digitalosmin is the odoriferous principle of digitalis, and is a
camphoroidal substance obtained as a fatty film by distilling
with water. When the crude digitaline, obtained after decom-
posing the tannin precipitate with litharge, is treated with ether
to purify it, an acrid matier is dissolved, to which Walz at first
gave the name of digitalacrin, thinking it a simple substance ;
but has since found that from it may be separated digitaline

* Watt's Dict. Chem., Art. ‘ Digitalis.” .

STRENGTH OF DIGITALINE, 37

fat or digitaloin in white crystalline scales, which melt to an oil
at a gentle heat, and digitaloic acid in white: nacreous lamin.
The residue left by the ether, and which constitutes commercial
digitaline, consists of two substances: one of which is much
more readily soluble in water than the other. This soluble
part is yellowish and amorphous, soluble in 120 parts of cold
and 40 of boiling water; is said by Walz to be the active
principle, and is called by him digitaline ; others: call it digita-
solin. The insoluble residue is called by him digitaletin, but
others called it digitaline. It is still.doubtful if.all these bodies
are really distinct or have been obtained quite pure, but Walz’s
analyses and formulas agree well. Kossman has given the
name digitalic acid to an acid in digitalis, and‘also.to a product
of boiling digitaline with soda, lye, or lime.

The name of the active principle has been spelt by Homolle
as digitaline with a finale, and by English writers indifferently
as digitalin* and digitaline.t It is to be regretted that Homolle
gave such similar names to different bodies, and also that other
chemists have given different names to the same body, as for
example, Walz, who calls the pure active principle digitaletin.
I have retained Homolle’s orthography.

That digitaline is the active principle, or: at least contains
it, has been shown by the physiological experiments and
clinical experienceof various observers, among.whom 'may be
mentioned Messrs. Hervieux, Shohl, Sandras, Bouillaud, Andral,
and Lemaishe,’ Corvisart, Laroche, Duroziez, and Mandl, who
have found that it produced the same effects:as the plant itself,
both as a poison and.a medicine.

Digitaline is estimated by Homolle and Quevenne as being
100 times as strong :as the leaves ofthe -plant; but Stadion
reckons it as only 30 times as strong, and from the trials:I
made on myself: I am inclined rather to agree with the latter
estimate. In: order to determine whether: there was no other
diuretic principle in digitalis; on account of! which it might: be
preferable to. administer: the plant itself; or: one of its pharma-
ceutical preparations,f. M:. Homolle made experiments on the

‘Bri: Pharm." *"* + Garrod, Mat: Med. bivse SS
t Arch. Gen., 5 ser., vol. xviii; p. 5, July, 1861 (vide Sydenham Soctety Year
Beck, 18€1, p. 434).

38 ON DIGITALIS, WITH SOME OBSERVATIONS ON THE URINE.

products obtained from the plant by various solvents. The first
substance was the residue, after exhausting the leaves with
weak alcohol; the second, tlie substance taken up from the
alcoholic solution by ether, consisting chiefly of a nauseous,
foetid, and acid principle, resembling the digitalic acid of
Kossman ; the third was the alcoholic solution after treatment
with ether; the fourth is obtained by treating the result of
evaporation of No. 3 with chloroform.

No. 1 he found to be comparatively inert, the result of taking
3 grams, or 46 grains, being only equal to 1 milligram of digi-
taline, which is, therefore, 3,000 times stronger. After taking
45 centigrams, or about 75 grains of No. 2; he had no symp-
toms for eight hours, but was then seized with great nausea,
faintness, and vomiting, which continued at intervals of 15
minutes for 30 hours. Next day his pulse had fallen, and, on
the fourth day, was as low as 48. Vision was impaired, and he
could not look steadily at a bright object. Urine was abundant,
but the bladder’s contractility was impaired, and external pres-
sure was required to expei the urine. He had pulsation of the
abdominal aorta, anxiety, epigastric constriction, and cough,
with pneumonic expectoration, lasting for a week: but these,
_he thought, were caused by the continuous vomiting. About a
year after this he took 2 centigrams, or about one-third of a
grain of No. 3. He repeated the dose in 40-hours, and again
after eight hours more. The symptoms were exactly those of
digitaline. No.4 had exactly the same action, but was much
more powerful. M. Homolle concludes that digitaline is the
only principle in digitalis which has any therapeutical value,
that the greater toleration of the stomach of preparations made
by water, is from the absence in them of the nauseating acrid
principle (digitalic acid) contained in No. 2, that digitalis owes
its sedative and diuretic effects entirely to digitaline, but that
its nauseating effect, and» probably the impairment. of vision it
produces, are due to digitalic acid. M. Homolle seems to prove
that digitaline is by far the most important and active of the
principles contained in digitalis, as the fall of the pulse, noticed
after taking No. 2, may have been produced by digitaline con-
tained in it; but as I experienced impairment of vision and nausea

PHYSIOLOGICAL ACTION OF DIGITALIS. 39

after taking digitaline, which I had got from Mr. Morson him-
self, who said it had been carefully prepared, and might be
relied on, I believe these effects may be produced by digitaline,
and are not, as M. Homolle seems to think, entirely owing to
digitalic acid.

PirysStoLoGIcAL ACTION.

On Plants—Marcet* found infusion of digitalis in a few
seconds caused a slight crisping of the leaves of a haricot plant
introduced into it by the root, and next day the plant was dead.
On treating a haricot in the same way with solution of digitaline
(3,ths of a grain in ii of water), I did not notice the
sudden crisping of the leaves, which, however, in the course of
a day became dry and rough, in two days were rolled in at the
edges, and finally became quite dry and shrivelled, but retained
their natural colour.

On Animals—As the general action of digitalis, in varying
doses, has been carefully examined, and the sequence of symp-
toms accurately noted by Messrs. Bouley and Reynalf in their

xperiments on horses, I subjoin their account of them.

Six or eight hours after giving a large dose of ‘digitalis to
horses, they stand at the stretch of their halter, sad, dejected,
and without appetite, and their coat lustreless and rough. Then
signs of general excitement appear. The conjunctive are
injected and of a bright red, the eyes brilliant and fixed, the
face pinched, the nostrils dilated and quivering, respiration
hurried, the number being 15 to 20 or 25 in a minute, circula-
tion more rapid, the beats of the heart being abrupt, their energy
much. increased, and accompanied, after a certain time, by a
vibratory thrill, with a decided metallic tinkling, and, as poison-
ing goes on, a distinct bellows nurmur becomes «audible, and is
rendered louder by any exertion; the beats then show a decided
intermittence, and the pulse is small, thready, and interniittent.
The heat of the body is increased,and hot sweats appear on the
ears, nose, shoulders, and flanks. The mouth is hot, and filled
with saliva, which is sticky and scanty. The tongne is of a

* Annals de Chem. et de Physique, v, xxix.
t Recueil de Med. Teterin. Pratique, 3 zer., toie vi, p. 207, 189 (IL. andQ.),

40 on DIGITALIS, WITH SOME OBSERVATIONS ON THE URINE.

purplish-red at its tip and edges, and is covered on the dorsum
by a thick coat, which gives it a leaden hue, the feces are of
their normal form or colour. During the first 12 hours the
animals often show signs of transitory intestinal pain.

At the end of 24 or 30 hours the stage of excitement has
passed, and the animals become comatose, their heavy heads
hanging down towards the litter, or kept at the bottom of the
manger completely insensible to external noises or stimuli, their
eyes fixed, without movement or expression, sometimes. half
covered by the falling lids, and at other times haggard and
ready to start from their orbits, the pupils greatly dilated, and
the conjunctive, previously of a bright red, are now of a violet
brown, and their secretion dried up. The previous acceleration
of the respirations is now succeeded by great slowness, their
number descending to 8, 7, or even 6 per minute, and being
deep, broken, and trembling. The heat of the body is dimi-
nished; the sweats stop, and the skin.becomes cold. The feces
are now of a browner character, and covered with a layer. of
mucus more or less thick. The urine is at first suppressed, but
at the end of .36 or 48 hours is passed in abundance, pale, clear,
and inodorous, voided very frequently, and in small quantity at
a time. There is great muscular weakness, staggering gait,
oscillation of the posterior extremities; and a kind of paralysis,
which slows their movements. In some there are slight
vertigoes, in others spasmodic fibrillary contractions of muscles
of .the face and of the alae nasi. The severity of the symptoms
rapidly increases. The muscular weakness becomes extreme,
the legs are no longer able to support the weight of the body,
and the animal falls en masse. The respiration becomes more
disturbed, sometimes jerking, difficult, and plaintive, most fre-
quently very slow, but in some instances slightly accelerated.
In some.it presents a remarkable intermittency, and its time of
stoppage coincides with that of the heart when the latter also
intermits.* In some cases 24 to 36 hours before death, there
has. been: noticed a paralysis of the lips, chiefly the upper, anda
thick .and .stringy saliva flows from’ the mouth. Diarrhcea
appears, and quantities of a very-~fcetid,. soft,. blackish paste

'* This also oceurs in dogs.— Exp., Appendix.

POISONOUS ACTION. “. 41

are discharged, and when the intestinal canal is completely
emptied, the diarrhcea becomes serous, the expelled matters
being liquid, blackish, and of a repulsive odour. The skin
becomes icy cold, the thermometer introduced into the mouth,
rectum, or subcutaneous cellular tissue ‘standing in some cases
at 31°5°C., or even before death at 25°C. Death generally
comes on quietly, but is sometimes accompanied by uncon-
nected movements.

When given in doses less rapidly fatal, so that each dose
would only produce shght symptoms, which would soon pass
away if the dose were not carefully repeated, the influence
which it exerts on the circulation is.by far the most pro-
minent phenomenon. At first there is slight excitement of the
heart, and its pulsations are a little quickened, then, later on,
they undergo a remarkable diminution, falling to 25 or even
20-per minute. If the dose be still repeated, the beats become
quicker and more energetic, rising to 55, 60, 65, and 70. The
cardiac: sounds are more clearly heard, more distinct from each
other than normally, and following a different rhythm, there
being occasionally intermittences, usually after the same number
of beats, but.this number varying in different subjeets, and in
the same subject according to the date of the poisoning. There
may be five or six pulsations between the intervals in some,
15 or 16 in others, and in yet others the intermissions are com-
pletely irregular. As the poisoning goes on, metallic ringing
appears, and becomes more and more distinct and sonorous.
Still later, a vibratory thrill appears, and is followed by a bellows
murmur. As death approaches the beats of the heart become
more and more rapid, being 92, 100, or even 114. The beats
of the pulse correspond in time to those of the heart ; but as the
latter increase in energy, in the same ratio the former become
more and more feeble, and less and less perceptible, till at
last, when poisoning is complete, it: becomes completely imper-
ceptible.

In doses so small as to have no poisonous effect, its action is
shown first on “the urine and secondly on the circulation. To
show * this, Messrs. Bouley and aaa give the following
typical ‘case :-— 7 : :

42 ON DIGITALIS, WITH SOME OBSERVATIONS U.S THE URINE.

A Hungarian horse of an excellent constitution, employed
in the service of the veterinary school of Alfort, aged 10 years.

Normal state at time of experiment:—Respirations 16,
pulse 37, full; mucous membranes rosy, digestive functtons~
intact,—all the signs of health.

Jan. 1, 1849, 10 AmM—6 grams (93 grains) of digitalis
powder were given in an electuary, when the animal was com-
pletely fasting. 2 pM —Respirations 14; passed water, which
was clear and plentiful. 6 P.m—Respirations 13; pulse. 35.
The water is always passed in abundance, and with the same
limpidity. The next day the effects had disappeared.

Jan. 4, 10 A.M.—6 grams given as before. At the time of
giving, respiration 16, pulse 37. 3 p.M.—Respirations 14; urine
clear, abundant, and odourless. 6 p.mM.—Respiration, circulation,
and urinary secretion the same. 8 pM.—Respirations 13;
cardiac beats a little diminished in intensity—otherwise quite
healthy.,

Jan. 5, 7 AM—Conjunctive pale, pulse 22, small and not
well felt ; the beats of the heart have diminished in intensity,
remain quite distinct, marked intermittence ,after.each. beat ;
respirations 6 to 7. Noon.—Same ‘state. 2 p.m—Pulse 25,
intermittence less sensible ; respirations 11; urine always clear,
less abundant. 7 P.M—Lying down quietly, the litter much
soaked with urine; pulse 30; intermittence has disappeared ;
respiration. 15.

. Jan. 6.—All.the symptoms of the medicine disappear, and
the functions return to their normal state.

Jan. 8.—6 grams of digitalis. At the moment of administra-
tion, pulse 30; respirations 10 to 11; thermometer in rectum
38°75°C., and 31:25°C., in the nasal cavities—all-the signs of
health. 1 pm.—Nothing particular. 4 pM—Pulse 28; no
change in the-rhythm of the heart ; respirations 10 ; urine clear,
and in considerable quantity, 36°25°C. in rectum ; a little ten-
derness of abdomen. 8 p.mM—Appetite good; pulse 26; cardiac
pulsations ringing ; respirations 14: urine always abundant.

Jan. 9.—Conjunctive pale; pulse 24, small, hardly sensible ;
beats of the heart enfeebled ; respirations 6; temperature
36°25° C. 2Pp.u.—Mucous membranes more coloured; pulse 30;

ACTION ON BLOOD. 43

beats of the heart more intense; respirations 12; urine less
abundant and less limpid. The functions now began to return
little by little to their normal state. In almost every case which
they experimented on, the history was exactly the same. In
these experiments we note a steady diminution of the respira-
tions, temperature, pulse, and intensity of cardiac beats, with
increase of the amount of urine, these effects reaching their
maximum in 24 to 36 hours, and then gradually disappearing.
The effects of digitalis upon other mammals and man seem,
ceteris paribus, to correspond closely to those on horses, except
that in the latter, and in herbivora generally, there is no
vomiting.

Having given this description of its general action, I will
now consider its action on various organs more in detail.

On the Blood—Majendie* states that decoction of digitalis,
when mixed with blood, prevents its coagulation, and Thackrah,t
that it suspended coagulation, and the clot at length resulting
was black. Davy says that 5ss. of extract of digitalis in zj of
water, added to 3ii of Llood as it flowed from the arm, gave it
the consistence of paste; after 36 hours it appeared much the
same; on the following day, the lower part was more viscid, as
if from subsidence of fibrin—it was coagulated on dilution
with water. It is impossible to draw any definite conclusion
from these statements, as to whether it has any specific action
on the blood or not, as the prevention or suspension of coagula-
tion in the first two cases may have been merely from dilution,
and the black colour of the clot may be due to the colouring
matter of the decoction. In the third case, the prevention of
coagulation seems due to the viscosity induced by mixing the
sticky extract with the blood, and as soon as this mechanical
effect was removed by dilution, the blood coagulated. Orfilat
found, that after poisoning dogs with watery extract of: digitalis,
the blood was fluid in all the five cases in which he mentions
its condition. He concludes that “alcoholic (resinous) extract
appears to act especially on the heart or blood, since this fluid is
constantly found coagulated immediately after death, whenever

* Quoted by Lancet, 1837.
t Orfila’s Toxicology, by Waller, 1817, vol. ii, p. 231.

44 ON DIGITALIS, WITH! SOME ‘OBSERVATIONS ON THE URINE.

this extract has been applied to the cellular tissue, or introduced
into the stomach.” This conclusion appears to be rather more
general than facts, at least those which he details, warrant, as
in five cases he found the blood coagulated in both ventricles
only in one case, in the right ventricle completely in one, and
partially in another, while it was fluid in the left ventricle in
both these cases, and in both ventricles:in‘two others. In four
cases in which dogs were poisoned with digitaline, I found the
blood coagulated in the right ventricle, the other being empty in
one case, partly fluid and as if curdled in both ventricles in
another case, and quite fluid in two: others.

What is wanted in this subject, however, is not so much loose
observations of this sort, but definite experiments on the changes
of the chemical relations of the blood in regard to the inter-
change of gases, such as Bernard made in reference to woorari,
and Harley has lately been doing with several of the: —
alkaloids.

On the Circulation—Before considering the effect of digitalis
on the circulation, it may be advisable to glance at the cause of
the pulse, and the arterial tension and the modifications they
undergo.* The pulse is the feeling of a sudden rise experienced
by the finger when it presses on an artery, and is caused by the
wall of the vessel, which had lost its cylindrical: form under thé
pressure, becoming tense and hard each time that the arterial
tension is raised by a‘systole of the heart, and tending to regain
its original form in which all the points in its wall offer an equa
resistance to the intense pressure of the blood within.

The arterial tension on which the pulse depends, is the force
expended by the heart, put in reserve by the aorta and large
arteries, and regulated by the elasticity of these vessels. If the
arterial system» were empty, and: the heart began to beat, the
blood: which it sent into’the arteries would remain there, very
little escaping by the capillaries,f as the arteries would have no
tendency to contract and press it on between each systole. As
_ ‘Marey, Physiologie Médicale de la Circulation de Sang.

t+ Wherever I: use the word capillaries, I do so in a general sense, and
without entering into the question as to the difference between capillaries

properly so called, and small arteries, so that if contractile power be denied to
capillaries proper, the word may be read “ sn:all arteries.”

CONDITIONS OF ARTERIAL TENSION. 45

they became fuller, however, their elastic force or the arterial
tension would increase, sending more and more blood through
the capillaries, till the quantity escaping through between each
systole exactly equalled the amount driven.in each time. The
arterial tension would then remain nearly fixed, or at. least
steadily oscillating round one point, becoming somewhat in-
creased as each wave of blood was sent in from the heart,
(each wave being equal, not only to the blood escaping by the
capillaries during its continuance, but to that escaping during
the interval, in addition; this additional. amount. of blood
distends the arteries, and increases their tension), and becoming
somewhat diminished as it escaped from the capillaries. The
arterial tension may be altered in two ways: (1) If, while the
cardiac pulsations remain the same (a) the capillaries be some-
what dilated, the blood will escape more quickly, and the
tension will be diminished. (6) If the capillaries be contracted,
less blood will escape, and the tension will be increased.

(2) The capillaries remaining the same, (a) if the beats of the
heart be reduced in number, less blood is sent in, and the ten-
sion falls; if they be increased, the tension rises. (d) If the
wave of blood sent in at each pulsation be increased in size, the _
tension rises ; if it be reduced, it falls. The arterial tension or
force with which they tend to drive the blood through the capil-
laries, is easily measured by the hemadynamometer, and its
amount expressed in inches of mercury. It is obvious, then,
that the arterial tension is the product of two factors, viz.—l1.
The amount of blood pumped into the arteries by the heart in
a given time. 2. The amount of blood escaping through the
capillaries in the same time. This was clearly enunciated by
Blake,* and more fully worked out by Marey. The first factor
depends on the amount of blood in each wave, multiplied by
the number of waves in the given time. The second, only on
the size of the capillaries, and the rapidity of the flow of blood
through them, and this latter, again, depends on the arterial
tension.

Influence of Respiration on Arterial Tension—lIf inspiration
and expiration be made with difficulty, as, for instance, by

* Edin. Med. Journ., 1839.

46 ON DIGITALIS, WITH SOME OBSERVATIONS ON TIE URINE.

closing one nostril, and thus obstructing the passage of air, the
arterial tension rises with expiration, and falls with inspiration.
But if respiration be freely performed as with open mouth, the
tension vises with daspiration, and falls with expiration. This
difference is due to the pressure upon the aorta and large vessels
of thorax and abdomen.

The enlargement of the thoracic cavity during inspiration
causes a vacuum which is at once filled by the external air, if
there be no obstacle to its entrance, and thus no great suction
is exerted. 1f the air enter with difficulty, the enlargement
of the thoracic cavity by the respiratory muscles acting like the
withdrawal of the piston of an exhausting syringe, greatly
lessens the internal pressure, and causes much suction, the blood
is drawn to the aorta and large vessels of the thorax from the
periphery, and the tension is much diminished. During ex-
piration, the contractility of the lung and the expiratory
muscles combine to expel the air; but this being done with
difficulty, the aorta and large vessels are much compressed, the
blood driven towards the periphery, and the tension raised.
While this is going on in the thorax, the diaphragm descends
into the abdomen during inspiration, lessening its cavity and
pressing on the abdominal aorta and increasing the tension,
while, during expiration, it ascends, lessening the pressure, and,
consequently, the tension. In anormal state, the thoracic and
abdominal pressures counteract each other; but when there is
any obstacle to the passage of air, the thoracic influence predo-
minates, and the abdominal, when there is any hindrance to
expansion of the abdominal parietes. In the normal state of
the animal economy, the number of the pulse and the arterial
tension are in inverse ratio to each other, the law given by Marey
on this point being, “The heart beats so much the more fre-
quently the less the difficulty it has in emptying itself.”*

I have entered at length on this question of arterial tension,
as a knowledge of the facts I have stated is necessary in order
to understand fully the way in which the circulation is modi-
fied by digitalis.

On the Pulse—When given in small doses, digitalis first

* Marey, op. cit.

a

ACTION ON PULSE RATE. 47

reduces the number of beats without rendering them irregular.
If its influence be pushed farther, the pulse remains slow, but
now and then a quick beat is interpolated.* These quick beats,
as. the influence increases, become more numerous, so that the
slow beats which now occur only occasionally become inter-
missions; and in a still further stage, the slow beats entirely
disappear, and the pulse becomes regular and extremely rapid.

This slowing, intermission, and final rapidity have been fre-
quently examined in animals, and though I am not aware that
the gradual succession of the quick beats to the slow, which
occasions the intermitterce, has been shown, probably from the
readiness with which it would escape the observation of the
finger, though at once detected by the eye, yet we see it with
great clearness in the case of Daniel G., and though this was
not during the increase but the decrease of the symptoms, I
think we may infer that these came on very much in the same
order in which they went off.

Some have held that there is an acceleration of the pulse
before the retardation appears. Bouley and Reynalf noticed
this in horses poisoned with large or moderate doses, but never
observed it after therapeutical doses had been given. The
doctrine of primitive acceleration from medicinal doses was
advanced by Sanders,t and supperted by Joerg§ and Hutchin-
son.|| This acceleration is of two kinds—Ist, following
en the administration of digitalis, and disappearing, or at least.
diminishing, much within half-an-hour or three quarters; and
2nd, amore permanent acceleration lasting for 24 to 48 hours
or longer: the effect of the temporary acceleration not passing
quite away during the interval between the doses, so that each
succeeding one raises the pulse a little higher than before, till
at last the acceleration gives place to retardation, and the
number gradully falls, passing even below the normal standard.
Though Sanders adduced 2,000 observations in support of his
view, yet most succeeding authors have denied it. I have

* Case of Daniel G. t Op. cit.

+ Sanders, ‘Ox Foxglove.’

§ Joerg, Arch. de Med., prem. ser., tome xxvii, p. 107 (II. and Q.).
|| Hutchinson (H. and Q.).

48 ON DIGITALIS, WITH. SOME OBSERVATIONS ON THE URINE.

occasionally found my pulse increased after taking digitaline,
but sometimes not; and even had the acceleration. been. fre-
quent, I would not have been; able to conclude very much from
it, as the pulse varies. not only with position but with mental
states, and that to.a considerable extent in a person of nervous
temperament. As to.the secondary acceleration, it is perfectly
true that you often find, on looking over a table of the pulse, a
seeming acceleration of the pulse on the second or third day
after beginning to take digitalis, yet it is to no great extent and
not greater than we find in health.

Though the primitive acceleration be denied by almost all
authorities, few doubt that digitalis causes retardation of the
pulse either immediately or in the course of a few days. I have
found that my pulse was sometimes quicker, sometimes slower,
while I took small doses of digitaline, but that under larger
doses there was marked lowering of the pulsations.

This lessening of the number of beats may have two causes :—
1st, it may be central, from the heart being primarily affected
by the drug, and contracting more slowly; 2nd, it may be
from contraction of the capillaries opposing greater resistance
to the passage of blood, and by thus requiring greater propul-
sive force, slowing the heart’s action according to the physical
law, that what is gained in power is lost in speed. If the latter
were the case, the blood flowing slowly through the capillaries
would cause the arteries to become full and tense, the heart
would be able only slowly to distend their resisting parietes,
and that only to a small extent; so that if we applied a
sphygmograph to the artery, we should find the line of ascent
very oblique, the height of the curve small, and the line of
descent also very oblique. But this is not the case, for if we
examine the tracing taken on March 15, we observe that whiie
the pulse is slow and the duration of each beat long, it presents
the very opposite characters of those we have mentioned, the
line of ascent being sudden and abrupt, the lever rising so
rapidly that its vis viva carries it too far, so that in its descent it
makes a point; the height of the curve is great, and the line of
descent is sudden and dichrotic. We see that the pulse in
Daniel G. presents the same characters. From these facts I

ACTION ON THE HEART. 49

believe we cannot avoid the conclusion that it exerts a slowing
action directly on the heart.

In poisoning by digitalis the force of the pulse bears no rela-
tion to that of the heart’s impulse; for while the latter is strong
and hammering, the former is small, thready, and nearly imper-
ceptible. Marey* gives this law, “The force of the pulse is not
in correspondence with the energy of the ventricular contrac-
tion, but is regulated by the state of the circulation in the
ultimate ramifications of the vascular system.” The force of
the pulse increasing with the arterial tension and diminishing
along with it, the weak pulse that occurs in digitalis poisoning
is due to the low tension: and this, again, as we shall see
hereafter, probably depends on the relaxation of the capillary
system, and the rapid transit of blood through it.

On the Heart—Having seen that digitalis exerts a primary
influence on the heart, the question now arises, What is this
action? And, first, as to its force. Does digitalis weaken the
muscular power of the heart? Does it increase it? or does it
do neither, but simply lessen the number of pulsations, either
by diminishing its irritability, and so rendering it less sensitive
to the stimulus of the blood, or by increasing the power of the
reculating part of the nervous system ?

Very different opinions have been held on these points by
different authors. Stanniusf says, that after the injection of a
strong dose of digitalis, there is at once a surprising feebleness
of the cardiac pulsations, which soon changes into paralysis of
this organ, at first partial and then complete ; and this he attri-
butes to paralysis of its muscular contractility, rather than to
any affection of its nervous arrangements.

- Kolliker,f Dybkowsky, and Pelikan hold a similar view. On .
the other hand, many observers have been inclined, by clinical
observation and physiological experiment, to think that digitalis
acts rather by increasing the power of the heart; and that it
causes death not so much by paralysis as by spasmodic contrac-
tion. Among others who have held this doctrine of stimulation

* Marey, Physiol. Med. de la Cire. de Sang, p. 235.
+ Stannius, quoted by Homolle and Quevenne, p. 234.
ft Carpenter’s Physiology, p 229.

50 ON DIGITALIS, WITH SOME OBSERVATIONS ON THE URINE.

may be mentioned Kinglake, Briquet, Handfield Jones, Fuller,
Winogradoff, and Traube. This opinion has been founded on
the observation that digitalis strengthens the weak and dilated
heart, and is injurious in hypertrophy, on the increase of the
arterial pressure often observed after its injection into the veins,
and on the contracted state of the ventricles found after death
constantly in frogs, but only occasionally in the mammalia.
Mosman thinks that it acts by diminishing the muscular irri-
tability of the heart, and thus lessening the number of pulsa-
tions without diminishing their force. Others believe that the
slowing of its action is produced through the nervous system,
and probably by an increased action of that part of it which
exercises a regulating influence.

The settlement of these questions is of extreme importance,
in reference to the medicinal administration of digitalis, in cases
of weak heart. In order to their solution, let us consider what
would be the effect of increasing the muscular power of the
heart. Supposing that the size of the capillaries and the num-
ber and size of the waves of blood remained the same, but the
muscular power of the heart were increased, how would the
arterial tension be influenced ?

The power of the heart being greater in proportion to the
resistance it has to overcome, it would act with greater abrupt-
ness, and force the wave of blood more quickly into the arterial
system; and as thus less blood would escape from the capil-
laries during the time of its systole, the arteries would be more »
distended and the tension higher. This greater amount of
arterial tension, in its turn, would force the blood more quickly
through the capillaries at first, and the tension would rapidly
diminish; but as the rapidity of the flow of blood would pro-
portionally decrease, the amount passing through the capillaries
in a given time would be much the same, and the mean arterial
tension much the same, but the oscillation much greater. If
now the capillaries be contracted, we will have the same
phenomena with a higher mean arterial tension, and if relaxed,
a lower tension. We would also say that when the capillaries
are contracted, less blood escaping by them during the systole,
there would be more surplus, and the height of the oscillation

PROOF OF INCREASED CARDIAC FORCE. 51

still farther increased; but the reverse when the capillaries
were relaxed. But what would be the effect of increasing the
size of the wave of blood, the muscular power remaining the
same? The increased quantity of blood would take longer to
be driven in, the escillation would not be abrupt, and, in fact,
it would merely cause a higher mean tension. The increase of
the wave, along with the increase of force, would cause a similar
effect.

Intermittence or slowness of the pulse would cause greater
oscillation, the long interval allowing the escape of more blood
from the capillaries; the tension would fall much. From the
length of the interval, the heart would have received more
blood than usual, and the succeeding wave would be larger; but
there being more room for it ia the arterial system, it would not
raise the maximum height of oscillation much, if at all, above
the normal. If the force of the heart were lessened, the oppo-
site results would take place, and the oscillations be less abrupt
and of smaller amplitude.

Let us now see with which of all these conditions the effects.
observed from digitalis agree.

In experiment 6, a strong well-fed dog was operated on. At.
3’ 48” the respiration was 20, the pulse 84, the mean tension
5°65 inches of mercury, and the oscillation 5—6°5. A grain
of digitaline was then injected into the jugular vein. At
59’ 45” the mean tension is 5°7, or only =},th of an inch
higher, but the oscillation is now 4—8, or 4 inches instead of
14. This increase in oscillation we have seen can be due only
to slowness or intermittence of the pulse or increase of the
force of the cardiac contractions, as far at least as the circula-
tory apparatus is concerned, and that in the former case the
maximum would not be much above the normal, which in this
case it is; and therefore we would consider as proved that the
force of the heart is increased, were it not that we observe the
remarkable decrease in the number of respirations, and are led
to inquire whether it is not to the greater influence of these,
rather than to any increase of the heart’s force, that the oscilla-
tions are due; and this indeed seems highly probable, as the

amount of oscillation is so great that we cannot easily imagine
E 2

52 ON DIGITALIS, WITH SOME OBSERVATIONS ON THE URINE.

it caused only by a difference in the rapidity with which the
blood is impelled into the arteries, and the fact that we notice,
that while the average oscillation at the cardiac beats in one
case is =3,ths of an inch, that at inspiration is 1 inch. Though
my own observations are as yet too incomplete to enable me
to eliminate the disturbing effect of respiration, and the obser-
vations of Winogradoff,* in the short abstract that I have seen
of them, are liable to the same fallacy, they yet seem to render
the increase of force somewhat probable. It is obvious, how-
ever, that by examining a tracing by an instrument such as
the registering hemadynometer of Setschenow, which was em-
ployed by Winogradoff, and which registers at once both the
cardiac pulsations and the respirations, and comparing its
indications with those which we have seen would occur from
increase or diminution of the heart’s force, the problem might
be solved with mathematical accuracy, not only for digitalis
but for any other poison.

Though unable at present thus to afford complete proof of
the increase of force, there is another line of argument open,
viz., the effect of increase or diminution of the contractile
power of the heart upon its impulse. If the contractile
power be increased relatively to the resistance to be overcome,
or arterial tension, the contraction will be rapid, and the
heart’s impulse abrupt and strong. If the power be lessened,
the contraction will be slow, and the impulse consequently weak.

Though this necessarily follows from physical laws, some
might yet be inclined to urge as an objection—* But you find
this strong and abrupt impuise in nervous palpitations and
weakly persons, and is it to be supposed that the power of the
heart is increased in these?” But in these cases, though the |
power of the heart be not absolutely increased, it is relatively -
to the resistance, for the arterial tension in these cases is low.
After the administration of digitalis, we find not only that the
impulse is abrupt and strong, showing increased power relative
to the tension, but that the tension itself is increased (Exp. V,
3, 25’ 50’), and the absolute increase of contractile power is
completely proved.

* Year Book Sydenham Society, 1862, p. 452.

ACTION ON THE HEART'S RHYTHM. 53

From the nature of the impulse generally remaining much
the same till the last, or nearly so, the power of the heart
appears to be relatively increased all along; but as the arterial
tension, though it may be increased at first, greatly diminishes
afterwards, the absolute force of the heart may be, and prob-
ably is, very greatly diminished before death.

From his observations on the effect of small doses, such as
slow the heart’s action, Winogradoff found that no change was
produced ; and as I found (Exp. X, 12, 35’ 20’) that not only
was there no change in the mean pressure, but none in the
oscillation, and the breathing quiet, though the pulse had fallen
from 140 to 78, though not certain, I am strongly inclined to
believe that the force of the heart is neither increased nor de-
ereased. Later on, and after a farther dose, as at 1.20’, I am
inclined to think that it may be feebler, though possibly it is
only because the pulsations are more frequent.

The observation of Stannius, that after a strong dose of
digitalis a surprising weakness of the cardiac pulsations be--
coming finally complete paralysis is observed, may be true in.
regard to overwhelmingly large doses; and in the sheep, which
I killed by 2 grains, the condition of the heart was not noted,
but in general the impulse is increased, so generally in fact,
that often I have not noted it, looking on it as to be always
expected.

(2) On the Heart's Rhythm.—Dybkowsky and Pelikan* found
in frogs which were poisoned by digitaline (or other cardiac
poisons, producing an identical effect), the rhythm of the
heart was at first unchanged, but soon after three, five, or
ten minutes (according to the poison), irregularity was notice-
able. This was of two kinds—-(1.) The ventricular contractions
became peristaltic, so that after the contraction of the auricles
the ventricle did not contract as a whole, but first its upper
third, whence the. contractions gradually passed down to the
apex ; but before this had contracted the upper third was again
dilated. Two or three minutes before complete paralysis the
contractions became still more irregular, so that the upper or

* Mém. de la Soc. de Biologie tome iii ser. 2, p 97.

54 ON DIGITALIS, WITH SOME OBSERVATIONS ON THE URINE

right half was dilated, while the lower or left half was con-
tracted, and sometimes the auricles did not contract simul-
taneously. Finally, when the ventricle completely stopped,
one or more palpitating points could still be observed in it.
(2.) The second form, which was especially notable in poison-
ing by digitaline and green hellebore, consisted in a notable
diminution of the number of beats, the heart contracting regu-
larly, but very slowly, just as under galvanisation of the vagi.
This sometimes happened before peristaltic movements occurred,
or even after their appearance. Fagge and Stevenson* found
that the beats are not necessarily diminished, and sometimes
the ventricle contracted only once for two pulsations of the
auricles, and often one part, generally the apex, continued
white, and contracted while the rest dilated regularly. They
also observed palpitating points such as Dybkowsky and
Pelikan had described, and liken them to little crimson pouches
on the white contracted ventricle. All these observers found
that the ventricle stopped always in a state of firm con-
traction.

(3) Impulse—The cardiac impulse seems almost invariably
to be increased both in the lower animals and man, and becomes
abrupt and hammering.

(4) Sounds.—When digitalis is given in poisonous doses, after
the pulse becomes intermittent, a change is noticed in the
cardiac sounds, there being first a vibratory thrill, and then a
lowing murmur with the first sound. The first I have not
observed; but Dr. Gamgee felt it in a dog on which I was
experimenting. The blowing murmur with the first sound I
have noticed several times. It occurs in horses, dogs, and the
human subject, and probably in all mammalia. It is probably
due to mitral or tricuspid regurgitation from irregular contraction
of the musculi papillares. I noticed it in one dog after section
of the vagi and before digitaline was injected; but unfortu-
nately, not having listened before dividing them, I cannot say
whether or not it was due to their section.

On the Arteriai Tension.—In small doses, digitalis, injected
into the veins, causes no change, either in the mean tension: or

»* Proceed. Roy. Soc., vol. xiv, 270.

ACTION ON THE CAPILLARIES. 55

amount of oscillation. In larger doses it almost invariably —
increases the tension, sometimes very slightly, at other times
considerably ; and in one case of Mr. Blake’s, where he injected
it into the arteries, the rise was enormous, the maximum being
14 inches instead of 5. The tension attains its maximum in
three or four to nine or ten minutes, and then gradually dimi-
nishes. The oscillation is generally greater at first, and also
eradually diminishes. Sometimes there is a rise just before
death, and the tension diminishes very slowly after the heart has
ceased to beat.

On the Capillaries—In small doses, digitalis, while it slows
the heart’s action, seems at the same time to contract the capil-
laries. If we look at the results of Exp. X, we see that,
although the cardiac pulsations were reduced from 140 to 78,
yet the mean tension remained the same. This can only be
explained by supposing that the capillaries are contracted, or
that the heart is sending in at each stroke nearly double the
amount it did before, This latter hypothesis seems extremely
improbable, for though the blood has longer time to collect in
the heart, yet we find when the same time is given by slowing
the cardiac pulsations directly, without any action on the
systemic capillaries, as we can easily do by galvanizing the
vagus, the arterial tension at once falls to a very considerable
extent. At other times we find that the tension not only does
not fall, but rises to a considerable extent, asin Exp. VI, where, at
3.41’ the number of pulsations was 85, and the mean tension 5°65,
and at 4. 4’ the pulse was 80, with a mean tension of 7 inches—
a fall of four beats, with a rise of nearly an inch and a half.
Few observers, if any, have noted a higher rise of the arterial
pressure than 84 inches, which was the maximum of oscillation
in this case, when they injected preparations of digitalis into the
veins, so that they passed through the heart first before getting
into the systemic circulation, but on one occasion in which
Mr. Blake injected infusion of digitalis into the carotid, pushing
it with some force, so that it entered into the systemic circula-
tion and had thus an opportunity of acting on the capillaries
before reaching the heart, the pressure rose to 12 or 14 inches.
From all these facts, I think we must conclude that it really

56 ON DIGITALIS, WITH SOME OBSERVATIONS ON THE URINE.

possesses the power of contracting the capillaries which Mr.
Blake assigned to it.

As the poisonous action of digitalis becomes more fully de-
veloped, the capillaries become dilated (and probably paralysed),
the arterial tension falls, and, there being less resistance, the
heart’s action becomes part passu (Bouley and Reynal) more
violent, while the arterial pulse becomes more weak and small,
and often seems rather a kind of indistinct wavering than
decided strokes. The objection may be raised that this is due
to the rapidity of the pulse, and the small size of the waves of
blood ; but we find that the heart is acting powerfully, and if
the capillaries were either of the same size or contracted, the
impulse being brisk, the waves of blood, however small, would
each give a distinct stroke to the finger, as is shown by Marey.*
Owing to this dilatation of the capillaries, and the easy transit
of blood through them, we find that almost immediately after
death the arterial system is empty, and the venous full and
turgid. From the patency of the capillaries less of the foree
of the heart will be expended in forcing the blood through them,
and we would expect to find a higher pressure in the veins, at
least if the heart be not much weakened. This I have not yet
been able to determine. It would be well also to see, in the
web of a frog’s foot, the changes caused by digitalis when
applied locally or generally. )

Occasionally, however, at or immediately before death, this
relaxed state of the capillaries seems to give place to one of
spasm, so that the arterial tension rises and cuntinues at the
same height for a considerable time after the heart has ceased
to beat, diminishing very slowly as in Exps. IV and VI. ‘This
could not possibly be owing to clots forming in the apparatus,
at any rate in VI; for if the tube had been stopped by one, the
two columns of mercury would have found their level by the
higher column decreasing, while the lower rose, and not by the
upper one remaining stationary, while the lower one rose up to
its own level.

Of the changes in the cranial circulation, caused by digitalis
I can say nothing, several trials which I made on animals to
trephine and lute in a glass plate having proved total failures.

* Marey, op cit., p. 243.

ACTION ON RESPIRATION AND DIGESTION. 57

On the Respiration.—Bouley and Reynal* found that digitalis
given to horses in large doses at first caused acceleration of the
respirations as well as of the pulse; and after this exciting
action had passed away the number became remarkably dimi-
nished, falling to 8, 7, or even 6 per minute, being deep,
broken, and trembling, and, in some instances, remarkably inter-
mittent, the intermittence coinciding with that of the heart.

Messrs. Delafond and Dupuyf also noticed primary accelera-
tion with subsequent retardation. My own observations on the
respiration are extremely imperfect ; and though I have no note
of previous acceleration in large doses, such may have existed.
In most cases, the respiration has become slower and deeper,
and, in one case, in a dog (Exp. XII), I noted that it was not
only slow (8 in 65 seconds), but distinctly intermittent, the inter-
missions being of 4 seconds’ duration, and coinciding exactly as.
to time and duration with those of the pulse. At the time I
noted this, and for a good while after, I was perfectly unaware
of Messrs. Bouley and Reynal’s observations.

In smaller doses, the primitive acceleration has not been
noticed, and the decrease has gone on gradually from the first.
In one case,f after injection of a small dose of digitaline, I
observed acceleration of the respiration, which might have been
accidental ; but there was no apparent cause for it, and I had
not noted it in the dog before, nor have I since, though he has.
been under constant observation.

In several sick persons, in whom M. Joret$ noted the respira-
tions before and after taking digitalis there was sometimes
acceleration, and sometimes slowing of the respiration ; but the
results show nothing, and he himself only mentions them in
passing. M. Duroziey|| has not found any slowing of the respi-
ration.

On Digestion—In small doses, digitalis is said to cause
increased appetite. While taking digitaline I have had a good

* Op. cit.

+ Bull. del Acad. de Med., tome xvi, p. 428 (H. and Q.).
ft Exp. XJ, vide p. 127.

§ Archives de Med., 2 ser., tome iv, p. 27 (H. ard Q.).

i Thesis, Paris, 1853, p. 36 (H. and Q.).
{| Germain, Med. Times and Gaz., Sept. 7, p. 250, 1861.

5S ON DIGITALIS, WITH SOME OBSERVATIONS ON THE URINE.

appetite, but I had this as well while I was not taking it; nor
do I think my appetite was better after recovering from the
sickness caused by the digitaline, than it was before beginning
to take the drug, as Withering* found, but his observations had
been made on invalids.

Its emetic and cathartic effects, when given in large doses,
have been long recognised, and seem to have been the first pro-
perties to attract attention. Before these effects appear, how-
ever, there are symptoms of digestive derangement of a slighter
character, consisting of loss of appetite, bad taste in mouth,
borborygmi, abdominal distension, pain in the stomach, occa-
sional nausea, and a vague desire to vomit.f When vomiting
occurs, it is violent and painful. Fauret describes its characters,
as seen by him in dogs, as being peculiar in the expulsive effort
of the stomach, far from being the »principal circumstances,
as in vomiting from other causes is only the result of a series
of convulsive contractions, beginning in the limbs, and extending,
first to the lower part of abdomen, and then to the upper part
and thorax, and under violent contractions the stomach is
exposed to pressure, and expels its contents. The vomited
matters are mixed with bile, sanguinolent mucus, and fluids of
the stomach. The vomitings are intermittent, and the animal
rapidly recovers from the effects of one, and seems well till
attacked by another fit, the amount vomited after the first fit or
or two having emptied the stomach, being very sinall. This
description I think correct in regard to dogs, except the small
share which Dr. Faure seems inclined to give the stomach in
the act of vomiting; for this must be considerable, if we may
judge by analogy from the human subject, as well as by the
extreme pressure necessary to make tle stomach reject so little
as a teaspoonful at a time, unless it were contracting violently
itself. The sensation I experienced, while vomiting on the
morning of the 16th March, was as if the stomach were con-
tracting with extreme violence as in cramp, much more so than
in vomiting in general, and a feeling of soreness continued
for some time after. The stomach was entirely empty on that

* Withering, ‘ On Foxglove.’ .
+ Appendix, March 17. + Edin. Med. Journ., Nov., 1864, p. 461.

ACTION ON THE BOWELS AND SECRETION. 59

occasion, and nothing (except perhaps a little mucus) was
ejected. After taking 30 milligrams more, during the course
of the next day, the vomiting recurred on the morning of the
17th ; and on this occasion I vomited some bilious matter, liquid,
and resembling somewhat yolk of egg, and the crampy contrac-
tion was less marked. Dr. Faure says that sometimes the con-
vulsions seem directed towards the intestines, and after contrac-
tions of the limbs, &c., such as he describes before -vomiting, a
glairy, greenish substance, often tinged with blood, is expelled
per anum. In horses there is no vomiting,* and the stools are
first natural, then covered by mucus, and gradually becoming
softer, are first pasty and then liquid, blackish, and feetid. This
blackish colour may be owing, however, to the colouring matter
of the digitalis.

On the morning of the 17th March, shortly after vomiting, I
had a loose stool, but no persistent diarrhoea, and in small doses
it seems to produce constipation, and this is occasionally the case
even when there is a fatal result.

The action of digitalis on the intestinal canal is not merely
local, for it produces it quite as certainly when introduced into
the subcutaneous tissue or injected into the veins. The pain in
the epigastrium, which.I felt after the vomiting passed off,
remained for several days, and just as it was going away it was
succeeded by severe pain in the left side, apparently in the
descending colon. At first I was afraid it was inflammatory ;
but when taken in connection with the peculiar form of the
stool passed on the 20th March, which was that of small round
pellets, like those of rabbits, I am now disposed to attribute it
to spasmodic contraction of some part of the intestines similar
to that which I think occurred in the stomach. ©

On Secretion —On the Saliva—When digitalis is taken in
rather large doses, there is occasionally a feeling of dryness in
the mouth,{ along with some salivation,§ but it is not con-

* Bouley and Reynal, op. cit...

+ Case related by Dr. Mazel, Gazette des Hépituux (vide Edin. Med. Journ.,
18 yy p. 170).

t Case of Daniel G.

§ Christison, ‘On Poisons, p. 887, and Shera, quoted: by Holland, Med.
Notes and Reflect., p. 555.

60° ON DIGITALIS, WITH SOME OBSERVATIONS ON THE URINE.

stantly observed.* I have occasionally noticed the salivation
from poisonous doses.t Bouley and Reynalf observe that tie
saliva is rather thick, and flows freely from the mouth.

On the Seerction of the Nasal Mucous Membrane.—Stadion$
found that a peculiar affection of this membrane resembling
corriza, was a characteristic symptom of digitaline, and I found
that for some days before vomiting came on, clear drops of wate
were always gathering at my nose: but I had no reason to
suppose that I had caught cold, and I believe. this increase of
the secretion in my case is confirmatory of Stadion’s view.

The conjunctival secretion was found by Bouley and Reynal
to be dried up in poisoning by large doses.

On the Sweat—In cases where it has been taken in doses a
little too large, for some time there is usually profuse sweating.{
In poisoning, hot sweats appear at first which, as death ap-
proaches, dry up and become cold.

On the Urine—Since Withering first brought the diuretic
properties of digitalis into notice, it has steadily kept its place
as one of the best remedies under this class. But though most
members of the medical profession believe that it possesses this
power, M. Duroziez,** though not entirely denying it, maintains
that it is much less frequent than has been alleged, and says
that he has not met with a single case clearly proving it. Dr.
Germaineff goes still farther, and boldly declares that “there is
no proof that digitalis possesses diuretic properties, the reputa-
tion conferred upon it to this effect by Withering having been
accepted without discussion ; and that the diuresis, which often
follows when an amelioration of the condition of the circulation
has been produced by it in organic disease of the heart, is only
a mediate effect resulting from the return of the circulation to
its normal condition.” The observations on its diuretic effect,
especially in anasarca, and to a less degree in effusion into
serous cavities, are so numerous that we can hardly doubt its

* Holland, op. cit., p. 555. t+ Exp. VI, 4, 42. t Op. cit.
§ Year Book Sydenham Society, 1862, p. 451.
|| I was then ignorant of Stadion’s observations.

{ Christison, op. cit., p. 888.

** Thesis, Paris, 1853 (H. and Q., p. 296).

tt Med. Times and Gaz., Sept. 7, p. 250, 1861.

ACTION ON THE URINE. 61

existence. Among others who have remarked it, may be men-
tioned Christison, Andral and Lemaitre, and Hervieux. Several,
who admit its diuretic action in disease, entirely deny its possess-
ing this power in health,—as, for instance, Krahmer, Kluyskens,
Vassal, and Shohl. Others again, as Pereira, say that it some-
times acts asa diuretic even in health. Joerg,* who experi-
mented on several healthy persons, men, women and children,
found the urine increased, with only one exception. Hutchin-
son, in experimenting on himself, found it increased in three
experiments. Hammond, from a three days’ observation, says
that the amount in health was 1474 cc, and, after taking
60 drops daily of the American tincture, found it was 1822.
The amount of water in the ingesta was not determined. Bou-
ley and Reynal, and Dupuy and Delafond noted the diuretic
action in health markedly on horses. In my own case, I found
that, with small doses, the urine varied just as my pulse had
done, being generally increased to a slight extent while I took
the digitaline, but sometimes not, while, with large doses, the
diuretic effect was marked, as will appear from the following
table :—

Feb. 2—14...... 1804 cub. cent. or 45°9 oz. Dose.

Grains. [ 10 milligrams of ex-
» 15—24...... 1826 9 46°6 ,, 35 tractiform digi-
taline.
» 25—Mar.2.. 1303 a 45°9 ,,
4 milligrams powdery
Mar. 83—6...... 1216 . 42°8 ;, 5 digitaline obtained
from Morson.
yp @—l14...6.. 1421 Po 50°0 ,, 2. 12 milligrams.
: 30 milli in-
ee fea 1O.c.c02 1187 - i a cee -
3) 17—22 eee e. 1517 33 53°4 ry)

From this we notice, that with the larger doses, especially of
the digitaline in powder, there is a marked increase in the
amount of urine before intoxication appears, then a sudden fall
during its continuance, and another rise of still greater extent
after it has passed off, and after the medicine had been discon-
tinued. The actual increase in the amount of urine may to
some appear small; but when it is considered that the amount

* Joerg, Archives de Med., prem. ser. t. xxvi, p. 107, H. and Q.

62 ON DIGITALIS, WITH SOME OBSERVATIONS ON THE URINE.

of fluid ingested is the same, and that, in a normal condition,
very rarely has a large amount of urine been passed on more
than two consecutive days, the distinct and persistent diuresis
from the digitaline is remarkable. Winogradoff, from his ex-
periments on moderately large doses of digitaline, concluded
that it cannot strictly be called a diuretic, as it was given
for five days without marked increase in the quantity of urine.
The doses given were from 33; to 2? of a grain. Stadion, sub-
jecting himself to a weighed diet of milk, eggs, bread, and butter,
found that during a period of 18 days, during which he took —
digitaline, beginning with 2 milligrams the first day, and in-
creasing it by one each day, the urine was somewhat diminished.
The amount of urine in my own case was markedly diminished
during the period of intoxication, when the gastro-intestinal
canal was most affected: and in the case of Daniel G., when the
pulse was most affected, it fell from an average of between 40
and 50 oz. to 30 oz. on December 2, 25 and 26 oz. on the 3rd
and 4th, and 18 oz. on the 5th and 6th, again slowly rising till on
the 10th it rose from 25 to 44 oz., and then remained at its normal
standard. In very large doses it occasionally causes not only
diminution, but total suppression of urine—lasting for three
days in a case quoted by Christison,* and one narrated by
Mazel.— Bouley and Reynal noticed suppression in horses for
about 36 or 48 hours,and then followed by abundant diuresis,
In Mazel’s case it is not noted whether or not there was
diuresis, only that urination was performed freely; but as it
was after rising to make water that death occurred, it seems not
improbable that it was present. Christison thinks that the
sedative and diuretic actions are mutually incompatible ; but in
horses Bouley and Reynal found them distinctly co-existing ;
and though my pulse was somewhat lowered at March 13, there
was yet diuresis. It is probable, however, that when the action
on the pulse is so great as to cause intermittence, the diuresis
is diminished. It increases the frequency of micturition.t
From all these observations, then, we may conclude—(1)

* Edin. Med. Journ., vii, 149; Christison, ‘On Poisons,’ p. 889.
+ Mazel, Gazette des Hopitaux in Edin, Med. Journ., 1864, p. 169.
$ Med. Times, 1855, p. 381.

ACTION ON TISSUE CHANGE. 63

That in anasarea, especially from heart disease, digitalis acts as a
diuretic. (2) That it sometimes, but not always, acts as such
even in health. (3) That when it acts upon the intestinal canal
so as to cause vomiting and purging, or when it affects the pulse
so much as to cause intermittence, and possibly before this
takes place, diuresis is much lessened, though a moderate degree
of retardation may coexist with diuresis. (4) That in large doses
it causes suppression of urine, lasting in the human subject for
three days.

On the composition of the urine, Stadion,* having put him-
self on a weighed diet of bread, butter, milk, and eggs, and
determined the normal amount of his urine and of its con-
stituents, took digitaline for 18 days, beginning with 2 milli-
grams, and daily increasing the dose by 1 milligram,
found that the urine was not only diminished in quantity, but
its specific gravity and chief solids were also diminished. The
acid reaction was unaltered, but the urea, chloride of sodium,
phosphates, and sulphates were lessened, and the uric acid in-
creased. Urea was determined by Liebig’s method, after the
elimination of phosphoric and sulphuric acid and chorine, and
the uric acid by Neubauer’s method. He draws the conclusion
that it causes rapid wasting of the body, and depression of the
exchange of material.

Winogeradoff,t from observations made for five days on several
healthy persons of all ages, while taking from ;3, to ? of a
grain in the 24 hours, found that there was no marked increase
in the total quantity of urine, and in one case a diminution.
In every case there was a falling off in the quantity of urea
and chlorides and salts which resist calcination, but there was
invariably an increase of the phosphoric and sulphuric acids.
The results which I obtained will be seen from the following
table, and the tables in the Appendix :—

* Stadion, Year Book Sydenham Society, 1862, p. 451.
+ Year Book Sydenham Society, 1862, p. 452.

64 ON DIGITALIS,

WITH SOME OBSERVATIONS ON THE URINE.

‘5 nd Work. Dose,
o cs) 3 g = < 8 2 g os o [ov Ped
= # | £& |€2!1-¢ |1#215 | 812 18 lséiss a
a 5 | > |85|2)8" |a1a | & la leis! g g
rel ere aah Sflea\ 2 em
ea oe | SSS |
oe = = a oS =
Nov. Dec.
J9—12 1048 | 31°88 | 30°4 | 2°67 | 2°54 6 43°6 | 68 8
13—22 1189 | 30-90 | 26 2°75 | 2°31 7°2 | 41°2 | 64°3 | 74 | 5 73 | 1-200th
dan.
4—16 1190 | 34°46 | 28°8 | 3°14 | 2°74 6 84°3 | 78 7215 72
Feb. ;
17—1 1196 | 31°63 | 27°4 | 8°09 | 2°734 | 7°4 | 41°3 | 76 8 44 | 74 | 1-16th
Keb.
2—14 1304 | 81°90 | 25°4 | 3°14 | 2°577 38°d | 71 8 33 | 65
15—24 1326 | 35°77 | 28°56] 3°36 | 2°69 7 37°6 | 75°6 | 74 | 3% 3-20th 10
extractiform
Mar.
25—2 1823 | 33°95 | 26°1 | 3°26 | 2°5 7°6 | 88°2 | 71°4 | 7 4}
38—14 1352 | 35°46 | 28°5 | 3:09 | 2°64 6°6 | 36°8 | 68 73 4 6-50th 9°6
Morson’s
15&16 | 1187 | 85°18 | 30°4 | 3°11 | 2°75 5°7 | 38 65 8 23 | 85 | 9-20th 30
17—22 1517 | 37°49. | 24°7 | 2°88 | 1°9 8°4 | 37°7 | 66 8 3

In determining the
acid, I used nitrate of

amount of urea, chlorine, and phosphoric
mercury for the two first, and nitrate of

uranium for the last, according to the processes described by
Neubauer and Vogel in their work on urine.

From this table it will be seen, that, like the pulse and the
amount of urine, the urinary constituents vary considerably when
small doses of digitaline were taken; but that, when the dose
was large, the pulse fell, the urine increased, its sp. gr. was
diminished, the urea was increased, and the PO, and Cl were
diminished. For comparison of these results with those of
Winogradoff and Stadion, I tabulate them—February 15—24,
I do not reckon, as I am not sure of the quality of the

digitaline.

Constituent. Stadion. Winogradoff. Brunton.
Water ...eeeee+-| Diminished. No marked increase. | Decided increase.
jibe. wey rrr ree Less. More.
Phosphoric acid..| Less. More. Less,
Chlorine....«...| Less. Less. Less.

Sp. QY.cece eeceaene Less. ee ee Less.

ACTION ON TEMPERATURE. 65

With the exception that I experienced diuresis, and had the
urea increased instead of diminished, my experience agrees with
that of Stadion. From the large increase of urea with less
work, I believe that when it acts as a diuretic it increases
tissue change ; and the diminution of phosphates, I think, is in
a great measure due to the dislike to and inability for any kind
of mental work.

On the Temperature of the Body.—Messrs. Bouley and Reynal*
found that poisonous doses of digitalis produced first increase
and then decrease of the animal temperature, but that thera-
peutic doses caused a steady diminution, without previous
increase ; Messrs. Aug, Dumeril, Demarquay, and Lecointe,f in
experimenting on dogs with digitalis and digitaline, the latter
in the dose of 10, 20, and 25 milligrams, and the extract of
digitalis 1 to 4 grams in a period of 11 or 12 hours found
the temperature rise eight times from 1° to 2°, and in the
only case in which it was lowered they used 50 milligrams of
digitaline, and death ensued within the hour. Schwelgue says
the fall of the pulse is accompanied by a fall in the animal
temperature. In Exp. XIII I noticed a remarkable diminution,
the animal feeling as cold as if dead for some hours before death
actually occurred, and in several cases I have noticed the limbs
grow cold a little while before death. Dr. Mazel, in his case
of poisoning, noticed that the temperature of the skin in those
parts exposed to the air was lower than usual. Hertz§ says
that there is first increase and then decrease of the tempera-
ture. Traubel| found that when infusion of digitalis was given
in acute rheumatism the temperature fell either with or a short
time after the reduction of the pulse appeared. Schneider|
says that the lowering of the temperature is independent of the
slowing of the pulse, and begins from 36 to 60 hours after
beginning to give the medicine; while the former begins within
from 24 to 48 hours, and they both continue to fall after the

* Op. cit.

+ Comptes Rendus, Mai, 1851, p. 801 (H. and Q.).

t Edin. Med. Journ., 1864, p. 168.
§ Bull. de Therap., Feb. 28 and March 15, 1862. Year Book Sydenham

Society, 1862, p. 110.
|| Annuaire de Thérapeutique, 1859, pp. 82-88.

-€6 ON DIGITALIS, WITH SOME OBSERVATIONS ON THE URINE.

remedy has been discontinued. Wunderlich* says that when
digitalis is given in typhoid fever, in doses of 30 to 60 grains in
three to five days, a remarkable diminution of the number of
pulsations, simultaneously with marked decrease of temperature,
takes place generally about the fourth day, and they fall after
the medicine is discontinued; but the effect on the pulse is
much more permanent than on the temperature, lasting in many
cases for several weeks in succession. It should only be used
when the pulse is 120 and the evening temperature is 105°, and
with slight remissions; and less of the drug is required to
produce its effects than in pneumonia and other acute diseases.

Notwithstanding the opinion of M. Schneider, it seems
probable that the diminution of the temperature from thera-
peutic doses of digitalis depends, at least in the first instance, on
the slower circulation of the blood through the periphery; but
though the weight of authority is in favour of this opinion, it
is possible that the diminution is owing to alteration of tissue
change, and that another alteration is the cause of the tempera-
ture rising while the pulse remains slow. I think that it is not
so much to the change in the circulation that the coldness in
poisoning is owing so much as to absolute decrease of the animal
heat, for on one occasion the breath felt cold to the hand, and
the relaxed state of the capillaries, while it would aid in rapidly
-cooling the blood and thus the internal parts, would rather tend
to keep the periphery warm.

Traube thinks that the lowering of the temperature is due to
less rapid oxygenation of the blood from the slower current
through the lungs. |

On the Nervous System.—In large doses in animals digitalis
affects both the sensory and motor system, causing a comatose
or semi-comatose state, and insensibility to external impres-
sions, muscular weakness which causes a stumbling, uncertain
guit, and an appearance of a kind of paralysis of the hind
quarters, so that the animal with difficulty drags them after
him. In some cases there are twitchings of the muscles of the
face and ale nasi, or the muscles of the skin over the body,
causing an appearance which is sometimes mistaken for convul-

* Med. Times and Gaz., July 12, 1862, and Arch. d. Heilk., 1862, p. 118.

ACTION ON THE NERVOUS SYSTEM AND EYES. ~~ 67

‘sions ;* and in other cases, and perhaps more frequently in dogs,
at least there is staggering as if giddy, and convulsive move-
inents of the extremities.

In smaller doses it produces giddiness, headache, tinnitus
aurium, disturbed vision, dazzling, weariness, languor and
general prostration, and in some cases a kind of intoxication,
weakening of the intellectual faculties, and hallucinations and
delirium, or even symptoms of acute mania. In some few cases
digitalis acts as a soporific. I am not sure whether to attribute
it to the digitaline or look upon it merely as a coincidence; but
on March 5, after taking 12 milligrams of Morson’s digitaline,
-I experienced a remarkable sleepiness at night, which continued
till the 12th, when symptoms of abdominal irritation began to
manifest themselves, and these increased till vomiting occurred.
On the 14th I felt great languor and prostration, and either on
this day, or at least while the languor continued, the mental
faculties seemed enfeebled, as, while reading for an examina-
tion, the eye glanced over the words, but the mind refused to
receive or retain their import. The derangement of sight
which I noticed was of two kinds—lIst, a general mistiness
of objects, such as is seen before fainting; and 2nd, a large
bright spot advancing before me, which sometimes resembled a
ring showing prismatic colours faintly, and similar in character
to, though less distinct than, that seen round a light when digi-
taline has been introduced into the eye. The headache ocea-
sioned by digitalis sometimes, as in the case of Daniel G.,
persists for some time after the medicine has been disused.

The motor nerves of musclesf have their power impaired by
digitalis, as the muscles of the limb of a frog, which was
prevented by a ligature from receiving the poisoned blood
circulating through the rest of the body, preserved their excita-
bility from eight to sixteen hours longer than the other limbs.

Action on the Eyes.—When digitaline is introduced into the
eye, it causes smarting and profuse lachrymation, which passes
off in a short time, and nothing more is felt, except perhaps an
occasional rough feeling of the conjunctiva, till four or five

* Bernard, Legons de la Physiologie.

t Mém. de la Soc. de Biologie, tome 3, ser. 3, p. 97.
F 2

68 ON DIGITALIS, WITH SOME OBSERVATIONS ON THE URINE.

hours after, when, on looking at a light, you see it surrounded
by a halo, presenting the prismatic colours, and not quite close
round the light, but with a dark space between. This halo
increases in diameter the farther you move from the light, and
becomes smaller and narrower as youapproach. I have noticed
an appearance exactly similar when light cirrhi were crossing
the moon. Homolle and Quevenne say that a slight opalescence
is noticeable in the lens (crystalline), and the pupil is somewhat
dilated and less contractile. I did not notice any particular
difference in the pupil, and the appearance is not due to its
dilatation, for I found it quite distinct on looking through a pin-
hole in a card. Though on looking I could not detect any
opalescence, Messrs. Homolle and Quevenne are probably right
as to there being opalescence somewhere, for this would produce
the effect noticed.

On the Uterus—Mr. Dickinson* found that digitalis has a
powerful influence in causing the uterus to contract and stop
hemorrhage. A few minutes after the draught of Jiss. of the
infusion is swallowed, the patient complains of acute pain in
the back and hypogastrium, like those of the first stage of
labour, then blood, solid and fluid, is ejected, and the discharge
is absent for some hours, when the pain subsides, and it
returns, but less and less, after each dose, till it disappears.

On the Genital Organs.—Stadionf finds that digitalis and digi-
taline possess the power of temporarily annulling the activity
of the sexual organs, and is thus a true antiaphrodisiac; with
this conclusion I am disposed to agree. M. Brughmans{ has
stated the same thing, and advises its use wherever turgidity of
these organs is to be averted, whether as after-treatment of
surgical operations or for other causes.

Mode of Action of Digitalis—Having considered the general
action of digitalis, and the manner in which it affects different
parts of the animal economy, we now come to a question of
ereat difficulty, and one on which there has been much dispute
—the mode in which it acts.

* Med. Chir. Trans., vol.:39, p. 4.
t+ Year Book Sydenham Society, 1862, p. 451.
t Revue Med. Chir., Paris, Dec. 1858. Half-yearly Abst., vol. 24, p. 108.

MODE OF ACTION OF DIGITALIS. 69

This question has generally been limited to the mode in
which it affects the heart, and the two great theories on this
point are—(1) that of Traube,* who thinks that digitalis
exerts its influence on the heart through the regulatory (vagus)
and musculo-motor system of nerves; and (2) that of Dybkow-
sky, Pelikan, and Kolliker, that it exerts its action on the
reculating and motor apparatus, contained in the heart itself,
without the intervention of the vagi. Traube at first proposed
the theory that digitalis (1) first stimulated the regulatory
nerves, (2) paralysed them, and (3) paralysed the musculo-
motor nerves. The musculo-motor nerves are the cardiac
ganglia, which can of themselves carry on the rhythmical
movements of the beart; but these are aided by the sympa-
thetic, as, according to the theory of Von Bezold, the cardiac
ganglia originate continuous excitations, which, meeting with
constant resistance in the cardiac nerves, are only able to over-
come it periodically, and then to act on the muscular tissue.
To these ganglia two sets of fibres pass from the central nervous
masses—‘“ One set reaches the heart partly through the cervical,
and partly through the dorsal and lumbar portions of the
sympathetic cord. The latter fibres originate in the medulla
oblongata, and descending to the cervical, and to some extent
through the dorsal and lumbar parts of the spinal cord, emerge
at many different points to unite with the sympathetic nerve.
The function of all these fibres consists in conveying an exciting
influence from the medulla to the heart, so that the resistance
in the cardiac nerves is more frequently overcome, and the
heart beats more vigorously and with greater rapidity. The
second set of fibres, when acting, increase the resistance, and
they run in the vagi, and probably also originate in the
medulla. When strongly excited they can increase the amount
of resistance to so great an extent that it becomes superior to
the combined influences of the exciting system of the medulla
oblongata and of the motor system in the heart itself. After
a short interval it diminishes, and the successive discharges
of the automatic centres can then reach the heart, though
after somewhat longer pauses. By galvanizing the vagus

* Year Book Sydenham Society, 1862, p. 453. f

—

70. ON DIGITALIS, WITH SOME OBSERVATIONS ON THE URINE.

this resistance is much increased, and the heart stops in
diastole. ;
_ The series of experiments on which Traube founded his views
were as follows:—He injected infusion of digitalis of such a
strength that one syringe-ful was equal to the extract of 8
grains of digitalis leaves, into the veins of dogs, and found that
while salt and water produced no effect on the pulse, and one
syringe-ful of infusion raised it from 128 to 132, four syringe-
fuls brought it down to 32; while after a fifth it suddenly
rose to 160, and in 10 minutes more to 174. In another, with
a pulse of 108, it was reduced by 24 syringe-fuls to 33, but.
with % of a syringe-ful more it rose to 202. Several other
experiments gave an exactly similar result. To find whether
the action was through the vagus or not, he made seven more.
experiments. In one, for example, after reducing the pulse
from 121 to 48, the right vagus was cut, and in two minutes,
when again counted, the pulse was 66. On dividing the left
vagus it then rose to 204. The same result was obtained by
dividing both vagi at the same time. After dividing both vagi,
the slowing of the pulse after the injection of digitalis was.
hardly observable. From these experiments Traube concluded
that digitalis operated through the regulating system only.
This theory was very generally adopted for some time, but
Winogradoff, finding from experiments with the hemadynamo- _
meter, that when the instrument was inserted into an artery,
and the vagi stimulated so as to cause slowness of the pulsa-
tions, the arterial tension immediately fell; while, when the
slowing was produced by the injection of digitalis, there was
neither increase nor diminution of the tension, concluded that
Traube’s view was erroneous, and totally denied that the slow-
ing of the pulse, produced by digitalis, was through stimulation
of the vagi or medulla oblongata. Traube being thus induced
to re-consider his theory, made some experiments by injecting a
weak solution of woorari into the veins of a dog, and keeping
up artificial respiration to obviate the disturbing influence
which the rise in tension consequent on division of the vagi
would, have caused, and then injecting infusion of digitalis, he
found that the tension rose in one instance from 159 to 260

THEORIES REGARDING ITS MODE OF ACTION. 71

millimetres, attaining its maximum in two or three minutes,
and then gradually declining.

Traube was thus lead to re-mould his theory, and to say that
at first there was stimulation of the musculo-motory as well as
the regulatory system, that the arterial tension was the product
of these two factors, and that digitalis finally paralysed both;
and here the theory at present stands (as far as I can find out).

When we look at Traube’s first experiments, they certainly
seem perfectly conclusively to prove that digitalis acts through
the vagus, and this I certainly believe to be the case. Wino-
gradoff’s denial of this is based on fallacious reasoning, assuming
as he does that because irritation of the vagi does not possess
the same action as injection of digitalis, therefore injection of
digitalis does not produce the same effect as irritation of the
vagi: whereas the action is the same so far as the latter goes,
but the former possesses the additional power of contracting
the capillaries, as Blake showed so long ago as 1839.

- Traube’s theory also is very imperfect, for he makes the
arterial tension the product of what is really only one factor,
leaving altogether out of account the other equally important
one, the size of the capillaries, and, as I have stated before, if
the capillaries remain the same, and the number of cardiac
pulsations be diminished, no amount of force which each may
exert from stimulation of the musculo-motory power will do
anything whatever towards raising the arterial tension by the
diminished quantity of waves and consequent amount of blood.

(2) The second theory, that of Messrs. Dybkowsky and
Pelikan, and (Kolliker ?) is that (a) digitalis exerts its action
directly on the regulating and musculo-motory apparatus in the
heart itself, and (0) not through the vagi, as their action is not
delayed or altered by destruction of the medulla oblongata or
division of the vagi, or by the previous administration of
woorari. The first part of this theory seems borne out by the
experiments of Eulenburg and Ehrenhaus on the extirpated
heart of the frog, which, when its lower third was immersed in
a solution of digitaline, had its motion completely stopped, if
the solution was strong, and if weaker it became slow and
intermittent. We see, too, that if we cut the vagus and irri-

72 ON DIGITALIS, WITH SOME OBSERVATIONS ON THE URINE,

tate the distal cut end, the pulsations are slow, and the same
result takes place if we apply galvanism to the uncut vagus,
and it is only natural to suppose that the poison circulating
over the heart’s parietes might act either upon the terminal
branches of the nerve, or on the apparatus in the heart on
which these branches act, and through which they produce their
effect, just as upon the central end of the vagus, though prob-
ably with less force. The second part (0) of this theory I am
not inciined to accept, because M. Traube’s experiments, I
think, prove that the action is altered in mammals by the divi-
sion of the vagi; and although Messrs. Dybkowsky and Pelikan
state that they have found the same results in mammals as
in frogs, they do not give definite details like M. Traube; and I
am further hindered from accepting it, asin one of the two frogs
which I have been able to obtain, and which was poisoned
with woorari, its heart laid bare, and first a moderate, and then
an enormous dose of digitaline introduced under the skin, the
action was not so marked and distinct as Dybkowsky, Pelikan,
Fagge, and Stephenson describe it to be.

The hypothesis. that I have myself formed in regard to the
action of digitalis is as follows :—

Digitalis causes contraction of the small arteries, and at the
same time acts on the regulating apparatus of the heart, both
directly, and to a much greater extent through the vagus, thus
causing slowing of the heart without loss of tension ; it stimu-
lates the musculo-motory apparatus, causing increased force of
the cardiac contractions. This primary stimulus then gives
place to paralysis—first partial, and then complete. ‘The regu-
lating force gradually loses its power, so that the musculo-
motory power causes a quick beat to be occasionally interpolated,
_ as the regulating power gets enfeebled, it can only occasionally
assert its influence, and the pulse, formerly slow with occasional
quick beats, is now a quick one, with occasional slow beats or
intermissions; as the regulating power becomes entirely lost,
the intermissions disappear, and the pulse becomes regular but
very quick, the capillaries have also become paralysed and
dilated, but occasionally, just before death, they become spas-
modically contracted. The musculo-motor power gets weakened,

AUTHOR’S VIEWS. 73
the fibres connecting the different ganglia of the heart, and
which by keeping up a perfect correspondence between the
different ganglia, enable the heart to contract rhythmically, now
- convey impressions slowly and imperfectly ; the different parts
of the heart no longer work in unison, and the contractions
* become irregular and peristaltic ; by-and-by the fibres do not
. transmit impressions at all, and the ganglia working in inde-
pendence of each other, we see some continuing to make the
little area they supply pulsate when the rest has stopped, and
finally the ganglia themselves become paralysed, and the heart
remains motionless and contracted. But it is probable this
stimulating influence is not exerted on the heart and capillaries
alone, but on involuntary muscular fibre throughout the body,
or on the sympathetic nerves which supply it, since we find it
causing contraction of the stomach, intestines, and uterus, and
in those organs also, its stimulating effect would probably be
followed by paralysis. Not only the nerves are affected, but
the power of the muscular tissues themselves is impaired, as
shown by Dybkowsky and Pelikan, who found that when two
muscles were taken from a frog, one having been taken from a
jeg which the poison was prevented from reaching by a ligature
applied previous to its administration, and the other being
taken from the poisoned animal, the curve described by the
former in the myographion was much higher than of the latter,
showing its greater power.

The cause of death from digitalis seems to be stoppage of the
heart’s action, and defective supply of blood to the nerve cen-
tres. When death occurs from not very large doses, it seems
often to be caused by some slight exertion at the time. As in
the case of Daniel G., the pulse was of low tension and irregular,
and when we know that any exertion still further lessens the
tension, we can easily imagine how in such a case there might
be syncope ending in death. This seems all the more probable,
as I noticed on the 17th of March, besides bright spots, a kind
of haziness such as one sees before fainting, though not of so
marked a character.

There are several points which I have not yet made up my
mind about, such as the remarkable intermissions observed in

74 ON DIGITALIS, WITM SOME OBSERVATIONS ON THE URINE,

the pulse and respiration coincidently, the topical action of
digitalis, the points of resemblance and difference between it.
and other cardiac poisons, and its action on the blood and
capillaries, but I hope that I may yet be able to clear up these.

THERAPEUTIC ACTION.

Soon after Withering announced the property digitalis
possesses of slowing the heart’s action, physicians began to
employ it in hemorrhages, and Ferriar especially used it in
hemoptysis, in the early stages of phthisis, and thought it might
possibly heal ulcerated cavities in more advanced stages. Dr.
Brinton thinks it is the best remedy for hemorrhage from pul-
monary cavities, in the dose of 30 to 90 minims every four or
six hours. It is also said to be useful in epistaxis, and Mr. W.
H. Dickinson found it of the utmost service in menorrhagia,
curing in a few days a case thought to be almost at the point of
death. He gives the infusion in the dose of 3ss. three times a
day. He thinks that as an oxytoxic it is quite as powerful as ergot.
Tt is from the contraction of the uterus itself, and not from the
contraction of its vessels, that the benefit is derived; and this
idea he supports, not only by showing that it causes pains like
labour pains, and expulsion of clots, but that, in a case of fun-
goid tumour of the os, it did no good whatever; while, if the
benefit had been from the contraction of the vessels, it ought
to have been as great in this case as it is when the cause of
hemorrhage is within the uterus. fFerriar thought that in
inflammatory fever it was useful instead of bleeding and purg-
ing, and Currie confirms his observations, saying he had found
it useful, not only in acute inflammation of the brain, heart,
and lungs, but in acute rheumatism. Several continental
authors have borne favourable testimony to its use in acute
inflammation. Hirtz gives a case of pneumonia, which he
treated first by tartar emetic and venesection ; but in two days
these produced no amendment, the pulse remaining at 118, and.
the temperature at 1046° Digitalis was then given for,
two days, and the pulse fell to 82, and the temperature to 98°6°. .
Although ‘the medicine was now discontinued, on the third day
the pulse was 53, and the temperature 97°3°, Returning crepi-

THERAPEUTIC USES. 79
tation was now heard on the eighth day of the attack, and the
pulse and temperature began to rise, and three days later the
patient was convalescent. He has found the same lowering of
the pulse and temperature in acute bronchitis, pleurisy, acute
phthisis, and acute rheumatism. He has rarely seen diuresis,
and never met with any bad results. The amount taken has
varied from 7 to 37 grains. He thinks that venesection may
be used with the digitalis. In pneumonia, Millet abjures vene-
section nearly altogether, but combines the digitalis with
kermes giving to adults on the first day +th of a grain of
each every hour, and gradually increasing the dose by 4th
of a grain daily, so that on the ninth day the dose is ?ths of
a grain. The medicine is not stopped at once, when improve-
ment takes place, but is continued some time longer. Improve-
ment generally occurs about the sixth or eighth days, and the
circulation is then affected. Among 87 cases of children, of
which 53 were very bad, with much delirium and adynamia,
there was but one death. Oppolzer gives it in small doses,
along with ipecacuan and cold effusion externally, where the
dyspnoea is more from the fever than from local changes. In
reference to acase of pneumonia, Traube remarks that the
rapidity of action of digitalis varies much in different cases,
taking much longer if the person be strong, and the disease at
its height, than when it is near a close, or in a chronic case.
Schneider says that in acute inflammation digitalis, in doses of
24 to 34 grains every two hours, reduces the pulse, and lowers
the temperature of the skin. These effects, he says, are inde-
pendent of each other. Clutterbuck advocated its employment:
in continued fever. Wunderlich recommends its employment
in severe cases of typhoid fever, when the evening temperature
rises above 108°, and the pulse one-half in the second week. It
has been proposed as an anti-periodic in ague by Davy. Graf-
feneuer, Gerard, and Bouillaud have treated between 40 and 50
cases successfully by it.

- Nervous Affections.—Serre, by the use of Debout’s pill of
quinine, 14 grains, and digitalis, gr. 4th, every night for three
months, has cured several cases of long standing hemicrania,.
and, among others, his own, which had lasted 15 years. Boison

76 ON DIGITALIS, WITH SOME

has used a pill of musk, 1 grain, ext. digital., 14 grains, and
ext. opil gr. 4, in neuralgia, and its effects he describes as being
magical. Mr. Hardwicke gives $ grain of the powder in the
same affection, and with similar results. According to Thomas,
it effects a permanent cure in epilepsy; and Parkinson, Moll,
Corrigan, Crampton, Sharkey, Nelegan, and Duclos, have all
employed it with success. In the second stage of general
paresis of the insane, that of mental alienation with maniacal
excitement, Dr. C. L. Robertson says, tinct. digit., in doses of
ss., is a specific, calming excitement and enabling the patient to
pass through this stage without wear or irritation. It steadies
the pulse, and thus supplies the brain better with blood, and
obviates the tendency to effusion of serum, consequent on in-
flammation going on in the arachnoid or pia mater.

In delirium tremens, Mr. G. M. Jones recommended ss. of
tinct. digit. at the first dose, to be repeated if necessary in four
hours, and in some cases a third might be given, which did not
exceed 511. It failed to produce sleep in only three cases out
of 70, in 67 it was the only remedy used, and 66 recovered,
the fatal case having a tumour of the brain. Peacock thinks
this treatment especially useful in young and strong persons,
and where the attack has been the immediate result of spirit
drinking, and believes that in fuil doses it does not produce
the depression which we would expect. Carey records four
successful cases.

In anasarea, especially where this depends on cardiac disease,
digitalis is one of our most potent remedies, especially when
combined with squill, which is also a cardiac poison of the
same class as digitalis. Withering* says it succeeds best when
the pulse is feeble or intermitting, the countenance pale, the
lips livid, the skin cold, and the swollen belly soft and fluctuat-
ing; but it seldom succeeds in men of great natural strength,
tense fibre, warm skin, and florid complexion, or those with a
tight and cordy pulse. In serous dropsy, its good effects are
not so marked, and in encysted dropsy, it is totally useless.
By some the infusion is preferred to the tincture as a diuretic,
and it is best to give it in half-ounce doses, three times a day.
i * Fagge and Stevenson, Proceed. Roy. Soc., May, 1865.

OBSERVATIONS ON THE URINE. 77

This action may sometimes be induced by cloths soaked in the
infusion being laid upon the abdomen.*

As a sedative it requires great care, and, when the circula-
tion fails, the remedy should be remitted; and though Sir
H. Holland thinks that doctors are too much afraid of the
intermittence caused by digitalis, I think it is a wholesome
dread, and that when this sign appears they should at once stop
the medicine, and have stimulants at hand in case of need. The
tincture in doses of 30 minims is of great service in nervous
palpitation, probably, I think, by inducing contraction in the
capillaries, and, by thus raising the arterial tension, restoring
the normal circulation.

With just one word of warning, I will close this brief sum-
mary of the therapeutical applications of digitalis, and that is
to those who, thinking that there can be no danger in giving
digitalis to those with very weak hearts, and that indeed it is
the best thing for them to use it indiscriminately. I believe
that I have proved that it increases the force of the cardiac
pulsations; but if, while the motor nerves were stimulating it
to contract, and the capillaries at the same time were opposing
a resistance, the fibres of the heart itself were not composed of
sound muscle, but were fatty and friable, some of them would
be pretty sure to rupture, and the results would be disastrous.
I therefore think that, in cases of fatty heart, great caution is
necessary in administering it.

OBSERVATIONS ON THE URINE.

Within late years the attention of physicians has been turned
much more than formerly to the observation of the urine for
purposes of diagnosis, and physiologists have carefully noted
the changes it undergoes in various circumstances, for the pur-
pose of determining the way in which these circumstances
affect the interchange of material in the living body.

Having lately made a very extensive series of observations on

* Christison, Dispensatory.

‘78 _ ON DIGITALIS, WITH SOME .

the urine and urinary constituents, with a view of determining,
if possible, the changes effected in tissue changes under the use
of digitalis, I have thought it not out of place to note down the
chief facts which I have personally observed, and, in doing this,
Iwill adhere strictly to the order adopted by Mr. Parkes in his
excellent work on the Urine. . .

AMOUNT OF CONSTITUENTS.

In the change of French into English weight, I have reckoned
the gramme as equal to 15°43 grains, and the English fluid oz.
as equal to 28-4 cubic centimetres.

On an average of 150 observations, chiefly taken ating
winter, but a few during summer, I find the amount of
urine casas 1124 cub. cent. or 394 ounces.

The maximum amount was 1855 ec. or 633 _—,,
The minimum ‘ » 610°, or213 _ ,,

This difference is, however, much more than my normal, the
one being in summer and the other in winter; and, moreover,
the large number occurred after I had been taking digitalis.

My mean variation, from the lowest to the highest, is about
A87.c.c. or 138 oz.

This variation amounts to more than a third of the total
amount, and this is therefore considerably above the average,
which is 4.

Ur val enh mean amount of 105 analyses of urea is—

33°44 grams, or 516 grains per day,
1:39 ia 21%. , ~ per hour.
The mean variation is 9°36 " 1444, or rather
more than }, while the average amount is } th.
Phosphoric Acid.—From 108 analyses I find the average
amount of PO,, to be 3:1 grams, or 47} grains daily,
2 » hourly. -
The mean variation is 0:96 _,, 144, 5
‘which is less than usual, the mean being 35 to 50 per cent.”
Chlorine—From 80 analyses I find the average amount to be

’

OBSERVATIONS ON THE URINE. 79

6°8 grams, or 105 grains daily, 44 grains hourly. This seems
much about the average amount. |

The analyses of chlorine, however, were not so exact as the
others, on account of there sometimes being a difficulty in
settling when the point of saturation was reached.

Section II.

Relative Proportions of the Constitwents.—The urea seems to be
about eleven times greater than the phosphoric acid, and about
five times greater than the chlorides. These, however, do not
keep their proportions constant, nor is that of the urea to: the
water so much so as it generally is.

Section III.

On the amount of each constituent excreted in 24 hours by a
definite amount of body weight.

In 24 hours. In 24 hours.
Constituent. 1 kilogram excretes 1 Ib. avoir. excretes in
in ¢c.c. and grams. drachms and grains.
Parkes’s
average.
Water... sccccccers 23 c.c. 2°53 f. oz. 2°93 f. oz.
WITOR < 4<0/08 00.0406 5 grams, 4°12 grains 3°53 grains.
Pi dared ed viveve 0°048 gram. 0°38 grain 0°336 grain.
tiemiae-ae ts be-ee8 0°126 ,, 0 ‘84 grain 0 *875 grain.

My weight is at present 134 lbs. and deducting 9 lbs. for
clothes, and 1 or 2 lbs. which I feel sure I have gained since
the end of the session, I have calculated this table for 125 lbs.
weight. JI have entered in the last column the average which
Parkes gives, showing that the average in my water and chlorine
is lower, but higher in the urea and PO,

80 ON DIGITALIS, WITH SOME

Section IV.

On the acidity I have no observations.*

SECTION V,

On the Specific Gravity—tThe sp. gr. of my urine is notably
high, though not more than that observed by Dr. Christison,
nnd a very great increase in it is always seen at night, probably
from the solids of dinner passing off.

With this I must at present conclude, but I hope to be yet
able to make farther use of the data I have collected; and I
would notice that my observations entirely contirm Dr. Bence
Jones’s opinion that the acidity of the urine is lessened or re-
placed by alkalinity during digestion, my urine being acid in
the morning, neutral at midday (from breakfast), acid before
dinner, and alkaline at night.

The close connection between brain work and increase of
phosphates in the urine is also well marked, there being almost
always an increase on the Saturday, from the effect of the dis-
cussions at the Royal Medical Society on the Friday nights, this
increase extending over Sunday; and, when I have been
attending examinations, or reading hard next day, the amount
of phosphoric acid is increased.

[* This statement applies only to quantitative determinations, About six
hundred qualitative observations were -made, the reaction being usually deter-
mined each time that urine was passed. These were all described in the
manuscript thesis, but those made from November 14, 1865, to March 16, 1866,
were not printed in full on account of the expense, especially as the recapitu-
latory tables gave the most important facts. In addition to these, however, it
may be noted that the urine during digestion was not only neutral or alkaline

but was frequently quite milky when passed, from the presence ef earthy phos.

phates. On Sundays, when no work whatever was done, the urine was iile
variably less in quantity, and was not milky.]

OBSERVATIONS ON THE URINE. 81
APPENDIX TO THESIS.

DIETARY TABLE.
After some preliminary experiments, the following diet was

adopted :—

BREAKFAST—

Coffee, 170 ¢.¢,

Bread, 7} 0z.

Butter not weighed, but much the same every morning, as the bread
was the same.

1 salt herring—from Jan. 6 to March 22, 1866, 1 egg instead,

Luxncu—

4 oz. bread.

24 oz. gingerbread.

190 c.c. milk.

DInnER—-

Mince collops, 8 0z. The water in which they were cook2d was not
measu'ed [but was almost exactly the same each day. The weight
is that of the raw minced beef before cocking].

Bread, 2 0z.; Nov. 16 to Dec. 2, 1865, 3 oz.

Potatoes, 19 oz.

Water, 320 c.c.

Tra—

Tea, 375 c.c.

Bread, 43 oz.; Nov. 16 to Dec. 3, 1865, 42 oz.

Butter [not weighed but almost the same every day].

[During the whole period of 121 days, from November 21st, 1865, to March
21st, 1866, inclusive, this diet was rigorously adhered to with the slight excep-
tions noted on March 17th, 18th, 20th, and 21st, when the action of digitalin as
an irritant to the stomach and as a powerful diuretic lessened appetite and
caused thirst.

The urine was passed into a small bottle which was afterwards emptied into
a Winchester flask. From this specimens of the mixed urine of 24 hours
were taken for analysis. ]

ABBREVIATIONS USED IN APPENDIX.

Bicsececssese Breakfast. Reactn....... Reaction.
Bivecectsatess LUNCH, a devtneseret Ont.

Th Sisk cenewcan DERNGM C.C. eee eeeeee Cubic Centimetres.
Divcewesedses LOR Clr. ossaee es Clear.

Amt. ........ Amount. OIG is 5 wield vis-0iss LOGS

L. & H..... Hours spent in Laboratory and Hospital.

R. M.8.... Hours spent at the Royal Medical Society, where debates were
held every Friday.

prop....... Proportion of the ingredient to the amount of urine.

Under the head dose the first numbers are fractions of a grain—the second
are milligrams. The dose was actually taken in milligrams,
and the fractions of a grain are only reckoned from them,

G

82 ON DIGITALIS, WITH SOME
J
Urine. Pulse.
Date. ee 3
ime ;
when | 3 | Specific! Reaction. Appearance, Time, Number.
passed. g gravity.
<
1865. CG. E
Mar. 17| §.45 41 1024 Acid Amber coloured,clouded | 9.25 | 67 mean, 59-71
at bottom
1.60 865 | 1020 Acid Straw, clouded at bot-
tom P.M.
7.18 820 | 1023°5 Acid Amber coloured,clouded | 10.25 | 72 mean, 71-76
’ at bottom
12 160 | 1025 eee Not perfectly clear
bow 1258 | 1023 +00 Turbid
>” 1g eee eee eee ove coe eee coe ee eee eee
ee 1200 | 1022 Acid Turbid
» 19 a 495 | 1021 Faintly | Not quite clear ... | 8°30 | 61 mean, 60-62
acid Somewhat cold
: at the time
me $90 | 1019 Alkaline | Very pale coloured at| 9 ine pis
top, clear
ane 398 | 1022 Faintly | Pale, clear, clouded at
acid top
1,30 572 | 1023 ose Pale straw, not quite
clear
ea 1855
Mar. 20| 9.5 848 ; 1019 Neutral | Amber, clear, clouded| 9°55 ; 63 mean, 60-67
at bottom
P.M. ae
3 525 | 1020°5 | Neutral | Straw do. 10°45 |80 regular, sitting)
in dining-room
7 205 | 1019°5 Acid Pale straw 40. 11°40 | 58-60 sitting in
bedroom
11.40 | 215 | 1025 Acid Amber do. <0 ove eee
vee 1293

* Consisting of about a dozen pellets like those of rabbits, and one

OBSERVATIONS ON THE URINE.

Meals.

Sleep.

Exercise.

to
2
re

ing.

Bowels.

Dose.

Time
when
taken.

Amount.

Remarks,

B. 9.40
L, none
D. 6.10
T. 7.30

B. 10

L. 12,45

T. ts 45

1, 45-4
4. 30-8, 30
63

12. 30-10
93

10. 45-7. 45

3. 15-9

53

hrs.

8 | Walk-

100

Open in
morning,
Stool copious.
Quite loose.
In the even-

good deal
of flatus.

Open

Open once...
Stool copious,
somewhat
soft,

Open once,
stool ex-
tremely
scanty*

on 8th and 9th 8 milligrams; on 10th and

; On 14th 20 milligrams; on 15th 30 milligrams; and on 16th

grams

4

h 21 milligrams,

llth 10 milligrams; on 12th J5 milligrams; on 13t

30 milligrams—altogether 173 milligrams in 15 days.

No digitalin was taken on these days, which show only the poisonous effects of previous doses.
On March 2nd 1 milligram; on 3rd, 4th, 5th, and 6th 4 milligrams daily; on 7th 6 milli

At 4 a.m. I awoke, and
vomited at intervals for
about an hour. Vomited
matter yellow and liquid,
somewhat like yolk of egg.
Vomited again on rising at
9a.mM. Again at 9.30. Fre-
quent epigastric uneasiness
and pain. In forenoon my
sight was occasionally not
quite clear (just as one sees
when about to faint, but
somewhat slighter), and a
large bright spot occasion-
ally seen, such as is seen
after looking at the sun,
and then looking away ata
dark object. Languor and
discomfort all day. Occa-
sional nausea—no more
vomiting. Pain in chest on
drawing breath, from sore-
ness of diaphragm from
vomiting. No lunch, but
took 200 c.c, water at 11.30
P.M.

Appetite improved, though
not very good. Sight some-
what dim, especially after
rising up or walking, and
bright spots occasionally
seen, chiefly after rising or
walking. Lunch, 63 oz. of
bread, some cheese, and
about 225 ¢.c. of water, and
25 c.c. of water at bed-time-
more than usual,

Appetite better to-day.
Sight dim, and I see a large -
bright spot, especially after
exertion. This not so bad
in afternoon. Slight pain in
epigastrium occasionally,
lasting some time when it
occurs. After dinner con-
stant pain in left side, ap-
parently in descending
colon. Much flatus at night.

Sight clear. After look-.
ing ata bright sky, and on
looking away I see a spot
as if I had been looking at
the sun. Appetite much
better to-day. Pain in leit
side still there on rising,
and continued for some
hours. Had a slice of bun
of about the same weight to
lunch instead of the ginger-
bread I have formerly taken,
and for which I at present
feel a disgust. Pain in side
again to-night. A slight

about the size of a walnut. The latter floated, the former sunk in water.

G 2

Nl

e4 ON DIGITALIS, WITH SOME
Urine. Pulse.
Date. 2
5 aie 8 Specific °
h iS) ion. : " ime. .
Apne & gravity. Reaction Appearance Time Number
1865. C.c,
Mar, 21 8.40 | 450 | 1020 Faintly | Pale amber colour, | 9°10 | 66, G5-67 de
acid clouded at top
P.M.
1 890 | 1020 Alkaline | Straw, clear, clouded at | 10°30 | 67-68 ... = «..
bottom
6 453 | 1021 Acid Pale straw do. rey eee shes
Il 230 1025 ece Straw do. eee eee ese
saa 1523
a 22] 8.35] 485 | 1023 Neutral oT CT 9°10 | 64 mean, 63-66
Night
12.20} 310 vee eee Straw, clear, clouded at| 1°25 | 72regular ...
top
5.35 | 3805 | 1019 Acid Not perfectly clear = ...| ose eee eee
12.20 | 555 | 1024 Neutral | Straw coloured, clouded ose eee ose
at bottom
eee 1655 | 1020
RECAPITULATORY TABLES.
Date. | Temp. | Moist. | Pulse. | Sleep. Work. Amount. Sp. gr. | Reaction.
~ 1865. . hrs. | hrs. | mins C.0; Oz.
Novy. 14 eee eee ece eee eee eee eee 1219
2” 15 ece eee eee eee eee eee eee 1161
2? 16 eee coe eee eee eee eee eee 1096
ig ak ase eve oes oes oes aie os 1062
45 18 eee arr ate ae ae 3 aes 1164 ies 1031°5 acid
» 19 ais “ bes ae uy ase “s 995 35 1032 acid
1» 20] 44°2 dry I, see ies tp ave 1240 43°6 | 1023°5 | neutral
yy 21{| 48°1 damp 71 mi Se eee bus 1005 85°3 | 1028
gg 22) 4d wet 67 ote — wae ens 969 83°8 | 1030 neutral
s, 28) 4792] Gey | GBB 1 oe | ace! Lees Pi aoe | 2010 | 85°51 1082 acid
i
», 24] 43°8 wet 71°5 ae see shee ove 1150 40°4 | 1031 eee

OBSERVATIONS ON THE URINE.

85
Exercise. Dose.
: Bowels, a Remarks,
Meals. Sleep. Slole. Ww. Time| #
= |= wo h °
F fe SH akan &§
-
hrs. |hrs, |min :
threatening of headache
before going to bed.

B. 9.15 | 12-8.30 34 |... | 85 | Open once,| ... ne Appetite good Still oc-
stool scan- casionally see a bright spot
ty, partly like a large bright soap
from large, bubble, or Jike the halo that
partly from is seen round a light when
small in- digitaline is putinto the eye
testine. without the central light,

L. 12.45 | 8} which is the cause of the halo

: in tne latter case. It seems

D. 6.10 to come more after exertion,

or after long writing, as in

T, 7.45 taking notes. I’m not sure

whether it is the attention,

or looking at the white

paper, or the stooping that

causes it. Took 1 orange

and 100 c.c. of water extra.

. 9.15 | 12.15-8.30 | 34 | ... | 90] Open once por pars Still see a bright spot
ci ' stool copi- occasionally. Attended the
ous, well Royal Medical dinner. _Li-

formed. quids above some soup, 1

-30] 8 glass champagne, 3 of a glass

aie ; of claret, about ‘100 or 150

Dy 7 c.c. of water and 1 cup

coffee,

keels

RECAPITULATORY TABLES.

Appearunce. Urea. Phosphoric acid. Chlorine. Dose. Date.

s amt. |grms.| grs. |prop. |grms. | grs, |prop. 1865.
grms.| grs, ry grms. : m ; ° Nov. 14

0

meet » 15
urine. ae

epee if

ye E

]
Clear yellow ...| 33°83 | 522 | 34 » (19
°
Clear yellow... 35°96 | 555 | 29 » 20
és 34°17 | 527 | 34 | 2°87 | 36°56 | 2°35 | 5°22] 80 | 51] oe » 21

vs 29°76 | 459 | 31 2°36 | 36°4 | 2°35 | 5°24 | Sl | 5°4 dee oy 2

Clear yellow ..| 31°81 | 490 | 31°5 | 2°51 | 38°7.| 2°48 | 4°72 | 93 | 4°6 see iy ae
eee 35°65 | 550 | 31 2°639| 40°7 29 |] 6°27 |} 97 | 574 oe » 24

86 ON DIGITALIS, WITH SOME

Recapitulatory Tables—continued.

Date. | Temp. | Moist. | Pulse. | Sleep. Work. Amount. Sp. gr. | Reaction.
1865. 2 hrs. | hrs. | min. €.¢; oz.
Nov.-25| 40°3 damp 71 eee “hs Nr 1010 83°5 =|: 1082°5 acid
4, 26 aed ees eee eee eee 1071 87°7 | 1031°5 acid
» 27| 86°6 | damp | 69 ae ves y se 1090 88°3 | 1030 acid
POUND Us webs fo TLS. hie 1 aed ee . | 1170 | 41°2 | 1027°5] acid
gay 28 72°5 ove «i * sa 1055 87°1 | 1029°5 | neutral
5 80 : 73°5 ove ove see 806 28°3 | 1033 neutral
Dec. 1] 41°2 dry 68°5 aes ese sen bee 1200 42°2 | 1030°5 | alkaline
eine.) 5880 dry eve eee ove des vee 738 26 1031 obs
ws aon poe 83 ae ne eed 1008 85°5 | 1031°5 | neutral
o» | 40°2 | damp } 62 8 on ée eee 1026 86°1 | 1028°5 acid
» 5] 43°8 dry 65 8 tie ove sss 1170 41°2 | 1026 faintly
alkaline
95 8 | 4275 damp | 66°5 8 ous os see 1058 37°2 | 1029 neutral
» 7] 46°5 dry 62°5 8 ase ede eee 1110 39 1030°5 | alkaline
yp. 8} 4898 dry 70 72 ove tee eee 1130 40 1028°5 | alkaline
9 9] 4693 dry 62°3 7 eee oss on 1120 39°4 | 1028°5 | neutral
a 10 Sse os ten 8 eee eos ~ 1000 35°2 | 1031 faintly
acid
>» 11] 38°6 | damp | 67 83 ove ees eve 1300 45°7 | 1024 acid
og 12] 42 dry 66°5 7% ove ove eee 1150 40°5 | 1028 neutral
Daily mean, not excluding Sundays,
436 | 68 |-:8
Daily mean, excluding Sunday's urine Por ee } 1048 36 °9 ose os
Mean on Sundays ss pee eee eee ooo ese eee 1018 35 °8 eve ose
Maximum oe eee eee oe eee eve eee one 1300 45°7 eee ove
Minimum Pe ek gee “alee pet een eg 738 26 see ove
Difference .. eee eve eee eve ee 562 19°7 eee ooo
Dee. 18, 40°5 dry 67°7 7 5 one 50 1075 87°8 | 1026°5 | neutral
gn 14) AES dry 67°5 13 5 ese 60 1054 37°1 1029 neutral
» 15| 34 dry | 66 . | 43 | 42 | 80 | 1464 | 51°5 | 1026°5 faintly
ga LE} Otee dry 62°5 6 4% «s v6) 1175 41°3 | 1025 acid
sir READ tees oe a 8 csi | ome | 600} 1220 | 80-4 | 1028 neutral
9, 18] 42°5 dry 62 8} 5 oes 60 1128 39°7 | 1028 acid
» 19| 39:4 | dry | 59° | 7} | 5 . | 65 | 1450 | 51 1022 | neutral
9, 20] 42.2 damp 60°5 7i 7i ae 75 1094 38°5 1029 neutral

a a

oat is te i as

ee ee ee

OBSERVATIONS ON THE URINE.

Recapitulatory Tables—continued.

87

Appearance. Urea, Phosphoric acid. Chlorine. Dose. | Date.
grms,| grs. | prop.|grms.| grs. | prop.| grms.| grs. |prop. 1865.
ose 82°82 | 506 | 32°5 | 3°41 | 52°6 | 3°37 | 5°77 |} 89 | 57 rf Nov. 25
Clear yellow. ...| 37°48 | 578 | 35 3°33 | 1°3 | 8°11 | 6°68 | 103 | 6:2 ar ‘3 Loe
Clear yellow ...| 31°06 | 479 | 28°4 | 2°75 | 42°4 | 2°52 | 7°23 | 111 | 6°6 eee 9 27
Clear yellow ...| 81°59 | +487 | 27 2°85 | 36°2 | 2 5°54] 85 | 4°7 “ » 28
Clear yellow... 30-38 | 469 | 28-8 | 2°52 | 38-8 | 2°39 | 5°76] 89 | 5-4 eee pene 2!
Clear yellow .,.] 29°01 | 447 | 36 2°18 | 338°6 | 2°70 | 4°86 | 75 | 5 rr » +30
Great deposit of | .. es ose | -1°95'| 80 1°62 | 7°14} 110 | 5:9 F Dec. 1
phosphates ,
Not quite clear ...| .. “te te. Yee 380°9 | 2°71 | 4°79 | 74 | 6°4 bes ”» 2
Clear yellow ...| «.. ens 2°98 | 35°9 | 2°95 | 5°24] 80 | 5°1 aes ys 8
Large deposit of | 31°39 | 484 | 30°5 | 2°48 | 88°2 | 2°41 | 5°46 | 84 | 5°32] ... a.
phosphates
Not quite clear ...| 29°62 | 457 2°42 | 37°3 | 2:06 | 5°93 | 91° | 5°06 ‘s » 5
Not quite clear ...| 29°62 | 477 | 28 2°46 | 37°9 | 2°32 | 5°63 | 86 | 5°32) a. » 6
Considerable de- | 30°63 | 492 | 27°6 | 2°84 | 45°8 | 2°55 | 7°07 | 109 | 6°36)... ret |
posit of phos, ;
Large deposit of | 31°86 | 491 | 28°2 | 2°94 | 45°3 | 2°63 | 7°34] 115 | 6°5 eee js 8
phosphates i
Turbid depositof| ... se « | 3°56 | 54°9 | 3°18 | 7°42 | 114° | 6°6 ose io 2
phosphates
Clear, clouded at re oo oo. | 3°3 | 50°9 | 3°3 | 5°46 | 84 | 524 che » 10
bottom
Cloudedat bottom | 28°6 441 | 22 2°76 | 42°5 | 2°125) 6°76"| 104° | 5°2 see oa f |
Large deposit 28°29 | 486 | 24°6 | 2°58 | 39°8 | 2°25 | 5°98 | 92 | 5°2 oe i, 42
aan 31°88 | 492 | 30°4 | 2°67 | 41 2°54 | 6 92 | 5°7
eee 35°65 | 550 | 35 3°2 | 49 3°l | 579; 89 | 5°6
eve 37°48 | 578 ws =| 8°56 | 55 « | 1°42] 114
ove 28°29] 436 a (a he 5 0 4°72} 73 |.
oes 8°19 | 142 Hy oe Sat ad ta « 2°7 4l
Clouded at bottom | 27°95 | 431 | 26 2°74 | 42°2 | 2°55 | 6 92 | 5°5 | 1/200 oy. a3
Flocculent cloud | 28°88 | 445 | 27-4 | 2°68 | 41°2| 2°55] .. 1/200 » (214
Large precipitate | 38°C6 | 587 | 26 3°16 | 48°7 | 2°16 | 8°8 | 185°6) 6 1/200 a3 20
of phosphates
Turbid through-| 27°96 | 431 | 23-8 | 2:7 | 41°6/2:3 | ... 1/200 » 16
out
Clouded at bottom | 32°14 | 496 | 28-7 | 2°63 | 40°5 | 2°35 | 8°36 | 129 | 7:1] 1 /200 me ff
Clear, clouded at | 28°76 443 | 25°5 | 2°76 | 42°5 | 2°45 | 6°74 104 | 5:9 1/200 ww ae
ottom
Clear, faint cloud | 30°45 | 470 | 21 2°64 | 40°7 | 1°82 | 7°06 | 109 | 4°8| 1/200 ee |
at bottom
, clouded at | 30°90 | 476 | 28:2 | 2°72|42 | 2-49] ... o 1/200 » 20
om

88

ON DIGITALIS, WITH SOME

Recapitulatory Table—continucd.

Date. | Temp. | Moist. | Pulse. | Sleep. Work. Amount, Sp. gr. | Reaction.
1865. ° hrs. | hrs. | min.| e.¢, oz.
Dec, 21 | 45°8 dry 60 72 6 ee 60 985 84°6 | 1030°5 faintly
99 22| 48°2 dry 65°5 14 4 eee 80 1278 45 1029 intitle
alkaline
Daily mean,
sl wn 2 OOS 1 MT BT Be) 73 yy:

Mean ... ne 906 eee seo ase 99 eee ay 1189 41°8 see ooo

Amount of Sunday’s... eee ese wee eee ose oon 1120 39 °4 eee eos

Maximum eae 499 eve eee oes eee eee eee 1464 51°5 oes eee

Minimum one ose eee eee oes ose ove eve 985 34°6 eee eee

Difference ore eee oes eee eee eee 479 16°9 eee eee
1866.

Jan, 4...) 46°2 | damp eee 7 4} coe 50 1100 38°7 | 1029-5 | alkaline
oc ave POs dry 74 7} 43 5 110 1383 48°7 | 1028 alkaline
o> 6...|- 37 dry 78 6} 3} oes 80 1655 58°2 1019 acid
aT Fas (Auer one “i 8} ove eos 20 1176 41°4 | 1026°5 acid
» &...| 87 damp | 75 8 5 is 60 1111 39*1 | 1026 acid
»» 9...| 34°7. | damp | 77 7} | 6 on Me 989 | 34°8 | 1031 pag
AeA, 66} ) OS Uh damp 73°5 73 8 aes 65 1005 35 °3 od
» 1l...| 24:1 | fine | 78°5 | 73 | 5 we | 55 | 13805 | 45°9 | 1026°5 | faintly
mae t- 26°5 fine: | 88 8 4} 5 90 1398 49°2 | 1027 weil
», 13. toa gee 82°5 7? 3} eee 50 987 34°7 | 1029°5 acid
ae Ar Eee ove ove 83 one avs 20 980 34°5 | 1081°5 | neutral
» 15.,.| 33°65 | damp | 78 gi | 5 eve | 6O | 1156 | 40°7 | 1227% falas
Peep |: es mameeee eee iT 7} 4} ove 65 1002 35°3 | 1027 faintly

acid
SES Peis 3 FR A PR OE ae ee

Daily mean, excluding Sunday’s urine. oon eee } ie gt a S

Sundays ... pee ase ose . gee ose oes : 1078 37 °9 gee ose

Maximum... eee ese eee eee ane eee vee . 1655 58 *2 eee

Minimum... ove ove ose tee eee eee ose ° 980 34°5 ace

Difference.., ve ove ase ose eee « 675 23°7 a eee

Jan. 17 | 39°7 { dump | 79°2 7} 4h ‘te 60 1073 37°7 | 1029°5 | faintly
op 184 46-204 otry ) 976 ee: | Ob | 90 | 1202 | 42-3 | 1025-5 fanny
eres CEN jl | damp 83 8} 4h 5 90 1266 44°5 1025°5 | alkaline
» 20] 40°5 | damp } 76 q 4 ous | 60 1164 40°9 | 1024°5 acid

ee oo

OBSERVATIONS ON THE URINE, 89
Recapitulatory Table—continued.
Appearance. Urea. Phosphoric acid. Chlorine. Dose. Date.
: grms. | grs. Trop.| grms.| grs. | prop. jgrms. | grs- |prop.| grams. | 1865.
Not quite clear ...| 33 509 83°5 | ase eee eas ese se eee 1/200 Dec. 21
Large deposit va eee eee eee eee eee eee see eee eee 1/200 ” 22
oe 30°9 | 476 26 2°75 | 42°4 | 2°31 | 7°4 | 114 | 62
ove 32°1 | 496 28°7 | 2°63 | 40°5 | 2°35 | 8°3 | 129 | 7-1
oo 88°06 | 587 ose | 8°16 | 48°F | oe PBS | ISS
ove 27°25 | 431 sas. 2°63.) 40°S)). oe 1S 92
eve 10°11 | 156 oes, TOSS BS. Tr sag anes 43
1866.
Clear, clouded at | 37°56 | 580 | 34°] | se | ove | one Rea ee har oe | dan. 4
bottom
coca at bot-| 40°79 | 630 29°5 | 4°92 | 75°9 | 3°92 | 98 | 151 | 7 <i a
m
Slightly turbid | 33°97 | 524 20°5.1.3°€0.).55°5 | 2°18] oi eee eee eee en
throughout
Clear, faintly eld. 36 "05 556 30 6 3 °42 52 “yf 2°91 ory eee eee Geo 9? 7
at bottom :
Clear, faintly cld.| 34°41 | 531 | 31 =| 2°34 | 36°1 | 2°11] ... ‘ es a
at bottom
Clear, faintly cld. | 33°62 | 518 34°2 | 2°98 | 46 3°02) — a5 obs eee eee » 9
in lower half
eee 30°75 | 474 30°6 | 2°51 | 88°7 | 2°5 Sia See . ~ Pree 0)
Pale, clear eee] 33°27 | 513 25°5 | 3°2 | 49°3 | 2°7 are ese ak
Turbid, pale | 40°38 | 623 | 26 | 3°45 | 53°2 | 2°47] ... ove okt
orange yellow
eee 32°57 | 502 27°5 | 2°98 | 45°9 | 3°02 we eve 9, 13
Clear ove e--| 32°34 | 499 33 2°98 | 45°9 | 3°05) ... . dee 5, 14
Slightly turbid, | 34°68 | 535 30 2°84 | 43°8 | 2°46 | 8°79 | 135-6] 7°6 bse 99 20
phosphate
Clear. clouded at | 27°65 | 419 | 29°6 | 2°54 | 34°1 | 2°54] ... ed w. | 1/50 »» 16
bottom
eve 34°46 | 531 28°8 | 3°14 | 48°4 | 2°74
ove 34°19 | 527 81°7 | 3°2 | 49°3 | 2°9
oes 40°79 | 630 oon. | 4°92... 75°9
ove 27°65 | 419 pe 2°34 | 36°1
eee 13 “14 lil ee Zz *48 39 *8
Somewhat turbid | 30°25 | 466 28°2 | 2°89 | 44°5 | 2°7 | 8°36] 129 | 7°7 1/25 |Jan.17
Do. —_—i| 81°01 | 478 25°1 | 2°76 | 42°5 | 2°3 | 8°98 | 138°&| 7°4 1/25 mae ||
Not quite clear ...} 31°65 ; 487°5 | 25 3°22 | 49°6 | 2°55 | 9°4 | 146 | 7°4 1/25 $9. 19
Turbid flocculent | 30°26 | 466°9 | 26 oes ove bon, 8 108 *4| 6 1/25 9, 20
phosphate

90 - ON DIGITALIS, WITH SOME

Recapitulatory Table—continued.

Date. | Temp. | Moist. | Pulse. | Sleep. Work. Amount, Sp. gr. | Reaction.
1866. - hrs, | hrs. | min. Gc. 0z.

Jan. 21 ose ose eve 103 m eee ees 990 34°8 | 1027°5 | neutral
oy 22] 40°1 dry 76°5 8 5 ses 60 1119 89 °4 eee ove
x O38): 42 dry | 78 7 7 -. | 50 | 1029 | 36:2 Pre ins
Nee 0°2 dry 78 8} 4} eee 60 992 84°9 eee ove
» 25 | 44:4 | dry | 765 | 72 | 4 oe mee ="
eo 26) 46°5 dry 77°6 7 3 4 90 1327 46°7 ese eee
s 27) 45° | dry | 77 7 2 2 85 | 1515 | 53°3 a -
928 oes eee eee 9 eee eee vee 827 20°1 ‘| cee eee
+ 29] 34°8 | damp | 70°5 | 8 | 4 woe lf e90 | WIT ane rae Pe
9 30] 383°1 damp 76°2 7 4 ee | 120 1637 54°1 eve ose
» 381] 38:7 | damp | 76°5 | 73 | 5 ee a: 977 | 34°4 oa ooo

Feb. 1} 45°5 | damp | 65°5 73 4} ove 60 1177 41°4 eee ooo

4045] « ‘| 726 | 86 7 le cs LA ips ns be

Daily mean, excluding Sundays ove ees ose eee

On Sundays ees ove eee eee ose son oo8 «| 908 31°9 one see

Maximum... cc cc cc cco evo cco cos cn] 1537 54°1 eee eee

MALU 5 ssn: ton tee ise wees eae aes] 827 |) 2047 ove oe

Difference ... ses ccc ove wees Swe] = LO 25 ove eee

Feb. 2, 44°7 dry 72°5 7 33 4% | 110 1341 47°2 ove ooo
y 8} 89°7 dry 74 73 5} oss 25 1440 50 eee “a
Pa OiS ee ie a 7 oes RO Une ak 915 | 30°2 is pr
» 5| 40°1 | wet | 67 8t | 2h | «. | 80 | 1204 | 42:2 de oda
o» 6} 41°9 wet 72°5 8 43 es 60 1196 41°4 eee eee
os 47 | 39°9 | wet | 67 7 3 w | 109 | 1208 | 30-2 is see
e S| 386°1 | damp| 73 73 4 ss 60 1315 46°3 eee on
e 2:| 89°1 damp 73 73 43 13 120 1446 50°9 oe eee
a 10] 39 damp | 70 7 l 2* 30 1145 40°3 eee sce
ee AD re . : 73 ous wea 60 ° eee eee
oy 12] 38-1 dry | 79 gz | 22 | 2* | 40 | 1685 | 59°3 see ne
» 13] 36°5 | ary | 72 7 | 2 . | 90 | 1246 | 43°8 oe
os 04 | 28°3 | snow | 69 72 | 4 wwe. | 60° | 1129] 89-7 ons ese

]

* In railway.

OBSERVATIONS ON THE URINE,

Rocapitulatory Table—continued.

91

~
om:

Appearance. Urea Phosphoric acid, Chlorine. Dose. | Date.
grms.| grs. | prop.| grms.| grs. | prop./ grms.| grs |prop.| grains. | 1866.
Clear, clouded at| 29°7 | 458°2 | 30 2°90 | 44°7 | 2°93) 5°8 90 | 5°38] 4/100 |Jan. 21
aaa 34°68 | 475°1 | 31 3°20 | 49°3 | 2°86 | 4°7 73 | 4°2| 4/100 syree
ees 29°32 | 451°4 | 28°5 | 2°76 | 42°5 | 2°69 | 8°4 30 | 8*1] 65/100 99 28
f vee es | 27°6 | 3°03 | 46°7 | 3°06 | 6°1 94 | 61} 6/100 #, 24
nee 34°6 | 533 29 3°14 | 48°4 | 2°64 | 7°3 | 113 | 6*1 | 6/100 99. 20
ii 33°44 | 515 | 25°2 | 3°39 | 52°3 | 2°56 | 5°6 | 86 | 42] 6/100 11 26
: we 28°78 | 444 19 3°29 | 50°7 | 2°39] ... ‘ie 6/100 Sacer
i a 26°71 | 412°1 | 82°3 | 3-08 | 47°5 | 3°73 | 48 74 | 5°8! 6/100 y¢.29
ose 32 *386 | 499°3 | 27°5 | 3:00 | 46°2 | 2°55 | 5°7 89 | 4°8| 7/100 ‘509
| eae 88°88 | 599°9 | 25°3 | 3°56 | 54°9 | 2°32 | 7°7 | 120 | 5 8/100 97 30
ney 29°31 | 452°2 | 30 2°90 | 44°7 | 2°97 | 5°5 85 | 5°6 | 10/100 $9 OF
{ een 33°54 | 517°5 | 28°5 | 3°23 | 49°8 | 2°75 | 7°8 | 120 | 66} 10/100 | Feb. 1
| she 31°63 | 488 27°4 | 3°09 | 47°6 | 2°73 | 7 108 | 5°8 1/16
eee 28°2 | 435 31 2°99 | 46°1 | 3:29 | 5°3 82 | 5°8
as 38°88 | 600 oe =| 8°56 | 55 ose 6| 8°98} 138
eee 26°71 | 412 wane Thee eG b Seo O tae, Nee 73
| tee 12°17 | 188 ee 0°80 | 12°5 eee 4°28 | 65
ms 32°85 | 506°8 | 24°5 | 2°91 | 44°9 | 218] .. a us oe | Feb, 2
* 31°32 | 483°2 | 21°75] 3°31 | 51 | 2°38 “s ne mee
me 27°45 | 423°5 | 30 8°68 | 56°7 | 4°02 | 7°7 | 119 | 8+4 fan we
as 83°11 | 510°8 | 27°5 | 3°04 | 46°9 | 2°52 | 7 108 | 5°8 eee TERE
Pa 31°09 | 479°7 | 26 3°18 | 49 2°66 | 6°6 | 102 | 5°5 ese ae
iat 27°66 | 426°7 | 23 2°77 | 42°7 | 2°38 | 8°4 | 130 | 7 eee epi
ea 85°50 | 450°7 | 27 3°12 | 48°1 | 2°61 | 6°2 96 | 4°7 eee 2 he
ect 84°70 | 535°4 | 24 3°16 | 48°7 | 2°41 | 8°5 | 182 | 5°8 eee » 9
Ph 84°35 | 516°9 | 30 3°35 | 51°7 | 2°93 | 5°3 82 | 4°6 eee 310
see tes eee eee ess ove eae ees ea eee ose Pape 8
eee 33°01 | 509°3 | 19 2°91 | 44°99} 1°73 | ... ces Pe eee + 12
eee 80°52 | 470°9 | 24°5 | 3°15 | 48°S | 2°53 | 6°7 | 103 | 5°3 eee ae
eve 31°36 | 482°3 | 27°7 | 3°07 | 47°3 | 2°72 | 5°5 85 | 4°6 oce »» 14

92 ON DIGITALIS, WITH SOME

Recapitulatory Table—continued.

Date. | Temp. | Moist. | Pulse. | Sleep. Work. Amount. Sp. gr. | Reaction.
1866. 9 | oii hrs. hrs. min.| ¢.c. Oz.
BOA eae V4" FFE oY SSF See ee
Daily mean, excluding Sundays = we eee eee eee } 1304 45°9 eee eee
On Sundays poe. Cham cine 9s. oe gels bomen”. wie apt a rae 32°2 ose ove
Maximum ee a ee ee ee ieee ee ey 59°3 one ove
Minimum... seo ose oe er et rrr sacl” | tS 30°2 ove oes
Difference ... eee eee eee eee eve sail ee 29°1 eee ose
Feb. 15) 35°3 |] damp | 70°2 iz 5 eee 65 1329 46°7 eve vee
» 16) 35°3 bee 79 7} 5} 44 | 1CO 1812 63°8 eee ose
oo 17] 384°2 dry 88°5 7 4 oo | 220 1118 39°3 vee ooo
» 18 ove eee ove 9 see eee 30 920 32°3 ose eee
9» 19| 35°1 | damp | 73°5 8} 5} ei 60 1158 40°7 | 1026°5
» 20| 38°6 dry 76°5 7} 1} 33* | 50 1430 50 1023 or)
oy 21) 37°83 dry 72°5 7} 4} ite 60 1249 40°4 | 1027 vee
» 22) 39°6 | damp bee 13 3} ay 90 1302 45°8 | 1025 ove
» 23| 42°8 | damp | 74 8 33 | 5 80 | 1296 | 45°6 | 1025 oeé
»» 24) 38 dry 70°5 53 4 2t 90 1245 43°8 | 1025 eve
37°6 |... | 75°6 | 7 | 33 | 4 | 85)
Daily mean, excluding Sundays .., eee ove $6 J 1326 46 °6 #05 one
On Sundays abe see An oe eee ise eee ext Bae 32°3 eon eee
Maximum... ‘oe eee eee eee ove eee ose oe} 1812 63°8 eee ove
Minimun... one aS eve ove ove eee wee e-| 920 32°3 aes eee
Difference ... eee te eee soe eee os 892 ne ms
Feb, 25 vce 72 ove ove 20 925 382 °5 1031 pee
» 26| 38°8 snow 70°5 8 4 ase 60 1287 45°3 | 1022 and
» 27| 863 | dry | 72 8 8b | ces | 00.) BB 7B * ] 4S*2 | 1085 sof
» 28| 31°2 | snow | 69° | 7} | 5 w. | 60 | 1305 | 45°9 | 1026 ‘is
March] | 33°2 snow 75 6} 5 ise 90 1488 52°3 | 1022 sieat
os eos dry 70 52 5 5 95 1209 42°2 1025 °5 eee
ete: Wed Eo Py ie Baad er ye te Fare oP)
Daily mean, excluding Sundays... ose eos ee J 1303 45°9 eee eee
On Sundays eas ive See gee one oes, tee esef «a0 32 °5 fe ess
Maximum see ose oes ose oon oes eee «| 1488 §2°3 eae ves
Minimum... sue ase Pa ao ose oe eve o-| 925 82°5 ven
Difference ... ma eae coe ove eee e.} 563 19°8 bss eee

* Readiig and examination, { Examination.

OBSERVATIONS ON THE URINE.

Recapitulatory Table—continued.

93

Appearance. Urea. Phosphoric acid. Chlorine. Dose. Date.
grms.| grs. | prop. | grms.| grs. | prop.| grms.| grs. ‘prop.| gr. mill.| 1866,
eee 31°9 | 492 25°4 | 3°14 | 48°4 | 2°57] 6°8 | 105 | 5:2 eee
ese 27°4 | 423 30 3°68 | 56°7 | 4 7°77 | 119 | 8°4 ose
exe 35°5 | 450 ose 3°68 | 56°7 eee 8°5 | 132 <9 ove
ee 27°45 | 423 ne 2°44.) 42°9 se 5'3 | 82 26 oes
eee 8°05 27 0°91 | 14 $i 3°2| 50 be
@ae 32°71 | 504°7 | 24°6 | 3°50 | 54 2°64| 8 108 | 6 3/200 1\Feb. 15
«se 39°00 | 601°7 | 21°5 | 3°31 | 51 1°83 | 9 140 | 4°9 | 6/100 4 9. 16
ove 34°97 | 639°5 | 31°2 | 3°24 | 50 2°9 7 108 | 6°2 | 6/100 4 Pom Y |
sae 35°71 | 551 39°7 | 3°40 | 52°4 | 3°7 6 94 | 6°5 | 6/100 4 ig
eee 33°84 | 522°1 | 29°2 | 3°17 | 48°9 ; 2°74] 6:5 | 100 | 5°6| 6/100 4 5, 49)
Not quite clear ...) 35°2 | 543°1 | 24°6 | 3°23 | 49°8 ; 2°26 | 8°4 | 130 | 5°38 | 9/100 6 99. 20
Not perfectly | 35°86 | 553°3 | 28°7 | 3 62 | 56°8 | 2°9 7°38 | 114 | 5°8 | 9/100 6 Ap) |
rich eee 36°05 | 556°2 | 27°6 | 3°33 | 51°3 | 2°56 | 7°6 | 118 | 5°8 {18/100 12 4 2
ee 39°87 | 615°1 | 30°7 | 3°36 | 51°8 | 2°6 7°7 | 119 | 5:9 ‘80/100 20 i ee
eee 34°47 | 531°8 | 27°6 | 3°43 | 52°9 | 2°76 7°8 | 121 | 6°2 52/100 35 Pe
ose 35°77 | 552 26°9 | 3°36 | 51°8 | 2°69} 7°5 | 117 | 5°6
eee 35°71 | 551 39°7 | 3°4 | 52°4 [3:7 6 94 | 6°5
ane 39°87 | 615 ee | 3°62 | 56°8 ‘< 9 140
ese 32°71 | 504 eee 3°17 | 48°9 tee 6 94
Ty tae 7°16 | Ill eo Q0°45 | 8 Se 3 46
Clear, clouded at | 31°30 | 482°9 | 33°8 | 3°55 | 54°7 | 3°84] G*1l| 95 | 6°6 ove Feb. 25
ue 34°31 | 529°4 | 26°7 | 3°03 | 46°7 | 2°36 | 8°5| 131 | 6°6 eee on
Cloudedat bottom | 32°11 | 495°4 | 26°1 | 3°07 | 47°3 | 2°5 8°5 | 1381 6°9 oe su) ae
Clear, clouded at | 34°8 | 536°9 | 25°9 | 3 13 48°2 | 2°4 9-3] 145. | 71 oe 9 2
bottom
Clear, clouded at | 35°81 | 621°6 | 24°1 | 3°75 | 57°8 | 2°52 | 6°4| 100 | 4°3 «e Mar. 1
bottom
ove 35°33 | 545°1 | 29°2 | 3°05 | 47 2°53 7°70 | 102 | 5°7 3/200 1 ie
ane 34°07 | 524 26°1 | 3°26 | 50°3 | 2°5 7°6 | 118 | 5°8 3
eee 313 | 483 83°8 | 3°55 | 54°7 | 3°84] 6:1 95 | 6°6 3
“rs 35°86 | 621 | ... | 3°75 | 57°8| .. | 9°3| 145 a
a 31-30| 483 | ... |3°03|46-7| ... | 6-1] 95 §
mA 4°56 | 138 oa 10°88 Tg eens re | 50 g

94 ON DIGITALIS, WITH SOME :

Recapitulatory Table—continued.

Date. | Temp. | Moist. | Pulse. | Sleep. Work. Amount. Sp. gr.| Reaction.
|
1866. % hrs. | hrs. | min.| c.c. 0Z.

March3} 33°5 | damp nae 64 3h Nes 50 1057 37°2 | 1031 eee
gs oe age eb 8 Ves ves 20 1090 38°3 | 1030 ose
Reape mi: ae sz | 4h | .. | 70 | 2371 | 492 | wn us
» 6| 33-4 | damp | 70 of | 4 | .. [| 60 | 1221 | 43 se us

a) 6274 ey a eT “|

Daily mean, excluding Sundays ... ose ose eee 1216 42°8 ose ase

On Sundays eee eee eee eee eee 7 eee eee eee 1090 38 3 eee eee

Maximum... eee ere eee eee eee eee oor eee 1371 48 3 eee eee

Minimum eee eee eee ere coe ene eee eee eee 1057 37 2 / eee eee

Difference ... eee eee ose een eee eee 314 ll ose eee

March7| 33°8 | snow ) 68°5 93 4 eee 60 1102 38°8 PP eee
”? 8 36 damp 67 "5 1k 3} eee 80 1228 45 eee eee
eo be ao'e dry 66 qt 53 4h 80 1313 46 °2 ess tee.
» 10} 39°8 | ary | 67 SA Qa goo! |i a4 ge a
Se &* ore ee ee 10 Pd | eo | aae8 | d+: | Ope a
» 12} 42-2 | ary | 65:5 | 93 | 3h | .. | 50 | 1259 | 4a3 |... at
» 13] 41-2 | ary | 64 7; | 33 | .. | 120 | 1488 | 52:3] .. ie
wt] 37-4 | ary | 68:5 | ck | 2 | .. | 80 | 1607 | ses |]. =

Mar.14} 38°6 | .. | 66°3 | 8 | 4 | 4% | 66

1421 50 eee soe

Mean, excluding Sundays nee vee oes eee ove

On Sundays soe eee eee eee eve eee eco eee 1123 39 5 eee coe

Maximum eee see eee ese eee coe eco eee eee 1607 56 dS eee eee

Minimum eee eee eee eee see see coe eos eer 890 3l 3 ore soe

Difference ove eee eee coe eve eee 717 25 °2 ove ees

Mar.15| 86 j; damp [{ 65°5 8 3} ees 80 1090 38°3 a eee

», 16 | 40°1 damp 64 8 2 | 4h 90 1184 41°7 aes ove
ie TE Oe 8 aa
f 1137 40 seo eee

Mean soe eco eoe eee ece eee eee eee

Mar.17 { 41°4 dull | 71 | 1% 14 | 13* | 200 1258 44°2 1023 eee
» 18 oes eee oes 94 ea ae 30 1200 42°2 1022 oat

* Examination.

OBSERVATIONS ON THE URINE. 95
Recapitulatory Table—continued.
Appearance. — Urea, Phosphoric acid. Chlorine, Dose, | Date.
grms. | grs. |prop. | grms.| gers. | prop.| grms,| grs. |prop.| gr. mill. | 1866.
eee 34°14 | 526°8 | 82°3 | 8°40 | 562°4 | 3 22] Bl} 49 | 2°9 | 6/100 4| Mar. 3
ese eee re 2 *43 53 7 3 2 eee ee see 6/100 4 ” 4
eee 87°96 | 585°5 | 27°6 | 3°05 | 47 2°23 | 6°2|) 96 | 4°6 | 6/100 4 9. 5
eee 25°80 | 552°3 | 29°3 | 3°06 | 47°2 | 2°52) 5°5 | W7 | 4 6/100 4 nn. ©
ise 35°96 | 555 29°5 | 3°25 | 50°1 | 2°82 | 4°38) 74 | 3°9
tee aes 3°48 | 53°7 | 3°2
wee 37°96 | 585 - | 3°48 | 53°7
ove 34°14 | 527 soe | 3°05 | 47
see 3°82} 58 ee | 0°43] 6°7
ese 29°38 | 453°3 | 26°6 | 2°44 | 37°6 | 2°22 | 7°5 | 116 | 6°38 | 9/100 6| Mar. 7
see 87°6 | 580°l | 30°6 | 3°10 | 47°8 | 2°41 | 10 155 | 8:1 /12/100 8] , 8&8
eee 87°51 | 578°7 | 28°5 | 3°30 | 50°9 | 2°52 | 9°3 | 145 | 7 12/100 8} ,,
eos 80°57 | 471°6 | 34°3 | 3°09 | 47°6 | 3°47 | 4°3 | 67 | 4°8 |15/1001G} ,, 10
Somewhat turbid | 39°73 | 613°3 | 35°3 | 3°30 | 50°9 | 2°97 |} 7°2| 113 | 6°4 /15/10010| ,, I?
ses 84°21 | 527°8 | 27°1 | 2°41 | 387°1 | 2°96 | 7-1 | 111 | 5°6 |22/10015| ,, 12
tee 87°31 | 575°6 | 25 3°27 | 50°4 | 2°2 7°1 | 110 | 4°3 /30/10021| ,, 13
ees 35°43 | 446°6 | 22 3°21 | 495 | 2 6°5 | 101 | 4 |31/10020; ,, 14
eve 35°21 | 543 24°7 | 3°01 | 46°4 | 2°46 | 7°3 | 114 | 5°1
eee 39°73 | 613 35°3 | 3°3 | 50°9 | 2°97 | 7°2 | 113 | 5°6
* 39°73 | 613 ee | 3°80] 50°9 |] ... |10 155
toe 29°38 | 453 oes | 2°41 | 37°1 =P NL Sn og i
eee 10°35 | 160 se | O'8Y] 18°8 | .. | 3°5 54
e009 85°77 | 551°9 | 32°8 | 3°18 | 49 2°92 | 5°4 84 |5 |45/100 30| Mar. 15
we 34°60 | 583°8 | 29°2 | 3°05 | 47 2°58 | 6°1 95 | 5°1 |45/10030| ,, 16
ose 35°18 | 542 30°9 | 3°11 | 48 2°75 | 5°7 89 | 5
ove o-.| 85°5 | 547°7 | 28°2 | 3°09 | 47°6 | 2°46 | 7°2 | 112 | 57 vee Mar. 17
Turbid soe eee 30 *66 473 25 9) 2 *65 40 8 2 % 1 5 24 1 2 eee 2? 1s

96 ON DIGITALIS, WITH SOME

Recapitulatory Table—continued.

Date. | Temp. | Moist. | | ulse. | Sleep. Work. Amount. Sp. gr. | Reaction
1866. hrs hrs. { min Cc. OZ.

Mar. 19 | 39°6 damp 63 °5 9 3} 100 1855 65°3 eee eee
9 20 | 384°2 dry 61 53 6 eas 50 1293 45°5 eos eee
2 21 35 6 snow 67 gh 3} eee 85 1523 53 6 eee ece
9 22 | 387°6 snow 68 8i 34 ss 90 1655 §8°2 eee ese
Fu eeo| Lanes wet 71 6} 2k 1} 80 1194 42 eee soe
9 24) 37°3 damp 73 8 3 23* | 110 1219 42°9 eee eee
+b) 25 . eee eee 9 eee eee eee 1080 38 eee eee

l
S776 J asa | 68 {| 8 | 3 1-1: | 105]
1428 50 2 eee ece

Daily mean, excluding Sundays sa re aed ies J

On Sundays... eee eee eee eee eee eee eee eee 1140 40 “1 eee eee

Maximum... eee eee eee ere eee eee eee eer 1855 65 3 see eee

Minimum eee eee eee eee eee oe eee * 1080 38 eee eee

Difference ene oee * 775 27°3 oes

2 * pall

tt ie

ON DIGITALIS, WITH SOME OBSERVATIONS ON THE URINE.

Recapitulatory Table—continued.

97

Appearance.

Urea. Phosphoric acid. Chlorine. Dose.
grms.| grs. | prop.|grms.; grs. | prop. | grms.| grs. |prop. grain, iS
43°70 | 674°2 | 23°5 | 3°C6 47°2 | 1°65 |12°6 | 195 | 6°7 rere
29°83 | 460°2 | 23 2°43 |.37°4 | 1°88 | 7°9 | 123 | 6°1 <0
85°14 | 542°2 | 23 2°61 | 40°2 | 1°71 | 5°9 91 | 3°8
43°28 | 667°8 | 26°1 | 3°24 | 50 1°96 | 8°4 | 131 | 5 ae
38°34 | 591 *4 | 32°1 | 3°25 | 50 2°72 | 3°8 60 | 3°1 eee
40°00 | 617°2 | 32°8 | 2°99 | 46°1 | 2°45 | 5°4 84 | 4°4 see
36°00 | 555°8 | 33°3 | 3°38 | 52°1 | 3°14 | 5°6 86 | 5°L =
36°9 | 569 25°8 | 2°95 | 45°S | 2°24] 64 | 100 | 4°4
83°33 | 514 29°2 | 3°23 | 49°8 | 2°83 | G°4 | 100 |; 4°4
43°70 | 674 3°38 | 52°] | we [126 | 195
30°66 | 473 2°61 | 40°2 15 24
13°04 | 201 re 0°77 | 12 ecm pean, 4g

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on)

CASE OF POISONING BY DIGITALIS. 99

CASE OF POISONING BY INFUSION OF DIGITALIS
—RECOVERY.

Dantet G., aged fifty-two. Admitted into Royal Infirmary, October 4, 1865.
The patient, who is a tall and powerful man, had an attack of pleurisy more
than three months before admission, and, after the acute symptoms were
relieved, he was unable to resume his occupation of using the fore-hammer on
account of shortness of breath, loss of appetite, and general weakness. On
applying to a medical man, it was discovered that there was effusion into the
left pleura, reaching up to the third rib; and after being treated by mercu-
rials, &c., for some time, he was admitted into the hospital, and the effusion
was found to be still at the same level. On admission, there was dulness over
the left front from base of lung to above the level of third rib, and on left back
partial dulness from above the scapula to its inferior angle, and thence down-
wards absolute. There was frequent cough, but no expectoration. The apex
beat was most distinct at left side of ziphoid cartilage. Heart sounds natural;
pulse 70, of moderate strength; tongue furred; appetite moderate; bowels
regular; urine in good quantity, natural in character. He was at first ordered
acetate of potash, 20 grs., three times a day; but this producing little benefit,
he was ordered half an ounce of infusion of digitalis three times a day.

After being ordered infusion of digitalis, he at first measured it, but soon
began to guessit, and had gradually increased the amount. Shortly after doing
tis, his appetite began to fail, and, at the same time, he had a bad taste in }:is
mouth, and his tongue felt very dry. He felt also a dull sickening pain over
the stomach, rising up the line of the sternum to the throat. Occasionally this
was like to make him sick. He felt weaker every day. This was about the
middle of November, about three weeks before the symptoms attracted atten-
tion. He went on gradually increasing the dose. When he lost his appetite
he also got occasional headache and, along with the pain in epigastrium, he had
palpitation. His bowels were costive. About the third week of November he
vomited once or twice after meals when seized by a severe fit of coughing. The
vomiting he attributes entirely to the cough. These symptoms grew worse, and
he felt weaker and weaker, and less able to walk. About the Ist or 2nd of
December he noticed his sight becoming dim, and when he looked at his own
hands, or another person’s face, they seemed blue. The pain in the stomach
was now almost constant; but the headache was not much worse—it was worst
in the afternoon. On themorning of the 5th December he complained of weak-
ness and want of appetite. His pulse was found weak and very irregular. At
the visit in the middle of the day the cardiac action was found increased, and
the pulse distinctly dichrotic. The general rhythm was about two beats in one
second, and then an interval of about two seconds. The pulse was 58—some-
what feeble. The pupils were natural and skin moist. Urine deposits a con-
siderable amount of lithates, otherwise normal. He got three ounces of brandy
before I saw him, which I did about 5.20 p.m. At that time the cardiac
impulse was very abrupt and felt strong, the impression to the hand being
exactly what I had felt in experimenting with dogs. The pulse was 66, but
very irregular. I took the following tracing with the sphygmograph :—

H 2)

100 ON DIGITALIS, WITH SOME OBSERVATIONS ON THE URINE.

Fic.1. 6 p.m.—-December 5.—Right radial; patient lying.

From this we see that the pulse is irregular and intermittent. The ligne
@ ensemble, or line which wonld connect the tops and bases of each beat, instead
of being straight, is curved, showing that the arterial tension is more influenced
than usual by respiration. The pulse is dichrotic, this being especially marked
in the last pulsation on the tracing. This dichrotism is not perceptible, or only
to a very slight extent in subsequent tracings, showing that the tension of the
pulse, when the present tracing was taken was not only low in itself, but much
below the ordinary arterial tension of the patient.* He got 3 ozs. more brandy,

and a diaphoretic mixture (spt. ammon. aromaticus), which lessened the dim-
ness of vision. .

Fia. 2. December 6.—Tracing taken from right radial about 6 P.M.
Patient lying.

The ligne densemble is much more nearly straight than yesterday, showing
that the arterial tension is less variable. Pulse very slow, and irregular as to
time; but while yesterday it was as it were a quick pulse with occasional inter-
missions, or perhaps it might be termed a quick pulse, becoming occasionally a
slow one, to-day it is a slow pulse with an interpolated beat or beats; or a slow
pulse, becoming occasionally, and for a brief period, a quick one.

The arterial tension is distinctly higher than yesterday, the line of ascent
being more blique, the top of the curve, instead of being sharp, is rounded,

and the line of descent gradual instead of sudden, and only the faintest trace of
dichrotism.

Fie. 3. December 7.—Tracing taken from right radial at 1 p.m. Patient lying.

’ Abe ‘a
aa eg d

The pulse is still irregular, and its. characters are almost identical with that
of yesterday. We see the distinct interpolation of a beat in the case of the
pulsation 4, which, if the line of descent prolonged to the same length as that
of a, would reach to the point d. If we join the bases a’ and 2’ of the lines of
ascent of the waves a, 6, and e, and prolong the line, we find that it passes
through the point d, and also that the distance between a’ and D’ is the same
as between 6 and d, showing that the rate of lowering of the arterial tension is
the same in both ; or, in other words, that the blood has been escaping with the
same degree of rapidity through the capillaries in both cases. So, when the

* Comparing the suddenwess with which the wave attains its maximum
height, and its sudden descent, with a tracing after recovery, we see that the
cardiac systole is very much more abrupt and shert than normally.

CASE OF POISONING BY DIGITALIS. 101

next wave c was impelled into the arteries before its usual time, the base ec’ of
the wave ec found the arterial tension greater than usual, and in consequence
is on a higher line. We notice also, that though the amount of blood sent
in by this wave, as indicated by its height, is less than usual, yet coming so
close upon the last, it has raised the arterial tension higher than usual, as
is shown by the height of the top of ¢ being above that of the others.

Fie 4. December 8.—Tracing taken at 3 P.M. Pulse, 93. Patient lying.

Ne ee oe ae

This tracing was taken about half an hour after patient had had his dinner,
and the rapidity of the pulse is probably due to this.

The pulse is much more regular, and the ligne d’ensemble nearly straight.
The line of ascent is comparatively abrupt, and then presents an ascending
plateau. This latter is probably due to loss of elasticity of the arteries from
commencing senile degeneration, which it is evident that patient has, from
the nature of the tracings after his return to health. The line of descent is
tremulous.

The dimness of sight and pain in epigastrium has been gradually diminishing.
This afternoon he had rigors, and went to bed complaining of intense frontal
headache.

Fie. 5. December 9.—Tracing from right radial, 8 p.m. Patient lying.
Pulse, 64.

a Se

Pulse much slower than yesterday. Ligne d’ensemble of bases pretty nearly
straight. ‘The waves vary slightly in height and length, each third one being
smaller, and the line of descent straighter, than the others. This is probably
due to the influence of’ respiration. The ascent is comparatively oblique at
first, and after ascending some way becomes still more so, and the line of
descent gradual, showing high arterial tension. To-day the headache is better,
and the shiverings have not returned.

December 10.—Being Sunday, I did not examine the case.
Fie. 6. December 11.—12.30 P.M.

Ligne d’ ensemble is not quite straight. The line of ascent almost perpendicu-
lar, then a well-marked ascending plateau. From the little moslification that
the cardiac impulse has undergone, one would be inclined to say that the

elasticity of the arteries was more impared than usual.
Headache almost gone; patient much better.

Fig. 7. December 12.—Tracing taken at 1.50 P.M.

ES ed oe ee ae ee

Plateau less marked ; tops more rounded.

102 oN DIGITALIS, WITH SOME OBSERVATIONS ON THE URINE.

Fie. 8. December 13.—Appetite slightly improved; still slight headache;
pulse 60; quite regular; seems now to have returned to its normal state com-
pletely.

Tracing taken at 6.80 P.M. Pulse then 66.

Fra. 9. December 14.

Pon PP

Tracing at 5.45 p.M. Pulse 56. Respiration, 20.
Tension slighly higher than yesterday, and pulse slower.

Fia. 10. December 15.—Patient was sitting up but went to bed, and had
been lying about forty minutes before the present tracing was taken.

Se ee ia i

1.28 p.m. Pulse, 60. Respiration, 24.
In this there is a nearly horizontal plateau, and the tension is consiGaaiay
affected by the respiration.

4

Fie. 11. December 16.—Tracing taken at 6 P.M. Pulse, 64. Respiration, 23.
Headache to-day only occasional.

Patient still complains of headache, which up to this time has been constant.

December 17.—Sunday.
Fie. 12. December 18.—Between 1 and 2 p.m. Pulse 63. Repiration, 273:

fT re

Appetite improving.. For the last two days headache has not been so bad.

December 19.—Appetite still improving; headache only occasional. The
headache over the right or left parietal bones and frontal bone, chiefly about
the parietal protuberances ; never on the vertex or occiput. It goes from side
to side—being to-day over the left, and yesterday over the right, parietal bone.
Some pain in back to-day.

Fig. 18. Tracing taken ot 6 P.M. Tulse, 73. Respiration, 26%.

NYINISINIKLRINIS

Pulse rather quicker ; tension rather less.

ee ee ae ees

ACTION OF DIGITALIS ON BLOOD PRESSURE. 103

Fie. 14. December 20.—Tracing at 5.30 p.m. Pulse, 68. Respiration, $2.

NINN

My observations were now stopped, as I was going to the country; but from
the constancy of the characters of the pulse during the last four days, we may
suppose that it had now returned to its normal condition.

EXPERIMENTS ON THE INFLUENCE OF DIGITALIS
ON THE PRESSURE OF BLOOD IN THE ARTERIES.

In order to determine the influence exerted by digitalis, or digitaline, on the
arterial pressure, the carotid of a dog was exposed; the nozzle of a hema-
dynamometer inserted, and the height to which the column of mercury rose was
noted. After waiting a short time to see if the pressure was constant, digitaline
suspended in water, or infusion of digitalis, was injected into the jugular vein,
and the pressure again noted.

The instruments which were commonly used consisted of a glass flask, partly
filled with mercury, into which two tubes dipped, and were held firm by being
cemented air-tight into a brass cap. The mouth of the flask is closed by an
india-rubber stopper, through which were passed a brass tube, provided with a
stop-cock, and having a funnel at its upper end, and a curved glass tube, by
means of which the instrument was connected to the artery. This brass nozzle
is small at the end, and grows rapidly wider, and is roughened at the small end
to prevent its being dragged out of the vessel by giving a better hold to the
ligatures securing it. By means of a piece of glass tubing, with a bulb upon it,
and india-rubber tubing, the nozzle was connected to the hemadynamometer.
A clip was placed on the tubing, so as to restrain the flow of blood at pleasure.
The whole apparatus having been filled up to the end of the nozzle with a
solution of bi-carbonate of soda, to prevent coagulation of blood, poured in by
the funnel, the stopcock was turned, and the apparatus ready for use. A
graduated scale was applied to the tubes to show the height to which the
mercury rose. As the volume of mercury in the flask was so much greater than
that in the tube, no corrective was employed for the lowering in the flask as it
rose in the tube, as would have been necessary had a simple bent tube been used.
An apparatus of this kind, with a plain tube, gives trustworthy indications so
long as the pressure is constant: but when it is variable, the indications become
fallacious from the mercury at each oscillation acquiring a rapidity which
carries it above and below the true maximum and minimum points.

To obviate this, the compensating tube of Marey was used. This consists of
a tube, whose bore is reduced to a capillary size near the lower end. The
mereury can only pass through this very slowly, and the influence exerted by
each oscillation on the height of the mercury in it being very small, the true
mean pressure of the blood is thus obtained.

104 oN DIGITALIS, WITH SOME OBSERVATICNS ON THE URINE.

Fie. 15. Marey’s Hemadynamometer. This figure was not in the original
Thesis, and I owe its appearance in this volume to Professor Marey’s kindness.

Exp. I.—-Nov. 25, 1865.—The dog experimented on was a pointer of the
usual size. It was tied down to a table, and chloroform administered while the
carotid was being exposed.

Mercury.

Time. | win & Mx. Mean.| Pulse.| Resp. Remarks.
P.M. Inches.
2.25' — an a = The first incision was made, Dr.

Gamgee kindly performing the
experiment for me.

2.5 = ee re .- | Nozzle introduced into carotid.

2.55/ 4—5 ve ee .. | Stopeock turned on—the mercury
rose immediately.

2.57’ 45 5*

2.59’ 4° 4,

2.59'30| 4°95 | 4-25

* Little oscillation. Probably clots already present.

ACTION ON CIRCULATION

‘
,

AND RESPIRATION. 105

Time.

Mercury.

Min. & Mx.

Mean.

Pulse. Resp.

Remarks.

P.M.
3.2’
3.5’
3.5’

3.9’
3.13’ 15
3.14’ 20
3.17’ 40
3.20’

3.22’ 15
3.26’

3.29’ 30

3.31’ 40
3.35’

3.45’ 45
3.47’
3.50’ 45

3.53’ 30

Inches.
4 °8—4,°9

4-4

i A

Slight irregularity of heart. Never
sinks, when animal struggles.
below 46; never rises above 4°
during struggle, but fell imme-
diately.

1 centigram of digitaline sus-
pended in distilled water.

The first part injected into jugular
vein.

The fourth part injected.

Injection completed.

Pulsation faint—tube probably
plugged.

Not above 4°8.

Oscillations barely perceptible.

Cardiac pulsations, 100—extreme-
ly irregular both in number and
force.

A solution of another centigram
of digitaline was now injected
into the cellular tissue of the
upper part of right thigh—com-
pleted at 32’ 10”,

Heart's action weaker, and more
irregular.

It was ascertained that there was
obstruction at some point in the
apparatus, and on examination,
the nozzle and the greater part
of the india-rubber tubing, were
found filled with clots. These
were removed, and the instru-
ment again readjusted at 3.41’.

| Oscillates with extreme irregu-

larity.

Hardly perceptible.

Clip placed on india-rubber tube,
and nozzle twice cleaned by suc-
tion.

The mercury soon again became
stationary, and after another in-
effectual attempt to clear the
apparatus, the nozzle was finallv
withdrawn at 4 P.m., and the
wound stitched up. The femoral
pulse was 90’, and, though still
very irregular, was less so than
when last estimated.

4.4’.—Dog released from the table.
about as if nothing had happened, and made water on the floor.

Seemed a little stiff at first, but soon ran

In this

* Less irregular.

106. ON DIGITALIS, WITH SOME OBSERVATIONS ON THE URINE.

experiment, instead of the nozzle which I had before described, a straight one
was used of a much smaller bore, which was farther diminished by a stopcock

upon it.

Exp. II.— Nov. 29.—In this experiment the nozzle was wider, and the
apparatus was just as described at the beginning, the hemadynamometer
showing the mean only being employed. The same dog was used which had
been experimented on on the 25th. Chloroform was given as formerly.

Time. ner its * |Pulse.| Resp. Remarks.
P.M. Inches.

1.58’ ay -- | [ made the first incision.

2.5’ 30 we . | Carotid exposed, and ligatured at distal
end.

2.11’ F ae -- | Nozzle inserted.

2.14’ ve 120 | .. | Clip relaxed.

2.17’ 5°55

2.19’ 5 4 125 | . 5 ‘4 appears to be about the average.

2.20’ 45 5°3 ee ° External jugular vein tied.

2.22’ 30 5°15 .

2.23’ 15 5 °4 ee : Ialfagrain of digitaline in water was in-
jected into the jugular vein. Mercury
immediately indicated 5 *4.

2.25’ 5°45

5 *5—5 °55

2.25’ 5°3 «+ «| «+ | Suddenly fell to 5°3. .

5°5 + . | As suddenly rose to 5°5. Then fell again.

2.26’ 5 ‘1—5°3 oe . | Heart’s action extremely irregular.

2.26’ 30| 4°8--5 es .. | Stillextreme irregularity in the pulsations,

2.26’ 40 4°7

2.26’ 55| 4°6—4°55

2.27’ Ad , Breathing extremely rapid.

2.27’ 45 4°5

2.28’ 15 4°4

2.29’ 40 4°8 26 | Mercury rose to 4°8. Respirations are not

' | so rapid as they were at 27’.

2.30° 4:7 172 Pulse more regular.

2.30’ 15 4°8

2.30° 30 me oe : Respiration much quieter.

2.30’ 45 4°6 148 | . Pulse still regular. Oscillations slight.
Column is, on an average, at 4°6, and is
less violently affected than before injec-
tion.

2.32’ 30 os 200 . | Regular.

2.337 4°3 wi . | Pupils dilated, and imperfectly contrac-
tile to light.

2.34’ 15 43

2.34’ 45 4°1

2.35’ 4°0

2.35/ 45 3°8 . | Pulse weaker.

2.36’ 10 3°6

2.36’ 30 3°5 180 Pulse very weak.

ACTION ON CIRCULATION AND RESPIRATION. 107

Time. ae J: | Pulse. Resp. Remarks.
P.M. Inches.
2.37’ 30 3°35 oe -. | Pupils contract more perfectly. Breath-
‘ing, abdominal laboured. Intercostal
muscles do not act properly. Chiefly the
accessory muscles of respiration act.
Thorax is raised as it were as a whole.
2.387 45 3°4
2.39’ 20 3°25
2.40’ 10 3°2
2.40’ 40 3:3
2.41’ 3°25 154 | .. | Pulse weak, and rather irregular.
2.42’ 3°2
2.42’ 10 3°3 es -- | Thermometer in axilla of dog 96°5° F.
Pupils smaller than at the beginning of
experiment, and continue to contract on
the application of light.
2.44! 3°2 ee : Pulse cannot well be estimated. Very
irregular.
2.4515} 38—3:1 150 | .. | Pulse irregular. Thermometer 99°.
2.47’ 30| 38 os 21 | Slimy saliva issuing from the mouth.
2.49’ 30 2°9 150 | .. | Pulse irregular. Thermometer 99°3° F.
2.53’ 2°9 -. | 18o0r| Dog appears to be sick, but does not
19 yomit; the muzzle preventing him from
opening his mouth at all.
rs 2°95 és -- | Dog moans.
2.55’ 10 om - .. | Groaning much increased, and louder.
2.56’ 15 2°85 155 . | Appears to be endeavouring to vomit.
2.57’ 15 3°1
2.58’ 3°2 ao -. | Steadily rising.
2.58’ 10| 3°3—3°5
2.58’ 45 3-1
2.59’ 3°0 ‘ .» | Gradual sinking.
2.59’ 10 2°5 ° -» | Convulsions. Passage of feces,
2°4 ss Stoppage of heart’s action.
2 °2
Down ee -- | Dog dead.
3

After this tremors were noticed.

Spasmodice twitching of the penis was

noticed after heart’s action and femoral pulse had ceased, and a fluid resembling»
and supposed to be, semen, was emitted; but on its being at once examined
microscopically, no spermatozoa were to be found, and only an abundance of
large cells like mucus or pus corpuscles were seen. Post-mortem examination
was made immediately. The thorax was opened, and the great veins tied.
They were much engorged. At 3.16’ the thoracic viscera were removed. A
great gush of fluid blood took place from the lower part of the vena cava
inferior on cutting it. The veins and right side of the heart were engorged and
swollen, stuffed like sausages, as Casper describes it. Right auricle distended.
3iii, of perfectly fluid blood of a very dark colour was got from the right
ventricle. At 3.21 the left ventricle was examined, and found firmly con-

108 ON DIGITALIS, WITH SOME OBSERVATIONS ON THE URINE.

tracted, containing a clot.
flowing from the body, coagulated in three minutes.
cava inferior coagulated very quickly into an extremely firm clot in the thoracic

It was not white from contraction.

cavity. The contents of the left side of the heart weighed 1 oz. 44 drachms.

Exp. Ili.—Wov. 29.—A full-grown sheep was experimented on—the hama-
dynamometer, showing the maximum and minimum, being employed.

8.35’ p.M.—Respirations 56 per minute; the sheep being at this time tied

down on the table.

No chloroform was given.

Carotid exposed.

The blood, om
The blood from the vena

Time. | Mx. & Min. |Mean.| Puise.| Resp. Remarks.
P.M. Inches.

8.49’ Distal end of carotid tied, and tube
inserted.

8.56’ a The clip removed; tube then broke
from the artery.

9.12’ ‘> ee .. | Tube replaced, and clip removed.

9.14’ 3°5—5 4,°2

9.16’ 3°5—5°2 | 4°2

9.19 3°5—5

9.22’ 3°5—3°6 | .. 78 -. | Animal excited by examining the
wound.

9.24’ 4—5 4,°3

9.25’ oe ° : -» | Half a grain of digitaline in water
was injected into the cellular
tissue of the thorax.

9.26’ 4 °1—4,°6

9.28’ 4,°7 oa es -- | On slight agitation.

9.30’ 5°0 es 82 36: | Breathing more laboured,

9.32’ 4*2—4°4 | .. 80 .. | Pulse steady at 80.

9.42’ 3°8—4°8 | 4°3

9.45’ 7°5 5 4 a2 -- | Sheep struggling,

9.47’ 4°1—4°4] .. 104

Sheep struggles. After this the
oscillations stopped, and clots
were suspected in the artery.

9°52’ an ‘ Clip applied, and tube removed.
Again applied at 10.6’, but at
10.10’ the india-rubber stopper
came out, and the experiment
thus interrupted was not re-
sumed,

10.10’ < b 93 89 |The sheep was loosed from the
table. Seemed very unsteady on
its legs. There was some amount
of venous oozing from the wound.

Expr. IV.—Nov. 30.—This morning the sheep seemed still much depressed ;

it had made a good deal of water during the night. Between 1 and 2 P.M. it was
again tied on the operating table. Chloroform administered, and the other
carotid opened,

ACTION ON CIRCULATION AND RESPIRATION. 109

Mercury.

Time. Méan’ | Pulse. Resp. Remarks,
P.M. Inches.

2. ee 166 - | Hemadynamometer connected with the
artery.

m3! ee . 21 | Clip removed. Thermometer in vagina
101°5° F.

2. 3” 2°1—3 ee - | Till this time the mercury in the tube has
oscillated between 2°1 and 3, neither
steadily nor regularly.

2. 5° ee ee The pupils have become contracted. At
the beginning of the experiment they
were dilated.

2. 6°40] 3°5 e -- | Pretty steady at 3°5. The sheep at this
3°6 os ee moment made a slight struggle, and mer-
3°7 «s as cury rose to 3°6 at once, then to 3°7.

2. 8’ 3°45—3°5 | .. .- | Thermometer 102°9° F.

2. 8’ 35| 3:2

2.945) 3°5 ee 20 | Steady at 3°5.

2.10’ 45 | 3°95 . | Thermometer 102°.

2.11’ 3°8 ee - | Sheep appears completely free from the

ee effects of the chloroform.

2.14’ 3°05 os - | Very feeble pulse.

2.14/10} 3°4 re .. | During violent struggles which now take

lace.
ee 3°05 ee . Then fell to 3°05.
ve 34 oe -- | During another struggle.
ee 3°1 2° -- | Then fell to 3:1.

2.1615 | 3°4 - -- | An apparently convulsive movement of
the head.

2.17/10} 3°4 oe -. | Pretty steady.

oe 4.°2 ve -. | Violent struggle. Mercury rises to 4°2,
a 4°3 4°3, 4-4,

== 4 *4

ee 4°5 ve -- | Another struggle.

2.20 3°7

2.20’ 10 ee , ++ | Injected the first half of 2 grains of digi-
taline suspended in water (into the
jugular vein—this from memory).

2.21" 10

2 21’ 25 ee . -« | Injected the remainder of the digitaline.

2.22'10} 5°2 : -- | Animal violently struggling. “

oe 5-5 oe -» | During another struggle.

2.23’ 10 se os -- | Pupil obviously contracted.

2.24 50| 4:9

2.25' 4°8 ee -» | Mercury stands at 4°8. Animal struggles.

ee ee ° -- | Pupil has becomemore dilated. Convul-
sive movement.

2.26’ 10 a ee -- | Another convulsion.

2.26’ 30) 4°7

2.27’ : se -- | No perceptible pulsation in the carotid.

ve 4 °6 oe +» | Cornea scarcely sensible to touch. Pupil
more dilated.

2.23’ 10 ee oe -« | Cornea insensible. Respiration just per-

ceptible.

110 ON DIGITALIS, WITH SOME OBSERVATIONS ON THE URINE.

Time. ghar * | Pulse.| Resp. Remarks.
P.M. Inches.
2.2945 | 4°4 a - Very faint pulsation in the artery.
sie 4°3
2.31’ 30 ” s .. | Pupil widely dilated. Respiration imper-
ceptible.
so i a a Pulse inappreciable. Thermometer 101°.
2.33’ ss as .. | Sheep allowed by all to be dead. Had
made water since it was placed on the
table. Mercury gradually fe!l.

The slow fall of the mercurial column was at first attributed to clots, but on
examination none were found to account for it.

Post-mortem examination made immediately.

On opening the thorax, the veins were found much congested. The vessels
were then ligatured, and the thoracic viscera removed. The left ventricle was
firmly contracted. Left auricle flaccid. The right auricle and ventricle were
both distended with blood. Pulmonary artery was full and turgid; the pul-
monary veins empty, or nearly so. Right ventricle contained no clot, but
2} ozs. of dark fluid blood. Left ventricle contaiaed no clot or blood, but was
markedly contracted, without any whitencss, however. Blood returning from
lungs was quite fluid, and very dark. Descending aorta contained no clot, so
the slow descent of the mercury could not thus be accounted for. Bladder was
firmly contracted and empty.

Exp. V.—Dec. 20.—A large dog—a kind of bloodhound, or a cross between
that and a mastiff, was experimented on. It took about 2 oz. of chloroform,
which was applied on a thick towel before it was anesthetised, though no doubt
the greater part of this was lost in the application. The time when it began to
get the chloroform was not noted. I cut down on and cleaned about 1} or 2
inches of the jugular vein, and tied it. After exposing the carotid, which lay
very deep, the dog was seized with convulsive tremors, which lasted a short time.
Dr. Gamgee then finished the cleaning of the artery, and inserted the nozzle
of the hemadynamometer. The instrument showing the mean only was used.

Time. fe oe * | Pulse.| Resp. Remarks,
P.M. Inches.
2.44" ea ns .. | Clip removed.
2.44’ 30 5 *4
2.44’ 40 ee abe .. |The tube of the hemadynamometer was
forced out by the pressure.
2.55 - af .. | Tube re-inserted. .
56’ 5°5
2.56’ 40 5°7
2.58’ 30 | 5'7—5 9 a“ .. | The dog being quiet.
2.59’ 201 5°5—5°6 | .. | Dog quiet.

ee Se.

. ACTION ON CIRCULATION AND RESPIRATION.

111

Time. seas * | Pulse.| Resp. Remarks.
P.M. Inches.

3. 5°7—5°75

3. 0! 45 5°6 +s . | Dog whines and barks as if dreaming.

3. 2’ 30| 5°4—5 6

3. 3’ 5°35 * . | Dog whines loudly.

3. 3’ 30| 5°5—5°7

3. 5’ 5°9 gs .. | Continuous barking, as if in a dream, more
loudly than before.

3. 5’ 6 5°8 -« | During inspiration, or attempts to bark,
_ the mercury falls. During expiration it
rises.

3. 7’ oe Still attempting tobay. Byajerk,adrop
of blood got above the mercurial column.

3. 9! 5°5—5 7

3.12’ +e 156

3.14’ 30 ee a The injection of one grain of digitaline sus-
pended in about 23 fluid drams of water.
into the jugular vein, was begun.

3.16’ 5 -9—6 ‘1 , The dog struggling and crying.

3.17’ 6°3

3.18’ 5 ‘8—6°1 : The dog cries loudly.

3.18’ 30 6 “4 : Still crying louder than ever.

3.18’ 40 6 °2

3.19’ 5°8—6

3.20/ 5 5—5 °7 “ Continuous crying.

3.20’ 20 |5 *35—5 °55

3.21’ 5 5°2—5°4 | 120 . | Pulse irregular.

3.21! 35 5 °4: re . | During a long howl.

3.22’ 10 5°5

3.22’ 15 5°0

3 22' 20 5—5 “1 as . | Respiration slow laboured, abdominal.

ats 5°3 oh . | Stops erying.

3.23” 5°6 ae . | Deep, slow, abdominal respiration.

3.23’ 30 5°5 ws . | Breath very laboured.

3.24’ 5-2 << . | Pulse small and irregular.

3.24’ 30} 5—5°15

3.2% 35 5°3

3.24! 45 5-5 ‘ The dog is quite quiet, and there is no
struggle whatever to cause the mercury
to rise.

3.25’ 5°8

3.25’ 15 5°9 ‘ . | No struggle whatever.

3.25’ 25 6°0 ; . | Pulse is weak and jerking. (Hemorrhagic
pulse, Maclagan).

3.25 40 6°1

3.25’ 50 6-2 . | Action of heart, violent thumping.

3.26! 6—6 °2 - | Dog ue Iris is sensitive, slightly

; contracted. —

3.26’ 40 6°3 ; .. | Durimg a deep howl.

3.27’ 20 5°8 , ., |Saphena veins tense, and femoral artery
feelsas if it were contracting against the
heart. (Dr. Maclagan.)

3.27’ 50 5-9

3.29 5 6—5 °8 . | Howling loudly as if suffering much.

112 on DIGITALIS, WITH SOME OBSERVATIONS ON THE URINE.

Time. ee * | Pulse.| Resp. Remarks.
P.M. Inches.

3.29' 30 | 5°5—5°7

3.30’ 30 | 5°5—5 °7

3.30’ 35 5°3 . | From 5°3, mercury rose straight to 5°7.

3.31’ 20 | 5°7—5 6 .

3.31’ 35 | 5°5—5°8

3.32’ 40 5°5 : - | Dog struggles, howls loudly, shakes his
tail; femoral pulse very small.

3.337 5°7 ‘ During the loudest howls, the mercury
only rises to 5°8.

3.34’ 5°53 —5'7

3.34’ 30 5 4 os .. | During a short but very violent struggle.

3.35/ 5°7 s .. | During a long struggle.

3.39’ 5 °38—5 5 es . | Pupils rather more dilated.

es 5°8 os . | During a very strong struggle.

3.40’ 55 5°9 és . | Half a grain of digitaline, suspended in
about 13 drams of water, was now in-
jected into the subcutaneous cellular
tissue of the abdomen.

3.41’ 35 5 °4

3.43’ 5°5 2° -e | Deep groans, Pulse very irregular.

* 5°0
3.43’ 5 5°2
3.43’ 10 5 °4
oe 5°2

3.43’ 39 5°5

3.43’ 33 5°3 ee -- | Great irregularity.

oe 5°2

3.43’ 40 i o .. | Pupil somewhat contracted.

3.44’ 10 5°d

3.44’ 20 5°2

3.44 25 5 136 | .. | Pulse extremely irregular. Pupil some-
what contracted. Iris sensitive.

3.45’ 80 | 5°3—5 4

3.46’ 20 5°3 oe . | The dog howls.

3.47! A °9 ee . |Ina struggle, the mercury now never rises
above 5. The dog cries loudly.

3.47’ 30 4°6

me 4°7 oe Only rises to 4°7 during a long struggle.

3.48’ 20 ee ee Loud moans, deep and frequent abdominal
respiration.

3.49’ 4°8 oe .. | Extreme irregularity of pulse. Weak
moans. Deep sighing respiration.

3.50! 4°3 120] .. | Pulse extremely irregular, intermits com-
pletely with inspiration. The heart seems
to be going all right, and not intermit-
ting.

3.51’ 40 4,°2 ve oe Pulse less intermittent.

3.52’ 10 4°7

3.52’ 30 4,0

3.52’ 40 3°8

3.52’ 55 4°3 oe -« | Pupil less contracted. Seems normal.
Sensitive.

3.53’ 40 4°4

ACTION ON CIRCULATION AND RESPIRATION, 113

Time.

Mercury.
Mean.

Pulse

Resp.

Remarks.

P.M.
3.53’ 50
3.54’ 5
3.54’ 10
3.55’ 30

3°56’ 15
3.56’ 25

3.57’ 30
3.58’ 5
3.58’ 20
3.58% 30
3.59’

3.59’ 5
3.59’ 40
3.59’ 45
3.59’ 50

ib

0’ 5
0’ 10

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4
4
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Dog groans. Long deep howls.

There is intermitting of femoral pulse, but
not of heart’s action.

Intermittency of pulse is distinctly heard
during inspiration. Dog moaning.

Gradual fall from 3°9.

Pupils as before.

Dog whining.

Gradual fall from 3°5.
Mercury rose suddeniy to 3°8.

Dog whines.
Respiration slightly convulsive.
Dog struggles.

Moaning slightly.
Falls during inspiration.

Whines and struggles.

The dog snores. Pupil normal.

Pulse intermits during a long inspiration,
and the femoral pulse gives a peculiar

114 ON DIGITALIS, WITH SOME OBSERVATIONS ON THE URINE.

Time.

Mercury.
Mean.

Pulse.

Resp.

Remarks.

P.M.
4.15’

4.16’ 30

4,25/
4,27!

4,50’
4,52’
4.53/

4.53’ 20

Inches.

5°7

ee
ee A

216

20

thrilling feeling to the finger when com-
pressed firmly.

Dog whines.

Breathing is quiet. Heart’s impulse, 216
in a minute—(Dr.Gamgee). 18 beatsin
5 seconds. In half a minute I counted
100 beats, strong, irregular. Dr. G. feels
a purring tremor over the cardiac region.

Loud double blowing murmur on auscul-
tation, which, I think, is regurgitant.

On auscultation over the carotid, no mur-
mur is audible Dog breathes very
quietly. The double murmur varies
much in intensity, the diastolic is far
more prolonged. The hemadynamo-
meter was now stopped by a clot, so the
nozzle was taken out of the artery, and
the apparatus cleaned. A jet or two of
blood issued from the artery before the
nozzle was re-inserted.

Re-inserted. Mercury stood at 4,

Convulsive movement. Head turned over.
There was a clot in the artery, just at
the end of the nozzle, and this was
broken up by pressure.

Dog dead. His heart was going pretty
regular'y,and the beats were apparently
of good strength just before the dog died.
On looking at the penis, no tremors were
observed, and no prostatic mucus was
seen. There was a good deal of water
about the point of penis, from dog’s
having emptied its bladder. This might
have possibly concealed a drop or two, if
such were there.

At 4.59 there were a kind of convulsive snorts,

Post-mortem examination made immediately.

The tongue seemed somewhat pale. On opening the thoracic cavity, the
veins were found very full, and perfectly turgid. The right side of the heart
was distended by dark fluid blood, and the veins on its surface were dark
The left heart contained a little fluid blood, and was flaccid. On
the surface were one or two milk spots. The ventricle Was opened before
the competency of the aortic valves was tried, and then they were scarcely com-
petent, but on examination seemed perfectly healthy. The trachea and larger
bronchi contained no mucus, but there was some frothy mucus in the smaller
bronchi. At 5.21’ the esophagus contracted rhythmically when laid along with
the heart and lungs on a plate. It continued to do so briskly when stimulated
on its mucous surface, after being cut open.

and full.

ACTION ON CIRCULATION AND RESPIRATION,

115

Exp, VI.—Jan. 10.—A dog of middle size was laid on the table, and chloro-
form administered. While this was being done, the dog salivated profusely

and passed urine.

The heart sounds at the time were perfectly normal.

The

operation of exposing the carotid was begun at 2.57’ p.m.

Time. Eaig Mo a Mean. | Pulse.| Resp. Remarks,
P.M. Inches.
2.57' ‘ ee 108 20 | First incision made.
3.41’ 30 , ee oe -» | Clip removed. Mercury rose.
ee 5—6°5] .. 84

3.45’ 5—6°5 | 5°65 . 20

3.48! 5—6'°5 | 5°65] .. - |The jugular vein was now tied.
No very marked effect on the
mercury.

3.55’ 5—8 6°3 ee : The injection of 1 grain or digita-
line in about 2 ozs. of water was
begun into jugular vein. It
filled the syringe four times.

3.55’ 20 oe . ve -. | Injectioncompleted. Dog moans.

5.56’ 30| 4°7—8°6 61-62) .. 12

3.59’ 30} 3°8—7°7 | 5°8 oe -- | Dog cries.

3.59’ 45 4—8 5°7

4. 0’ 4°2—8 3

4. 0’ 15 5—8

4. 0'45| 6°9—7°'2

4, 1’20| 4°8—8:2 | 6°4

4.1'50| 6°2—7°4

4, 2’ 15 e 6°7

4, 2’ 30 za 6°8

4. 2'45| 6°3—7°5

4, 3 25 6—8 6°95

4, 4 5°2—8°2 | 7°0 80

4, 445| 6°3—7°6 °

4.5'15| 5°8—8

4, 5’ 30 6—7'°8 | 6°9 ee ig™

4, 7’ 6—7°8 | 6°7 ee -- | Pulse irregular

4. '7'20| 6°1—7°7

4, 8’ 5‘8—7'6 | 6°6

4. 8'15| 5:°5—7°2 | 6°5

4, 840} 6°3—8°0

4. 8’50| 6°1—6°'9

4, 9° 5*8—6'8 | 6°4

4. 9'40| 5°8—7°2 | 6°35

4.10’ 20| 5°5—6°7 | .. ee 30

4.10’ 30} 5°56—7°4 | 6:2

4.1040] 5°3—6°7 | 6°15

4.1140] 5°5—6°5 | 6'0

4.12’ 5| 5°5—7-0

4.12’ 25) 5°3—6°2

4,12'40| 5°0—6°7 | 5°8

4,13'30| 4°5-6°3 | 5°7 -- | 88 | Pulse irregular.

4.1345] 4°5—6°2| .. ee .. | For about three pulsations, or so,
the mercury oscillates within
0°2 of an inch, and then there is
a sudden rise or fall.

To

i

116 ON DIGITALIS, WITH SOME OBSERVATIONS ON THE URINE,

Mercury.

Time. Mx. & Min, | Mea™- Pulse | Resp. Remarks.
P.M. Inches.

4.14’ 40} 4°5—8°0 | 5°4

4.15’ 5) 4°3—5°2 | 5°3

4.15’ 10} 4°5—6°0 | 5°25

4.15’ 45} 4°2—5°9] .. oe .- | With inspiration,

4.16’ 5'0O—7°0 | 5°3

4.16°10| 4°0—5°8 | 5:0

4.16’ 35 | 4°2—6°0 | 5:1

4.16’ 45 | 4°56—6°7 | 5°2

4.16’ 50} 4:°0—6°8

4.1655 | 3°3—6°0 | 5:1

4.17/10} 8:7—7°0 | 5°0 ‘ .. | Dog very restless. Struggles,

4.177 40| 4:0—6°2 | 4°9

4.18°10| 4°5—5°9 | 5°1

4.18°35| 4°7—6°2 | 5°35

4.18’ 45| 5:°0—6°0 | 5:3

4.19’ 15 an “s ‘ A blowing murmur is heard with
one of the heart’s sounds, but it
is difficult to distinguish with
which.

4.19’ 45 Ss 5°4

4.21'10| 4°0—6°0 | 5°0

4.21’ 30| 4°3—5°7 | 5-0

4.22’ 3 ‘8—6°0 | 4°9

4.22°25| 3°5—6°0 | 4°7

4.23’ 30| 8°2—5°8 | 4°5

4.24! 3°1—5'5 | 4°4

4.24/10} 8°2—5°2 | 4°35

4.24°15| 2°9—5:'1 | 4°3

4,24’ 25| 3°2—5°0

4.24’ 30}; 2°9

4.24’ 45 | 8°3—5°0

4.25! ; 4°25

4.2510} 8°2—5*0

4.25’ 15 6°G to, is .. | Dog attempts to barz,

4.20’ 4 °2—5°3

4.26’ 7 . 4°,

4.26’ 25 , 4°5

4.26’ 45 ; 46

4.27’ 4°2—5°3 | 4°65 | .. 22

4.2740} 4 0—5°8 | 4°6

4,28’ 3°8—5'8 | 4°6

4.2830 | 3:°3—5'4 | 4°5

4.2859} 3:2—5°2 | 4°3

4.2910] 3°3—5°8

4.29’ 30} 2°9—5°4

4.29’ 45 we 4°] ; Dog howling.

4.30’ 20 os 3°95

4.30’ 55 | 3:°0—5°5 | 4°0

4,31’ as ss ee .. |Heart’s impulse strong. Loud

blowing murmur, which almost
seems te be with both sounds,
and certainly is with one—I
think the first.

ACTION ON CIRCULATION AND RESPIRATION,

117

Time. bet Mean. | Pulse.} Resp. Remarks.
P.M. Inches.
4.3240] 3°0—5'2 | 3°9
4.33” 2°9 ee ee +. | Very irregular.
4.3310] 2°8—4°7 | 3°8
4,34’ 20| 3°2—4°0 | 3°8
4,34’ 40| 3°0—4°8/| .. *e 26 |The mercury goes up suddenly,
and falls, as it were, by several
short steps.
4.35’ 40} 3°1—4‘5
4.35’ 50| 3°3—4°7
4.36°15| 2°8—4°2 | 3°8
4.36’ 50| 2°9—4°5 | 3°75
4,37’ 15 ea 3°7
4.37’ 30| 3°1—4°4
4,38’ 10 ee 3°65
4,38’ 20 ee 3°6
4.38’ 40 ee ee oe -» | Heart’s impulse felt distinctly
and apparently increased. Mur-
mur still present. Pulse cannot
well be counted, it is so quick,
small, and irregular.
4,89’15| 3°2—4°3 | 3°55
4.40’ 30| 3°1—4'2| .. ee 18 | Breathing quiet.
4.41’ 10 ° 3°4
4.41’ 20; 2°8—3°7 | 3°3
4.4150! 3°0—3°7 | 3°15
4.42’35:! 2°7—3°4| .. : -- | White frothy saliva flows freely
from the mouth. Dog lies
quiet.
4.43’20; 2°8—3°7 | 3°15
4.44’ 30| 2°7—3°3 | 3:0
4°45/ 2°6—3'6 | ..
4.45’ 40| 2°4—3:°2 | 2°9
4.46’ 2°5—3°3 | 2°9
4.47’ 2°6—3°'1| ..
4.4720} 2°7—3°7| . nt -. | Breathing quite quiet.
4.4810] 2°7—3°6| .
generally, 2°8—3°'2| .
4.49’ 20 oF 2°8
4.49’ 45 os 2°75
4.49’ 50| 2°4—2°7
4.50’ 10 se 3°1 ; Moans slightly.
4.50’ 50 oe 2°65
4.5110! 2°4—2°8/ .. Moans, and makes slight effort.
4.51’ 40 3°56 28 The oscillating column stopped

quite still at 3.56. The mean
column steadi'y rose till they
both attained the same height,
and there they remained.
Thinking that there was a clot
formed, the nozzle was removed,
but there was none in the instru-
ment. The artery was then
pressed to break up any clots

118 ON DIGITALIS, WITH SOME OBSERVATIONS ON THE URINE

Time. Soar ek Mean. | Pulse. Resp. Remarks.
P.M. Inches.
that might be in it, though none
were felt.
4.54! ee vs ae .. | Both have stopped.
4.57’ oe ‘ ¢e .. | The artery opened.
4.58’ oe “s +s .. |The dog threw back his head,
. made several convulsive respira-
tions, and died.

Post-mortem examination made immediately. ;

On opening the thorax, air rushed in, The lungs were natural in colour, and
very much collapsed. Both sides of the heart were full of blood. The vena
cava and venous system generally turgid. The veins of intestines and viscera
congested. The venous blood was dark in colour. On pinching the phrenic
nerve, the diaphragm contracted ; and on pinching the left phrenic, the contrac-
tion was not confined to the left side, the fibres of the right half visibly and
plainly contracting. On tying the vena cava infericr, and cutting it beyond
the ligature, the fluid blood, which issued from the lower end into the thoracic
cavity, and which was very dark coloured coagulated in about a minute. (This
is by guess, not bya watch.) ‘The heart seems quite normal. Bladder was full.
No emission of semen or mucus was observed. Half a grain of the digitaline
used in this experiment had been dissolved in a small quantity of spirit for
another purpose, but not used. The spirit had evaporated, and the digitaline was
in a resinous-looking mass —not in powder.

Exp. VII.—Jan. 23.—The dog operated on was a large mongrel. It was
thin and weak, and had had loose and sometimes bloody stools for some days
back. It was tied down and chloroformed. I then exposed both vagi, and
passed ligatures under them, so as to pull them nearer the surface, when they
were wanted for section. The hemadynamometer was then inserted into the
left carotid.. The mean tube seemed somewhat choked at the capillary part,
so as not to work freely, and its indications were therefore not quite trust-
worthy.

Time. eae Mean.} Pulse | Resp. Remarks.
P.M. Inches.
2.56’ 45 | 3°44
vs 3°4—3 9 | 2°6
2.59” 3°3—3'°8 | .. The mercury oscillates steadily.
3. “e i“ abe .. | Both vagi were cut.
ee 2°5—4°5 | .. e .. | Mercury fell to 2°5,
ee 3°5—4°5 | 3
8.1’ 2°9—3°3
3.1’ 30 2°3 3 °4

ACTION ON CIRCULATION AND RESPIRATION.

119

Time. Paar Mean. | Pulse.| Resp. Remarks.
P.M. Inches. -

3.2’ 10 3°0—4°0 : -. | Pulse slower.

3.2’ 30 3 °3—4°0 .

3.2’ 40 és ‘ : ‘ The dog’s breathing is gasping.

eee 4°0—4'5
oe 3°3—4'2 | .. és . | Gasping.

8.330 | 2°8-3°5 | 3°4 ; . | Ala nasi are working.

3.4’ 3 '2—3 ‘6 .

3.4’ 20 4. °0—4°5

3.4’ 40 3 °8—4'2

3.5’ 4°0—4°3 | 3°4

3°5’ 10 4:°0—4°3

3.57 40 4°2—4°5 | 3°4

3.6’ 15 4 °-2—4,°5

3.6’ 30 4, °2—4°5

3.10’ 4°1—4°4

8.10’ 30) 4°1—4°3 P - .. | Mucus runs from nose.

‘z 4°1—4°4 | 0. - 20 | Respiration becomes more jerking.

3.12’ 3 °9—4°3

3.12/15 3 :°8—4°2

_ 8.1845) 8-7-4

3.14.15 | 3°5—3°9

3.15’ 35 —4 .

3.17’ $°4—3°9] .. ys .. | Cheeks puff out with every respi-
ration. Whole chest and abdo-
men heaves up en masse.

3.1715 | 3:°4—3°7

iF 3°9—4°1]| .. ee .. | Breathing suddenly very geutle.

8.19’ 4 *25—4°3 : és 14 | Inspiration is made by a series of
little jerks—expiration made at
once.

3.21’ 40 ee ae eH .. | Distinct blowing murmur with
the sound.

8.24’ 30| 4°0—4°25) .. o« .. |The mercury rises suddenly with
expiration, and falls by a series
of little jerks. Brcathing
stronger—a kind of coughing
or snorting respiration.

8.26’ 10 “is , Ae Dog throws back head. Mercury
fails.

ve 4, °2—4°3
wo + | 89—4°1

8.28’ 20| 4°2—4°3

3.28’ 30} 4:°0—4°2 ; : Dog snorting.

a 3 °5—3 °9 oe : Convulsive movement.

3.30’ 35| 3°9—4°3

3.31’ 4 °3— 4°5

3.3215 | 4°4—4°5

3.33’ 30| 4°2—4°3

3.37’ 4, °O—4 °2 . bia .. | Jugular vein cleaned. Dog snores.

3.38’ oe ‘ bus .. | Jugular vein tied, and } grain of

digitaline in water injected into
it. (The time of the injection
is from memory.) .

120 on DIGITALIS, WITH SOME OBSERVATIONS ON THE URINE.

Time. Ha am Mean.| Pulse.| Resp. Remarks.
P.M. Inches,
ee 4 ‘O—4 4 |
3.39 30} 4°5—5 oe ee -- | Convulsive movement.
ee 4, *4,—4, 9 ee ee ee Low sighs.
die —5°5 .
3.40'10| 4°7—5°5
3.40’ 30 —6
re —5°S8 | 5
3.41’ 4°9—5°4 | 5°1
3.41/10} 4°9—5°7 | 5
oe 4°2—5°6 | 5
ee 4 ‘7—5 J} ee ee . Stops.

3.43" oe oe oe .. | Heart acts very irregularly. The
sounds are like toot-toot-toot-
toot-toot-toot-toot-toot-too.

Heart very weak. Loud snort-
ing.

3.47’ ee ee we .- | Convulsive movement.

3.48” ee oe oe -- | Coughing.

3.59 30| 5°3—5°4] .. ee .. | Breathing very slow. Heart

thumping against the ribs.
Breath laboured.

4.5’ 4°5—4°6 | .. os .. | Heartirregular. Breathing, sigh-
ing. Dog put back head con-
vulsively but gently.

4.730 | 3°7—4:°5] .. v0 10 | Respirations long, and sighing.

oe 4°1—4°7

4.8’ 5 3 °5—4°4

4.9’ 10 4°0—4 5

es 3°7—4°3

4.10'10| &*8—4°4

411/10} 8°5—4°4] .. ee .. | Breathing very quiet.

4,12’ 3 °6—4°3

4,13’ 3 °2—4

4,14’ 3°2—4°5 |. oe .- | Dog moans.

4.14’ 45 | 3°4—-4°7 | .. ee «» | Convulsive movements.

4.15’ 4 °3—5

4.1650) 3°9—4°5

4.17’ 30 ie : oe -- | Oscillations stopped.

oe 4°0—4°1
4,18’ 4°1—4:'4 | .. oe .. | Strong beat of heart.
ee 3 °5—4 ‘2 ; ar .. | Veryirregular. Mercury ascends
with expiration, and occasionally
stops.

420° 3 °5—4 ‘ es . | Snoring, respiration, and a quick

weak moaning.
oe 3 °0—4

4.22” 50 ee ee oe .. | Oscillations stopped, blowing

murmur at heart still present.

After trying to dislodge the clot,
without effect, the apparatus
was removed.

4,35’ 30 ae es : -» | Dog moans. Convulsive breath-

ing. Heart strong and regular.

ACTION ON CIRCULATION AND RESPIRATION.

121

Time. ase Mean. | Pulse.| Resp. Remarks.
t l
P.M. Inches.
4.50’ ee va As the dog did not seem about to

die, and we could not wait any
longer, his spinal cord was
severed just between the occiput
and atlas.

Post-mortem made immediately.
On opening the chest the lungs
collapsed. The heart was beat-
ing vigorously. At 4.55’ the
heart stopped, but could be re-
excited to contract. The venous
system was much congested.
Both sides of the heart contained
fluid blood.

Expr. VIII.—March 9.-—-A middle-sized dog was put under chloroform, and
the hemadynamometer applied to the carotid.

Time. yee Mean.| Pulse.| Resp. Remarks.
P.M. Inches.
3.20’ 6°0O—6°7 6°5
3.26’ 5 '5—6°7 5°9 . .» | Mercury sinks markedly with ex-
piration (inspiration ?). Dog ap-
pears to be free from chloroform,
and seems to feel pain as he
groans.
3.30/ wie oe 116 18
ee 5°5—6 5 6:0
3.35’ es $e oe .. | Injected {th of a grain of digita-
line in water into the jugular
vein.
3.36' oe : ee .. | Dog micturated and voided feces.
3.40/ 5 ‘5—7 6°4 | 114] 14 | Pulse regular and stronger than
before.
aint 5°2—7 6°4
3.45/ % er tie
3.49’ 35 3 ‘ a Injected 4 of a grain more.
3.50 5°7—7°8 : 106 Pulse regular.
3.55’ 4°8 ‘ ‘ Mercury went down as low as 48.
3.56’ 30 | 5-0-7 . 108 Pulse markedly smaller, irregular,
and with occasional intermis-
sions.
With respiration the mercury falls
more markedly than before.
4, 5°7—7°5

122 ON DIGITALIS, WITH SOME OBSERVATIONS ON THE URINE.

Time. ee Mean.| Pulse.| Resp. Remaiks.
P.M. Inches.
4.4! wi a we .. | Pulse very markedly intermittent,
and the mercury falls at each in-
termission as low as 4.
y 4°0
4.8’ ny as = .. | Pulse gives one strong beat and
then % or 4 feeble ones.
4.10’ a nie pa .. | A drop of prostatic mucus exudes
from the point of the urethra. —
4.16’ = wa Se .. | Pulse very intermittent. Animal

shivers every minute, or even
more frequently.

The hemadynamometer stopped
working.

4.24’ oe se oe .. | Readjusted the apparatus.
Zs 5°0—7°7 6'0
4,26’ ae 104 | .. | Pulse intermittent.
et 5°8--7°5 (65-66) .. .. | Animal continues to tremble.
4.29’ oe 6°65 _ .- | Oscillations more steady.
4,29’ 30 “ve ee os .. |Clot again formed. Almost con-

stant tremors.

The apparatus was cleaned, and again adjusted at 4.40, but the nozzle came
out, and there was a gush of blood, and as this would have thrown some fallacy
into the future reading of the mercury, the artery was ligatured, the wound
stitched, and the dog released from the table. It lay for a few minutes, and
then began to try and get off the muzzle. When this was removed, the dog
rose and walked about. It seemed rather stiff at first.

Exe. IX.—Warch 20.—The dog operated on on the 9th, having recovered,
was put under chloroform, and the carotid exposed. The dog was then allowed
to come out from the chloroform, which it did at 2.15 p.w. Instead of digita-
line, the extract obtained from commercial tincture of digitalis was employed;
the tincture being gently evaporated, and the extract then dissolved in water
and injected. The hemadynamometer giving the mean was employed.

Time. a Pes Pulse. | Res p. Remarks.
P.M. Inches.
2. ee 104
2.37’ 55 es .- | Hemadynamometer set working.
2.37’ 20 5°7 bs .. | Prolonged sigh.
2.38’ 51
2.39’ 5 *1—5°3
se 5°4 During a long sighing inspiration.
2.41’ 5°3
2.42! 5°0

ACTION ON CIRCULATION AND RESPIRATION.

123

Mercury.

Time Mean, | /ulse.| Resp. Remarks.
P.M. Inches J
2.42’ 10 5 °2
2.42’ 25 5°65 100
2.44/ oa ee 14 | Pulse slightly intermittent. Respiration
very sighing.
2.44’ 30| 5°4—5°5
2.45’ 5°9 -« | Injection of extract equal to 4 dr. of tine-
2.46’ 4°5 ture.
2.46’ 45 3°9
2.47’ 3°7
2.47’ 5 3°9 oe -. | Injection of extract of 1 dr. of tincture.
2.47 25 4°8 108
2.47’ 40 54
2.48’ 20 5°5
2.49’ 5°7 . Under the strongest expiration.
2.49’ 5°9
2.49’ 15 6°0
2.49’ 30 6°3
2.50’ 15 6°15
2.51’ 45 6°0 102
2.53’ 5°6—6'1
a 5°7—5'°8 | .. . | When lying quiet.
ee oe oe . | At every expiration there is intermittence
of pulse.
2.54’ 5°9—6°0
2.55’ 5°6—5 °7
2.56’ 5°5 76 . | Intermittence and irregalarity both as to
the length and strength of pulsations.
ee ee ee 12
2.57 20| 5°4—5°5 98
2.59’ 5°8
3. 5°5 100 | 14
3.2’ 5'8 : .. | Dog howling.
3.3’ 5 °5—5 °7 .
3.4’ 30 5°9 : .. | During a struggle.
3.4’ 45 6°0 ee .. | During another.
3.5/ 6°1 ‘ .. | Still another.
ee 6-0
3.7 5°7 “s Steady. A clot was suspected, so the in-
strument was removed and examined.
3.11’ 30 5°3 ve . | Instrument replaced.
3.12’ 5°5 131 | .. | Heart’s action against the ribs is strong.
3.12’ 15 5°7
3.13’ 5°6
3.14’ 6°5 ‘ Steady. Clot again suspected. Instru-
ment removed.
3.16’ 40 5°8 Pulse is more regular.
3.24’ 15 v Instrument again replaced. The mercury
rises in a jerking fashion.
3.25’ 30 5°5
3.25' 45 5°8 ee Injected part of extract of 1 dr. of tinc-
ture. No struggle.
3.26’ 5°9 96 . | Respirations few and slight, quite quiet.

124° oN DIGITALIS, WITH. SOME OBSERVATIONS ON THE URINE.

: Mercury.
Time. Mente
P.M. Inches.
3.26’ 15 4°5
3.26’ 30 4.7
a.27" 5°0
53.273 5°3
3.28’ 5 °35—5'5
oe 5°1—5'3
2.28’ 45 | 4°8—5°0
3.29’ 4°5—4°7
S 4°5—4'6
3.31 25| 4°7—4°8
3.31’ 40 4:9
3.34' 50] 4°95—5 °0
3.35’ 20 ‘
3.43’ 5 ;
3.48’ 20 3°3
3.48’ 50 $°2
3.50’ 3°2
3.52’ 3°3
3.54! 3°2
3.57’ 15 31
4.0’ 30 3 °2
4.1’ 30 32
4.3’ 40 3320
4.15’ +s
4,26’ 20 2°8
4.27’ 10 2°6
4.27’ 30 2°8
4.31’ 20 ss
4.32’ 10 2°4
4.32’ 40 2 °4
4.33’ 40 2°7
4.34’ 40 3°4
4.38’ 30 3°0
4.40’ 10 2°9
ae 3—3°1

Pulse.| Resp. Remarks.
100 Injected the remainder of the water and
extract.
: Dog’s breathing is loud and whistling.
: During a great struggle:
G4
‘ .. | Pulse very intermittent. Dog quite quiet.
‘ 12 | Gasping respirations.
, .. | Respiration much less deep.
44,
50 Movement of mercurial column barely
perceptible.
ve Heart’s action weak.
80 Pulse feels rather a wavering than distinct
beats.
F Hemadynamometer stopped.
116
i Dog perfectly quiet.
180
172 There are variations in the quickness of
the pulse without variations in arterial
tension.
140
196
170
, Breath feels distinctly cool on the hand.
; Clot again formed. In adjusting the in-
strument again, the blood from the
artery was noticed not to be very florid.
156
be . | Injected extract of 1 dr.more. Mercury
rose 0°3 during injection, and then fell
down 0°4 below former level.
174 Whistling respirations.
vs Dog struggling.
156 | .. | Quiet again.
<'s 12
175 |

}

At 4.50 the experiment stopped, and dog released from the table at 5 o’clock,
the wound having been sewed up. It walked about, but was weak, stiff, and
staggering, and almost immediately began to vomit, and did so several times.
It died several days afterwards.

Exp. X.—April 5.—A large dog was operated on.

ACTION ON CIRCULATION AND RESPIRATION.

.
12

Nochloroform was

given, as after I had seen an operation conducted on a dog without chloroform,
I concluded that the uneasiness they suffered while getting it was worse than

they seemed to experience from the operation.

The first incision was made

about 11.38, cleaned a part of jugular vein and carotid artery, and inserted the
hemadynamometer.
partly choked, and not working well, I had another made, but not being drawn
to a fine enough bore, the mercury oscillated too much in it.

The mean tube of the double instrument having been

Time. ack Mean. | Pulse.| Resp. Remarks.
P.M. Inches.

12. 2’20| 5°5—6°3 |5°9-6'2| 132 -- | Clip restraining blood removed,
mercury at once rose.

i Ray ig 5°9—6°5 | .. ee - | Dog moaning.

12.11’ 5°5—6°5 |5°9-6°2) 134 - |Mercury rises with expiration,

falls with inspiration.

12.15’ 5 °5—6°5 |5°8-6'2/ .. +» |From groaning its respiration is
quick.

12.20’ 5°4—6'°4 |5°9-671) .. -» | Maximum on a deep inspiration
descends to 5, and mean to 5'3.

12.24’30| 5°4—6°4 |5°9-61) .. .. | Jugular vein tied.

12.2450; 6°0—6°5| .. ‘ -» | Injection of one syringe-full of
infusion of digitalis completed.

ws 5 °8—6 *4

12.2630} 5°8—6°2] .. 140

12.27’ 5°*56—6°2 | .. 120

12.30’ * 5°9-6°2) 86 -. | Pulse intermittent.

12.31’ 5 6—6°3 |5°8-6'°2

12.32’ ae 5°9-6°3) 78 -- | Dog quiet, not moaning.

12.34’ os 5°9-6'3) .. 14

12.35’ 20| 5°5—6°5 |5°9-6°3) 78 ‘ Oscillating very steadily.

12.38’ ee 5°7-6°2

12.40’ 5 °5 5°9-6.2| .. : Pulse varies from 22—27 in + of
@ minute, not in! ermittent.

12.41’ 5 ‘5—6°3 |5°9-6'1] 88

12.42’ i Fe 84 ee For about four or five beats it is
very slow, and then quick for a
few more. Dog has passed some:
prostatic mucus.

12.45’ 5°5—6°3 |5°8-6°2; .. -» ) Mean occasionally descends to 5°6,
and then rises. Dog whining
and whistling slightly.

12.48’ 5 *5—6°2 |5°7-6°0} 90 -» | Mercury descends on inspiration
to 54, and next. pulsation goes
up to 62, §ths of an inch of
oscillation. Then there are se-
veral small pulsations of about
ths of an inch oscillation
euch.

12.51’ 30 ee 5°8-6'1

12.53’ 80| 5°5—6°0 |5°5-5°7| 104 »» | Dog whining. Average oscilla-

tion of maximum column ‘is-
=5ths of an inch.

126 ON DIGITALIS, WITH SOME OBSERVATIONS ON THE URINE.

Time.

12.56’ 15
12.58’

1.20!
1.25’

1.26’
1.27’ 15

1.28 15
1.29’ 15
1.40’

1.45/15

1.49’

1.50’
1.50’ 15
1.50’ 30
1.50’ 45
1.52’

Ste Mean.| Pulse. | Resp. Remarks.
Inches.
as 20 | But dog whining more loudly,
and respiration thus disturbed.
5 5—6 °0 |5°9-6'2
5 *5—6 °0 |5'5-5°7| 100 -» | Pulse has continued irregular
since that was noted first. Dog
quite quiet. Maximum column
goes down to 5 on inspiration.
ee 5°8-6°0
oe 55 es Injection of one syringe-full more.
os 5°5-6'1
5 ‘5—6°4 |5°7-61
5 °4-—6 0 |5°6-5'9) 84 Maximum occasionally descends
to 5. General oscillation is
y5ths of an inch,
7 aie ee Dog moans loudly.
4 *8—6 0 |4°9-6°0! .. During long inspiration it de-
scended.
5°5 5°5 os During long expiration.
4 ‘5—5°O |4°8-5°0) .. Dog tries to vomit.
ee 75-7°7| «. During vomiting.
5 °5—6°5 |f:0-6'3| 70
5'0—6 0 |5°5-5'8
oe 5°5-5'7, 100
5°0 5°0 | 124 Pulse regular. Again tries to
vomit.
5 *O—5 *7 |5°0-5°7
5 ‘3—65°5 [5°0-5°3) .. : Mean oscillation of maximum
column ;%;ths of an inch.
5 °O—5 ‘7 (5°3-5°5) 112 : Both tub _ecasionally descend
to 4°9.
ee is oe .. | Again vomits.
5 '5—6 0 |5°5-5'8) .. In ordinary pulsations the oscilla-
tions are ;yths of an inch.
ca 5°3
5 °2—5 °6 |5°3-5'6| 116
5 °3—5'5 |5'4 5.5) 116
4°5 4°5 ¢s .. | Injected one syringe-full more-—
mercury at once fell.
5°5—5 6 |5°3-5'6
5 O—5 5 |4'9-5°5| 118
At 5. 5 °0 é Breathing very rapidly and deeply.
4°0O—6°0} .. : .. | Tries to vomit.
oe i : Again vomits.
oe 5°0-7°0
ai 5°0-6°5
5°0-6°0 |5°5-5°8) 66 ‘ Oscillation of max. column, after
a deep inspiration, is about
1 inch, and then about ths
each after.
ee 7 . |Nocardiacmurmur. Dog whines.
ie 102 . | Dog loosed.
ee oe He walked steadily, and recovered

in a few days.

ACTION ON CIRCULATION AND RESPIRATION. 127

The infusion used in this case was made by infusing 2 drachms of powdered
- digitalis leaves in 4 ozs. of water.

Exe. XI.—WNor. 25, 1864.—At 10.12 a.m. I injected 4 milligrams of
digitaline, about ~;th of a grain, suspended in about 30 minims of distilled water
into the subcutaneous cellular tissue of the lumbar region of a Skye terrier.
Three minutes after he began to lick the part, and when the injection was made,
showed signs of irritation. In 4$ minutes he seemed a little confused, and
began to lick the corresponding part on the opposite side. In 5 minutes his
tongue began to loll out (which I have hardly ever observed in him before or
since), and he continued restless till 7; minutes, when he lay down, his breathing
being rather hurried, and his tongue still out. In another minute he rose, and
sat apparently intently listening, and as there was no particular sound at the
time, I thought this probably indicated ringing in his ears. With the exception
of some restlessness he seemed well till 25 minutes after the injection, when he
sat down panting and lolling his tongue, as if he had had a smart run, though
he had made no particular exertion to account for this. Soon after he seemed
quite in his usual, and was none the worse.

Expr. X1I.—Dec. 12.—A mongrel dog had some blood drawn from one jugular
for examination, about the 6th, and on the 9th one of its carotids was exposed,
and the hemadynamometer applied under chloroform, but clots formed imme-
diately, and the experiment was abandoned. On the 12th the dog was very
weak,

At 2.5’. pvm., I began to inject 4a grain (from memory) of digitaline in
water into the subcutaneous cellular tissue in the lumbar
region.

2.12’ Injection finished. The dog seemed uneasy and lay down.

2.16’ Till now he has been rising, turning round, and lying down again

constantly. He now seems unable to stand well—grumbles.

2.17'30 Up again, grumbles, shakes his head listlessly about, seems
uneasy.

2.18’ Seems inclined to vomit.

2.19’ Shakes his head and licks his foot.

2.20 Paws his bed.

2.21’ Opens and shuts jaws.

2.23’ Sits up. The light is shining in his eyes, and his pupils are much
contracted. Seems livelier. Shakes his head and paws his bed.
I was then called away, and returned at 2.35’.

2.35’ Dog lying quite still, but there is a tremor all over and twitchings
of the subcutaneous muscle of limbs, causing the movement of
skin to be distinctly visible, but causing no movement of the
limb. Breathing slow and laboured. Respirations are 8 in
65 seconds,

2.43’ Pulse 30 per minute, 2 or 3 beats coming close together during
inspiration and expiration, and then an interval of 4 seconds
between the beats, as well as one of exactly the same length
between the end of one expiration and the beginning of
another.

128 ON DIGITALIS, WITH SOME OBSERVATIONS ON TIIE URINE.

At 2.55’ Much the same—grumbling.

3. I now had to go to a class, and did not see the dog again till I
returned at 5.30’. The dog was then stiff and cold. The
tongue was protruded at the side of the mouth; the jaws shut;
saliva on the chops; some prostatic mucus at the orifice of the
urethra (not examined microscopically). Post-mortem—Lungs
were of a light pink colour, much collapsed. Vena cava and
venous system generally, full of black blood, and very turgid.
Right auricle and ventricle distended with black blood, which
was somewhat curdled—not in firm clots. Left side of heart
natural in colour; contained a little blood, also somewhat
curdled. Liver congested. Gall-bladder distended. Bladder
firmly contracted, and empty.

Exp. XIII.—Jan. 16.—A small English terrier, very thin, was taken for
experiment.

2.29’ p.m.—The dog was shivering; the heart sounds normal in character, but
altered in rhythm, being very slow between the rigors, but during their continu-
ance the beats were very rapid. The shiverings lasting each for about 4 seconds,.
and the interval about 1 minute. There was no murmur with the cardiac
sounds. In the back room in which the dog had been kept, there was a bag of
digitalis leaves on which it had lain, and a good many were scattered on the floor,
so that the dog may have taken some along with its food before, and this possibly
may have been the cause of the curious rbythm of the heart, and of the
shiverings.

2.36’ p.m.—I injected 4 a grain of digitaline suspended in rather less than
1 oz. of water into the cellular tissue at the side of the lumbar vertebra.

2.37’ 15.—The dog suddenly started up, and ran to the end of his tether.

2.37’ 40.—Sat down on haunches. 2.38’ 30.—Rose again. 2.39’-—Straddles
and whimpers, and jumps about. In attitude of attention; then runs about,
and again stands, apparently listening intently.

4.40’ 20.—Whines and licks the place where the injection was made. On
being loosed he shook himself, ran off, and sat down. Was restless, and seemed
thirsty, so I gave him some water.

2.50’.—Heart sounds as before. 3.30’.—As before; no murmur.

3.50’.—Vomiting. 4.—Purging. 4.10’—Vomiting. 4.20’—Again vomiting,
and again at 5.30’. I then left for the night.

On the following day (the 17th) the dog lay curled up on the floor for the
greatest part of the day, but could stand or walk. At 5.35’ p.m. the dog had
refused food, so to kill it at once I poured into its mouth some alcoholic solution
of extract of digitalis, most of which it swallowed, 5.37'.—The dog vomited
some white mucus, then lay quite quiet. 5°40’.—Again vomiting. 5.44.—
Seems livelier. 5.45’—Again vomiting. 5.46’.—Purging.

On the 18th, at 10 a.m., the dog was lying curled up; it rose once or twice,
but with some difficulty, and straddled very much when standing. Gait totter-
ing and unsteady. 10.30’.—Struggles in vain to rise. Progresses along the
floor, partly on its side and partly on its belly. Ineffectual efforts to rise.
Heart’s action very weak, but seems more regular. Surface cold. Respirations
74 per minute. Pupils contracted. The dog lay so, occasionally making slight
vain efforts to rise for about an hour more, and then till 3.2U’ p.m. it lay as if

SPHYGMCGRAPHIC OBSERVATIONS. 129

quite dead, only very feeble respiration being seen, and the eyelids contracting
when the finger touched one of them or the cornea. The caruncula lachrymalis
covered almost one-fourth of the eye. At 3.20’ it was lying as if quite dead;
the surface quite co!d; the limbs flaccid; and the pulse inappreciable when it
gave one or two yawns. At 3.23’ it gave a short, weak, low howl, and imme-
diately after the cornea was found insensible. Post-mortem was made between
five and ten minutes after death. On opening the body, a small quantity of
urine trickled irom the urethra, probably from pressure on the bladder, which
was quite full. The lungs were of a natural colour. The heart was well filled
with blood in both cavities. The venous system turgid. The heart contracted
readily on irritation. At 4 P.M. the dissection was interrupted. It was resumed
at 5.7’. The pericardium, when opened, contained a small quantity of serum,
about one or two drachms. The heart still showed signs of contractility. At
4 p.M. the diaphragm contracted readily on irritation of the phrenic nerve; the
esophagus and thoracic duct contracted on pinching them.

Jan, 26.—One centigram of digitaline was injected into the cellular tissue of
the loins of a rabbit. It produced no apparent effect.

SPHYGMOGRAPHIC TRACINGS.

The following are fac-similes of sphygmographic tracings of my
own pulse, taken from 6th December, 1865, to 24th March, 1866 :—

Fie. 16. 1865—Dec. 6—10.45 P mu.
Fie.17. Dec. 8—Right radial—12.35 midnight.
Fies. 18 and 19. Dec. 9~Right radial—11 P.M.

L—-L SILLY fr~_ ff
en Net eh me! Pn fm fay

Fie. 20. Dec. 11—10.40 p.m.

~~ f+ f+ f—~_ SS

Fig. 21. Dec. 12—10.80 p.m:

oe el ff AS

130 ON DIGITALIS,.WITH SOME OBSERVATIONS ON THE URINE.
Fig. 22. Dec. 18,
Fig. 23. Dec. 14—9.45 P.M.
Fie. 24. Dec. 15—12 midnight.
Fia@. 25. Dec. 16—11.10 p.m. Pulse 75. . ‘
Fig. 26. Dec, 18—11 p.m.
Fie. 27. Dec. 19—11 P.M.
Sipe 2 Bem eos ape ae Ge Ra

Fias. 28 anp 29. Dec. 20—10.35 p.m.
Re ee Oe
1 TSS OS

9+ ONG ots SS ome

(1) Not tied very tightly; (2) Tied very tightly on the arm.
Fig. 30. Dec. 21—10.50 p.m.
. Fie. 31. Dec. 28—10.40 P.m.
Fie. 82. Dec. 29—10.20 p.m.
Bi rt i a AG ay Oe,
Fia. 33. Dec. 30—10 P.M.

oa te re Se

Fig. 84. 1866—Jan. 1—11 P.M.

LOL LO LOO LO LSS

SPHYGMOGRAPHIC OBSERVATIONS. 131

Fie. 35. Jan. 2—1.5 at night.

PAN NPR NTO.

Fig. 36, Jan. 3—11 p.m.

FEDS SLE NS RT Nag fe

Fie. 37. Jan. 4—10.45 p.m.

Fig, 38. Jan. 5—1.2 at night.

Fie. 39. Jan. 9—11 p.m.

Pe IT

Fie. 40, Jan. 10—11 p.m. Had had a little exercise just a few minutes before.
Fie. 41. Jan. 11—10.30 p.m.

Fig. 42. Jan. 12—1.10 at night.

Poe

Fig. 43. Jan. 13—11 p.m.

Fie. 44. Jan. 15—10-11 p.m.

Pf 9 ce SS Bi A Bee 0 a

Fig. 45. Jan. 16—10-ll pw. Pulse 89.

a SS,

KS

132 ON DIGITALIS, WITH SOME OBSERVATIONS ON TIE URINE.

Fic.46. Jan. 17—10.20 p.m. Pulse 82.

ORF NN Se

Fie. 47. Jan. 19—12.45 midnight.

Fia. 48. Jan. 20—10.20 p.m. Pulse 80.

Fig. 49. Jan. 22—10 p.m.

[St | ENT

Tie. 50.. Jan. 283—10-11 p.m.

RCP Skeet ie ENS

Fie. 51. Jan. 24—10.55 p.m.

Fig. 52. Jan. 25—10.17 p.m.

BBS (i Be pis as Bk

Fie. 53. Jan. 26—12.18 midnight.
Fig. 54. Jan. 27—11.27 pu

BN Bx ink sta

Fia. 55. Jan. 29—11.15 p.x.

aN Ne

Fie. 56. Jan. 31—10.30 P.M.

MINAS

SPHYGMOGRAPHIC OBSERVATIONS. 133
Fia. 57. Feb. 1—11.30 p.m.
‘Fic. 58, Feb. 2—1 at night.
Fie. 59. Feb. 3—11.30 p.m,

‘J time ene Ma ae, cae

Fia. 60. Feb. 5—10.25 p.m.
Fie. 61. Feb. 6—10.50 P.m.
1 NG ne SO a Seg i a Sa i _—

Fia. 62. Feb. 7—10.50 p.m.

INNS

Fia. 63. Feb. 10—ahout 12 p.m.

Fic. 64. Feb. 17—10.50 p.m.

Tig. 65. Feb. 19—10.20 p.m.
Fig. 66. Feb. 20—11 p.m.

Dao ecu, oS Bae ea

Fies, 67 and 68. Feb. 21—11.30 p.m. Sphygmograph not so tightly tied in
No. 2 as in No. 1.

ee ee et
C2 as OS 2 Sle i) fis A Bice, SO fe

134 ON DIGITALIS, WITH SOME OBSERVATIONS ON THE URINE,

Fia. 69. Feb. 22—11 p.m.

1 te i Dh oat On

Fie. 70. Feb. 23—1 at night.

Fie. 71. Feb..24—11.20 p.m.

PAPA er SS

Fie. 72. Feb. 26—11.30 p.m.

Fie. 73. Feb. 27—12.30 midnight.

Spada

Fie. 74. Feb, 28—10.80 p.m.

Fie. 75. March 1—1 at night.
Fia. 76. March 2—1 at night.

PICS

Fia. 77. March 8—11 P.M.
Fia. 78. March 5—11 p.m.
Fig. 79. March 6—11.25 p.m.

pas tes toe Po bea ne

SPHYGMOGRAPHIC OBSERVATIONS.

Fie. 80. March 7—11.30 P.M.

PP PP aap ci I

Fie. 81. March 8—11.30 P.M,
Fie. 82. March 9—11.50 p.m.

Pa Pe Se pe

135

Figs. 83 anp 84. March 10—11.15 and 11.30 p.m. No.1—11.15 p.m. The

sphygmograph not so tightly tied as in No. 2.

Pe a, PT

: |: a ee nk
Fig. 85. March 12—11.45 P.M,

PPPS

Fie. 86. March 13—2.50 at night.

MENAAIYS

Fie. 87. March 14—11.15 P.M.

Fie. 88. March 15-—11.20 p.m.

poe NSS

Fie. 89. March 16—5 a.m.

Fie. 90. March 16—1 at night.

a

136 ON DIGITALIS, WITH SOME OBSERVATIONS ON THE URINE.

Fia. 91. March 17—11 p.m.

Fig. 92. March 17—about 11 p.m.

Fie. $3. March 19—2.30 at night.

[Se ee ee

Fie. 94. March 20—11.23 p.m.
Fia. 95. March 23—12 midnight.

MERI

Fie. 96. March 24—10.46 p.m.

INN

Fie. 97. March 24—10.40 p.m.

ON THE USE OF NITRITE OF AMYL IN
ANGINA PECTORIS.

(Reprinted from The Lancet for July 27th, 1867.)

Few things are more distressing to a physician than to stand
beside a suffering patient who is anxiously looking to him for
that relief from pain which he feels himself utterly unable to
afford. His sympathy for the sufferer, and the regret he feels
for the impotence of his art, engrave the picture indelibly on
his mind, and serve as a constant and urgent stimulus in his
search after the causes of the pain, and the means by which it
may be alleviated.

Perhaps there is no class of cases in which such occurrences
as this take place so frequently as in some kinds of cardiac
disease, in which angina pectoris forms at once the most promi-
nent and the most painful and distressing symptom. This
painful affection is defined by Dr. Walshe as a paroxysmal
neurosis, in which the heart is essentially concerned, and the
cases included in this definition may be divided into two
classes.

In the first and most typical, there is severe pain in tiie pre-
cordial region, often shooting up the neck and down the arms,
accompanied by dyspneea, and a most distressing sense of im-
pending dissolution. The occurrence and departure of the
attack are both equally sudden, and its duration is only a few
minutes.

In the second class, which, from its greater frequency, is
probably the more important, though the pain and dyspnoea
may both be very great, the occurrence of the attack is some-
times gradual, and its departure generally so; its duration is
from a few minutes to an hour and a half or more, and the
sense of impending dissolution is less marked or altogether
absent.

Brandy, ether, chloroform, ammonia, and other stimulants

138 ON THE USE OF NITRITE OF AMYL IN ANGINA PECTORIS.

have hitherto been chiefly relied upon for the relief of angina
pectoris ; but the alleviation which they produce is but slight,
and the duration of the attack is but little affected by them.

In now publishing a statement of the results which I have
obtained in the treatment of angina pectoris by nitrite of amyl,
I have to observe that the cases in which I employed this
remarkable substance belonged rather to the second than the
first of the classes above described.

Nitrite of amyl was discovered by Balard; and further
investigated by Guthrie,* who noticed its property of causing
flushing in the face, throbbing of the carotids, and acceleration
of the heart’s action, and proposed it as a resuscitative in
drowning, suffocation, and protracted fainting.

Little attention, however, was paid to it for some years, till
it was again taken up by Dr. B. W. Richardson, who found that
it caused paralysis of the nerves from the periphery inwards,
diminished.the contractility of the muscles, and caused dilata-
tion of the capillaries, as seen in the web of the frog’s foot.

Dr. Arthur Gamgee, in an unpublished series of experiments,
both with the sphygmograph and hemadynamometer has found
that it greatly lessens the arterial tension both in animals and
man; and it was: these experiments—some of which I was
fortunate enough to witness—which led me to try it in angina
pectoris.

_During the past winter there has been in the clinical wards
one case in which the anginal pain was very severe, lasting
from an hour to an hour and a half, and recurring every night,
generally between 2 and 44.M.; besides several others in whom
the affection, though present, was less frequent and less severe.
Digitalis, aconite, and lobelia inflata were given in the intervals,
without producing any benefit ; and brandy and other diffusible
stimulants during the fit produced little or no relief. When
chloroform was given, so as to produce partial stupefaction, it
relieved the pain for the time ; but whenever the senses again
became clear, the pain was as bad as before. Small bleedings,
of. three or,four ounces, whether by cupping or venesection,
were, however, always beneficial; the pain being completely

* Journal of the Chemical Sceiety, 1859.

PRACTICAL USE OF SCIENTIFIC RESULTS. 139

absent for one night after the operation, but generally returning
on the second. As I believed the relief produced by the
bleeding to be due to the diminution it occasioned in the
arterial tension, 16 occurred to me that a substance which
possesses the power of lessening it in such an eminent degree
2s nitrite of amyl would probably produce the same effect, and
might be repeated as often as necessary without detriment to
the patient’s health. On application to my friend Dr. Gamgee,
he kindly furnished me with a supply of pure nitrite, which he
himself had made; and on proceeding to try it in the wards,
with the sanction of the visiting physician, Dr. J. Hughes
Bennett, my hopes were completely fulfilled. On pouring from
five to ten drops of the nitrite on a cloth, and giving it to the
patient to inhale, the physiological action took place in from
thirty to sixty seconds; and simultaneously with the flushing
of the face the pain completely disappeared, and generally did
not return till its wonted *time next night. Occasionally it
began to return about five minutes after its first disappearance ;
but on giving a few drops more it again disappeared, and did
not return. Ona few occasions I have found that, while the
pain disappeared from every other part of the chest, it remained
persistent at a spot about two inches to the inside of the
right nipple, and the action of the remedy had to be kept up for
several minutes before this completely subsided. In almost all
the other cases in which I have given it, as well as in those in
which it has been tried by my friends, the pain has at once
completely disappeared. In cases of aneurism, where the pain
was constant, inhalation of the nitrite gave no relief, but where
it was spasmodic, or subject to occasional exacerbatiors, it
either completely removed or greatly relieved it. It may be as
well to note that in those cases in which it failed small bleed-
ings were likewise useless.

From observations during the attack, and from an examina-
tion of numerous sphygmographic tracings taken while the
patients were free from pain, while it was coming on, at its
height, passing off under the influence of amyl, and again com-
pletely gone, I find that when the attack comes on gradually
the pulse becomes smaller and the arterial tension greater as

140 ON THE USE OF NITRITE OF AMYL IN ANGINA PECTORIS.

the pain increases in severity. During the attack the breathing
is quick, the pulse small and rapid, and the arterial tension
high, owing, I believe, to contraction of the systemic capillaries.
As the nitrite is inhaled the pulse becomes slower and fuller,
the tension diminished, and the breathing less hurried. On
those occasions when the pain returned after an interval of a
few minutes, the pulse, though showing small tension, remained
small in volume, and not tiil the volume as well as tension of
the pulse became normal did I feel sure that the pain would not
return.

As patients who suffer from angina are apt to become
plethoric, and greater relaxation of the vessels is then required
before the tension is sufficiently lowered, I think it is advisable
to take away a few ounces of blood every four weeks. When
the remedy is used for a long time, the dose requires to be
increased before the effect is produced. A less quantity is
sufficient when it is used with a*cone of blotting-paper, as
recommended by Dr. Richardson, than when it is poured ona
large cloth. From its power of paralysing both nerves and
muscles, Dr. Richardson thinks it may prove useful in tetanus;
and I believe that, by relaxing the spasm of the bronchial tubes,
it might be very beneficial in SPASMODIC ASTHMA. I have tried
it in a case of EPILEPSY, but the duration of the fit seemed little
affected by it. It produces relief in some kinds of HEADACHE
and in one of NEURALGIA of the scalp it relieved the severe
shooting pain, though an aching fecling still remained.

While cholera was present in Edinburgh during last autumn,
Dr. Gamgee proposed it as a remedy during the stage of
collapse, a condition in which there are good grounds for
supposing that the small arteries, both systemic and pulmonic,
are in a state of great contraction. No well-marked case after-
wards occurring in the town, le was deprived of an opportunity
of putting it to the test; but it is a medicine well worthy of a
trial, and, should another epidemic unhappily occur, it may
prove our most valuable remedy.

ACTION OF DIGITALIS ON THE BLOOD-
VESSELS.

In conjunction with ADOLPH BERNHARD MEYER, M.D.

(Reprinted from the Journal of Anatomy and Physiology, vol. vii, 1873.)

INDEPENDENTLY of each other, and in different ways, we both
arrived at the conclusion that digitalin causes contraction of the
small blood-vessels.* Wishing to support our views by still
more conclusive proofs, we took advantage of the opportunities
afforded to us in the physiological laboratory of the Berlin
University to perform together, in January, 1868, some experi-
ments on the subject. We are perfectly aware of their incom-
pleteness, but circumstances having prevented us from continu-
ing them, and the departure of one of us for a distant land
rendering it improbable that we shall be able to resume them
together, we now publish their results.

We believed that by a comparison of the form of the curves
indicating the blood-pressure before and after the injection of
digitalin into the circulation, we should be able to determine
exactly whether it caused contraction of the arterioles or not.
The kymographion we employed was that of Ludwig, as modi-
fied by Traube, and the experiments were conducted on dogs in
the following manner. The animal being narcotised by hydro-
chlorate of morphia, a cannula was inserted into the crural
artery, and a curve (fig. 98) showing the normal blood-pressure
was described. Digitalin, suspended in a small quantity of dis-
tilled water, was then injected into the carotid artery, and
pressure-curves again described. Injection into the artery was

* T. Lauder Brunton On Digitalis: wilh some Observations on the Urine,
London, 1868, p. 52 (vide p. 55), and A. Bernhard Meyer, Zur Lehre von den
Herzgiftenin Untersuchungen aus dem physiologischen Laboratorium der Ziiricher
Hochschule herausgegeben von Professor Fick. Wien, 1869, p. 71.

142 ACTION OF DIGITALIS ON THE BLOOD-VESSELS.

employed because Blake* found that digitalin produced a much
greater effect on the blood-pressure when introduced into the
circulation in this way than if injected into a vein. A com-
parison of the tracings thus obtained, after the injection, with
that of the normal pressure and _puise (fig. 98), showed a slow-

100
90
G0

70

60

50
Fie. 98.

ing of the pulse, accompanied by an increase in the mean blood-
pressure, while the height of the wave occasioned by each
cardiac pulsation remained much the same (fig 99). The pres-

90
50

70

€0

Fig. 99.

sure continued to rise gradually although the pulse not only
became slower and slower, but the oscillations of the mercurial
* Blake, Hd. Med. Journ. 1889.

PROOF OF CONTRACTION OF ARTERIOLES. 143

column at each pulsation diminished in extent (fig. 100). This
rise could be due either to the heart propelling a greater quan-
tity of blood into the aorta at each pulsation, or to the arteries,
contracting so as to hinder it from escaping from the arterial
into the venous system. The diminished height of the pulse-
wave seems sufficient of itself to negative the former idea and
to show that the increased pressure can only be due to con-
traction of the arterioles, but we think that a still clearer proof
is afforded by the form of the wave. The time occupied in the
ascent of the pressure-wave (indicated by the horizontal dis-
tance between the lowest and highest parts of the ascending
limb) is nearly the same in figs. 98 and 100, but the descending
limb of the latter sinks very gradually indeed, while in the

ly
100
on /

60

70

Fie. 100.

former it falls almost as quickly as it rises. What then is the
explanation of this phenomenon? Turing the diastole of the
heart, the sigmoid valves when healthy, as they were in this
case, completely close the cardiac end of the aorta. The whole
arterial system may then be compared to an elongated elastic
vessel, from which fluid is issuing by a narrow opening. The
ereater the pressure of fluid in the vessel the more rapidly will
it escape by the opening, the more quickly will the pressure
consequently fall, and the more abrupt will be the descent of
the pressure-curve. Now, the mean blood-pressure in the
normal tracing is somewhat over 70 millimetres,* and the maxi-

* The true heights are of course nearly double these, but for convenient
comparison with the tracings we have taken the numbers as they stand in the

144 ACTION OF DIGITALIS ON THE BLOOD-VESSELS.

mum height of the wave 44, while in that taken when the
action of the digitalin was greatest, the mean pressure is some-
what over 90 millimetres, and the maximum 104. The fall of
yressure ought, therefore, to be more abrupt, but instead of this
it is more gradual. This alteration cannot, we think, be ex-
plained by any oscillations of the mercurial column indepen-
dently of the blood-pressure, and can only be due to contraction
of the arterioles retarding the flow of blood from the arterial
into the venous system during the cardiac diastole. In a recent
paper,* Boehm considers that the rise in blood-pressure pro-
duced by digitalis, is chiefly due to the inzreased action of the
heart, and that the condition of the arterioles has little or
nothing to do with it. He seems, however, to interpret tracings
of the blood-pressure in the arteries of mammals in the same
way as those obtained from the excised heart of the frog, and
apparently forgets that while in the latter the form of the
diastolic as well as of the systolic curve depends on the heart
alone, in the former the heart can have but little or no influence
on the pressure in the arterial system during the diastole, since
all communication between them is prevented by the closure of
the sigmoid valves. The curves which he gives confirm our
views, for they show the same gradual fall in the pulse-wave,
after the injection of digitalis, that ours do, and being traced
with Fick’s spring-kymographion, are free from any fallacies
due to oscillations of the mercurial column. The continued
high pressure he observed during prolonged stoppage of the
heart, which he attributes to continuous cardiac systole, we
would ascribe to contraction of the vessels so far as it is not due
to changes in the respiration. If the arterioles were not con-
tracted the pressure would fall, as, eg.,in the experiments of
Ludwig and Hafiz.t

We next attempted to ascertain whether the slowing of the

figures. (These curves only show the ascent of the mercurial column above the
level in one limb of the U-tube of the manometer, whereas the true height is
got by adding to this the descent of the mercury below tlhe level in the other
limb with a slight correction for the weight of the carbonate of soda solution in
the descending limb.)

* Pfliiger’s Archiv, vol. v, p. 190.

+ Ludwig’s Arbeiten, 1870,

ee

PULSE RATE AND ARTERIAL PRESSURE. 145

pulse is due to a direct specific influence of the drug on the
roots of the vagus as supposed by one of us,* or to the stimula-
tion of these roots by the increased pressure of blood in the
cranium produced by the contraction of the arterioles, as sup-
posed by the other.f In order to do this we diminished the
blood-pressure by the inhalation of nitrite of amyl after it had
become high and the pulse slow from the injection of digitalin.
If the slowing of the pulse were due to a specific action of the
digitalin on the vagus roots, it ought to continue although the
pressure falls, but if due to stimulation of these roots by the
high blood-pressure, it should disappear whenever the pressure
is reduced. Our experiments showed that whenever the pres-
sure fell after the inhalation of the nitrite of amyl the pulse
became quick. It might thus appear that the slowing is due in
part at least to the high pressure, and not altogether to a direct
influence of the digitalin on the vagus; but this must be decided
by farther experiment.

Lastly, we tried to discover whether digitalis causes contrac-
tion of the vessels by acting directly on their walls or on the
vaso-motor centre. This we sought to do by observing whether
the injection of digitalin into the circulation caused any altera-
tion in the calibre of the vessels of the rabbit’s ear after the
sympathetic nerve of the same side as well as both vagi had
been divided in the neck. The vagi were divided in order to
prevent the digitalin from slowing the heart, and thus disturbing
the circulation, and the sympathetic to prevent any influence
being transmitted to the vessels of the ear from the vaso-motor
centre. The results of these experiments were not constant,
and we are unable to draw any definite conclusions from them ;
but the fact that the vessels of the ears were occasionally seen
to empty themselves more quickly after the injection of digitalin
than before, seems to us to indicate an action upon the walls
of the vessels themselves.

The conclusions to which we have arrived are shortly, 1st,
that digitalin causes contraction of the arterioles. This is
proved by the small height of the pulse-wave, and by its descent

* Bruaton, Op. cit. (vide antea, pp. 71 and 72).
t+ Meyer, Op. cit.

146 ACTION OF DIGITALIS ON TIE BLOOD-VESSELS.

becoming more gradual after the injection notwithstanding the
increased blood-pressure. 2nd, that the slowing of the pulse is
probably due in part to the increased blood-pressure which
results from the contraction of the arterioles. We gladly take
this opportunity of expressing our obligations to Professor
Rosenthal for the assistance and advice which he so constantly
and kindly afforded us, and to Herr Merck, of Darmstadt, to
whose kindness we owe the digitalin we employed. .

[The kymographion employed was of the same kind as the
one figured on p. 281.]

ST ee ae

te

ON THE CHEMICAL COMPOSITION OF THE
NUCLEI OF BLOOD CORPUSCLES.

A RESEARCH CARRIED ON IN PROFESSOR Ktune’s LABORATORY, IN AMSTER-
DAM, IN THE WINTER OF 1868-69.

{Reprinted from The Journal of Anatomy and Physiology for November, 1869.)

DurRinG the course of last summer (1868) Professor Kiihne dis-
covered that the chief constituent of the nuclei of blood corpuscles
agreed in its reactions with mucin rather than fibrin or albumen.
It had previously been found by Hoppe-Seyler,* associated in
the nuclei with a small amount of paraglobulin, and, previous to
Professor Kiihne’s discovery, had been supposed to be an albu-
minous substance, resembling fibrin. I was informed by Pro-
fessor Kiihne, while working in his laboratory in Amsterdam,
of the observations he had already made, and having repeated
them, I publish the result with his permission. The observa-
tions are not complete, but I give them now, as I am unable to
prosecute them further at present.

The nuclei of the blood corpuscles of eels and frogs yield a
substance similar to that obtained from the blood of fowls;
but as the latter could be much more readily obtained in con-
siderable quantity, it alone was used in studying the reactions
in detail.

To obtain the nuclei, the defibrinated blood, mixed with ten
or twelve times its volume of NaCl solution of 3 per cent., is
filtered through linen, and the corpuscles allowed to subside in
a flat tray. The supernatant fluid is then removed by a syphon,
and the corpuscles, thus freed from serum, are either washed
repeatedly with much water in the same manner, or after being
allowed to settle in the salt solution for at least twenty-four
hours, when they form a kind of film, are scraped together, and
washed on a linen filter. In the former case, the nuclei or

* Kithne, Lehrbuch der Physiologischen Chemie,
L 2

148 CHEMICAL COMPOSITION OF NUCLEI OF BLOOD CORPUSCLES.

rather zooids of the blood corpuscles are obtained as a white
powder, which sinks very slowly in water; in the latter, as a
mass resembling fibrin in appearance. Microscopic examina-
tion shows this powder to consist of the nuclei in the form of
small round bodies containing several dark granules, surrounded
by a ring of transparent colourless substance, apparently a
remnant of stroma, whose breadth is about equal to the diameter
of the nucleus, and whose edge is so delicate as to be scarcely
perceptible. On the addition of aniline red or blue, dissolved
in dilute alcohol, the nucleus becomes deeply coloured, the
stroma slightly so, and its edges much more distinct. Weakly
alkaline solutions of carmine and solutions of iodine also colour
the nucleus deeply, but the stroma very slightly, or not at all.
The nucleus is generally in the middle, but, occasionally, is more
or less eccentric, and sometimes sticks quite close to one side of
the surrounding substance. This last may possibly be its con-
stant situation, and its central one only apparent, and it may
thus correspond to the point in mammalian blood corpuscles,
which was found by Roberts* and Rindfleischf to become
deeply coloured by magenta. If the powder be then shaken
with ether and water it forms a layer between the two; and
when this is microscopically examined, the nuclei alone are seen,
the stroma formerly surrounding them being no longer percep-
tible even after the addition of aniline. The nuclei may be got
at once by treating the corpuscles with ether, separating the
nuclear layer by a stoppered funnel, and then washing in water.
Alkalis cause the nuclei to swell, to run together in clumps,
become indistinct, and finally disappear. Dilute mineral acids
or acetic acid cause them to shrink and become more sharply
defined. A small, strongly refracting point, resembling a
nucleolus, and seeming to take up the colowing matter more
strongly than the rest, also becomes visible; but this appear-
ance may be due to a change of shape in the nucleus, occasioned
by the acid. Concentrated mineral acids cause them to shrink
much, to run together, become indistinct and disappear. The
stroma surrounding the nuclei swells and shrinks somewhat,

* Proceedings of Royal Society, 1865.
+ Experimental Studien iiber die Histologie des Blutes.

COAGULATION (?) OF ZOOIDS. 149

but not so markedly as thenuclei. If ferrocyanide of potassium
be added to the nuclei shrivelled by acetic acid they swell up
and become so indistinct as to be hardly visible. A solution of
taurocholate or glycocholate of soda dissolves both nuclei and
stroma. A little concentrated NaCl solution also causes the
nuclei to disappear. When the corpuscles are washed on a
linen filter, a fibrinous-looking mass is obtained, which, on
microscopic examination, is seen to consist of shreds of fibrous
membrane, or of bundles of fibres, studded with darker spots,
and arranged in a manner resembling those of fibrin, though
more regular and with less intercrossing. These spots seem tc
be the nuclei, but their outline is not so distinct, nor do they
take the deep tint with aniline which they do in the powdery
condition, the fibres becoming quite as deeply tinted as they.

The zovids are insoluble in water, and when suspended in
it sink very slowly, but do so much more quickly after the
addition of alcohol, concentrated acetic or oxalic acid, or dilute
mineral acids. The mixture with water is quite mobile, and
does not foam when shaken ; but: does so after the addition of a
little NaCl solution, becoming at the saine time somewhat tena-
cious and much clearer, the nuclei being partly dissolved and
partly suspended. A concentrated mixture with NaCl solution
gives a white flocky precipitate when much diluted. Salt solu-
tions, of even one-fourth per cent., dissolve them to a consider-
able extent. The solubility in NaCl solution varies much,
diminishing when the zooids stay long in water, but more
slowly when the temperature is low. The same is the case
with mucin obtained from tendons.

When many zooids are suspended in water, one drop of con-
centrated solution of potash or soda is sometimes sufficient to
convert 40 cubie centimetres of the mixture from a milky
mobile liquid to a clear gelatinous mass, resembling albuminate
ef potash in appearance, though not quite so firm. When this is
thrown on a filter, the filtrate gives no precipitate with acetic
acid. When more potash is added, a tenacious ropy fluid is
pruduced, which filters very slowly; the filtrate is mobile, and
though generally more or less alkaline, is sometimes neutral.

Alkaline carbonates dissolve them, but. much more slowly,

150 CHEMICAL COMPOSITION OF NUCLEI OF BLOOD CORPUSCLES.

uor do they form a jelly like the caustic alkalis ; sometimes,
llowever, they cause the zooids to stick together and form flocks,
which, rising to the top, form a sticky mass. Lime and baryta
water leave them apparently unchanged, and, after standing on
them some time, give no precipitate with acetic acid, but an
immediate turbidity if ferrocyanide of potassium be then added.
Concentrated mineral acids dissolve the zooids, and give a pre-
cipitate on the addition of alkalis or much water.

Dilute mineral acids, such as HCl of 10 per cent., cause the
mixture with water to foam on shaking, but when the filtered
fluid is made alkaline by potash it gives no precipitate with
acetic acid, but a turbidity when ferrocyanide of potassium is
then added. ‘The filtered solutions of the zooids in alkalis give
the reactions of albumin, but the precipitate by acetic acid is
generally insoluble in excess. Sometimes, however, not only
the mucin from nuclei, but that from glands and tendons,
appears quite soluble in large excess of glacial acetic acid, If
the zooids be treated with HCl of one-tenth per cent., or acetic
acid or NaCl solution of 10 per cent., and the filtered solution be
precipitated by acetic acid and again filtered, the clear fluid in
each case gives the reactions of albumin. The HCl solution is
precipitated on neutralization, and the precipitate is insoluble
in NaCl soiutions of 10 per cent. |

The albuminous body thus belongs to that class which
includes, according to Hoppe-Seyler, fibrinogen, fibrinoplastic
substance and myosin.

That the zooids contain fibrinoplastic substance or para-
globulin, as stated by Hoppe-Seyler, is shown by the distinct
fibrinoplastic action which they exert when well washed. Some-
times they possess none at all; and this is probably due to the
removal of the substance in the washing, the salt solution with
which the corpuscles were washed not having been sufficiently
carefully removed, and rendering the first water a dilute salt
solution. This dissolves a certain amount both of albuminous
substance and of mucin, becomes milky after standing or pass-
iny CO, through it, and possesses a slight fibrinoplastic effect,
The fibrinoplastic effect was tried in all cases with a mixture of
horse plasma and sulphate of magnesia,

—-~

iste ape a a ee ee a ee
°F EES Ga aS ggpince 4 jae nee Cen &

REACTIONS OF NUCLEI, 151

From the way in which fibres are formed when the zooids are
washed on a linen filter, it seems probable that fibrinogenic
substance may also be present; but whether this be the same as
mucin, or what the relation between mucin and the generators
of fibrin or myosin, if any such relation exists, is still to be
investigated.

When the precipitate from solutions in alkalis or NaCl by
acetic acid is washed with acetic acid, then with dilute alcohol,
and afterwards dissolved in a small quantity of potash and
filtered, the filtrate is generally alkaline, but sometimes neutral.
It is unchanged by boiling, gives with mineral acids a precipitate
soluble in excess, and with acetic acid a precipitate insoluble in
excess. On exceptional occasions, I have seen it, as well as
mucin from tendons dissolved by excess of glacial acetic acid,
give with acetic acid and ferrocyanide of potassium no turbid-
ity, the ferrocyanide of potassium causing any turbidity from
the acetic acid to become less and disappear ; but after standing
a considerable time a precipitate forms. Chloride of mercury
causes no precipitate; with tannin, acetate of lead, or dilute
sulphate of copper or chloride of iron it gives a precipitate.
Added to potash and sulphate of copper it prevents the pre-
cipitation of the hydrated oxide of copper, but the solution
remains blue even after boiling.
| Nuclei, freed from stroma by ether and water and then dis-
solved in potash, give the same reactions. These reactions
differ from those of mucin as given by Eichwald (Kiiline, Lehr-
buch der Physiologischen Chemie), inasmuch as tannin, sul-
phate of copper and chloride of iron give a slight precipitate or
turbidity, but on treating nuclei and mucin from glands and
tendons in the same way they give the same reactions. ‘When |
a salivary gland is treated by potash, and the solution precipi-
tated by acetic acid, the precipitate is sticky, and seems to differ
much from that given by acetic acid in solutions of nuclei in
potash, which is flocky, and gathers on a linen filter into a mass
looking like boiled fibrin; but if the strongly acid and sticky
precipitate from the gland be allowed to stand some time in
water, it becomes exactly like that obtained from the nuclei.

The zooids and their solution in NaCl act briskly on peroxide

152 CHEMICAL COMPOSITION OF NUCLEI OF BLOOD CORPUSCLES.

of hydrogen ; the nuclei, after treatment by ether and water, do
so also but less vigorously. |

When boiled with dilute sulphuric acid they gave no trave of
sugar.

I have never succeeded in obtaining them free from sulphur
even after repeatedly dissolving in potash, and precipitating and
washing by acetic acid; but the more carefully they were
cleaned the less sulphur was found; and Professor Kiihne on
one occasion obtained no trace of sulphur after burning with
nitrate of potash and adding chloride of barium. This trace of
sulphur may possibly depend on a little albumen carried down
with the mucin; more especially as one sees that if the haemo-
globin be not entirely removed by washing before dissolving in
potash and precipitating by acetic acid, hematin is constantly
carried down with the precipitate, and cannot again be sepa-
rated.

When chicken blood is treated by NaCl solution of 10 per
cent., as in Professor Heynsius’ experiments lately published,
the nuclei are dissolved and form a large portion of the
fibrincus-iooking substance he describes.

Whether mucin exists in mammalian blood or not I cannot
certainly say, though the substance got by treating dogs’ blood
with salt solution of 10 per cent., and then washing the slimy
mass, seemed, after solution in potash, to give a precipitate with
acetic acid insoluble in excess. The quantity obtained pure was,
however, so small that I was unable to try any other reaction.

Shortly, then, the substance of the nuclei, both with and
without the stroma, agrees with mucin, and differs from
albumin in its insolubility in HCl of 0:1 to 1 per cent. in its
alkaline solutions being precipitated by nitric, hylrochlorie
or sulphuric acid, and the precipitate dissolved without diffi-
culty by excess; in being precipitated by acetic acid, and the
precipitate insoluble in excess, ferrocyanide of potassium
causing no further turbidity, but clearing up any formed by the
acetic acid; in neutral solutions being unchanged by boiling,
and giving no precipitate with chloride of mercury, and when
boiled with caustic potash and sulphate of copper remaining
clear blue. It agrees with alburain and with mucin as I found

DIFFERENCES BETWEEN NUCLEL AND MUCIN, 153

it (though differing from it, as described by Eichwald) in giving
a turbidity or slight precipitate with tannin, chloride of iron
and sulphate of copper. It differs from mucin in being in-
soluble in lime or baryta water, or in HCl of 10 per cent. Its
most remarkable reaction is the change it undergoes by the
addition of a very small quantity of caustic potash to the water
in which it is suspended. It is then much more closely allied
to mucin than to albumin. From the solubility and reactions
of mucin being somewhat variable it is not improbable that,
like albumin, it may occur in several forms, of which this
may be one; but its composition and relations must be deter-
mined by analyses, which I hope at a future period to be able to
make.

OFFENTLICHE GESAMMTSITZUNG AM 12 DECEMBER,

1869, ZUR FEIER DES GEBURTSTAGES SEINER
MAJESTAT DES KONIGs.

Dr. T. Lauder Brunton, Ueber die Wirkung des salpetrig-sauren Amyloxyds
auf den Blutstrom. Aus dem physiolcgischen Institute zu Leipzig. Vorgelegt
von dem wirklichen Mitgliede Prof. C. Ludwig. (Mit. 6 Holzsclinitten.)

(Aus den Berichten der Mathem.-Phys. Classe der Kénigl.-Sdchs. Gesellschaft
der Wissenschaften, 1869, s. 285, und Ludwig’s Arbeiten 4ter Jahrgang fiir
1869, s. 101.)

Aur das salpetrigssure Amyloxyd hat Guthrie zuerst die

Aufmerksamkeit der Aerzte und Physiologen gelenkt ; bei einer

chemischen Untersuchung dieses von Balard entdeckten Stoffes

bemerkte er, dass sich nach Einathmung seiner Dimpfe das

Gesicht lebhaft rothe, dass die Carotiden heftiger klopfen und

dass der Herzschlag beschleunigt werde. Einige Jahre nach-

her behauptete J’chardson, dass das salpetrigsaure Amyloxyd
die Nerven von der Peripherie nach dem Centrum hin lahme,
die Contractilitét der Muskeln vermindere und Erweiterungen
der Blutcapillaren in der Schwimmhaut des Froschfusses her-
beifithre. Diese Mittheilung gab Professor Arthur Gamgee Ver-
anlassung neue Versuche zu unternehmen, Aus seinen noch
nicht verdffentlichten Beobachtungen war der eben genannte ©

Gelehrte so freundlich mir das Folgende mitzutheilen: Ein

Einfluss auf die Lebenseigenschaften der motorischen und sen-

siblen Nerven ist nicht zu finden, ebenso wenig gelang es, eine

Erweiterung der Gefiisse in der Schwimmhaut zusehen. Athmet

der Mensch die Daimpfe der Verbindung ein, so réthet sich das

Gesicht, und die Pulscurve der art. radialis, welche der Sphyg-

mograph aufzeichnet, nimmt eine eigenthtimliche Form an; die

bedeutendste Abweichung von der normalen Gestalt bietet der
absteigende Curvenschenkel, insofern er statt des allmaligen
einen sehr plétzlichen Abfall zeigt. Wird in die Carotis des

Kaninchens ein Manometer eingesetzt und werden darauf die

Diimpfe des salpetrigsauren Amyloxyds durch die Nase einge-

VERSUCIISANORDNUNG. 155

fiihrt, so mindert sich. die Haufigkeit des Herzschlags und der
mittlere Blutdruck nimmt ab.

Auf Grund dieser Beobachtungen habe ich selbst das sal-
petrigsaure Amyloxyd zuerst mit Erfolg hei Kranken angewen-
det, die an gewissen Formen von Angina pectoris litten.* Hier
durch fiir das neue Arneimittel interessirt, ergriff ich wihrend
meines Aufenthalts in Leipzig die Gelegenheit um in dem phy-
siologischen Institute dieser Stadt einige Versuche dariiber
anzustellen, wie die Erscheinungen zu erkliiren seien, die ma»
mittelst desselben im Blutstrom erzeugt hatte.

Als Versuchsthiere dienten Kaninchen. Im Anschluss an
den bisherigen Gebrauch verleibte ich ihnen die Diaimpfe des
Amylpraparates ein, welche durch die kiinstliche Respiration
in die Lungen geblasen wurden. Zu dem Ende schaltete ich in
das Verbindungsrohr zwischen dem Blasebalg und der Trachea
eine Nebenschliessung ein; mit andern Worten der an der Trachea.
und dem Blasebalg einfache Luftkanal war auf einem beschrink-
ten Abschnitt in zwei Zweige zerlegt. In jedem der beiden
Zweige sass ein Hahn, durch welchen die Lichtungen eines jeden
Réhrenschenkels nach Belieben verschlossen werden konnten.
Das Hauptrohr ging unmittelbar aus dem Blasebalg in die Luft-
rohre, in dem Nebenzweig war dagegen eine kleine Spritztlasche
elngesetzt, deren Boden mit salpetrigsaurem Amyloxyd bedeckt.
war. Je nach der Stellung der Hihne konnte man also der
Lunge die atmosphirische Luft rein oder im Gemenge mit den
Daimpfen der Amylverbindung-zufiihren. Die eben geschil-
derte Einrichtung zog ich der unmittelbaren Anwendung der
Diimpfe auf die Nase darum vor, weil es mir darauf ankam, die
Wirkung derselben auf den Herzschlag festzustellen. Das Herz
des Kaninchens, beziehungsweise die betreffenden Vagusiste
desselben sind bekanntlich ungemein empfindlich gegen jede
Aenderung in dem O-Gehalt des Arterienblutes; jede merk-
liche Abminderung des letztern hat sogleich eine Abnahme der
Schlagzahl zur Folge. Nun ereignet es sich aber gewdéhnlich,
dass die Kaninchen die Athembewegungen einstellen, wenn so
stark riechende Dimpfe wie die des salpetrigsauren Amyloxy-
des vor ihre Nase gehalten werden und dass sie erst mit der

* The Lancet for July 27, 1867.

156 WIRKUNG DES SALPETRIG-SAUREN AMYLOXYDS.

beginnenden Athemnoth die Bewegungen wieder ausfiihren
Damit aber ist auch schon eine Vagusreizung ganz unabhiingig
von den zugefiihrten Diimpfen eingeleitet. Zur Anwendung der
kiinstlichen Respiration griff ich diesmal um so lieber, weil der
Blasebalg, welcher mir hier zu Gebote stand, durch eine sehr
regelmissig arbeitende Maschine getrieben ward, somit konnte
ich sicher sein vor Storungen, welche durch ein ungleichfor-
miges Athmen eingefiihrt werden—Das Manometer, mit wel-
chem ich den Druck mass, wurde in die Carotis eingesetzt.

Mit diesen Hiilfsmitteln sah ich zuniichst, dass der Blut-
druck, unmittelbar nachdem die Dimpfe des Amyloxyds einge-
blasen waren, rasch absank, ohne dass sich die Zahl der Herz-
schlige merklich gemindert oder gemehrt hatte. Mit dem
Absinken des Drucks steliten sich zugleich Kriimpfe in allen
Muskeln des Rumpfs und der Gliedmaassen ein, wodurch die von
der Amylverbindung eingeleiteten Aenderungen des Blutstroms
getriibt wurden. Denn mit dem Eintritt der Krimpfe hob sich
der Blutdruck wieder und es wurden zugleich an der aufge-
schriebenen Druckcurve die Herzchlige gar nicht oder unge-
mau zihlbar. Um die Krimpfe und darnit, wie ich glaubte,
auch die Stérungen zu vermeiden, welche sich dem reinen Her-
vortreten der Amylwirkung entgegensetzen, griff ich zur Ver-
giftung mit Curare. Hiernach schwanden allerdings die Krampfe;
aber es trat ein neues stdrendes Element ein, was, wie igh ver-
muthe, in dem Reizungszustande gelegen ist, in den die Gefiiss-
muskeln durch das Curare verfallen.

Allerdings sank auch am curarisirten Thiere der Druck
alsbald nachdem das Einblasen der fliichtigen Amylverbindung
seinen Anfang genommen hatte, und der Druck erreichte seine
ursprtingliche Hohe nicht wieder, wihrend mit der Zufiihrung
des Dampfes forteefahren wurde: aber das Sinken war kein
stetiges, sodass schliesslich der Druck dauernd auf einem be-
stimmten Minimalwerth angelangt wire. Im Gegentheil die
Quecksilbersiiule hob sich und senkte sich und dieses zwar
etwa so, wie es Z. 7raube an der Druckcurve des curarisirten
Thieres gesehn hat.*

Diese Schwankungen sind jedenfalls der Ausdruck zweier

* L. Traube, Centralilalt fiir die med. Wissenschaften, 1865. 851.

se

WIRKUNG AUF KANINCHEN,

. Fia, 101.
Druck in mm, He.
a
b c ?
|
x
x
ne

.<77 y 20 3 sO go z
Secun-
on,

Unvergiftet. Curarevergiftung.

x Hinblasen beendet.

157

158 WIRKUNG DES SALPETRIG-SAUREN AMYLOXYDS.

im entgegengesetzten Sinne wirksamer Einfliisse. Dieselben
kénnten gefunden werden einerseits in der Anwesenheit der
unzersetzten Molekiile des salpetrigsauren Amyloxyds und
anderseits in den aus dem letztern enstandenen Umsetzungs-
producten, sodass Alles auf die dauernde Anwesenheit der
Amylverbindung zu beziehen ware, aber nach den vielfach
bestatigten Erfahrungen von LZ. Zraube konnte auch das Curare,
also eine der Amylverbindung fremde Wirkung, fiir die Ursache
der Druckvariation gehalten werden.

In Ermangelung einer andern unverfinglicheren Methode,
durch welche auch am unvergifteten Thiere die Wirkung des
wahrend einer lingern Zeit eingeflossten Amyldampfes sichtbar
zu machen ware, muss ich mich darauf beschrinken, die Folgen
seiner sehr voriibergehenden Hinwirkung vorzulegen. Zu diesem
Ende, namentlich aber um dem Umfang und den zeitlichen
Ablauf der Druckerniedrigung zu versinnlichen, theile ich die
in Figur 101 dargestellten Curven mit, welche durch die ihnen
beigegebene Erklarung verstindlich sein werden. Beim Beginn
jeder der drei hintereinander ausgefiihrten Beobachtungen, a,
4, c fangt das Einblasen an; schon 10 Secunden nach demselben
ist der Blutdruck sehr tief herabgegangen. Traten Kriimpfe
ein, wie dieses in der Curve a und 6 der Fall ist, welche vor der
Curarevergiftung von dem Thiere gewonnen wurden, so stieg
der Druck wieder an, trotzdem dass das Einblasen noch fort-
gesetzt wurde. Wenn aber mit dem Einblasen 20 Secunden
nach Beginn desselben aufgehért wurde, so stieg der Druck
rasch wieder empor, sodass er in héchstens einer Minute seinen
friiheren Werth wieder erreicht hatte. Diese Erscheinungsreihe
habe ich so oft bestatigt gefunden, als ich die Beobachtung
anstellte. Sie weist darauf hin, dass schon minimale Mengen
unsres Stoffes von der gréssten Wirkung sind; und sie zeigt
ausserdem, dass das in das Blut gekommene Gift sehr bald
wieder unwirksam gemacht wird, entweder weil dasselbe inner-
halb des K6rpers zerstért wird oder weil es aus demselben
verdunstet. ag tte

Die Erniedrigung des Blutdrucks kann nun herriihren ent-
weder von einer Verminderung der Herzkrafte oder von einer
solchen der Widerstiinde. Fiir die zweite dieser Unterstellun-

SELBSTSTANDIGE BEWEGUNGEN DER ARTERIEN. 159

gen spricht die betrichtliche Erweiterung der peripherischen
Gefiissbezirke, wie man sie nicht allein am Ohr des Kaninchens,
sondern auch in auffallendster Weise an der menschlichen Ge-
sichtshaut sieht, namentlich wenn ein Individuum mit sehr
reizbarem, leicht errdthendem und erblassendem Gesicht einige
mit dem Dampf geschwiangerte Athemziige ausfiihrte. Immer-
hin erschien es mir noch nothwendig die Frage durch einen
Versuch zu entscheiden, um so mehr, als ich dabei auch zu
erfahren wiinschte, ob die eintretende Gefisserweiterung ab-
hangig sei von einer unmittelbaren Aenderung der Gefisswand
oder von einer solchen, die herbeigefiihrt ist durch die Ab-
schwiichung des Tonus, den die Gefissnerven im verlingerten
Marke empfangen.

Um verstindlich zu machen wesshalb sich mir diese Frage-
stellung aufdringte, will ich hier in der Kiirze einige Resultate
einer andern Versuchsreihe einschalten, die ich ebenfalls in
Leipzig begonnen aber leider noch nicht vollendet habe.

Durch die bemerkenswerthen Beobachtungen von JZ. Schiff;
welche eine allseitige Bestatigung erfahren haben, ist es be-
kannt, dass der Durchmesser der Arterien des Kaninchenohres
sehr hiufig in Schwankungen begriffen ist. Ich habe nun ge-
funden, dass diese Erscheinung dem Ohr der Kaninchen keines-
wegs allein eigenthtimlich ist, sondern dass man sie in gleich
ausgesprochener Weise auch an allen andern freigelegten Ar-
terienzweigen der Haut und des Bindegewebes beobachten
kann. Diese Schwankungen des Durchmessers zeigen ander-
wirts grade so wie am Kaninchenohr grosse Unregelmiissig-
keiten, indem sie an demselben Ort bei dem einen Thiere deut-
licher und haufiger auftreten als bei einem andern und als sie
zu verschiedenen Zeiten bei demselben Thier fehlen und vor-
handen sein kénnen. ,

Diese Verainderungen des Arteriendurchmessers sind min-
destens zum Theil vollkommen unabhingig von den Erregun-
gen, welchen die Gefiissnerven im Hirn ausgesetzt sind; denn
sie bestehen an den Arterien des Ohrs und an denen der tibri-
gen Kérpertheile unveraindert fort, wenn man auch simmtliche
Nerven, sympathische und cerebrospinale durchschnitten hat,
die in dem zu beobachtenden Orte sich verbreiten, ja sie ver-

160 WIRKUNG DES SALPETRIG-SAUREN AMYLOXYDS.

schwinden nicht nach der Durchschneidung des Halsmarkes
trotz des sehr niedrigen Blutdruckes, der dann noeh ibrig
bleibt. Die beschriebenen Bewegungen der grossen und klei-
nen Arterien treten, wie erwihnt, nicht bei jedem Thiere und
nicht zu jeder Zeit gleich deutlich ein. Fehlen dieselben, so
kann man sie in der Regel hervorrufen, entweder durch Vergif-
tung mit Curare oder durch Unterbrechung der Athmung. Sind
dieselben einmal geweckt, so pflegen sie sich auch dann noch
fortzuerhalten, wenn selbst nachtriglich die Athmung auf das
Sorgfaltigste geregelt wird. Da durch die Untersuchungen von
L. Traube, Thiry und Kowalewsky* bekannt ist, dass in Folge
der Curarevergiftung und der gestirten Athmung der Blutdruck
in den Arterien erster Ordnung sehr grosse Variationen erfihrt,
so muss der Gedanke erwachen, es seien diese letztern Schuld
an den Veriainderungen der Durchmesser der kleinsten Arterien.
Diese an und fiir sich annehmbare Erklirung erweist sich aber
als unhaltbar wegen des Ganges, den die Verengerungen und
Erweiterungen in den kleinen Arterien darbieten. Sehr hiufig
stellt sich niimlich plétzlich im Verlauf einer kleinen Arterie
mitten zwischen zwei mit Blut erfiillten Stiicken eine Ein-
schniirung ein, sodass ein Verhalten zum Vorschein kommt,
wie man es schon seit langer Zeit am ausgeschnittenen Diinn-
darm kennt.—In den Bezirken, deren Nerven simmtlich
durchschnitten sind, erhalten sich die Arterienwinde auch noch
in einer andern Beziehung dem ausgeschnittenen Darme ahn-
lich. Jede leiseste Beriihrung einer beschrénkten Stelle ruft
eine Bewegung hervor, die sich meist auf den getroffenen Ort
beschrinkt. Diese durch den unmittelbaren Einfluss erzeugte
Verinderung besteht jedoch, so weit ich gesehen, nicht vor-
wiegend in einer Verengerung der Lichtung wie beim Darm,
sondern vorzugsweise in einer Erweiterung derselben, welche
sehr lange als eine partielle Ausbuchtung bestehen bleibt und
die sich nur allmahlig ausgleicht. Da schon Gunning und
Cohnheim Aehnliches an der Schwimmhaut und der Zunge des.
Frosches beobachtet haben und da Sadler auch an den Ge-
fissen der Skeletmuskeln der Hunde auf Thatsachen gestossen’
ist, die sich nur durch Eigenbewegung der Gefisswand erkliren

* Centralllatt fiir die med, Wissenschaft, 1868, 579.

—— Slee le!

WIRKUNG BEI DURCHSCHNITTENEM RKUCKENMARK. 161

\

Fig. 102.
x Das Einblasen beendet.

Riickenmark am Epistropheus zerquetscht.

Unverictzt.

rails 0
ee a et

lassen, so scheint die selbststiindige Verinderung dieser letztern
ein weit verbreitetes und darum wichtiges Ereigniss zu sein,
4 : . -

162 WIRKUNG DES SALPETRIG-SAUREN AMYLOXYDS.

Wenn ich nun zu den Versuchen mit salpetrigsaurem Amyl-
oxyd zurtickkehre, so wird es einleuchten, warum ich den

? ba .
\

{
=~
SS

Dampf der genannten Verbindung auch solchen Thieren
einblies, deren Riickenmark vorgiingig durchschnitten worden
war.

Meine Vermuthung, dass an den Thieren, die dieser Ope-
ration unterworfen worden waren, die Druckminderung in
Folge der Amylwirkung nicht ausbleiben werde, hat sich voll-
kommen bestiitigt. Als Beispiele ftir den Befund mégen die in

Fre. 108.
x Das Einblasen beendet.

Riickenmark am Hinterhauptsbein durchschnitten.

e "4
Unvenietzt.

.
ere

-* Ae oe Ss ee eee Sea

NACHWIRKUNG DES EINBLASENS, 163

Fig. 102 und 103 wiedergegebenen Beobachtungen an zwei ver-
schiedenen Kaninchen dienen.

Jedem der beiden Thiere wurden vor der Durchschneidung
des Halsmarks die Dimpfe des salpetrigsauren Amyloxyds
eingeblasen. In diesem Stadium des Versuchs trat das schon
bekannte Resultat zu Tage, Nach der Durchschneidung des
Halsmarks, welche unmittelbar unter dem Atlas geschah, sank
bei dem Thier II der Druck ungewéhnlich tief herab; als er
constant geworden war, bewirkte das Einblasen der Dimpfe ein
neues Sinken des Blutdruckes, das also auf die Rechnung des
salpetrigsauren Amyioxyds zu setzen war. Der Werth des
Abfalls war nach absolutem Maasse gemessen allerdings ein
geringer ; nach relativem Maasse war dagegen die Aenderung
noch eine sehr bedeutende. Die Erscheinungen des Sinkens
eines schon an und fiir sich niedern Druckes sind hier denen
analog, welche man zu sehen pflegt wenn der zweite n. splanch-
micus noch durchschnitten wird, nachdem vorher schon der
erste durchtrennt war.

Als das Einblasen ausgesetzt wurde erhob sich der Blut-
druck nicht alsbald wieder auf seine friihere Hihe, sondern er
sank vorerst noch tiefer um sich dann erst ganz allmahlig zu
erholen. Dieser Erfolg kann zwei Erklirungen finden. Aus
andern Versuchen, die im hiesigen Laboratorium unternommen
wurden, ist mir bekannt, dass die Geschwindigkeit des Blut-
stroms sehr stark heruntergeht, wenn das Halsmark durch-
schnitten ist. Da die Zufiihrung und die nazhfolgende Entfer-
nung der Amylverbindung in Abhiangigkeit von der Strom-
geschwindigkeit des Blutes stehen muss, so wire der langsame
Ablauf der Druckschwankung vielleicht hieraus zu erléutern.
Méglich ist aber noch ein anderer Grund. Bei dem vorliegen-
den Thiere sank niémlich die Pulszahl in der Zeiteinheit von 9
auf 4 herab. Dieses Herabgehn, welches wohl die Folge des
sehr verminderten Druckes gewesen ist, kann ebenfalls an der
langsamen Erholung Schuld sein—Eine Wiederholung der
Kinathmung bei dem Thier ergab dasselbe Resultat.

Bei dem zweiten Kaninchen (Fig. 103) erniedrigte sich nach
Durchschneidung des Halsmarks der Druck nicht so bedeutend
als im vorhergehenden Fall. Auch bei ihm sehen wir durch

M 2

164 WIRKUNG DES SALPETRIG-SAUREN AMYLOXYDS,

die Einathmung der Amylverbindung den Druck noch weiter
heruntersteigen. Da das Thier wegen seines héhern Blutdrucks
eine -6ftere Wiederholung des Versuchs vertrug, so benutzte ich
die Gelegenheit, um statt der bis dahin geiibten kurzdauernden
Einverleibung eine langere 87 Secunden anhaltende stattfinden
zu lassen. Wihrend dieser langen Einblasung ging der Druck
nicht tiefer herab als wahrend der kiirzern, ja gegen Ende des
Einblasens erhob er sich sogar wiederum ein Kleines. Diese
Thatsache ist mit Riicksicht auf die friihere Bemerkung das
curarisirte Kaninchen betreffend nicht ohne Bedeutung. Dieses
Thier (3) zeigte von dem vorhergehenden auch insofern ein ab-
weichendes Verhalten, als sich die Pulszahl wahrend und nach
der Einblasung nicht anderte; trotzdem trat auch hier die
Wiederherstellung des héhern Druckes sehr langsam ein und
als die Lungen des Thiers den Amyldimpfen sehr anhaltend
ausgesetzt gewesen waren erhob sich zwar der Druck nach
Beendigung des Einathmens der Amyldimpfe, aber er kehrte
nicht mehr zu seiner friihern Hohe zurtick. Dieser Umstand
muss es sehr wiinschenswerth erscheinen lassen, eine Methode
zu finden, die an dem unversehrten Thier eine lingere Einwir-
kung des salpetrigsauren Amyloxyds erlaubt.

Nach diesen Versuchen, denen ich noch einige gleich-
beschaffene zufiigen kénnte, wird es keinem Zweifel unterliegen,
dass das salpetrigsaure Amyloxyd zu den Stoffen gehért, welche
unmittelbar auf die Gefaésswand lihmend wirken. Zweifelhaft
bleibt es nur noch, ob die Nervenendigungen oder die Muskeln
selbst ergriffen werden. Zudem werden weitere Versuche
dartiber anzustellen sein, ob die Gefiaisswand die einzige unter
den aus glatten Muskeln hergestellten Hauten ist, welche der
Vergiftung durch salpetrigsaures Amyloxyd zugiinglich ist.

Um auch den letzten Einwand wegzuriiumen, der gegen das
soeben mitgetheilte Ergebniss erhoben werden kénnte, habe
ich mich um den directen Beweis dafiir bemiiht, dass die Er-
niedrigung des Blutdruckes in Folge des salpetrigsauren Amyl-
oxyds unabhingig ist von einer Schwiachung der Herzkrafte.
Der Plan, nach welchem ich die hierauvf zielenden Versuche
ausfiihrte, bestand darin, den Thieren die a. aorta unmittelbar
unterhalb des Zwergfells zusammenzupressen und sie wahrend-

EINFLUSS DER VERSCHLIESSUNG DER AORTA. 165

dess den Dimpfen dor Amylverbindung auszusetzen. Wenn
das salpetrigsaure Amyloxyd eine schwichende Wirkung auf
das Herz ausiibt, so hatte nun der Druck, auf welchen sich das

Fie, 104

| | ee

| Une

~— Einblasen begonnen ; + Einblasen beendet; im Beginn der drei letzten
Beobachtungen Aorta comprimirt ; 0 Aorta geiffnet.

Blut nach der Verschliessung der Aorta erhoben hatte, alsbald
wieder absinken miissen, nachdem mit dem Einblasen der ge-
nannten Verbindung der Anfang gemacht worden war. Dieses
Absinken hatte sich selbstverstindlich in einem um so héheren

166 WIRKUNG DES SALPETRIG-SAUREN AMYLOXYDS.

Grade einstellen miissen, je bedeutender das Herz unter der
Kinwirkung unseres Giftes gelitten hiitte. Aus einer nihern
Ueberlegung der Bedingungen, unter welchen der goeben
skizzirte Versuch ausgefiihrt wird, ergiebt sich jedoch sogleich,

Fiag. 105.

Halsmark durchschnitten.
In den 4 letzten Beobachitungen Aorta comprimirt; bei 0 Aorta gedffnet;
— Einblasuag begonnen; + Einblasung beendet.

dass man nicht immer auf ein vollstiindiges Ausbleiben der
Drucksenkung rechnen kénne; dieses darum nicht, weil ja durch
die Verschliessung der Bauchaorta nicht alle Wege abgeschnit-
ten sind, durch welche das Blut aus der Brustaorta entweichen

kann. Diese noch offen gelassenen Wege werden sich unter

RUCKENMARK DURCHSCHNITTEN UND AORTA COMPRIMIRT. 167

dem Einflusse des Amyloxyds erweitern und hierdurch wird
eine Druckerniedrigung méglich werden. Um den Werth dieser

Tn den drei letzten Beobacht-

Fie. 106.

Bs
Die Ordinaten, welche den Druck angeben, beginnen 50 mm. iiber der Abscisse.

—)

|

|

ungen Riickenmark durchschnitten und Aorta comprimirt; bei 0 Aorta geéffnet; — Finblasung begonnen;

+ Einblasung aufgehért.

letzteren in engere Grenzen einzuschliessen, unternahm ich die
Aortencompression nur an solchen Thieren, denen das Hals-

168 WIRKUNG DES SALPETRIG-SAUREN AMYLOXYDS,

mark zerschnitten war, Durch diese Operation war auch die
Wandung der nicht verschlossenen Gefisse erschlafft und ich
hatte somit zu erwarten, dass die durch die Wirkung des Amyl-
oxyds hinzutretende Abspannung von einer geringern Folge fiir
das beschleunigte Abfliessen des Blutes sein werde, als wenn
das Amyloxyd auf die noch dem normalen Tonus ausgesetzten
Gefisswandungen wirksam geworden wire,

Die Resultate dieser Versuche sind reprasentirt durch die
Figuren 104,105 und 106. Zum Verstiinduniss derselben fiihre ich
an, dass die erste Einathmung an jedem der drei Thiere geschah,
bevor das Riickenmark verletzt oder die Aorta comprimirt war.
Diese Versuche wurden in der Absicht vorausgeschickt um die
Empfinglichkeit des méglichst normalen Thieres gegen das Gift
zu priifen. Nachden hierauf das Riickenmark durchschnitten
war, wurde entweder noch vor der Compression der Aorta ein
Versuch angestellt, wie ihn Fig. 105 zeigt, oder es wurde auch
sogleich die Bauchaorta mit dem Finger zusammengedriickt.
Als in Folge dieses Eingriffs der Blutdruck hoch angewachsen
war, wurde nun mit dem Einblasen der giftigen Dimpfe be-
gonnen. Ueberblickt man die Folgen, welche hierdurch in
zweien der vorgefiihrten Versuche (Fig. 104 und 105) eintraten, so
gewahrt man ein verdnderliches Verhalten. Oecefter halt sich
wiihrend des Einblasens der Druck unverindert oder er steigt
sogar, statt wie sonst zu sinken. Zuweilen aber stellte sich
wihrend desselben auch ein Sinken des Drucks ein, das jedoch
viel geringer ist als es wihrend der ersten Einathmung am un-
verletzten Thiere gewesen. Bei dem dritten Versuche (Fig. 106)
findet sich wihrend der Aortencompression und des gleich-
zeitigen Einblasens jedesmal ein Absinken des Druckes ein,
das auch rasch wieder verschwindet, wenn mit dem Einblasen
der giftigen Dampfe aufgehort wurde. Aber auch diese Druck-
verminderung ist um ein Betyriichtliches geringer als die vor
der Markzerschneidung und der Aortencompression aufgetre-
ten war.

Aus diesem Resultate diirfte man zu der Ueberzeugung
gelangen, dass das salpetrigsaure Amyloxyd, wenn tiberhaupt,
doch zum mindesten nicht michtig genug auf das Herz wirke
um das betriichtliche Abfallen des Druckes zu erkliren, wel-

mgyerre 8

ee Se

ALLEINIGE WIRKUNG AUF DIE BLUTGEFASSE. 169

ches seine Einathmung vor der Aortencompression herbeifiihrt.
Ueberlegt man nun, dass es Fiille giebt, in welchben der Druck
gar nicht absinkt nachdem er durch die Verschliessung der
Aorta emporgetrieben wurde, und bedenkt man ferner, dass
die schwiichern Druckabfille, welche wihrend des Aorten-
schlusses eintraten, ihre geniigende Erklirung durch die Er-
weiterung der Schliisselbein- und Kopfarterienzweige finden ;
erwiigt man endlich, dass die Zahl der Herzschlige durch das
Einblasen des giftigen Dampfes keine Veranderung erfahrt, so
diirfte man zu der Ueberzeugung gelangen, dass das salpetrig-
saure Amyloxyd auf das Herz tiberhaupt keine unmittelbare
Wirkung iibi.

Ein Symptom, welches eine besondere Erklirung bediirfte,
sind die Kriimpfe der Skeletmuskeln, welche ausnahmslos beim
Kaninchen eintreten, das nicht mit Curare vergiftet und dessen
Niickenmark nicht durchschnitten ist. Ich habe es einstweilen
unterlassen, nach einer Erkliirung fiir dieselben zu suchen, da
ich ihren Eintritt niemals bei den Menschen beobachtet habe,
welche salpetrigsauren Amyloxyd einathmeten.

Schliesslich lasse ich noch die Zahlen folgen aus denen
die Figuren der vorstehenden Abhandlung construirt sind.—
Ich bitte bei der Durchsicht die Pulszahlen zu beachten.

Datum des | 7:4 in Einathmen — airs op
Versuchs ; von ruc in der
und No. der sot tongs salpetrigs. |inMm.| Zeit- Femerkungrs:
Beobachtung.| ©°"* | Amyloxyd. | Hg. einheit.
Juli 9, 1869. Zu Fig. 101.
1. 0 begonnen 104°5 9
10 57 9 Krimpfe.
22 aufgehért 65
59 90
87 108
2. 0 begonnen 83 9
19 aufgehért 52 9 Kriimpfe.
33 102
36 92
3. 3 141 11,5
6 157 11,5 Mit Curare vergiftet
12 | angefangen | 139 11,5
19 29

170

WIRKUNG DES SALPETRIG-SAUREN AMYLOXYDS.

Datum des | 7,;, ;,| Einathmen Blut- | Puls-Zahl
Versuchs stauteg von druck | in der
: Secun- . : Bemerkungen.
und No. der en salpetrigs. |in Mm Zeit- © |
Beobachtung. * | Amyloxyd. | Hg. einheit.
Juli 9. Zu Fig. 101.
30 112
At 106
59 108 .
72 88
77 101
151 85
159 126 11,0
165 101
4. 75 12?
1 | angefangen 38
aufgehort 67
3 | angefangen 78
6 67
14 62
21 aufgehért 64
36 64
Juli 24, Zu Fig. 102.
1. 0 | angefangen 72 10
8 aufgehért 41 Krampfe.
17 38 1l
30 68
108 68
2. 0 | angefangen 18 9 Rechte Hialfte des
20 aufgehort 11 5 Riickenmark
25 8,5 4 durchschnitten.
53 8 4
114 11 8
3. 0 | angefangen 9 9
4 aufgehoit 3,5 6
20 4 4
46 6 8
spiter 9 9
Juli 23. Zu Fig, 103.
2 0 | angefangen 81 9u. 11
14 aufgehort 56 11
87 70
2. 0 | angefangen 43 8 Riickenmark am
6 43 8 occiput durel-
25 aufgehért 32 8 u. 7,5 schnitten.
33 30 8
64 42

VERSUCHSPROTOKOLL.

171

Datum des | 7,.,;| Einathmen | Blut- | Puls-Zahl
Zeit in .
Versuchs “pelag von druck in der B is
und No. der | “Gon salpetrigs. |in Mm| = Zeit- cata ce
Beobaclitung " | Amyloxyd. | Hg. einheit.
Juli 23. Zu Fig. 103.
3. 0 | angefangen 42
7 34
20 aufgehidrt 32
112 36
4. 0 | angefangen 38
42 29
87 aufgehirt 31
5. 0 32
E fing an 27
123 32
Juli 31 Zu Fig. 104.
i. 95
7 | angefangen 65
12 aufgehért 95
36 Riickenmarkdurch-
schnitt. zwischen
atias u. occiput.
2. 0 | angefangen 95 6,5 Aorta comprimirt.
8 aufgehért 95 6
16 90
33 97 G
100 40 8 Aorta losgelassen.
3. 36
angefangen 86 5,5 Aorta comprimirt.
12 92 5
31 97 5
50 22> G Aorta losgelassen.
4, 0 38 6
28 | angeiangen | 105 7 Aorta comprimirt.
42 aufgehért 107 7
70 | angefangen | 112 6
84, aufgehirt 114
92 116
106 47 Aorta losgelassen.
134, 44
Aug. 9. Zu Fig. 105.
i O | angefangen $7
8 aufgehirt 65 Kriimpfe.
14 52
56 85 ,
2. O | angefangen 32 6 Riickenmark durch-
i aufgehort 30 6 schnitten,

172

WIRKUNG DES SALPETRIG-SAUREN AMYLOXYDS.

Datum des | 7,.,;,| Einathmen | Blut- | Puls-Zahl
Versuchs chia von druck | in der
S Secun- ; . . Bemerkungen
und No. der jan salpetrigs. |in Mm Zeit- Sens
Beobachtung. |. * | Amyloxyd. | Hg. einheit.
Aug. 9. Zu Fig. 105.
36 24
70 24 6
76 26 6
3 25
98 24,
3. 0 13
17 | angefangen 55 Aorta comprimirt.
24 58
27 aufgehort, 45
33 41
47 40
53 7 Aorta losgelassen.
67 3
4, 14 | 65u7
11 | angefangen 47 6, 5 Aorta comprimirt.
16 49 6
23 aufgehort 38 6
28 37 8
33 14 7 Aorta losgelassen.
5. 13 6
12 | angefangen 23 6 Aorta comprimirt.
22 aufgehort 26 5, 5
33 26 5, 5
47 17 7 Aorta losgelassen.
6. 19 5
12 | angefangen 41 6 Aorta comprimirt.
19 aufgehort 4.4 6
26 45
32 23 6 Aorta losgelassen.
50 16 6, 5
Aug. 12 Zu Fig. 106,
a; 0 | angefangen 97
5 aufgehirt 76 Krimpfe.
47 126
110 119
2. 20 8 Riickenmark durch.
schnitten.
25 | angefangen 92 7 Aorta comprimirt.
31 95 8
33 aufgehért 80 6,5
38 75 8
61 78 7,5
72 20

Aorta losgelassen,

VERSUCHSPROTOKOLL.
Datum des | 7... ;,,| Einathmen | Blut- | Puls-Zahl
Versuchs ipa yon druck | in der
Secun- : ; ; Bemerkungen
und No. der dau salpetrigs. |in Mm.| Zeit- ey
Beobachtung. Amyloxyd. | Hg. einheit.
Aug. 12. Zu Fig. 105.
3. 24, Z
14 | angefangen | 107 7 Aorta comprimirt..
21 113 7
22 aufgehért 105 6, 5
25 96 7
84 | angefangen | 118 7
86 114 vt
98 aufgehort 99 Z
103 94 8
115 1138 7
127 26 7 Aorta losgelassen
140 24 7
4, 23 8
O | angefangen | 110 7 Aorta comprimirt..
6 110 7
8 aufgehért 92 7
18 82 7
34 108
67 108 7
70 33 Y Aorta losgelassen..
77 20 rs
137 17 7
5. 18
5 | angefangen | 106 Aorta comprimirt..
10 108
15 aufgehért. 92
24 85
82 104
84 27 Aorta losgelassen.
93 2 ie

ON THE ACTION OF NITRITE OF AMYL ON
THE CIRCULATION [AND ON ACTIVE DI-
LATATION AND CONTRACTION OF ARTE-
RIOLES INDEPENDENTLY OF NERVE-
CENTRES}.*

(From the Journal of Anatomy and Physiology, vol. v, 1871, pp. 92 to 101.)

THE property of causing flushing of the face and throbbing
of the carotids, which nitrite of amyl possesses, was first
observed by Guthrie in 1859, but no further notice of it was
taken till Dr. Richardson, in 1866, again drew attention to it.
His experiments led him to conclude that it paralysed the
nerves from the periphery to the centre, lessened the con-
tractility of the muscles, and dilated the capillaries in the
web of the frog. They were shortly afterwards repeated by
Drs. Gamgee and Rutherford, who, however, found no action on
the nerves, either sensory or motor, and rarely any on the
capillaries of the frog. In some other experiments, also un-
published, but whose results they have kindly communicated to
me, they found that the sphygmographic tracing of the radial
pulse underwent a remarkable change, the waves becoiing
much more frequent, and their ascent, but especially descent,
much more rapid; and the pulse-rate and pressure in a mano-

* The chief research on which I was engaged in Professor Ludwig’s labora-
tory during the summer of 1869 and winter of 1869-70 was that relating to the
local dilatation and contraction of arterioles independently of nerve-centres.
This was the research which Professor Ludwig had suggested and on which he
worked with me, while that on nitrite of amyl was only carried on at those
times when Professor Ludwig was engaged with other students. As time did
not allow me to finish the research on the arterioles, that on nitrite of amyl
was published and, only a brief abstract given of the results obtained during
the research on the arterioles, both Professor Ludwig and I hoping that cir-
cumstances might allow me to return to his laboratory and finish it. This was

unfortunately not the case, and he continued to work at the subject with Hafiz,
Lépine, A. Mosso, Von Frey, and Gaskell,

METHOD OF EXPERIMENTATION, 175

meter connected with the carotid of a rabbit falling, when the
vapour of the nitrite was inhaled. Previous division of the
depressor nerves did not affect the result.

The diminished blood-pressure which it produces, led me to
apply it in angina pectoris, and the goud results I obtained
made me anxious to investigate more closely the nature of its
action. An excellent opportunity for doing so was afforded me
by the kindness of Professor Ludwig, in whose laboratory at
Leipzig the experiments, the result of which I am about to
give, were carried on. With the exception of one or two on
dogs, they were made upon rabbits ; and instead of allowing the
animals simply to inhale the vapour, artificial respiration was
employed, the apparatus being so arranged that the air could be
either sent direct from the bellows, through a tube in the
trachea, to the lungs, or passed through a vessel containing the
vapour of the nitrite. The advantages of this arrangement
were that the bellows being worked by an engine with great
regularity, the disturbing influences of unequal respiration on
the blood-pressure were to a great extent avoided. One of the
chief of these is that any strongly smelling vapour, and nitrite
of amyl among others, acting on the nose of rabbits, causes
suspension of the respiration for a short time; and the alteration
in the condition of the blood thus produced causes irritation of
the vagus and slowing of the heart’s action; such as Drs.
Rutherford and Gamgee found accompanying the sinking of the
blood-pressure in rabbits.

When air charged with the vapour was passed directly into
the trachea of a rabbit the blood-pressure almost immediately
sank very much, but the pulse-rate remained nearly unchanged.
As the pressure sank general convulsions took plaée and the
pressure immediately rose, notwithstanding the continued
inhalation of the vapour, the pulse curves becoming at the same
time indistinct, so that the rate could not be well ascertained.

When the vapour was discontinued after twenty seconds
the pressure rose still more quickly, and in a minute at most
attained its normal height, as is seen in Fig. 107, where the
distance along the abscissa indicates the time, and the ordinate
the pressure in millimetres of mercury. This shows that very

176 ACTION OF NITRITE OF AMYL ON THE CIRCULATION, ETC.

small quantities of the drug produce a great effect, and that its.
action speedily passes off, the vapour being either excreted or
destroyed in the body.

In crder tv avoid the disturbance occasioned by the convul-
sions, the animals were then poisoned by curare and the vapour
administered. The pressure, as before, sank immediately and
did not return to the normal amount so long as the inhalation
was continued. It did not, however, sink constantly, and then
remain at a definite minimum, but oscillated up and down, just
as Traube observed it in curarised animals, and as is shown in
the last two curves of Fig. 107.

It is possible that the convulsions which occur readily in
rabbits, but which I have only once, and that to a very slight
extent, seen in man, are suffocative, like those produced by CO,
for Dr. Gamgee has shown that nitrites acting on the blood
prevent hemoglobin from giving up its O. This is the more
probable as the respiration is first affected, and if a drop of
nitrite of amyl be mixed with water and the vapour thus
diluted be administered, the hmbs remain quiet, but the animal
begins to make. respiratory movements independently of the
bellows, and when the vapour is less diluted these become more
and more marked till general convulsions take place.

The diminished blood-pressure might be due either to a
lessened power of the heart, or a dilatation of the arteries and
a consequently diminished resistance. That the latter is the
true cause is rendered probable by the flushing which the
vapour causes, both in the human face and the rabbit’s ear, and
is shown by what might at first seem an anomalous action in
some dogs. When the pulse in dogs is slow, the inhalation of
amyl produces comparatively little effect on the blood-pressure ;
and it might be thought that its action was different in them
from rabbits, but the reason is that the pulse, which in rabbits
is naturally rapid, and remains unchanged by the vapour,
becomes in these dogs remarkably quick, almost as much so as
in rabbits. If the vagi be first divided, so that the pulse in the
dog becomes quick like that of the rabbit, and the nitrite be
then inhaled, the pressure falls just as in rabbits. In order to
confirm this view, and at the same time to decide the question,

ACTION ON RABBITS. 177

Fic. 107.
Pressure in mm. Hg.
\
‘
a
5 Cc
i
|
'
;
\
a ;
x
4
4 t a ae Cee Y 1 1
ar ee ee ae
Not poisoned. Poisoned with curare. Seconds.

x Inhalation stopped.

whether the dilatation of the vessels was due to a direct action
of the substance upon them or to a diminution in the tone which
N

*

178 ACTION OF NITRITE OF AMYL ON THE CIRCULATION, ETC,

the vaso-motor nerves derive from the medulla oblongata, another
series of experiments was undertaken. This question was the
more interesting from its connection with another research
which I began under Professor Ludwig’s direction, but unfortu-
nately have not yet finished. Professor Ludwig observed, and
directed my attention to the fact, that the alterations in the
lumen of arteries noticed by Schiff in the rabbit’s ear, may be
seen also in all exposed arterial twigs in the skin and connective
tissue They varyin amount and rapidity in different animals,
and in the same animal at different times. They are sometimes
absent, but in such cases may be generally produced by poison-
ing with curare, or by suspending the respiration; and when
once aroused, they continue some time, although the respiration
be afterwards most carefully performed.

That these alterations are, at least in part, completely inde-
pendent of the vaso-motor nerves in the brain is shown by their
occurrence in the ear and other parts, after all the nerves,
sympathetic and cerebrospinal, going to the part have been
divided, and after division of the cord in the neck notwithstand-
ing the low pressure which then remains.

The form of the variation shows that they do not depend on
varying blood-pressure in the large arteries; for sometimes a
contraction suddenly appears between two parts of the artery
filled with blood, and in one case in the rabbit’s ear I noticed
such a contraction take place in a small artery at the point
where it branched off from a larger one, and proceed peristaltically
dowuwards.

The lightest touch on an artery after division of the nerves
causes a movement generally limited to the part, and consisting
not in a contraction, but in dilatation, which remains for some
time, and gradually disappears. As Gunning and Cohnheim
have made similar observations on the tongue and web of the
frog, and some facts in Sadler’s research (Ludwig's Arbeien,
Ater Jahre.) can only be explained by an independent motion of
the vascular walls, it seems to be a widely extended and there-
fore important phenomenon. If the nitrite acts through the
vaso-motor centres in the brain, it should have no effect if these
be separated from the vessels by dividing the cord in the neck,

INDEPENDENT MOVEMENTS OF ARTERIES. 179

but if its action be exerted directly on the vessels, the division
of the cord will not prevent it, and that it in fact does not do so,
will be seen from figs.108 and 109. The blood-pressure, which

=——

in

@1e. 108,
x Inhalation stopped,

Spinal cord destroyed at the axis,

Uninjured.

180 ACTION OF NITRITE OF AMYL ON THE CIRCULATION, ETC.

had sunk very low after division of the cord, sank yet farther
when the nitrite was inhaled. Although the sinking was not
absolutely great, it was so relatively to the very low pressure
already existing, and was analogous to that observed on the

<
ee

section of a second splanchnic nerve after division of the first.
The other experiments, to prove that the diminished blood-
pressure after inhalation is due to dilatation of the vessels, and
not to a weakened heart, consisted in compressing the aorta
below the diaphragm and then administering the nitrite. If

Fre. 109.
x Inhalation stopped.

Spinal cord cut at the occiput.

Uninjured.

———

EFFECT OF DIVISION OF THE SPINAL CORD. 181

the diminution in pressure was due to a weakened heart, the
inhalation of the nitrite should at once cause a diminution in
the pressure to which the blood had attained after compression
of the aorta. As only the circulation in the lower part of the
hody was in this way cut off, we cannot expect that no sinking
should take place, but only that it should be less than the
normal. In order to diminish the error from this source, tliese

Fie. 110.

At

|

—Inhalation begun. x Inhalation stopped ; at the beginning of the last
three observations the aorta was compressed. o Aorta opened.

182 ACTION OF NITRITE OF AMYL ON THE CIRCULATION, ETC.

experiments were made after previous division of the cord in
the neck so that the vessels should become relaxed, and the
difference produced in their calibre by the vapour being thus less.
The results obtained were, as shown in figs. 110, 111 and 112

Fie. 111.

A

eae x 0

¢

Cord cut in the neck.
In the last four observations the aorta was compressed ; at o the aorta was
opened. — Inhalation begun. + Inhalation stopped.

that sometimes a rise took place during the inhalation, but
generally a sinking, much less, however, than in the normal
condition.

We may therefore conclude that the diminution in the blood-
pressure is not due to weakening of the heart’s action, but to a

c
EFFECT OF COMPRESSION OF THE AORTA. . 188

dilatation of the vessels, and that this depends on the action of
the nitrite on the walls of the vessels themselves. Whether

+ Inhalation stopped.

reas aM
—

oe

In the last three observations the spinal cord

— Inhalation begun.

Fra. 112.

was divided, and the aorta compressed; at o the aorta was opened.

The ordinates indicating the pressure begin 50 mm. above the abscissa.

this is due to its action on the muscular walls themselves, or the
nerve-ends in them, cannot at present be with certainty said ;

e
184 ACTION OF NITRITE OF AMYL ON THE CIRCULATION.

and further experiments must be made to determine whether
the walls of the arteries are the only structures consisting of
unstriped muscle which are affected by it.

The further dilatation which takes place after the usual tone
of the vessels has been destroyed by division of the cord, seems
to indicate that it is of an active nature analogous to that in the
vessels of the penis after irritation of its nerves; and this would
point rather to an affection of the nerves than of the muscular
fibres. In conclusion, I desire to express my warmest thanks
to Professor Ludwig for the great kindness he has shown
me, and for his invaluable advice and assistance in this investi-
catlOes

NITRITE OF AMYL IN ANGINA PECTORIS.

(Reprinted from the Clinical Society’s Reports, vol. iii, 1870.)

Wittiam H—, et. 26; formerly a blacksmith, now a toll-
keeper, admitted to Ward I, Royal Infirmary, Edinburgh,
December 7th, 1866.

Antecedent History.— Patient was strong and healthy till his
tenth year, when he was confined to bed for six months by a
severe attack of rheumatism. During the next twelve years he
had four other less severe attacks, and after recovering from the
last of these his feet began to swell during the day.

In April, 1866, he had a seventh attack, which lasted for a
month, and six weeks after it was over he noticed an unusual
palpitation of his heart, for which he entered the infirmary, and
remained there three weeks, but left unrelieved. The palpita-
tion gradually increased till he felt it along the line of the
carotids as high up as the ears ; and in November last he began
to feel besides a dull heavy pain about the left nipple. At first
this came on every three days, usually during the night, and
lasted half an hour. During the day he felt little inconvenience
from the palpitation unless he exerted himself.

On admission, the pain was no longer confined to the region
of the left nipple, but was worst along the right border of the
sternum, and extended up to the right arm. This pain was
more severe if he walked about much, otherwise he felt well.
Professor Maclagan had charge of the clinical wards at this
time, and the patient was treated for six weeks with tincture of
aconite, and then with tincture of digitalis; but under these
remedies the pulse became intermittent, and the pain was not
relieved by either, and rather aggravated by digitalis. They
were therefore discontinued, the digitalis being stopped on
January 31st. During their employment wet cupping over the
cardiac region to the extent of 3iv temporarily relieved the
pal,

186 NITRITE OF AMYL IN ANGINA PECTORIS.

February 1st, Professor Maclagan’s term of office having
expired, Professor Bennett took charge of the clinical wards.

On February 6th the patient began to complain of pain in
the back, neck, head, thighs, and elbow-joints ; he had no appe-
tite, was perspiring profusely, and his pulse was 116, full and
strong. Next day the pain was most severe in the shoulders,
back, hip, and knee-joints. 3

On the 8th he was examined by Professor Bennett and the
clinical class, and the following was found to be the condition —
of his circulatory system :—Apex beat 24 inches below and
24 inches to the outside of the left nipple. On palpation, pul-
sation is felt over the whole left front and side of thorax, most
strongly between the fourth and sixth ribs, and faintly 07 over the
supra-clavicular region.

Cardiac dulness commences at the middle line of the sternum
and extends laterally outwards for 5 inches.

A loud, double, blowing sound is heard over the whole of the
cardiac region, but is loudest at the base. Over the right
sterno-clavicular articulation a single blowing is heard. Pulse
104, strong and jerking. The respiratory system was normal,
the skin covered with an acid sweat, the tongue furred, no
appetite, urine high-coloured and slightly albuminous. The
pain in the joints continued aleng with pain in the neck in the
line of the -carotids, but the pain in the cardiac region was
absent.

On the 11th the pulse fell to 80, and the pain in the joints
diminished, but the patient was still troubled by pain in the
left ear, and along the line of the carotids, with violent pulsation
in them at night.

On the 18th the rheumatic pains in the joints and shoulders
had entirely disappeared, but the pain in the cardiac region came
on during the night.

On the 19th four ounces of blood were taken from the arm,
with immediate relief from the pain and violent pulsation, and
the pain over the heart, which usually came on at 3 a.m., was
much less on the ensuing night.

25th.—Patient’s appetite remains unimpaired by the pain,
and he takes all his food, consisting of steak diet, beef tea,

sae eae

RELIEF BY BLOOD-LETTING. 187

potatoes, and bread. Pil. Colocynth. c. Hyoscy. every other
night. Ordered Tinct. Lobelize, 20 drops three times a day.

27th——The pain continued to come on during the night.
Siv of blood were taken from the arm at 10 p.m. An hour after
patient went to sleep, had a good night, and the pain did not
come on.

March 3rd.—Pain felt at 11 p.m. in breast and ears. A
poultice applied over the breast gave scme relief.

6th.—Pain severe at 3 a.m., lasting for about one hour. At
9 a.m. 5iij of blood were taken from the arm. At 10 a.m. pulse
76, not so forcible as yesterday.

7th—No pain during the night.

Sth —Pain came on as usual during the night. Tinct.
Lobelise to be stopped.

9th.—3j of brandy to be taken when the pain comes on.

10th.—The pain came on in the night and was not relieved
by the brandy.

12th.—The pain came on as usual at 3am. <A few drops of
nitrite of amyl were put on a towel and inhaled by the patient.
The primary effect noticed was a suffusion of the face, and the
patient felt a glow over his face and chest. The pain dis-
appeared almost simultaneously with the occurrence of these
phenomena, but returned in three minutes. He then inhaled
5 drops more; the pain again disappeared and did not return.

16th.—The pain has recurred each night and been relieved
by the inhalation of 10 drops of nitrite of amyl. Last night it
came on about 10°30 p.m., the same in position and character
as before. On the patient’s taking 10 drops of nitrite of amyl
in 38s of brandy, the pain went away, but returned in three
minutes ; 5 drops were then inhaled from a towel, and the pain
disappeared. He went to sleep in an hour and slept till 3 a.m.,
when he was awakened by a return of the pain. He drank
10 drops in a little brandy, but, no effect following, he inhaled
afew drops. The pain disappeared and did not return.

17th.—Pain came on at 1 a.m.; 10 drops were given inter-
nally. The pain was relieved, but returned in a few minutes ;
10 drops were then inhaled. The pain disappeared and did
not return.

188 NITRITE OF AMYL IN ANGINA PECTORIS.

Dr. Bennett, thinking the relief of pain by the amyl might
be due to anesthesia, ordered chloroform to be tried during the
attack.

18th— About 2 a.m. the pain came on as usual, and chloro-
form was inhaled by the patient. He was only partly put
under it, and as soon as he again became completely conscious
the pain was found to be present as before ; 6 drops of nitrite
of amyl were then given by inhalation. The pain disappeared
and did not return. .

25th:—The pain came on at 1.58 a.m., but was not very bad.
While it was present the pulse was 100, respirations 32. After
amyl was given, but the pain was not quite gone, the pulse was
130, it fell with the disappearance of the pain to 100, and twelve
minutes after was 80, and the respirations 24.

April 6th—The pain had come on about 2.35 a.m., and the
patient was relieved by a whiff of amyl, but it began to return
at the end of the sternum, right eur, and right shoulder. The
chest was auscultated, but no abnormal sounds could be
detected to indicate any coincident spasm of the bronchial
tubes.

10th.—Patient continues to have the pain every night, and
instead of inhaling the nitrite of amyl from a cloth, does so
from the bottle. Two or three inhalations usually suffice to
relieve the pain. Up to the 8th he used pure nitrite made by
Dr, Gamgee, but this being finished, he then began to use some
made by Macfarlane & Co., but the smell of it was not so agree-
able, and it sometimes occasioned headache, which the pure
amyl never did.

14th.—The pain has been coming on several times during
the night, is most intense at a spot two inches inside of the
right nipple, remains there after it has gone from the rest of the
chest, and is only removed by repeated inhalation. Last night
it came on three times, and was rclieved by amyl each time, but
five or six inhalations were required. To-day at 11 a.m. 3iv of
blood were taken from the patient’s arm, and he was ordered
Potass. Iod. gr. viij, three times a day.

17th—Pain came on during the night and continued unin-
terruptedly for one hour and a half. By Dr. Bennett’s order

DESCRIPTION OF SPHYGMOGRAPHIC TRACINGS. 189

no amyl was taken, in order to determine whether the relief of
the pain was due to it or to some change in the symptoms inde-
pendent of it. Three dry cups were applied over the cardiac
region. They did not relieve the pain.

18th.—No pain during the night. No amyl taken.

19th.—Very little pain, lasting half an hour. Took no
amyl.

May 9th.—Has had the spasmodic pain every night. Last
night it came on five times at intervals of about an hour, and
was in each case relieved by inhalation.

15th.—Pain has been rather less during the past two nights.
Attention was called to-day to purpuric spots upon both legs,
which the patient had noticed some days previously. The gums
were neither swollen nor tender. His diet for some time past
has been beef-steak and potatoes, with porridge and milk for
breakfast. The use of iodide of potassium to be suspended.

17th.—Pain came on severely in the chest a little after
midnight. It was worst 2 inches inside of the right nipple.

Tracing 1 (fig. 117)—Oh. 22’a.m. Pulse 104 small, resp. 36.
There is a thrill to be heard and
felt with the second sound at the
apex.

22’ 40” 13 drops inhaled from a cloth.
Tracing 2 (fig. 118).—Oh. 24’ 0” The lever of the sphygmo-
graph has risen very much. The
pain has gone, except at a point
2 inches inside of right nipple.
25’ 30” 5 drops more given; pulse 112.
Oh. 28’ 0” Pain almost gone; patient now
inhaled from the bottle; pulse
100.

Tracing 3 (fig. 119).—Oh. 34’ 0” Pain has been gone for
4 minutes, but at 37’ it began to
return inside the right nipple, and
a little more was inhaled.

Oh. 40’ 0” Pain quite gone; pulse 92; resp.
28.
4 (fig. 120)—Oh. 47’ 0” Pain did not return.

—

Tracin:

g

190 NITRITE OF AMYL IN ANGINA PECTORIS.

In these tracings, like the others, the patient’s position was
unchanged, and neither the band nor pressure screw of sphyg-
mograph was touched.

18th.—Pain came three times last night, and was very severe.
He has had it during the day three times. The purpurie spots
on the legs are much paler. To recommence iodide of
potassium.

21st.—The purpuric spots have reappeared on both legs. To
stop the Pot. lod. He had pain last night, but none during the
day.

24th—Bled to 3iv on account of general uneasiness and
powerful pulsations of the heart. The bleeding was immediately
followed by a sense of relief.

28th.—The pain has only been absent one night since the
bleeding, but it has been much less severe than before it. The
sphygmograph was fixed to his arm to-night in order to take a
normal tracing for comparison with one to be taken during the
attack. This had scarcely been done when the pain unex-
pectedly came on. The tracing (fig. 121, p. 195), though
unfortunately very imperfect, shows the diminished volume and
increased tension of the pulse. In 2 (fig. 122) the pain was
severe, and 3 (fig. 123) was taken after inhalation of amyl.

June 1st.—Condition remains the same, spasmodic pain in
the cardiac region occurring every night, but not severe, and
easily relieved by a few inhalations of nitrite of amyl. Patient
wished to resume his former occupation of toll-keeper, and was
to-day discharged at his own request. Recommended to have
occasional small bleedings.

Remarks.—In this case of Dr. Bennett’s, which by his kind
permission I now publish, we have a history of numerous
attacks of rheumatic fever, followed by cardiac lesion, which
was accompanied by palpitation of the heart, throbbing in the
carotids extending as high as the ears, and a spasmodic pain in
the chest. This pain was sometimes most severe near the left
nipple, and sometimes at the right border of the sternum, but
extended over the whole cardiac region, and shot up to the right
ear and down the right arm. It used to come on suddenly

Ds 2]

aT Ce Fe

a pr" IN

PATHOLOGY OF ANGINA PECTORIS. 191

during the night, generally between midnight and 3 a.m., was
accompanied by little or no feeling of dyspnoea, and was some-
what relieved by the patient’s sitting up. It generally came on
every third night at first, but latterly every night, and was
worse when the patient had used much exertion during the day.
It was not relieved by tincture of aconite, tincture of lobelia
inflata, brandy, or dry cupping over the cardiac region. It was
made worse rather than better by tincture of digitalis. It was
temporarily relieved by chloroform, but whenever the stupefy-
ing effect passed off the pain was as bad as before. It was
somewhat relieved by warm poultices to the chest, and was
generally absent for one night after a small bleeding, either
from the arm or by cupping the chest. Under the use of iodide
of potassium the attacks became less frequent, but purpuric
spots appeared on the limbs, and each attack was at once re-
lieved by the inhalation of nitrite of amyl. During an attack
of rheumatic fever it disappeared completely, again returning
with the departure of the rheumatic pains.

Angina pectoris is defined by Dr. Walshe as a paroxysmal
neurosis, in which the heart is essentially concerned, and he
divides it into pseudo and true angina, which differ mainly in
the intensity of the symptoms. Friedreich and others divide it
into functional and organic, according as it is accompanied by
cardiac lesion or not. From the absence of a sense of impend-
ing death, the present case might be reckoned as one of pseudo-
angina, but in the intensity of the pain and the manner of its
radiation it more closely resembles true angina. As a cardiac
lesion was present, it belongs to the class organic angina.

- Various opinions have been advanced as to the pathology of
this disease, some saying it is a mere brachio-thoracic neuralgia,
but most holding that it is a neuralgic affection of the cardiac
plexus. Some are of opinion that it is associated with cramp
of the heart, others with weakness of that organ.

Hichwald* thinks that there is not only weakness of the
heart, but a mechanical impediment to its action, produced by
irritation of its regulating nerves, and that the pain is caused

* Wiirzburg. med. Zeitschr., vol. iv, 249; Chit. f. med. Wiss., vol. i, 877.

192 NITRITE OF AMYL IN ANGINA PECTORIS.

by unavailing efforts to overcome this obstacle. Nothnagel*
states that during angina there is pallor and coldness of the
extremities, small pulse, and other symptoms of a cramp-like
contraction of the systemic arteries, and that the spasm is
relieved by remedies which cause their relaxation, such as warm
baths and friction.

It is quite possible that the pathology of all cases classed
under angina pectoris is not the same, and that the differences
of opinion are not due merely to the want of exact methods of
observation. What the nature of the attack was in the present
case may be learned to some extent from an examination of the
sphygmographic tracings, which were begun by direction of Dr.
Maclagan, and continued during the time the case was in the
wards under the care of Dr. Bennett. In taking these tracings,
the instrument, which was one of Marey’s, without any means
of estimating the pressure employed, was applied to the arm
above the end of the radius, as it was found to cause pain when
applied over the bone for any length of time. The amplitude
of the curve thus obtained is greater, and it did not occur to me,
) till after studying the physiology of the circulation under Pro-
fessor Ludwig, that in such cases as the present, where sudden
changes occur in the vessels, I was increasing the fallacy which
the variation in the height of the lever from turgescence of the
tissues produces, and which may be confounded with a rise
from increased tension in the vessels. Except where marked
otherwise, the tracings were all taken with the patient in a
- recumbent position, and ueither the cord by which the instru-
ment was attached to the arm, nor the screw regulating the
pressure, was touched during the observation.

The case excited considerable interest, and was carefully ob-
served and commented on by Professor Bennett to the clinical
class, and the cardiac lesion was diagnosed by him from the
physical signs to be aortic obstruction and regurgitation, with
dilatation of the aorta, but no sacculated aneurism.

The tracings confirm this diagnosis, showing in a typical
manner the abrupt ascent, terminating in a hook, of each wave,
characteristic of the unfilled arteries, which aortic regurgitation

* Deut. Arch. f. klin. Med., vol. iii, 309; Colt. med. Wiss., vol. vy, 715.

EXPLANATION OF SIITYGMOGRAPHIC TRACINGS, 193

produces, and the long and rounded apex. of aortic obstruction.
There is, however, a marked difference between the tracings
from the two radials, the ascent of the wave being more abrupt,
the top flatter, and the descent distinctly dichrotic in’ the right,
while in the left the ascent is less abrupt, as shown by the
smaller hook at the top; the maximum height is not attained
til] near the end of the systole, and there is generally little or
no dichrotism in the descent. This might be due to aneurisin ;
but there were no physical signs to show its presence, and in
the absence of a post-mortem examination, or experiment with a
schema, hypotheses as to the cause of difference are of little
value.

The tracings taken during an attack were chiefly from the
right radial. The only one I got while the pain was actually
coming on is unfortunately an imperfect one (No. 1, May 28th,
Fig. 121). From this tracing, and from those taken when the
pain was becoming worse (Nos. 1 and 2 of May 17th, Figs. 117
and 118), it will be seen that as the pain increased the curve
became lower, beth the ascent and descent more gradual, and
the dichrotism disappeared. This form of curve clearly indicates,
that the arterial tension is much increased, and this increase can,
I think, be due only to contraction of the small systemic vessels,
so sudden and so great as well to deserve the name of spasmodic.
As I have stated in a former paper,” this increased tension led me
to suggest nitrite of amyl to relieve the spasm.f The rapidity
with which this increase in tension takes place is shown by the
great change which the form of the pulse has undergone in
Tracing 1, May 28th, during the short time occupied in re-ink-
ing the pen. It would seem from Tracings 3 and 4 (Figs. 115
and 116) of the plate that the tension in the right radial was
raised more than in the left, and farther experiments with
simultaneous tracings are necessary to decide whether the spasm
extends to all systemic vessels or to all alike.

At the same time that the tension increases the pulse be-
comes somewhat quicker, which shows that there is some dis-

* Lancet, July 27th, 1867, cf. dntea, p. 137.
+ Dr. Bennett, on being informed of the successful result of tue first experi-
ment, ordered the inhalation to be continued.

0

194 NILRITE OF AMYL IN ANGINA PECTORIS.

turbance of the regulating apparatus of the heart, as normally
the increased tension acting on the roots of the vagus should
slow the pulse. It has been suggested to me (by Professor
Ludwig) that the pain in the heart may be due to irritation of
its sensory nerves by the great pressure of the blood, and
that in the right arm and neck may be due to the same
cause acting on the arteries, those of the right side being pos-
sibly contracted more than the left. Whenever the tension was
lowered by nitrite of amyl the pain disappeared from the
greater part of the cardiac region, the neck and the arm, but
sometimes remained persistent at a point about 2 inches to the
inside of the right nipple. This I think indicates that the tension
in the right ventricle was not yet relieved, and the small volume
of the pulse (see Tracing 3, May 17th, Fig. 119) seems to show
that the amount of blood passing through the small pulmonary
vessels at each systole was small, probably from contraction of
their lumen. So long as this condition remained the pain was
almost certain to return. It is possible that the right ventricle
might not be able to empty itself completely at each systole,
was therefore quickly refilled, and consequently contracted
frequently, forcing the left ventricle to contract with it, and
producing the rapid pulse with small volume seen in Tracing 3
of May 17th, Fig. 119. The influence of the small vessels of
the lungs over the circulation, though in all probability of
extreme importance, is a subject of which we know as yet
almost nothing.

The question whether the contractile power of either ven-
tricle is lessened during the attack is one which cannot be
decided with certainty from the present tracings. Digitalis
which has been recommended on the supposition that the
heart is weak during the attack, proved productive in this case
of more harm than good, contracting, as it does, the small
vessels. :

We may, I think, conclude that (1) the attack in the present
case consisted in a spasmodic contraction of some, if not all, of
the small systemic, and probably of the pulmonary vessels,
causing great increase in the blood-pressure in both sides of the
heart, such as is found in animals after division of the vagi;

TRACINGS OF THE PULSE.
In ANGINA PECTORIS.

RY Nyy

NORMAL PULSE.

Right radial.

Fie. 112.

Left radial.

Fie, 114,

DuRING ANGINA.

Right radial.

Fie. 115,

Left radial.

Fie. 116.

May 17th.

. Pain severe.

Fie. 117.

. Pain gone, except

near the nipple.
Fie. 118.

. Pain quite gone, but

afterwards returned.
Fie. 119,

. Pain gone, and did

not return.
Fie, 129.

May 28th

. Pain coming on.

Fic, 121.

Pain severe.
Fig. 122.

. Pain relievec oy

Amyl.
Fie, 125,

HD

196 NITRITE OF AMYL IN ANGINA PECTORIS.

(2) that this was probably due to a derangement of the vaso-

motor system, and accompanied by a derangement of the cardiac

regulating apparatus, producing quickened instead cf slowed
pulsation; (3) that the pain was not primarily due to irritation _ ;
of the nerves composing the cardiac plexus, but produced by

the pressure of the blood on those of the heart and arteries ;

and (4) from the alternation of the attacks with rheumatic

pains in other parts of the body, that they were of rheumatic

origin.

EFFECT OF WARMTH IN PREVENTING
DEATH FROM CHLORAL.

(From the Journal of Anatomy and Physiology, vol. 8, May 1874, pp. 332 to 3 9 )

SINCE chloral was first brought into notice, and its action inves-
tigated by Liebreich, it has been made the subject of numercus
experiments, and has not only proved a most useful medicine
but a valuable aid to physiological research. During the stay
made in this country by Professor Stricker four years ago he
used chloral frequently as an anesthetic while making some
experiments with Dr. Burdon Sanderson on the circulation in
mammals. At his suggestion I made the following experi-
ments as well as many others which it is quite unneces-
sary to give at length, as they simply confirm the observations
of Liebreich and others. The general results were that the
subcutaneous injection of a solution of chloral induced sleep,
which was light and readily broken if the dose were small, but.
passed into coma if the dose were large. In dogs considerable
restlessness was observed before sleep came on. The power of
muscular co-ordination was affected in dogs before sopor was.
induced, so that they staggered and fell when attempting to.
walk either of their own accord or in obedience to a call. A.
similar loss of co-erdination was observed in rabbits, but in
general they and guinea-pigs sat quietly after the administra-.
tion of the chloral, and thus the motor affection was less percep-
tible in them than in dogs. In dogs the respiration occasion-
ally became very vapid immediately after the subcutaneous.
injection of chloral, but it became slow after the animal began
to exhibit symptoms of drowsiness. In rabbits and guinea-pigs
the number of respirations was also diminished, but a pre-
liminary acceleration was not observed in them. The pulse
was not affected to the same extent as the respiration, and the
heart always continued te beat after the respiratory move-

198 EFFECT OF WARMTH IN PREVENTING DEATH FROM CHLORAL.

ments had ceased. One of the most important phenomena,
and the one to which I wish to call particular attention at
present, is the diminution of temperature which chloral in-
duces, and the extraordinary effects of warmth in hastening
recovery from its action, and preventing death from an over-
dose. The fali of temperature has been noticed by Liebreich
and most other writers, but the effect of warmth applied to
the animal’s body has not, I think, received sufficient attention,
although Dr. Richardson has pointed out its usefulness in pre-
venting death. The diminution of animal heat is partly due
in all probability to greater loss from the surface caused by
the vessels of the skin becoming much dilated under the in-
fluence of the drug, and allowing the blood to be cooled more
readily by a low external temperature. It is partly due also
to the diminished production of heat which cessation of mus-
cular action always causes, whether it be induced by simply
tying down an animal so as to prevent motion, or by the
administration of curare or narcotics.

Professor Stricker having noticed that the animals on which
he experimented often required a second dose of chloral to
maintain anesthesia, when they were wrapped in cotton-wool
so as to prevent loss of heat, and still more when they were
laid in a warm place, I made the following experiments at. his
suggestion. They show clearly that an animal wrapped in
cotton-wool may recover perfectly from a dose of chloral which
is sufficient to kill it when exposed to the cooling action of the
air (which in the laboratory was about 20° C.), and that recovery
frem the narcotic action is much quicker when the temperature
is maintained in this way, and still more rapid when the animal
is placed in a warm bath. Ifthe temperature of the bath is
too high the animal may die from excessive heat, as I have
shown in a former paper.*

The bearing of these experiments on the treatment of
persons suffering from an overdose of chloral is so obvious as
hardly to require any observations from me. The patient
should be put to bed, and the temperature of the body main-

* “On the Effect of Temperature on the Mammalian Heart and on the Action
of the Vagus,”’ St. Bartholomew’s Hospital Reports, vol. 7, 1871 (vide p. 209).

a

PRACTICAL APPLICATION. 199

tained by warm blankets and hot-water bottles to various parts
of the body, and especially the cardiac region. Warmth over the
heart is an excellent stimulant to the circulation, which, like
the respiration, is enfeebled by chloral, the heart, according to
Rajewsky, being more or less paralysed by the drug. If respi-
ration threatens to fail it should be maintained artificially so
as to allow time for the chloral to be excreted and the normal
functions to be restored.

Expt. I. Into two guinea-pigs of nearly equal size 0°6 c.c.
of a 50 per cent. solution of chloral (equal to about 5 grains or
0°3 gramme of chloral) was injected subcutaneously.

Temp. of animal.

No. 1. No. 2.

Before injection.. |} 103 8° F, | 104°6° F.

Alter injection — ee ee No. 1 was almost motionless, and
5 min. was rolled in cotton-wadding.
oe ve No. 2 was left uncovered.
27 min. | 99°7 101°5
Lhr. 20min. | 96°0 92°6
Lhr. 40 min. | 95°2 91°0
2 hr. 38 min. | 94°3 about 80° | The graduation of the thermometer
did not extend so low as 80°, and
the temperature was calculated
approximately, or guessed, by the
height of the mercury.
2hr.57 min. | 93°8 ee The legs of No. 2 are shivering.
4hr. Omin. | 87°3
4hr. 42 min. | 88°4 ee No. 1 was now deprived of its

covering. It shivered and grunted

but lay in whatever position it

was put, and was still completely

narcotised,

5 hr. 27 min. | 88°'8

5 hr. 42 min. ee ee No. 1 awakened.

No. 2 remained as before, motion-
less, except for the shivering.

5 hr.52 min. | 95°'8 es It did not recover, and died some

little time afterwards.

Expt. Ii. Into two guinea-pigs, No. 1 weighing 655 grammes,
and No. 2 weighing 670 grammes, 1:1 c.c. of 50 per cent. solu-
‘tion of chloral hydrate was injected.

200. EFFECT OF WARMTH IN PREVENTING DEATH FROM CHLORAI.

After injection—
7 min.

1 hr. 3 min.

Zhr. 7 min.

2 hr. 20 min.
2 hr. 34 min.
8 hr. O min.
24 hr. O min.

No. 1. No. 2.
Temp.) Resp. |Temp.} Resp.
102 -4°
101°8 | 89 101° ee

ee ee 91°S| 24
102°9 | 78
LO2 *4 50 ee ee
abt. 87} 12
98 8 ee ee 1s

Both animals nearly narco-
tised.

No. 1 put into a warm-air
bath.

No. 2 allowed to lie withou’s
cover.

Kicks vigorously when pinched.
Does not kick when pinched.
No. L is now awake.

Le nperature of No. 2 cannot
be taken or estimated, as it
is so low that the mercury
does not rise from the bulb
of the thermometer. No re-
spiration is visible, but occa-
sionslly the animal opens
its mouth convulsively. No
reflex. It was put in the
warm bath, but respiration
did not become re-estab-
lished, and all signs of life
shortly disappeared.

Expt. TIL.

Into a guinea-pig, No. 1, weighing 272 erammes,
was injected 0°65 c.c. of a 50 per cent. solution of hydrate of
chloral. Into another, No. 2, weighing 330 grammes, the same
quantity ut the solution was also injected,

WARM AIR-BATH. 201

No. 1. No. 2.

Temp.| Resp. | Temp.| Resp.

At injection.....|100°9°} .. |100°8°
Aiter injection
7min. | oe ve ee «- | No. 1 fast asleep. It was put
into a warm-air bath. No, 2
not quite asleep.
12 min. | ee ee ee «> | No. 2 nearly quite asleep.
Lies as it is placed. Reflex
movements are slight.

26 min. oe és 93°1 | 46
50 min. 107°0 | 62
1 hr. 26 min. ee ee ee 28 Shivers very much with ex-

piration, so that the respira-

tions are difficult to count.

Grunts slightly when the

thermometer is introduced

about into the rectum.

2hr. 4min. |102 104 | 59°5 | 380 | Both animals are chewing.

2 hr. 88 min. |101°8 Pr CBG: h 4 No. 1 is awake. Though still
somewhat sleepy, it will no
longer lie on its back.

No. 2 cries when pinched. It
was put into the warm bath.

4hr. Gmin./| «- oe 25°6; .. | No. 2 is now awake.

In this experiment (No. III) the dose was small, and guinea-
pig No. 2 recovered. although it was not kept warm, but not till
an hour anda half after No. 1, although the latter was the
smaller animal, and the dose it received was therefore much
greater in proportion to its size.

Expt. IV. Into each of three guinea-pigs 1:1 e.c. of 50 per
cent. solution of hydrate of chloral was injected subcutaneously.
No. 1 weighed 640 grammes, No. 2, 670 grammes, and No, 3,
717 gramines,

202 EFFECT OF WARMTH IN PREVENTING DEATH FROM CHLORAL,

After injection
19 min.

9 min.

2 hr. 20 min.
2 hr. 40 min.
2 hr. 50 min.
3 hr. O min.

5 hr. 30 min.
5 hr. 60 min.
6 hr. O min.
7 hr. 50 min.
8 hr. 10 min.

8 hr. 20 min.

22 hr. O min.

No. 1 No. 2. No. 3.
Temp. | Resp. | Temp.| Resp. | Temp.| Resp.
101°6°| .. |402°6°| .. j201 4°),

se es ee ee 85 a7,
ee ee 97 36
104°4 | 74
ee ee o 83 20
95°3
103 *d 70
ee ee ee ee ? 10
. ee 94 ‘6 ee ee e
100°6 | 76
ee ee ee ee ee 8
ee . 93 2 ee e ae
100 °8 ; as in ee :

No. 1 was put at
once into a hot-air
bath after the in-
jection.

No. 2 was quite nar-
cotised and was
wrapped in cotton-
wool.

No. 3 was narcotised
and was left lying
on table.

Saliva runs from
mouth.

Begins to show signs
of reflex when
pinched.

Is_ beginning to
awake.

No. i is dead. It
appeared to have
had convulsions,
for some of the
cotton-wool lining
the bath was
caught in its teeth.

No. 3 is still alive.
On pinching one
hind foot he moves
both it and the
other one. Occa-
sionally opens its
mouth in aconvul-
sive manner and
paws with its feet
while it lies on its
side. It died a
short while after.

In this experiment the animal No. 1 died in
too high a temperature of the bath.

consequence of

WARM AIR-BATH VERSUS COTTON: WOOL. 203

Expt. V. Into the flank of a guinea-pig, No. 1, weighing 392
grammes, was injected 0°75 cc. of a 50 per cent. solution of
chloral, and into the axilla of another, No. 2, weighing 335
grammes, 0*9 c.c. of the same solution.

Temp. of animal.

No. 1. No. 2.

After injection—
3 min. ee ee No. 1 lies quite quiet. No. 2 put

into a warm-air bath at 98°6°.
5 min. 98 *2 98 °0

12 min. oe? 98 *3 No. 1 is dead. The heart beat after
the respiration stopped.

The respirations of No. 2 became
very rapid and deep after it was
put in the air bath.

2 hr. 26 min. oe 111 *4 No. 2 was heard to give a grunt, and

on taking it out almost immedi-

ately after it was found to be
dead.

The dose was here either too large or the temperature of the
bath rose too high.

Expt. VI. Into each of three guinea-pigs, No. 1 weighing
490 grammes, No. 2 weighing 425 grammes, and No. 3 weighing
+15 grammes, 1‘1 c.c. of a 50 per cent. solution of chloral hydrate
was injected subcutaneously.

204 EFFECT OF WARMTH IN PREVENTING DEATH FROM CHLORAL

A minute or

two

after

injection ..

1 hr.

2 hr.
2 hr.
2 hr.
8 hr.

3 hr.
4 hr.

4 hr.
6 hr.
6 hr.

10 hr.

2) hr.

22 hr.

5 min.

81 min.

13 min.

15 min.
26 min.
35 min.
35 min.

56 min.
7 min.

16 min.
45 min.
56 min.

O min.
30 min.

O min.

No. 1 No. 2. No. 3.
Temp.| Resp. | Temp.| Resp. | Temp.) Resp.
100° | 90 | 99°4°| 96 | 100° | 84

ee 26 ee ee
about

87 13 s e* ee ee

ee ee 96 8 36

es e- ° es 105°4} 90

? 8

ee 4 e e ee

ee «» | 938°C | 27

ee ee ee 102 “€ 94,

Oo eel |

ee ee . 102 ¢ .

ee ee 850] 8h

ee ee 93 O ee e ee

Nos. 2 and 3 quite
narcotised.

No. 1 quite narco-
tised.

No. 1 left exposed.
No. 2 rolled up in
cotton wadding,
and No.8 put into
a warm-air bath
at 86°.

No. 1 shows some
reflex action of
foot when it is
pinched.

Respirations of No.1
are very deep.

Pulse of No. 1 is 89
per minute.

No. 3 grunts when
pinched.

No. 1 is dead.

No. 3 is awaking.

No. 3 is running
about.

No. 2 has just been
delivered of a
young one, which
is dead.

No. 2 can run about.

No. 2 seems quite
well; eats heartily.

This experiment shows the effect of warmth in preventing
death, and the rapidity of recovery when the onimal is put in a
warm bath, compared with that which it makes when encased
in cotton-wool.

All these experiments were made in August, 1870, in the
laboratory of my friend, Dr. Burdon Sanderson, and I gladly
take this opportunity of returning him my most hearty thanks
for the facilities and aid he afforded, and the kindness which
he then and ever has shown me.

INFLUENCE OF TEMPERATURE ON THE
PULSATIONS OF THE MAMMALIAN HEART
AND ON THE ACTION OF THE VAGUS.

(Reprinted from St. Bartholomew’s Hospital Reports, vol. vii, 1871,
pp. 216 to 228.)

THE influence of warmth in quickening the pulse has been
long known, but the hypothesis put forward by Budge,* and
again by Liebermeister,f that the quickness of the pulse in
fever is due to the increased temperature of the body, gives
it an interest to physicians which it would not otherwise possess.
This hypothesis is grounded on the fact that increased tem-
perature, within certain limits, causes the hearts of frogs and
mammals to beat more quickly, both when they are in the body
and after they have been separated from it. This has been
observed in the frog’s heart by Humboldt,t Pickford,§ Weber,
Budge,{ Tigger,** Panum,fft Calliburces,ff Schelske,§§ and by
Cyon,|||| in Ludwig’s laboratory. As the experiments of the
last-mentioned observer were more complete and extended than
those of the others, I shall give the results which he obtained.
His experiments were performed by removing the heart
entirely from the body of the frog, filling it with serum
through the vena cava, and connecting the aorta with a
manometer, by which the number and force of the pulsations
could be measured and registered. The heart was then enclosed
in a vessel whose temperature could be altered at will. Any

* Budge, quoted by Panum.

+ Liebermeister, Deutsch. Arch. f. klin, Med., vol. i, 464.

~ Quoted by Panum.

§ Pickfurd, Henle u. Pf. Zeitsct., vol. xi, 2, 1851.

|| Weber, quoted by Panum.

{ Budge, Arch. f. phys. Heilk, vol. v, 599.

** Tigger, Dissertation, 1853, yuuted by Panum.

t+ Panum, Bibliothek fiir Layer, Bd. x, p. 46, and Schmidt’s Jahrb., 1858.
tt Calliburces, Gaz. hebd., 1857, p. 458.

§§ Schelske, Ueber die Verdnderung der Erregbarkeit durch die Wdrme, 1860,
\|\| Cyon, Ludwig’s Arbeiten, 1866.

%06 INFLUENCE OF TEMPERATURE ON THE MAMMALIAN HEART.

change in the number of the heart-beats which was produced
by an alteration of temperature was of course due to its action
on the nerves or muscular substance of the heart itself, as it
had been severed from all connection with other structures,
In this way he found that it is only within a certain limited
range of temperature that the frog’s heart pulsates at all, the
lower limit being from 32° to 288° F., and the upper one
between 86° and 104° F., the limits varying somewhat with
each individual heart. When itis cooled down, its beats become
slower and slower till it reaches the lower limit, and then they
stop altogether. When it is slowly warmed, they beconie
quicker and quicker till they 1each their maximum rapidity,
within a few degrees of the upper limit. They then become
slower and slower, and finally stop when the limit itself is
reached. During the time the heart is being warmed, the -
number of its beats does not steadily increase throughout in
the same proportion to the rise of temperature. From the
lower limit the number of beats increases at first very slowly,
‘and then more and more quickly for each increment of tempera-
ture, till the maximum rapidity is attained, and then, with each
degree of rise in the temperature, the pulsations diminish in
number, rapidly though irregularly, and soon cease. In the
two or three degrees which precede complete stillstand the
beats become not only slow but irregular, so that almost no two
intervals between them are of the same length.

At the under limit of temperature the heart contracts only
to a small extent, but a few degrees above it the maximum
amount of contraction is reached, and this amount continues
the same up to from 572° to 66°2° F., when the contractions
again begin to get smaller and smaller.

Just before it is stopped altogether by the heat, the. ventricle
no longer contracts as a whole, but does so in a peristaltic
manner, so that it sometimes seems to be contracting vigor-
ously, and yet not a drop of the fluid it contains is expelled,
but it is merely moved about from place to place in the
ventricular cavity, one part expanding as another contracts,

and vice versd.
When the heart is beating regularly, at moderate tempera-

ACTION ON THE HEART AND VAGUS IN FROGS. 207

tures, irritation of the venous sinus causes cessation of the
beats; but during stillstand from cold, each irritation of it
produces a single contraction, and during stillstand from heat
produces tetanus of the heart. The inhibitory centres through
which the irritation of the sinus acts, at ordinary temperatures
in producing slowing and stoppage of the heart, seem there-
fore to be completely paralysed by heat, as otherwise they
would prevent the contraction from becoming tetanic, and
would only allow it to be intermittent.

Schelske also found that if the vagus, which usually causes
slowing, be irritated by a strong electric current, while the
heart is in this condition of stillstand from heat, an undulating
contraction is produced.

This may be due, as Cyon thinks, to the current being partly
conducted to the heart, and irritating it directly ; but it seems
to strengthen the supposition that the inhibitory centres in
the heart, and through which the vagus usually produces slow-
ing, are paralysed.

Pickford, Budge, Tigger, and Panum found that the hearts
which were exposed to a high temperature soon ceased beating
and lost their irritability, so that they no longer contracted on the
application of a stimulus either mechanical or electrical, while
those exposed to a moderate temperature continued to beat, and
retained their irritability for a very much longer time.

Budge and Tigger had assumed that the action of tempera-
ture on the mammalian heart was the same as on that of the
frog; but as Nysten had not noticed temperature to exert any
particular influence over the time that the mammalian heart
retained its irritability after separation from the body, while its.
action was so marked in frogs, Panum thought it well to test.
this assumption by experiment. 3

He took three rabbits of exactly the same age, and as nearly
as possible of the same size and strength, killed them by divid-
ing the spinal cord in the neck, and at once removed the heart

and lungs. These were then placed in vessels in which the air

was kept moist so as to prevent the irritability of the heart.
being injured by drying. The temperature in one vessel was
42°8° F., in a second 61°7° F., and in the third 91:'4° F. The

208 INFLUENCE OF TEMPERATURE ON THE MAMMALIAN HEART.

heart which was put into the warmest vessel beat much more
rapidly, and that in the coldest vessel more slowly, than the ~
one which was exposed to a moderate temperature. He also
found, although Nystén had failed to observe it, that, just as
with the frog’s heart, the rabbit’s heart which had been put in
the warm vessel, and thus caused to beat more quickly, stopped
pulsating and lost its irritability by tactile or electrical stimuli
much sooner than that in the temperate one. The heart which
was put in the cold vessel lost its irritability even sooner than
that which was warmed, or rather it seemed to lose it, for the
irritability was not destroyed but was merely dormant, and
when moderately warmed the heart again became irritable, and
remained so for a considerable time.

I have made several experiments on the effect of temperature
on the rabbit’s heart while it still remained in the body, some-
times leaving all its nervous connections untouched, and some-
times dividing the vagi. These experiments were made by
narcotising the animal with opium or chloral, and laying it in
a tin vessel about 20 inches long by 6 inches broad, and 3
inches deep in the inside, and well padded with cotton wool.
The vessel was double, and by pouring hot water into it, the
temperature of the rabbit was gradually raised. The belly of
the animal was also covered with cotton wool, and sometimes
with an india-rubber bag containing hot water. To make
respiration easier, a cannula was introduced into the trachea,
and in some experiments the inspired air was passed over warm
water, so as to warm it and saturate it with moisture and lessen
the loss of heat from the lungs. The pulsations of the heart
were counted by pushing a fine needle through the thoracic walls
into the heart, so that it vibrated with each pulsation, and con-
necting its outer end, by means of a fine thread, with the lever
of one of Marey’s cardiographs, which registered the beats on a
revolving cylinder covered with smoked paper. (Vide p. 294.)
By means of this arrangement, which I owe to Professor
Stricker of Vienna, it is possible to count the pulsations with
great exactitude, even when the heart is beating at the rate of
470 in a minute, as it did in one instance. The temperature
was measured by a thermometer in the rectum. As the animals

UPPER LIMIT OF TEMPERATURE. 209

were completely narcotised, and remained perfectly motionless,
the thermometer remained undisplaced in the rectum from the
beginning to the end of the experiments. |

The results are shown in the following table :—

Pulsations in 15 Seconds.
Tempera-
ture.
No. of Experiment.
I. x} 00. | IV. Vv. VI. VII. Vii.
vagus cut. vagus cut.
99° F. ee ee 7. 76 es ee 98

100 ee oe ee 71 oe 78
101 ee ee ee 73 ee 81
1u2 ee ee oe 76 ee 86 83 82
103 ee ee 85 77 78 87 &4 83
104 . ee ee ay 82 81 89 $7 &9
105 oe ee 85 85 85 86 91 118
106 ee oe ee 89 87 58 91 103
107 a ee 88 91 &8 ee 97 91
108 oe ee 7 94 90 oe 97 89
109 es es 97 96 ee oe 101 102
110 ee ee 97 97 ee ee 110 102
111 ee ee 101 | 102 ar ee 108 105
112 ee ve 99 ee ee ee 109 103
113 oe ee 85 ee ve ee 90 112
114 ee ee ee ee ee ee ee bay
115
116

«A

From this table it will be seen that the heart beats more
quickly as the temperature of the animal rises, till it reaches
its maximum, and then becomes slower, and finally stops. The
increase in the number of beats is not the same for each degree
of rise in the temperature, and the number of beats at the same
temperature, and also the amount of quickening for each degree
of rise of temperature, differs in the different animals.

The upper limit of which the heart stands still varies in
different animals, but in the stronger animals it is between
113° and 114° F., or even above it. It must be remembered,
however, that this was the temperature of the rectum; and as
the back of the animal lay on the warm cotton wool covering
the tin vessel, and its belly was covered with cotton wool as

well, while the thorax was not covered, so as not to interfere
P

210 INFLUENCE OF TEMPERATURE ON THE MAMMALIAN HEART.

with the working of the cardiac needle, it is probable that the
- temperature in the rectum was higher than in the thorax. In
Experiment VIII the heart became markedly irregular just
before it stopped.

The effect of increased temperature on the pulse of healthy
men has been studied by Lemonnier, Currie, Bartels, Lieber-
meister,* and others, and they all agree that the pulse rises
“with the temperature.

From an analysis of 280 cases, Liebermeister found that the
‘pulse became quick as the temperature rose, although the
amount of quickening was not the same for each degree of
increase. The regularity of the quickening was, however, quite
as great as that which I have found in rabbits, as is evident
from the numbers which he gives. and which I append here:
Temperature 98°6° F. 99°5 100°4 101°3 102°2 103°1 104 104°9 105°8 106°7 107°6
Mean pulse

rate .. 786 841 91:2 94°7 99°8 1025 10851094110 1186 1375
Increase for

each ‘9° F. SO. TL 8S FLV S7 > oe) 8. 6 ee ee

We see then that the number of pulsations increases with
the temperature in the hearts of frogs and rabbits, both when
exercised and when in the body; that it does so in healthy men,
and also in exactly the same way in a fever patient.

In view of all these facts, even although we find so high an
authority as Wunderlich? stating that it is by no means cer-
tainly shown that the cardiac contractions are determined by
the temperature, it seems to me that we can hardly avoid the
conclusion that the quickness of the pulse in fever is mainly
<lue to the higher temperature of the heart.

Another question, however, now arises. Although the
higher temperature be the chief, is it the only cause of the
quickened pulse ?

Liebermeister says that the rise of temperature can be
occasionally observed to precede the rise of the pulse; but
Wunderlich states, on the other hand, that it is more common
to find that the changes in the pulse have slightly preceded

* Liebermeister, Deutsch. Arch. f. klin. Med., i, 463.
+ Wunderlich, Medical Thermometry, Syd. Soc. Trans., p. 440.

2 a nt —— .

INACTION OF DIGITALIS IN PNEUMONIA. 211

the alteration of temperature, and, as it were, announced the
occurrence of the latter.

Here, then, at the very beginning of fever, we have a quick-
ening of the pulse which cannot be due to temperature. It
might be produced by stimulation of the motor ganglia in the
heart itself by some cause yet unknown, by stimulation of
the quickening centres in the brain and cord, or by dimi-
nution of the power of the vagus, either through some impres-
sion made directly on the brain, or indirectly through some
change occurring in the arteries and altering the blood pres-
sure. The first cause seems very unlikely, and it is more
probably due to either the second or third, but this must be
decided by future investigations. On this point I have made
no experiments, my attention having been attracted rather to
the effect which high temperatures in fever would have upon
the vagus, and to the way in which this might modify the
action of the remedies then employed.

Thomas* found that digitalis sometimes had no action on the

pulse when given in pneumonia, and as digitalis acts chiefly
through the vagus it seemed to me possible that its want of
action might be due to paralysis of the inhibitory apparatus in
the heart through which the vagus acts upon it.
This appeared all the more probable since Schelske and
Cyon had found that a high temperature paralysed it in
the heart of the frog, and the rapid increase in the pulsations
noticed by Liebermeister between the temperatures of 105°8°
and 107°6° F., seemed to indicate that the same thing occurred
in the mammalian heart. In order to test the truth of this
supposition, I performed the Experiments I, III, LV, V, and
VIII, which are given in detail below.

The animals were narcotised, the vagi exposed, and their
power tested by irritating them by an induced current from one
of Du Bois Reymond’s coils. The temperature of the animal
was then raised, and the power of the vagus tested from time
to time with a current of the same strength as that used at first.
From these experiments, and especially from No. VIII, it will
be seen that as the temperature was raised and the pulse quick-

* Thomas, Arch. f. Heilk., vi, 4, p. 329, 1865,
P 2

212 INFLUENCE OF TEMPERATURE ON THE MAMMALIAN HEART.

ened the power of the vagus diminished; but when the tem-
perature had risen nearly to the upper limit, and the pulsations
were becoming slow, the power of the vagus again increased,
and, contrary to my expectation, was strongly marked just
before the heart ceased to beat. Few as these experiments are,
the results are so definite that we may, I think, conclude that
in the heart of the rabbit, and probably other mammalian —
hearts, a temperature sufficiently high to produce stoppage of
the heart does not paralyse the vagus or the inhibitory appa-
ratus through which it acts. It is possible that a longer
exposure to a high temperature, such as occurs in fevers, may
produce this result; but it seems probable that it is not so,
and that if digitalis, or other similar drugs, should not act on
the pulse during fever, we must seek for some cther explanation
of their failure than paralysis of the structures through which
they act. Unfortunately I did not carefully look for clots in
the vessels after death ; but on dividing the carotids and jugulars
the animals bled freely, and in one which I examined no trace
of a clot could be found in the heart or vena cava. I am inclined,
therefore, to reject Weikart’s* hypothesis that death from heat
is due to coagulation of blood in the vessels, and rather to look
on the impairment of the muscular power of the heart by the
heat, possibly from coagulation of the myosin in its muscular
substance, as the cause of death, as suggested by Bernard,f and
to regard the rapid loss of irritability, noticed by Panum, in the
heart exposed to a high temperature, and therefore beating
quickly, as an indication of the great importance of keeping
down the temperature and pulse-rate in fever patients by every
means in our power.

I gladly take this opportunity of expressing my thanks to
Professor Burdon Sanderson for the kindness with which he
placed his apparatus at my disposal and allowed me the use of
his laboratory in which the greater number of my experiments
were performed.

Experiment I—A. young rabbit was fastened in the apparatus
and narcotised by the injection of 14 cub. cent. of laudanum

* Arch. d. Heilk., p. 193, 1838.
+ Bernard, Compte-rend. de la Soc. de Bioloyie, p. 51, 1859.

RETENTION OF INHIBITORY ACTION BY VAGUS. 213

inte the jugular vein. A cannula was then put into the trachea,
and a thread passed under the right vagus. The temperature
in the rectum was 948° F. Hot water was then poured into
the apparatus ; an india-rubber bottle containing hot water was
placed on the belly, and the cannula in the trachea was con-
nected with a flask containing warm water, so that the inspired
air should be warm and moist. The temperature gradually
rose, and the power of the vagus over the heart was tested by
irritating it from time to time.

Temp. 105°2° F. Irritation of vagus stops the heart.

106 Ps * acts, but not so strongly.
109°2 ” ” causes slowing, but no stoppage.
115 ” ” ” ”? ”? ”

The pulse became slow and weak, and the animal was removed
and put under a tap of cold water, but its pulsations were not
restored. On post-mortem examination the venous system was
found much congested.

Experiment II.—A rabbit, weighing about 3} lbs., was narco-
tised by injecting a solution of chloral subcutaneously. An
hour and a half after it was put in the apparatus, a cannula put
in the trachea, and a thread passed under the right vagus; but
the nerve was not cut. Temperature in rectum 100°:2° F. Hot
water was poured into the apparatus, and the inspired air passed
over hot water. The temperature sank to 100° F.; it then
began to rise, but the animal died before it rose much above
104° F,

Experiment III—A young rabbit, weighing about 3 lbs., was
narcotised by the subcutaneous injection of about 30 ers. of
chloral. It was fastened in the apparatus; a fine needle was
thrust into the heart, and connected with one of Marey’s cardo-
graphic levers. The needle was removed at the end of each

tracing. Cannula in trachea.

Temp. Pulse in 15”,

85

PRN E WORMS AITUMIOR ctuedeetcts sk cetetcevdecceess 6

85

2006: Tr casa: Oe

SUE NOROE TITRE Gadasebbsecccccctesecsccessese ©

82

1054 secece » 88

214: INFLUENCE: OF TEMPERATURE ON THE MAMMALIAN HEART,

Temp. Pulse in 15”, -
Right yagus irritated CRCSCHH SH CH EH OH SESS HOSE EEHO LESS 34

91
A piece of wood had been placed under it

the previous time to isolate it, and not removed,
so it. was probably weakened by exposure to air.

TOT Ei ikava cae
Right vagus irritated COOH ee se eee Ee eeeseeee DELE EE 28

109 esetee 97
Right vagus irritated CO CHCH LEH CHER OBOE EE EE Ee ee SORE 38

Right vagus irritated eoeeeeeeveseee 109 *2 eeeece 26

110 eseane fer
Right yagus irritated CO ee eee eereseeeeseeeseoererecs 34

Right-vagus irritated eeoreeeseresees TAL 2. a ecce 48

TIS 3 cecece , OF
Right vagus irritated CO CC CO EEHH CH CHLOE Less eeeeeese 38

113 2 eeeeee 85
Heart has almost ceased to beat .ece 113°6

Respiration had entirely ceased. Artificial respiration was
tried, but it did not stimulate the heart in the least. The
tracheal cannula was found to be full of moisture. The animal
was allowed to lie in the apparatus.

The heart stopped at5h.8m.pP.mu.. Temp. 113 °6° F.

»” 2 ” 8 ” ”» 114 6
39 ” ” 11 92 9 115

‘39 > ” 20 33 29 115 ‘8
3? 3) ” 30 ” Bins 116 “4

The animal was now removed from the apparatus. In taking
off the head-holder, the animal’s jaws were found to be so firmly
locked together that it was with considerable difficulty that the
bar of the holder could be removed from between the teeth.
On opening the abdomen the muscular walls were found to be
somewhat congested; the viscera were rather pale. Behind the
right kidney, in the cellular tissue, over the psoas muscle, there
was an extravasation of blood, about 2 inches long by about
4 an inch broad. Lungs natural. Left ventricle was firmly
contracted ; right ventricle nearly empty. The left ventricle

Fe, Sa

EXPERIMENT WITH SMALL DOSE OF CHLORAL. 215

was quite hard, and the septum seemed to have contracted so
firmly that the apex of the heart had a cleft appearance. Both
auricles were moderately filled; the bladder contained a good
deal of urine. During the experiments the muscles of the neck
seemed somewhat cedematous.

Experiment IV.—A young rabbit was narcotised by the sub-
cutaneous injection of chloral. The amount seemed insufficient ;
and after the animal was placed in the apparatus, the right
jugular was exposed for the purpose of injecting some into it.
The vein had several irregular branches, one of which was un-
fortunately wounded, and the animal lost some blood. The vein
was then tied, and the choral injected into the carotid artery.
No cannula was placed in the trachea. A thread was passed
under the right vagus, but it was not cut. No hot-water |
bottle was placed on the abdomen, but only a piece of cotton

wadding.
Temp. Pulse.
70

Right vagus irritated CORSO OREO TE RT ERED OEE OE ee OEED 30
7 seconds after Sere eer er eee ee ee eee eee eee eee ee | 72

72
Vagus WTILALOM «0.0 cocece ct veces ceceseress ce ceccce 13
OE. iesce 76
100 Siece as
101 rere? gee
102 eevee 76
Oe ie I 5
104°2 sesoee 82
105 covces 80
106 cocsee 89
107 coosee 91
108 coccce =
109 severe 96
110 cocece “OF
111 eoveee 102
TI1L°*S wcseee 102
Vagus irritated secereseseeesesese yt OS ara ore 37

The animal now awoke, so I removed it from the apparatus
and administered a fresh dose of chloral. Unfortunaely, how-
ever, I injected it into the abdominal cavity, and the rabbit died
in a few minutes. |

Experiment V.—A rabbit was chloralised and placed in the
apparatus, a cannula put in the trachea, and both vagi exposed.

216 INFLUENCE OF TEMPERATURE ON THE MAMMALIAN HEART.

Temp. 103 °5° F. ...eeeeceee. Pulse 78
Right FACIE Cub. arivecocesesess LOD O 40.00 megs cp aetete ae
PiGTe Vath Cat Ls cas cadececeus U2 'O" Sine sane teesn 6 see
Right irritated 2... cccocccscccescccessvccesesssesdcveccece a0
ASEOVWRIOS 5.0 sida. 50.40.06 60:6.0:40,ae dt be we hee see se den vane ae eee
Left vagus irritate 1 2. cess cccvccsccescrccccccaseccecccsssce 26
PE RECON WEPAG ka 50.40 s 0 eaulere d eb aq AN Sle cues usdaebe 6040 meee tne
Temperature rising rapidly, about
0-3? ina minute -sccuseescecs, BOG O-LUS'S (5s50 ca aew eeu
B secccecesece § SL
105 °5-105°B wccevecceeee 889
106 *5-106-°7 wccevecovece - OF
LOT 5 -1076: vcicnss seve une
108 °5-103°6 cecccccccese «90
Heart sudderly became slow and
WEAK .. cecccccccecasscevens 109 2 sececevecseccccess stopped

Experiment VI.—A young rabbit, weighing about 14 lbs., was
narcotised by the injection of 4 ¢.c. of 50 per cent. chloral solu-
tion under the skin of the flank. Shortly after it was placed
in the apparatus the respiration stopped, but the carotids were
seen vigorously pulsating. The trachea was quickly opened,
a cannula inserted, and artificial respiration begun. The heart,
which had begun to get weak, soon pulsated normally again.
A thread was passed under the right vagus, but it was not cut

Temp. 104°4° F. .....2.... Pulse 82
100 °*1 eevee eeeeeeeeeeene 78
POISIOIE As rnsarnivns ee
102-102 °2 eeeee eeeeeeee 86
108-1031 ...... rake os ae
1089-103 Bo. isvevtwve se OF
FS pants as Peay gins Oe
1: Pat Ree BD eae . 86
BOG Aus ahecevawaesske Lee
PO ener ty Sia aeata ee

Began artificial respiration .. 106‘2 ....ceeceseseees. G4

Respiration began to go on again naturally, but soon stopped ;
and on again beginning artificial respiration the animal did not
recover. On post-mortem examination, blood was found to have
extravasated into the pericardium from the heart.

Experiment VII.—A young rabbit, weighing about 14 Ib.,
was narcotised by injecting 3 c.c. of a 50 per cent. chloral
solution subeutaneously. Anhour afterwards a cannula was
introduced into the trachea.

MOTOR ACTION OF VAGUS. 217

Temp. 99°S° F. .....e0e++ Pulse 76
DORR eva whadnuceen oe) FO

Both vagi cut.ccccccccescee DIDI coccccescccscceee. 98
Animal was now warmed.... 1O2Z*4 wccccccesscccceee 83
L0G oa daweateeewcese, 84

104 cecccccccccvccece 87

105,-- cecccccodestivcves, OL

106 OP ee rr ry re et |

AGT. scan seeecadencshe (ae
WFD)... ccawds wacineaeeuat Oa

108 +1089 kk cinwesaeten De

1039 ob abt onibes doetee A
10976 =100"7D) sce awsianes) Sue
410°3-110-°4. wn cecesenen, LAV
TERT AL, veces pease
BIDIG=IAIE Te ois cedmseises eee
BESTS lis isiasceacate: a0e
BAS Se 1187 ss bs ceeecen 200

FIG Gases esabesGucken, ee
RES A Wi wi.tdttadies seen ee OOM
LNG <a bd se snes de onda - i ke
TIOSO 50 45 60.5600 0040000. 10

The beats of the heart now became imperceptible. The
thorax was quickly opened, and the heart seen to be at rest
and moderately contracted. On irritating the left vagus in the
neck by a strong induced current a slight undulating contrac-
tion began in the heart and lasted for a few seconds. After
stopping, it was again excited by direct irritation of the heart.
After stopping a second time, it could not be excited to move
by irritating either vagus, but slight movement occurred on
irritating the heart directly. The abdominal parietes were
slightly, but the viscera were not, congested. The blood was
(uid.

Experiment VIII.—A strong rabbit; weighing between 3 and
4 lbs., was narcotised by the subcutaneous injection of 5 c.c. of
a 50 per cent. solution of chloral. Three-quarters of an hour
afterwards a cannula was placed in the trachea, and a thread
passed under each vagus, great care being taken to injure the
nerve as little as possible.

218 . INFLUENCE OF TEMPERATURE ON THE MAMMALIAN HEART.

Temp. 100°9°F. Pulse 76,
Right vagus irritated. The secondary coil had
been placed by mistake over the primary one,
and convulsive movement of the thorax occurred,
which obscured the pulse. It was then pushed
back 120 mm. during the irritation, but the
movements still continued
After irritation ........ 404 bs Sh 00 sen dneewebbeceeeeed ee be eeamul tne
Left vagus irritated. Slowing and stillstand
of heart, and irregular contractions of the thorax
occurred.
Right vagus again irritated. Similar result
as before.
AfterwarGer. sis svssinnn cian ivnsdeu el bbve casese ccesouts ss nee wee
Left vagus irritated .....ccccosccescccccccccceseserecescescess 20
After WarEs o2.0's v6.65 dees eueanee eee des oe be 5b0b oe b080 006040 nee
Right vagus irritated ; distance of secondary
COU 100 MM. 2. crcrecercvecescvevcestesevcsevececccsesesece stillstand
Afterwards. .o.ccceesiss sd eNGeeeacsenecses secs cocseece 1 00
Left vagus irritated ; ebidaas of ot 100 MM, seeceeecseeeevese Stillstand
In 34 of a minute it was again perfectly re-
gular.
102 sovccecece 82
103 tecevccece 83
104-104°4 ....002 89
105-105°S .....+6 118
106 .ccccevescee 103
LOT sescscccceee Ql
108 escsccceseee 89
10D wecvceseceee LUZ
110 wevcceseccee 102
Left vagus irritated ; distance of coil LOO mm. .erececesesceereree 40
In 3 seconds after ....cccsccccccscscccvcccesvcccsescesveseve LOZ
Left vagus again irritated ...ccccccccevcrevecccesesecesecssese 38
In 7% Seconds: BfET . soc occ cocesetocsececevessecccsveevccesee! LUG
Pulsations are now very small .eeesececcee LIB wesevevecece 112
Left vagus irritated ..cecccccevcccvevececcccescessesessecseee 22
15 seconds after ..sccocccesceccsccvcvevcccrsssssressesssseee LOS
L13°4 ceocccccece, 106
A TESS’ 2050's ses sree
Left vagus irritated ssevenectenssinnsn seanceceeaceosseseos 4 giigaag
Convulsive movement of the thorax occurred,
and lasted nearly } a minute. The pulse then
became regular......seseceeeee seececcccccccecevecvevees 82
It continued so for 35 Soode: ant der ak
Genly fell to sscccccccccccccccccccecccesccsesserssssesssssevess BO
1144. ccseeapee we
The pulse now became irregular, 4 beats oc-
curring together in one second, followed by a

RETENTION OF INHIBITORY ACTION, 219

Temp. 100°9° F, Pulse 76.
pause of another second, and then 3 or 4 beats

occurring together again.

L145 wceeeeesess 144
Left vagus irritated ...ccoscccccccssocccccccsccccesecoscce Stilletand |
DT MNOEETAG As 6-60 wd KAR 900d 0s Ads wig ke Oe Rete eee ama Oe we ee D6 18
The beats now became slow and almost imper-

DENTS 5 505 t-c wien chine wdck 0644.60 64.90 deerme 1148 eeeeceee stopped

The thorax was quickly opened. The heart was still. On
irritating the left vagus in the neck by a strong induced cur-
rent, a slight vermicular movement occurred in the heart.
After stopping it could be again excited by direct irritation of,
the heart.

The viscera were not congested ; there was no extravasation;
the blood was fluid; and there was no trace of a clot in the
heart or vena cava.

EXPERIMENTAL INVESTIGATION OF THE
ACTION OF MEDICINES.

(Reprinted from The British Medical Journal, 1871, 1872, and 1875.)

I.—TuHE STANDARD OF HEALTH.
British Medical Journal, 1871, April 22nd, p. 413, and April 29th, p. 439.

Modes of Investization.—Pathology.—Pharmacology.—Life.—-Conditions of
Health and Disease.—Etlect of Drugs.—Direct and Indirect Action.—Local
and Remote Action.—Dose.—Modification of Dose —Cumulative Action.—
Effect of Habit, Climate, Fasting —Form of Administration.— Effect cf

Large and £ma!l Doses.—Homeopathy.—onstitution and Idiosyncrasy.— ~

Explanation of these from Experiments on Animals.—Connection of
Chemical Constitution and Physiological Action.

THE usual mode of investigating the action of a remedy is to
give it to a patient during an illness and observe what changes
occur in the symptoms after its administration. But it not
unfrequently happens_that medicines are given without any
distinct change in the symptoms ensuing. Even when one does
take place, we very often cannot be sure that it is due to the
medicine, and not to the course of the disease or some other
modifying cause. or, if the remedy and the disease are both
at work together, it is obviously impossible for us to decide
what part of the result is due to the one and what part to the
other, unless we know what the course of the disease would
have been without the medicine, and what action the medicine
would have had if the disease had not been present. Any
attempt to investigate the action of a remedy by giving it under
such circumstances is like that of a rifleman who should
attempt to learn shooting by practising only at dusk, when he
could not see the butt, much less the bull’s eye. He might go
on practising for ever in this way without making any improve-
ment; for, when he missed, he would never know whether it
was because he had not seen the mark properly or had not
aimed steadily at it. If he wish to learn, he must practise by
daylight, when he can clearly see the mark, and can thus be

“lis TREC Vie te 5

a

EEE a =

NECESSITY FOR EMPIRICAL TREATMENT. 291

sure that every miss is due to unsteady aim. He must fire
high or low, to one side or the other, as he finds necessary, and,
by gradually correcting every error, his aim will at last be sure.
Should he then be called on to stand sentry on some dark night,
and shoot at some suspicious object without hitting it, he would
know that his failure was due to his not having seen the object
distinctly, and having consequently aimed in a wrong direction.
And just as the rifleman, before he stands sentry in the dark,
must learn to shoot by daylight, when he can note the effect of
each alteration in the position of his rifle on the course of the
bullet, so ought we to investigate the action of our remedies in
circumstances and under conditions which we know and can
vary at will, marking the effect of each variation upon their
action tjll we thoroughly and exactly understand what it is,
before we proceed to give them in disease, when not only the
conditions under which they operate are at present in a great
measure unknown, but the effects they produce cannot be
definitely ascertained from insufficient knowledge of what the
result would have been had they been withheld. Of late years,
it is true, vigorous efforts have bce: made to determine what
course diseases rin when not interfered with by medicines;
and, although it is often difficult to say what the sequence of
symptoms will be in any particular case, depending as it does
not only on the general course of the disease but on individual
peculiarities of the patient and_on the varying circumstances
in which he is placed, we may nevertheless ascertain with
tolerable accuracy whether or not our treatment is beneficial in
a general way, even when we cannot determine its effects in
detail.

Very inexact and very unsatisfactory as such a knowledge of
medicines as this necessarily is, it must for the present be our
suide in practice in a large number of instances ; and our treat-
ment at present and for some time to come will be chiefly em-
pirical, because our knowledge of pharmacology, and perhaps
still more of pathology, is not yet sufficiently advanced. For
there is hardly any disease in which we know the exact nature
of the morbid changes which are occurring, or the precise organs
or tissuez which are their seats ; and, with some exceptions, we

222 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

are but very imperfectly acquainted with the structures on which
our remedies act, and the exact mode in which these are affected
by them. Day by day, however, our ignorance is diminishing ;
-and we may hope that ere long rational treatment will to a great
extent supersede blind empiricism. It not unfrequently hap-
pens at present that we meet with a case which bears a very
close resemblance to others which we have treated successfully,
and which nevertheless obstinately resists the remedies which
we had previously found serviceable. Our failure astonishes
and vexes us; but we are ignorant of its cause, and we can only
select some other drug by guess and try it: we cannot at once
choose the one which will have the desired effect.

Patholoyy.—In order to choose a drug which will have the
effect that we desire to obtain, we must know where the morbid
changes are taking place, and what their nature is; and we
must be sure that our medicine will act on the affected part, and
in such a way as to counteract the disease. We must trace every
symptom which we see, back to its unseen source; every flush
on the cheek, every quickening of the pulse, back to the vaso-
motor or cardiac nerves, which have allowed the capillaries to
become dilated, and thus produced the redness, or have per-
mitted the heart to beat more rapidly than its wont. We must
then inquire what has produced this alteration in the nervous
system, and so on, till at last we discover, if possible, the hidden
cause of the mischief. We will then give that remedy which
will act in the proper way on the part which we believe to be
the seat of the morbid process; and, if the expected result does
not ensue, we shall, at any rate, have discovered what the
pathology of the disease is not; and, by trying a remedy which
will act in a different way or on a different structure, we may
find out what it really is.

When I speak of the pathology of a disease, I do not mean
those obvious alterations in the structure of an organ which we
‘meet with in post mortem examinations, but the so-called func-
tional changes which precede and are the cause of both them
and the symptoms. For example, the disorganisation of a man’s
liver by the presence of an abscess, or of his kidneys by fatty
degeneration, is not the disease from which he suffered, any

STUDY OF PHARMACOLOGY. 223

more than a field strewn with slain or crowded with heaps of
wounded is a battle. The disease was the alteration in the
nervous and vascular systems, and in the nutrition of tissues,
which we call the inflammatory process, and which produced
the abscess and degeneration, and the disturbance of the same
systems, to which these lesions in their turn give rise; just as
an army may not only lose the battle for want of the assistance ~
which its slain and wounded would have given, but its retreat
may be embarrassed by their presence.

The insufficiency of present modes of treatment, and the
urgent necessity which exists for an accurate knowledge of
pathology and pharmacology, are shown by the manner in which
any new remedy is seized upon and applied in all sorts of cases,
even in those where a knowledge of the morbid processes going
on, and of the action of the remedy itself would at once have
indicated that harm, and not benefit, must ensue from its appli-
cation. It is unnecessary to discuss here the manner in which
pathology must be studied in order that an accurate knowledge
of it may be obtained: I may merely indicate as examples the
works of Cohnheim, Brown-Séquard, Sanderson, Stockvis,
Stricker, and many others.

Pharmacology—In studying pharmacology, our first object is
to find out on what structures a remedy acts. For this purpose,
it is of no use to give it to a man either sick or well. We may
do so in order to find out what general symptoms it produces ;
and from these symptoms we may guess at the structures
affected; but, in order to convert our hypothesis into certainty,
we must have recourse to an experiment which may be of two
kinds. Firstly, we may apply the drug to those structures or
organs which we suppose to be affected by it, and to them alone,
and see whether the general result is the same. This we
generally do either by immersing them in a solution of it, or by
causing blood containing it to circulate through them.

Secondly, we may prevent the drug from reaching these
tissues or organs while it is applied to all other parts of the
_ body, and observe whether the effect is absent. For this pur-
pose, we cut off from one or other ene ts of the body the supply
of blood which carries the drug along with it, or we may so

22.4 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

injure the part that its function is abolished, and no action
exerted upon it can produce any effect. But it is impossible to
do this in man, and so we must have recourse to the lower
animals, in which we can produce at will the conditiors
we desire. Although the administration of a medicine to a
patient is really an experiment, we vary the conditions in
which it acts to so much greater extent in animals that it is
convenient to call the latter mode of investigation the expert-
mental method, and the former that of clinical observation.

Now pathology and pharmacology may go on hand in hand
both in teaching and study, but they must always be preceded by
physiology ; fo, unless we know the processes which take place
in the healthy organism, it is impossible to understand the
changes they undergo in disease, or the effect of drugs upon
them. I will, therefore, here say a few words regarding the
processes in which life consists, before proceeding to speak of
the mode in which they may be modified by the action of
remedies.

Life-—We meet with life only in certain bodies composed of
carbon combined in a very complicated manner with oxygen,
hydrogen, and nitrogen ; and it may, generally speaking, be said
to be the power which these bodies possess of assimilating to
themselves other substances, of decomposing them, and of
evolving energy, which is shown in active motion, active
erowth, &c. Evolution of energy in this way is the distinguish-
ing mark of life. When we look ata grain of wheat, an egg, or
a dried wheel-animalcule, we are unable to say whether or not
it is alive ; it is only when it begins to evolve energy, either by
moulding other substances into conformity with its own con-
stitution in active growth, as in the seed or egg, or by active
motion, as in the animalcule, that we are able to decide the
question. We cannot say how these bodies originally came to
possess their complicated constitution and wonderful powers;
but the evolution of energy by which we recognise the continued
presence of life seems to be more intimately associated with
chemical affinity than with other forms of energy, such as light,
heat, or electricity. All these forms of energy modify the pro-
cesses which occur in living beings, both those which are

CONNECTION OF CITEMICAL AND VITAL ACTIVITY. 225

chemical and those which we term vital, and apparently in
much the same degree ; but whether they modify the vital only
through the chemical, we are at present unable to say. In-
stances may readily be found in which hfe continues active,
although one or other of the forces mentioned is not supplied to
the living body from without, and is only secondarily present as
a result of chemical changes going on within. Thus a seed in
the earth, a fungus in a cellar, or a proteus in its dark cave,
live and thrive without a ray of light; and the whale and wal-
rus in the Arctic seas are independent of any external heat,
their temperature being only maintained by combustion taking
place within their own bodies. But there seems to be no in-
stance of vitality alone continuing active when a stop has been
put to the occurrence of chemical changes. Sometimes both
chemical and vital processes are suspended together for a time,
as in a grain of wheat or a rotifer when it is kept dry, or in an
egg when kept cool and coated with varnish to exclude air. So
long as chemical activity remains dormant, no other form of
energy can awake the latent vitality. Only when the conditions
necessary for chemical transformation of the proper kind and
amount are supplied, does it again become manifest. Thus
light or heat may be applied in any amount or any proportion
to an egg, a seed, or a dried rotifer, and still they will not grow
or move if the air be withheld from the former or the moisture
from the two latter, which is essential for the production cf
chemical changes within them.

Conditions of Health and Disease—These changes of which
I have been speaking consist in the assimilation of certain sub-
stances, their decomposition within the organism, and the re-
jection of waste products. A due proportion between these
constitutes health. Just as a fire can only be kept bright by
raking out the ashes and supplying fresh fuel as that in the
erate burns away, so an organism can only be kept healthy
by removing the products of waste and supplying fresh nutri-
ment as its tissues get decomposed during action. The condi-
tions necessary for this purpose are secured in the simplest
forms of life, such as the amceba, by the little mass of pro-
toplasm moving about in a fluid, which can not only supply

Q

226 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

the oxygen to keep up combustion and evolve energy, and the
nourishment necessary to replace the material thus used up, but -
can at the same time remove the products of waste. In higher

Fie. 124.—Ameeba Princeps.

An ameba figured at two different periods during movement.
n, nucleus; 7, ingested bacillus.

organisms, the little masses of living material of which they are
composed, and which are for the most part fixed, are nourished
by a fluid in which they are bathed, fresh portions of it being
supplied by its constantly flowing over them, instead of their
moving like the amceba through it. In sponges, for example,
where amceba-like bodies are attached “to a framework, as
shown in the diagram (Fig. 125), a current of water is kept flow-

Fig. 125.—Hypothetical Section of Spongilla.

~~. .

[After Huxley.] It consists. of a number of particles, each resembling an
ameba, and supported by a fibrous framework. It is divided into a super-
ficial layer (a) and a deeper part (e), separated by a cavity. The particles of
which e is composed would not get enough nourishment were it not that a
constant current of water is kept flowing over them by the action of the cilia
with which some of them (c) are provided. These move constantly in one
direction, and thus draw the water in at 6 and cause it to flow out again at d
in the direction of the arrows.

LIFE AND HEALTH OF CELLS. 227

ing over them by ciliary action. If we imagine this sponge
placed in a vessel of water we will have no very unfair picture
of the body of amammal. The little masses of protoplasm in
the sponge may be compared to the cells which torm our
bodies, the vessel to our skin, the water to the intercellular
fluid or lymph in which our tissues are bathed, and its surface
whereby oxygen is absorbed from the air to our lungs. Just
as the sponge cannot ‘be said to live in air, so we do not really
live in air. We—that is, the tissues which compose our bodies
—live in what Claude Bernard* has termed an internal medium,
viz. the intercellular fluid which exudes from the blood-vessels,
gives nutriment and oxygen to the tissues, and returns again to
the general circulation by the lymphatics and veins.

It will simplify our conception of this subject if we fix in our
mind’s eye one little mass of protoplasm or cell, and consider
what changes will be produced in it by different conditions.
Any alteration in the amount of the nutrient fluid, or in its
composition, will necessarily produce a change in the nutrition
of the living matter to which itis supplied. If nutriment be
withdrawn, the cell will begin to burn away. If oxygen be
withheld,f or the products of waste be not removed, combustion
will cease, and the cell will die. If nutriment or oxygen be
supplied in insufficient quantity, or the products of waste only
partially removed, the cell may adapt itself to the altered cir-
cumstances, and its nutritive and functional processes go on in
the same way, but toa less extent than before; or they may
become deranged—that is to say, the cell Hawchies diseased.
The limits within which the cell can adapt itself to changes in
nutrition are the limits of its health. The higher animals, how-
ever, are no mere aggregation of cells, each nourishing itself
independently of the others ; for each cell has its own peculiar
function, each its special kind and amount of nourishment; and
none must do either too much or too little work, none must have
too much or too little nourishment, or the nutrition and func-
tional activity of the body as a whole cannot be properly main-
tained. ‘This delicate adjustment of the several parts to cne

* Bernard, Revue des Cours Scientifiques, 1863-4, p. 278.
¢ Kihne, Untersuchungen iiber Protop'asn:a u. Contractilitdt, p. 58.

Q 2

228 EXPERIMENTAL INVESTIGATION OF TIE ACTION OF MEDICINES.

another is secured by means of the nervous system, which
regulates at once the activity of any organ, the quantity of
nutritive fluid supplied to it, and the amount of material it shall
take up. The means by which it acts are, its direct influence
on the nutrition of cells themselves,* as is seen in the salivary
glands ;f or its indirect action through the circulation in slowing
or quickening the heart, which propels the blood ; in contracting.
or dilating the vessels which convey it to any part ;{ or, on the
capillaries which allow the actual nutritive fluid or lymph to
filter out and bathe the tissues. LDesides thus regulating the
supply, it also regulates the composition of the nutritive fluid
by maintaining a due relation between the activity of the body,
the supply of new material by digestion, and the separation of
effete products by the excreting glands. On account of this
mutual dependence of all the parts of the body on one another,
if one gets wrong it puts the others out of order. Thus a
sudden chill may act on the vaso-motor nerves, and cause con-
traction of the vessels of the skin; the blood they contain is
thus thrown hack on the internal vessels§ and congestion and
inflammation of the kidneys ensue. In consequence of this,
they no longer excrete as they ought the effete products, which
then accumulate in the blood, react on the nervous system, and
this again on the muscles; and so the circle goes on. In the
- ease supposed, the vaso-motor nerves of the kidneys have also
been reflexly affected by the chill, and in consequence the renal
arteries have not contracted sufficiently to resist the increased
pressure and prevent congestion ; while in another they might
have done so, only allowing so much blood to pass as to in-
crease secretion, and, by thus lessening the flow in the renal
vessels have counteracted the effect of vascular contraction in the
skin, restored the normal pressure in the kidneys and preserved
health. When all the organs are able to accommodate their
nutrition and function to great alterations, we say the health
is strong; but when they can only do so to slight ones, we say

* Ludwig, Physiologie d. Menschen, vol. ii, p. 346.

+ Heidenhain, Studien aus d. Physiolog. Institut zu Pistind Heft iv, 1868.
t Ranvier, Compt. rend., 1869, vol. ii, p. 1326.

§ Fide Johnson, British Medical Journal, Dec. 6th, 1873, p. 664.

ACTION OF DRUGS ON CELL LIFE. 220

the health is weak ; and when this is the case with one organ
alone, we say that it is specially weak.

Effect of Drugs.—The nutrition of a cell may not only be
altered by changes in its supplies of nutriment and oxygen, but
it may be modified or destroyed by the addition of certain sub-
stances to the nutrient fluid. Thus a weak solution of alkali
may increase or diminish the rapidity of the changes which it
undergoes, by hastening the removal of waste products if they
be acid, or retarding it if they be alkaline; while a weak acid
will have an opposite effect. Certain metallic salts may stop
them altogether by forming a firm compound with the substance
of the cell, while other bodies may enter into combination with
it for a time (possibly replacing some ordinary ingredient of its
nutriment), again passing out and leaving it in its primitive con-
dition, but altering during their stay its physical characters and
functional properties. Such seems to be the case with curare,
which, when injected into the blood, paralyses the peripheral
ends of motor nerves; but, if life be preserved by artificial
respiration, the poison is excreted, and its effect passes off.* No
change can be noticed in the nerve-fibres, either by the naked
eye or microscopically, during the paralysis ; and this was sup-
posed to show that great functional alterations may occur with-
out any structural change. But this is not the case; for Kiihnef
has ascertained that, when the ends of motor nerves in muscles -
are examined microscopically, their outline is found to be more
distinct during the action of the poison. It is possible that the
change in physical properties shown by this distinctness of out-
line may be only the indication of some more important altera-
tion in their chemical composition; but, whether it be more
chemical or physical, a change at any rate takes place; and to
this, I believe, we must attribute the alteration in function.

Whatever be the composition of protoplasm, the substances
which are associated with it in the composition of different cells
are at any rate different; and, although the same nutritive fluid
is supplied to them, they do not all take out from it, or give out
to it the same substances in the same proportions, but some take

* Brodie, Phil. Trans., 1812, p. 205.
+ Stricker’s Histology, Power’s translation, vol. i, p. 221.

230 EXPERIMENTAL INVESTIGATION OF TIE ACTION OF MEDICINES.

up more of one thing aud some more of another. And they de
just the same with drugs added to the nutritive fluid. Thus
lime salts naturally exist in the blood, and are carried by it to
every part of the body; but while the bone-cells take them up
in large amount, nerve-cells assimilate an almost infinitesimal
quantity.* And if we feed an animal on madder, which has an
affinity for lime-salts, the bones become deeply stained, while
the nerves and fat retain their normal colour. It is possible,
too, though experiments on this point are wanting, that a sub-
stance added to the nutritive fluid may be taken up by two
structures, but may have a very different effect on the one from
what it has on the other; just as a grain of sand, which would
have no effect on the machinery of a locomotive, may totally
stop the movements of a watch. We do not know whether
sulphocyanide of potassium and curare are taken up equally by
nerves and muscles or not; but the former salt will paralyse the
muscles without affecting the nerves, while curare will paralyse
the nerves, but leaves the muscles intact.T

The cells composing one structure, then, take up and are
acted on by some drugs, and not at all by others; while other
structures are much affected by the very substances which had -
so little action on the first.

Direct and Indirect Action—When any drug is taken up by
a structure and acts upon it as curare on the ends of motor
nerves, we term this its direct action. Thus paralysis is due to
the direct action of curare on the motor nerves. But, as all
parts of the body are dependent on one another, some other
structure may be affected, not by the action of the drug upon it
but by that which it has exerted on the first part. This is its
indirect action. Thus, when curare has been given to an animal,
it occasionally happens that the nerves going to the respiratory
muscles become paralysed before those which go to the extremi-
ties.t The muscles of respiration then cease to act, the blood is
no longer arterialised, carbonic acid accumulates, and, by irri-

* Buchheim, Arzneimittellehre, p. 25.

+ Bernard, Lecons sur les Effets des Substances Toxiques, p. 314,

t Hermann, “Ueber eine Bedingung des Zustandekommens von Vergif-
tungen,” Du-Bois Raymond und Reicharl’s Archiv, 1867, p. 64.

VARIETIES OF ACTION—DOSE. 231

tating the nerve-centres, produces convulsions, which cease when
the action of the poison extends to other nerves. In this case
neither the muscles, the blood, nor the nerve-centres, are acted
. on directly by the curare. The muscles will contract if stimu-
lated, and, if the lungs be artificially supplied with air, the blood

will be arterialised as usual, the convulsions will cease, and life
' may be preserved. These asphyxial convulsions, which are pro-
duced by the circulation of venous blood in the nerve-centres,
are thus due to the indirect action of curare.

Local and Remote Action.—Before curare could reach the
nerves on which it acted directly, it was necessary for it to enter
the circulation, but it had no marked action on the spot whence
it was absorbed. Other substances, however, produce an effect
on the spot to which they are applied, and this may be inde-
pendent of any effect which they produce after absorption. This
is termed their /ocal action. Thus strong sulphuric acid taken
into the stomach combines with its tissues and forms a slough :
this is its local action. But besides this, the irritation in the
stomach produces through the nervous system a weakening effect
on the heart, the circulation stops, and the person dies. It is
not the sulphuric acid which has found its way into the circula-
tion and acted on the heart that arrests its pulsations, but the
irritation in the stomach which has influenced it through its
nerves. This is the remote effect of the acid.

Dose.—The effect produced by-any remedy depends on several
conditions. ‘The first of these is the amount existing wn the blood
at any given time, which we may call the actual dose, to distin-
guish it from the usual dose administered by the stomach or
otherwise, a part of which may not be absorbed, but remain
inert at the point of introduction. The action which a drug has
on the body is not dependent on its absolute amount, but on the

proportion it bears to the body on which it is to act, so that an
- amount which is a small dose for one person is a very large one
for another.* Thus if a grain of some active substance be
injected at the same time into the veins of a full-grown man and
into those of a boy of only half his weight, it will be distributed
through twice as much blood in the man as in the boy, and

* Buchheim, Arzneimitiellehre, p. 65.

232 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

each tissue will only receive half as much of it. The dose of a
drug must therefore be regulated by the weight of the patient ;
and thus women, being lighter, require a smaller amount than
men, and children less than adults. Though it would be more
exact, it is not always convenient, to weigh patients; but in
experiments on animals the weight of the animal should always
be carefully ascertained, as well as the amount of the drug
administered. If a substance be injected into the veins, the
whole of it mixes with the blood and becomes active imme-
diately, and-the maximum effect is thus at once obtained and
will again diminish as the substance is excreted. But the case
is different if it be injected subcutaneously, and if it be given
by the stomach or any other mucous cavity the difference is still
ereater ; for as soon as some of it is absorbed excretion begins,
and thus part of the drug is passing out of the blood while
another part is being taken in. The amount in the blood is,
then, only the difference between that absorbed and that excreted in a.
given time, and absorption may be so slow or excretion so quick
that there is never a sufficient amount of the substance in the
blood to produce any effect. Thus Bernard found that a dose of
curare which would certainly paralyse an animal when injected
into the veins or even subcutaneously, would have no effect
when introduced into the stomach;* and showed that this
was due to the kidneys excreting the poison as fast as it was
absorbed from the stomach, by extirpating the kidneys,f when
the animal became paralysed as surely as if the poison had
been introduced at once into the veins, though not so quickly.
Hermann also discovered, without being acquainted with
Bernard’s observations, that curare taken into the stomach
would produce paralysis if excretion were prevented by ligature
of the renal vessels. 7

The more rapid the absorption, or the slower the excretion, of
uny drug, the greater will be its effect. Thus the effect produced
by the same dose of a medicine will be in proportion to the
rapidity of its absorption from the different parts to which it
has been applied, unless the differences be so slight or the excre-

* Bernard, Lecons sur les Effels des Substances Toxiques, p. 282.
+ Bernard, Revue des Cours Scientifiques, 1865.

ABSORPTION—CUMULATIVE ACTION, 233

tion so slow that there has not been sufficient time for the
removal of any considerable quantity from the blood, On this
account we must diminish the dose of a medicine in order to
obtain the same effect, according to the rapidity of absorption
from the place to which we apply it. Absorption is quickest
from a serous membrane, then from intercellular tissue, and
lastly, from mucous membrane. ‘he vascularity and rate of
absofption from intercellular tissue is greater on the temples,
breast, and inner side of the arms and legs than on their outer
surfaces or on the back.* It should not be forgotten that any
drug introduced into the stomach but not absorbed into the blood
is as inuch outside the body as if it were in the hand, for any
effect it will have on the system, provided always it have no
local effect on the gastric walls. For if it act directly on the
walls of the stomach, it may have an effect which it would not
have when held in the hand or applied to the skin. Thus
mustard, which would produce redness and burning of the skin,
will cause vomiting when swallowed; but opium, which does
not act on the stomach itself, produces no effect until after it
has been absorbed.

By the difference between absorption and excretion under
(lifferent circumstances or in different individuals,f the cumula-
tive action of drugs, the erfect of idiosyncrasy, habit, climate,
condition of body, as fasting, etc., disease, and form of adminis-
tration, can to a great extent, though not entirely, be explained ;
but experiments on some of these points are deficient, and the
explanations now given are to some extent theoretical.

Cumulative Action.—If a substance be naturally so slowly
excreted from the body that the whole of the dose in ordinary
use is not excreted before another is given, the amount present
in the body will gradually increase, just like the curare in
Hermann’s experiment, and will produce an increasing or cumu-
lative effect. Examples of this are to be found in metallic pre-
parations, such as those of mercury or lead, which are excreted
very slowly; or in some of the organic alkaloids, if given in

* Eulenburg, Hypodermatische Injection der Arzneimitiel, 3rd edition, p. 65.
+ Children absorb more quickly than adults, so opium is more dangerous to
them. Marx, Lehre von den Giften, vol. ii, p. 117,

234 EXPERIMENTAL INVESTIGATION OF TUE ACTION OF MEDICINES.

sufficiently large and frequent doses. The size of the dose and
the frequency with which it must be repeated in order to pro-
duce a cumulative effect will differ according to the rapidity
with which the drug is excreted; for, if excretion be rapid, a
larger dose, or more frequent repetition, will be required. The
long time which elapses before a dose of opium takes effect on
some individuals is probably due to its being very slowly
absorbed ; and the power of one man to take, without apparent
effect, an amount of alcohol or opium which would intoxicate
another, to its either being more slowly absorbed from the
stomach or intvstine, or more quickly excreted by the lungs,
skin, or kidneys, so that the amount present in the blood at any
one time is never sufficient to produce toxic effects. There are
two vegetable active principles, digitalin and strychnia, to which
an especial cumulative action is ascribed. After moderate doses
of these drugs have been taken for some time, it is found that
instead of the effects they produce increasing gradually, as we
would expect from a gradual accumulation in the blood, the
symptoms of poisoning become suddenly developed in some-
what the same way as if the dose had been suddenly increased.
It is evident that a diminution in the quantity excreted will
produce this effect as readily as an increase in the quantity
taken, and this is probably the true cause of the phenomenon.
When digitalin has been taken for some time and accumulated
to a certain extent in the blood it causes a diminution in the
amount of urine excreted, and this diminution is either accom-
panied or quickly followed by the other symptoms of poison-
ing.* The effect indeed seems exactly the same as Hermann
would have obtained in his experiment if he had only partially
compressed the renal arteries instead of ligaturing them com-
pletely. For digitalin appears to diminish the secretion of urine
by exerting a powerful action on the renal vessels,t and in large
doses may completely arrest the secretion of urine,f and prob-
ably also the circulation through the kidneys.

* Brunton, On Digitalis, with some Observations on Urine, p. 39 (vide antea,
p- 61).

+ Brunton and Power, Proc. Roy. Soc., 1874, No. 153, and Centralblatt d.
Med. Wiiss., 1874, p. 497 (vide postea, pp. 410 and 412). |

t Christison, Hdin. Med. Journ., vol. vii, p. 149. Mazel, Gazette des
Hépitaux 1864-74.

EFFECTS OF VARIOUS CONDITIONS —HOM@OPATHY. 235

Effect of Habit, Climate, Fasting, and Form of Administration.
—The effect of habit in lessening the action of drugs may be
due to increased power of excretion or diminished absorption ;
and that of a warm climate in increasing the action of narco-
tics, such as hyoscyamus, to their excretion being hindered by
the diminution in the amount of urine consequent on the
increased cutaneous transpiration. A medicine taken by a fast-
ing person is generally more rapidly absorbed and has a greater
effect than if the stomach be full, as is well known in the case
of alcohol. The form of administration has also an effect on the
rapidity of absorption. When a drug is given in a soluble form
in small bulk it is more quickly absorbed, and will have greater
effect than when given in an insoluble form or much diluted.
Thus two glasses of raw brandy may intoxicate a man, espe-
cially if taken on an empty stomach when the person is thirsty
and absorption therefore rapid. The same quantity diluted
with two quarts of water would have little or no effect, for
before the stomach could get the whole absorbed, the alcohol
which had first found its way into the blood would have been
in great part either excreted or consumed.

Large and Small Doses.—The effect produced by a small dose
of a drug is sometimes exactly the opposite of that produced by
a large one. We cannot say exactly why it is so; but we very
generally find that any substance or any condition, whether it
be acid or alkali, heat or electricity, which in moderate amount
increases the activity of cells, destroys it when excessive.*

Homeopathy.—This opposite action of large and small doses
seems to be the basis of truth on which the doctrine of homceo-
pathy has been founded. The irrational practice of giving
infinitesimal doses has of course nothing to do with the prin-
ciple of homeopathy—similia similibus curantur: the only
requisite is that mentioned by Hippocrates, when he recom-
mended mandrake in mania; viz., that the dose be smaller than
would be sufficient to produce in a healthy man symptoms
similar to those of the disease. Now in the case of some drugs
this may be exactly equivalent to giving a drug which pro-

* Kiihne, Untersuchungen iiber Protoplasma und Contractilitdt, pp. 49, 31,
33, and 43.

236 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

duces symptoms opposite to those of the disease; and then we
can readily see the possibility of the morbid changes being
counteracted by the action of the drug and benefit resulting
from the treatment. For example, large doses of digitalis
render the pulse extremely rapid, but moderate ones slow it.*
In this instance its moderate administration when there is a
rapid pulse is homceopathic treatment, and this has sometimes
been beneficial. But it is not proved that all drugs have an
opposite action in large and small doses, and homeopathy,
therefore, cannot be accepted as an universal rule of practice.
Constitution and Idiosyncrasy.— Variations in the action of a
drug cannot be entirely explained, however, by the varying
amount in which it may be actually present in the circulation
and acting on the body. Another modifying element of great
power is constitution. In animals generally we have certain
motor arrangements in the bones and muscles, regulating
arrangements in the nervous system, and yet other arrangements
in the circulatory system for supplying them with the material
necessary for the performance of their functions. But the parts
which enter into each of these are not equally developed in all
animals; in some one part preponderates; in others, another.
Even in animals of different, species, and in individuals of the
same species where the relative size of organs seems the same,
differences nevertheless exist; and the presence of a few cells
more or less in a ganglion, and a few fibres more or less in a
nerve, may alter to a very great extent the action of any sub-
stance on the organism. When a medicine given to one person
produces an effect slightly differing from that which it gener-
ally causes, the difference is said to be due to constitution ;
when its difference is great, it is said to be due to ¢diosyncrasy.
Now, these effects may be merely due to differences in absorp-
tion and excretion, as has been already explained, or to the
different relative development of other parts, especially parts of
the nervous system. It is easy to understand the altered effect
which may be thus produced, and to perceive the ambiguity of
such terms as “nervous stimulant,’ when we recollect that

* Vide Traube, Med. Centr. Ztg., vol. xxx, p. 94, 1861, and Brunton On
Digitalis, p. 21 (vide antea, p. 47).

a

~ ee er

LFFECT OF CONSTITUTION, 237

different parts of the nervous system act exactly in the opposite
way to others; and if anything should act on both of these, it
will produce an opposite effect according as one or other part is
more developed and more powerful. ‘Thus, the vagus nerve has
the power of rendering the heart’s action slow, and the accele-
rator nerve of quickening it ; and any drug which irritates them
both will make the heart’s action slow if the vagus be more
developed, or quicken it if the sympathetic be stronger. Thus,
two horses of unequal strength, pulling in opposite directions,
may counterbalance each other; but if both be struck with a
whip at the same moment, the power of the stronger becomes
evident and he pulls the weaker after him. )

A good example of this action is given by muscarin, an alka-
loid obtained from a poisonous mushroom, Agaricus muscarius.
Professor Schmiedeberg, of Strassburg,* has shown that this
alkaloid produces great irritation of the vagus nerve, so that in
frogs the heart will stand still for hours together. When given
to dogs, it sometimes makes the pulse slow, but sometimes.
quickens it; and one might therefore be inclined to say that
when it produces quickening it cannot be acting on the vagus.
But the explanation of this phenomenon is, that muscarin does
not act on the vagus alone, but has also an effect on the vaso-
motor nerves, producing dilatation of the vessels and diminu-
tion of the blood-pressure in them.f Now, lessened pressure
acts as a stimulant to the accelerator, and quickens the heart.
In this way muscarin stimulates both vagus and accelerator, and
the pulse is rendered quick or slow according as the power of
the one or other is greater in the particular dog to which it is.
given. In frogs, the blood-pressure has no great action on the
heart, and in them the effect of the vagus is not interfered
with.

Another instance may be given where an apparent difference
in the effect of a drug on two animals may be removed by
reducing their organs to the same condition. In most animals,
the slowing action of the vagus on the heart is constantly
exerted during health ; and when it is cut the heart beats much

* Schmiedeberg und Koppe, Das Muscarin, p. 28.
t+ Schmiedeberg, op. cit., pp. 43 and 48.

238 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

faster. But in the rabbit, its power is comparatively small, and
the increased rapidity of the pulse after its division is but
slight. In most dogs, on the contrary, its power is great, and if
it be cut, the heart beats very much quicker, and cone more
blood into the arteries, so as to raise the pressure in them. If
we measure the pressure of the blood in the arteries of a rabbit
and of a dog, and then cause them to inhale nitrite of amyl, we
find that the small vessels have become widened and allow the
blood to pass easily out of the arterial system into the veins, so
that the pressure sinks considerably in the rabbit, but it sinks
only slightly in the dog. The effect seems at first sight
different ; but when we examine it more closely, we find that
the heart of the dog is no longer beating slowly, but very
quickly, so as to keep up the pressure, notwithstanding the
rapid flow of blood throvgh the widened vessels, while the
heart of the rabbit was going so fast before that it could not go
much more quickly. If we cut the vaci in the dog, so that the
heart goes as quickly as in the rabbit before it begins to inhale,
the blood pressure sinks during the inhalation, just as it does in
the rabbit.*

I have given these examples at leneth, because of their
important bearing on the question how far conclusions as to
the action of medicines on man may be drawn froin those
which they exert on the lower animals. Now, the action of
curare in paralysing the ends of motor nerves is one of the
simplest and least complicated examples that we can take, as
the very nature of its action prevents disturbances in other
systems from showing themselves; and we find that it is
exactly the same in the Indian who accidentally wounds him-
self with his poisoned arrow, in the game which he shoots, or in
the frog on which we experiment.

Motor nerves, the structure on which curare acts, are alike
present, and in all are its results the same.

. As we have seen that in the lower animals, differences in
the action of drugs are produced by differences in the structure
of the animal, and that the former disappear when the latter

* Lauder Brunton, “ Action of Nitrite of Amyl on the Circulation,” Journal
of Anatomy and Physiology, vol. v, p. 95 (vide antea, p. 176).

ACTION IN HEALTIT AND DISEASE. 239

are removed, we are, I think, justified in concluding that, when
the organs or structures on which a drug acts are similar in
man and the lower animals, the action will be alike, and that
variations will be observed just in proportion to the difference
between his structure and theirs. But as it may be difficult or
impossible to detect these differences except from the effects,
we ought to test our conclusions as to the action of remedies
by giving them to a healthy man, and observing whether their
effects are such as we have been led, from our experiments on
animals, to expect.

Disease—The different effects of a medicine in health or
disease may be partly due (1st) to alterations in the relative
amount of absorption or excretion produced by the disease and
consequent changes in the quantity of the drug actually present
in the blood. Thus, enormous quantities of opium have been
given during the collapse of cholera without producing any
effect, because no absorption took place, and the opium re-
mained in the stomach so long as the collapse persisted. When
it passed off and absorption again began, the opium was taken
into the circulation and exerted its usual action, so that persons
have died of the remedy after recovering from the disease.

The difference in action is due (2nd) to the alterations pro-
duced by disease in the organs and tissues of the body which
may interfere with both the indirect and direct actions of the
drug. Thus, digitalis usually slows the pulse by acting on the
heart through the vagus. But in febrile diseases it sometimes
has little or no perceptible action on the pulse. This is prob-
ably due to the fact, that the accelerating ganglia of the heart
are stimulated by the high temperature to such an extent that
the vagus can no longer restrain them. For irritation of the
vagus trunk by galvanism, which has a stronger action on the
heart than digitalis and usually stops its pulsations entirely,
ceases to do so when the temperature of the animal is raised,
and yet the vagi are not paralysed, for when the motor power
of the heart diminishes they can again stop it, although the
temperature may still be high.* What the alterations in each

* Lauder Brunton, “On the Action of Heat upon the Mammalian Heart,”
St. Bartholomew Hospital Reports, vol. vii, p. 221 (vide p. 212).

240 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

disease, and the ways in which they will modify either the.

direct or indirect action of remedies, really are, can only be
determined by an increased knowledge of pathology and by
actval clinical observation. | |

Chemical Constitution and Physiological Action. —1 have
spoken thus far only of the changes in the body and the
various effects which they produce; but I must not leave this
subject without mentioning the wide field of research which
has been opened up bythe remarkable discovery made by
Drs. Crum Brown and Fraser,* of the relation which exists
between chemical constitution and physiological action. It was
known before that one drug would act only on one part of the
body, another on another; but they have shown that changes
in the chemical composition of a drug may not only alter its
action, but transfer it to a different structure: so the addition
of sulphate of methyl to strychnia, brucia, or thebaia, causes
them to act on the terminal branches of motor nerves instead

of on the spinal cord, while a similar addition to other alkaloids:

removes some of their actions but leaves others unchanged.
Further researches of this kind may enable us to determine
what parts will be acted on by a drug after a definite change
has been effected in its chemical constitution; and the progress

of physiological chemistry in ascertaining the composition and

properties of the tissues renders it not impossible that such
knowledge may yet be acquired as that spoken of by Locke in
the following words: “ Did we know the (mechanical) affections
of the particles of rhubarb, hemlock, opium, and a man, as a
watchmaker does those of a watch, whereby it performs its
operations, and of a file, which by rubbing on them will alter
the figure of any of the wheels, we should be able to tell before-
hand that rhubarb will purge, hemlock kill, and opium make a
man sleep.” And even though our knowledge should never
reach this extent, the rapid advances which it has made of late
years, the power which we now possess of altering the chemical
composition of the organic alkaloids, and along with it their
physiological action, and the fact that two of them (conia and
muscaria) have already been made synthetically, incline us to

* Transactions of the Royal Society of Edinburgh, vol. xxv, pp. 1 and €93.

LOCALISATION OF ACTION. 241

believe that we may by-and-by make the substances which
will produce the physiological effects which we desire, and that
a future lies before therapeutics of which at present we can
hardly dream.

II.—AcTION oF DRUGS ON PROTOPLASM: GENERAL DIRECTIONS
FOR EXPERIMENTAL INVESTIGATION.

British Medical Journal, 1871, May 138th, p. 435, and May 20th, p. 521.

Modes of Fxperimenting.—Caution.—Action of Drugs on Protoplasm.—Action
on Vibriones and Bacteria.—Contagium Vivum.—Action on Fungi; on
Fermentation; on Putrefaction; on Oxidation; on White Blood Cor-
puscles; on Inflammation.—Action of Gases.— Steps of an Investigation —
Administration of Drugs.—Observation of Effects.—Interpretation of
Results.—Minimum Fatal Dose.—Various Channels of Administration.—
Excretion.— Mode of Securing Animals.—Instruments required.—Mode of
making Cannule, T-tubes, and Pens.—Narcotising Animals.—Action of
Narcotics.—Introduction of Cannule into Vessels—Injection of Fluids.—
Division and Irritation of Nerves.—Artificial Respiration ; in Mammals;
in Frogs.—Administration of Gases or Vapours.

GENTLEMEN,—In experimenting on the effect of drugs, our great
object must be to localise their action—to be able to say with
certainty, This is the organ on which this medicine acts, and
such and such is the action which it exerts upon it. There are
two ways in which this might be done.

1. We might give the medicine to animals of all kinds, from
those consisting of one simple cell upwards to the highest
forms of life, and mark how its action became modified as we
advanced farther and farther from the simple mass of sarcode,
and organ after organ became differentiated and developed.
Unfortunately, however, the knowledge of comparative anatomy
and physiology which is required to interpret the effects that
we might thus obtain is so great, and possessed by so few, that
this method is at present of little use.

2. We might take a highly organised animal, not very unlike
man in its general structure, and, by operative procedures, allow
the medicine to act now on one and now on another part of the
body, but never cn all at once, till we fiud out those parts for
which it has a particular affinity.

This second method is the one which we chiefly employ, but

Rh

242 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

sometimes we may very conveniently use them both, as in the
case of protoplasm, the physical basis of life.
- Caution—As I intend not only to describe the ways in |
which experiments on the action of medicines are to be per-
formed, but also to give examples of the conclusions drawn by
various observers from the experiments which they have made,
and of the way in which these conclusions have been applied, I
take this opportunity of strongly warning you, once for all, that
you, must distinguish very carefully between the observations
‘actually made by any one and the conclusions which he draws
from them. Observations on the effect of a drug may be
correct, and yet the theory of its mode of action be erroneous ;
and both of these may be right, and still the proposed applica-
tion of it to a disease may be valueless from ignorance of its
real pathology. All observations, too, are not to be taken as
facts: they must be confirmed by frequent repetition either by
the first observer himself or by others before they can lay claim
to this title. Their value depends to a great extent on the
observer, and is in proportion to his power of seeing correctly
what is before him, and the exactness of his description of what
he has seen. Perhaps erroneous statements are due in great
measure to the results of experiments not being noted at the
time when they were done, but written down from memory
some time afterwards. When this is the case, they lose in a
creat measure their claim to the name of observations, and they
become merely thoughts or ideas of the observer. All experi-
ments should be noted down at the time when they are performed ;
and if they are not, the time which elapsed before they were
written should be stated, that future workers may know what
value to attach to the observation, and not be put to the
unnecessary trouble of disproving it if it be erroneous. Before
beginning an investigation, it is convenient to write out the
questions which we propose to ourselves, and to note down
what experiments will be necessary to answer them. We are
thus less likely to make experiments at random, and to waste.
time without coming to any certain conclusion.

Action on Protoplasm.—We may study the action of drugs on
protoplasm either in unicellular organisms like the Infusoria, in

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ACTION ON INFUSORIA. 213

cilia, in white blood-corpuscles, or in those minute bodies—
bacteria and vibriones—to which attention has of late been so
much directed, and which, despite their minuteness, possess so
much importance from their power of producing fermentation
and decomposition in dead organic matter, and not improbably
‘of causing disease in living beings. For the purpose of study-
ing it in Infusoria, we prepare an infusion of hay some days
before we wish to experiment, and a solution in water of the
drug which we wish to investigate. We then heat a piece of
glass tubing in the middle, draw it out and cut it across, so as
to obtain two little pipettes, which will deliver drops of nearly
equal size.. From one of these we let fall a drop of infusion of
hay on a glass slide, and examine it under a low power of the
microscope without a covering glass. We then let fall a drop
of the solution of our drug upon it, mix the two drops well with
a glass rod, and again examine them microscopically to see
whether or not the infusorial animalcules are still moving. If
they be moving, and continue to do so for some time, we pre-
pare a stronger solution of the drug; but if they have com-
pletely stopped when we looked, we make a weaker one, and
again mix a drop with one of hay infusion, repeating the experi-
ment till we have got a solution of such a strength that a slight
movement of the animalcules can be observed just after mixing
the drops, but ceases almost immediately, and eannot be brought
back by adding water. We can then compare the action of
‘different drugs by observing of what strength the solution of
each must be, in order to produce precisely this effect.

Professor Binz of Bonn has found in this way that certain
substances, such as common salt, chlorate, chloride and bro-
mide of potassium, alum, &c., appear to stop the movements of
Infusoria by altering the amount of water which they contain,
as strong solutions cause them to shrivel at first, and then to
swell up and become motionless. Weaker ones make them
swell likewise; but their effect at first is different, as they do
not shrivel up the animals, but, on the contrary, render their
movements more lively.

Other substances kill them in a way which we do not under-
stand, stopping the movements at once without producing any

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244 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

apparent change in the animal’s body to account for it. The
most active of these substances are chlorine, bromine, corrosive
sublimate, iodine, permanganate of potash, and creasote. After
these comes quinine, less powerful than they, but far more so
than other erganic alkaloids. Even strychnia, so fatal to higher
animals, has barely one-fourth the power over these lower
organisms which is possessed by quinine, a substance which is
dangerous to mammals only in such large doses that we are
accustomed to look upon it as a remedy, but hardly at all as a
poison.

Action on Vibriones and Bacieria.—If a piece of boiled meat
or white of egg be allowed to lie in water for a few days, or a
little of Pasteur’s solution be exposed in a glass, the fluid
becomes milky, and vibriones and bacteria are formed in large
numbers. Pasteur’s solution is made by dissolving 10 grams of
sugar, 5 decigrams of tartrate of ammonia, and 1 decigram of
yeast-ash, in 100 c.c. of water; or a little white of egg may be
added to the hay infusion, when the Infusoria soon disappear,
and it remains full of bacteria and vibriones. A drop may
now be taken, diluted with another drop of water, and the
action of drugs on vibriones examined in the same way as on
Infusoria.

In this way it is found that the same substances which kill
Infusoria also prove destructive to vibriones and bacteria: and
if they kill these organisms when outside the animal body, they
should do so likewise when they are inside, and thus cure
diseases that may be caused by their presence. Now, bacteria
have been said to be the cause of malignant pustule, and they
are at all events frequently present in large numbers in the
blood of animals affected by it, and their destruction can hardly
fail to be advantageous. We are, therefore, not at all surprised
to learn that Bouley and the French Commission found* that,
while all animals which they inoculated with this disease died
when left to themselves, four recovered out of five to which
they had given carbolic acid, and that other cases treated in the
same way by others gave a like favourable result. The striking
correspondence between the effect actually produced on the

* Compt. rend., vol. Ixviii, p. 82.

ACTION ON BACTERIA, FUNGI AND FERMENTATION. 245

disease an! that which we should expect from its action on
dacteria, which we suppose to be the cause of it, seems also to
be an evidence of the truth of the hypothesis that bacteria are
the cause of the disease, and that carbolic acid cures it by
killing them. Before we accept this as a fact, however, we
should test it by adding to one portion of the blood of a diseased
animal, carbolic acid in the same proportion as was likely to
be present in the blood of the one cured, and comparing it with
another portion to which none had been added, and see whether
the amount was sufficient to have any action on the bacteria.
If it were not sufficient, we should have to look for some other
action of the acid to explain its effect.

As cases of malignant pustule or other diseases in which
bacteria and vibriones are found in the blood happily do not
present themselves every day, Binz produced fever in dogs
artificially by injecting infusion of hay or putrid animal matter
into their veins, and then tested the action of quinine by inject-
ing it either at the same time or shortly afterwards. The
quinine diminished the effect of the infusion, but not to the
extent which he expected; and this he thinks due to the infu-
sion not containing vibriones alone, but gases and other pro-
ducts of decomposition, whose action would not be affected by
quinine. Whether this be so or not, must be decided by further
experiments. He believes also that hay-fever is due to vibri-
ones; and he cured Helmholtz, who had suffered from it for
several years, by injecting a solution of quinine into his
nostrils.

Action on Fungii—When spores of the ordinary penicillium
or mould-fungus are thrown into Pasteur’s fluid or syrup, they
grow and develop new spores. Two portions must be taken, and
the drug to be tested added to one and not to the other, and
the amount of it necessary to prevent the formation of spores
must be noted. If carbolic acid, corrosive sublimate, or very
strong solutions of quinine be added to them their growth is
prevented.

Action on Fermentation—As butyric fermentation depends
on the presence of vibriones and alcoholic on the yeast-fungus,
we should expect that substances which kill these would

216 EXPERIMENTAL INVESTIGATION OF TIIE ACTION OF MEDICINES.

prevent fermentation. To test this, two glass-tubes or flasks
are filled with a mixture of milk-water, grape-sugar, and chalk
(from which carbonic acid will be set free by the lactic acid
formed), or with a solution of grape-sugar or yeast. To one of
them a certain amount of the substance to be tested is added,
and both are then inverted over mercury and kept in a warm
place for several days. The amount of gas developed is then
measured ; and, if the addition of the substance have hindered
the production of gas, we know that it has hindered fermenta-
tion in the same proportion. It has thus been found that
quinine, amounting to ;1,th part of the mixture, completely
stopped the development of vibriones or the production of gas ;
and other substances have a similar effect.

As many cases of indigestion, acidity, flatulence, vomiting,
and summer diarrhoea, more especially in children fed by hand,
are most probably due to the fermentation of starchy and sac-
charine food caused by vibriones, Binz thinks that creasote,
quinine, &c., are serviceable in their treatment by stopping this.
As it is the local action that is wanted, the longer the medicine
remains in the intestine before being absorbed, so much the
better will its effect be; and thus the greater benefit derived
from bark than quinine in some such cases might be explained.

Action on Putrefaction.—The antiputrescent action of drugs is
tested by putting a square of boiled white of egg into each of
two vessels containing water and setting them in the sun. To
the liquid in one vessel the drug is added, and the rapidity with
which the edges of the square of white of egg on it become
decomposed and soft is noted and compared with that in the
other vessel. Instead of white of egg, a piece of meat or bread
may be used. The relative power of different drugs in stopping
putrefaction does not always correspond to the ideas which we
would be inclined to form; for who would think that quinine
would be. more powerful than such antiseptics as creasote,
chloride of lime, or arsenic ? and yet such is said to be the case.
So powerful is quinine, that a piece of meat placed in a solu-
tion of 4 per cent. of the sulphate, with a little dilute acid,
remained in summer without decomposition till the fluid was
dried up. ;

ACTION ON OXIDATION AND LEUCOCYTES. * ‘ 247

Action on Oxidation.—If fresh leaves of lettuce or dandelion
are triturated with five or ten times their weight of water, with
free access of air, the fluid filtered, and fresh guaiac tincture
added to it, a blue colour is produced, showing that’ozone is
present in it. To test the action of a drug on the forma-
tion of ozone, two portions of the filtered fluid are put in test-
glasses, and the drug added to one. Both are allowed to stand
for one or two hours, with occasional shaking, fresh guaiac tinc-
ture is dropped cautiously into both, and by the greater or less
depth of blue produced in each fluid we judge of the amount
of ozone present in each. In this way it is found that quinine
diminishes or stops the formation of ozone in these fluids, and
at the same time the little protoplasma-granules with which
they abound are rendered motionless and altered in appearauce.
There seems to be some connection between these protoplasma-
granules and the formation of ozone, as the stoppage of the one
runs parallel with the alteration in the other.

Quinine seems to have the power of diminishing oxidation
within the body as well as out of it, since when injected into
the blood it lessens the excretion’of urea and diminishes the
temperature both in health and disease during life, and hinders
its rise after death, and this action is apparently not due
to nervous centres regulating temperature, or to changes in the
circulation allowing quicker cooling by the skin.

Action on White Blood-Corpuscles.—To examine this, we take
a drop of blood from the finger, put it on the under surface of a
thin glass, and lay it over the opening in Stricker’s warm
stage,* and examine it with a high power of the microscope,
such as Ross’s ;4 or Hartnack’s No. 10, at a temperature of
98° F. After satisfying ourselves that the white corpuscles are
in active motion, we take a solution of the drug in fresh serum,
or in half per cent. solution of common salt; mix a drop of it
with the blood and examine again. Or we may use Max
Schultze’s warm stage, which consists of a flat piece of brass
covering the stage of the microscope, and having a long arm
projecting at each side and a thermometer in front. When a
lamp is placed under one or both arms, they conduct the heat

* Stricker’s Histology, New Sydenham Society's translation, p. 13.

248 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES,

to the middle part on which the object les, and thus warm it to
any desired temperature. The drop of blood must be placed on
a piece of glass 34 inches long and 23 broad, which is then laid
on the warm stage. The drop is next covered by a thin
glass, and over all is put the lower part of a lamp-cylinder,
through whose upper end the tube of the microscope slides, and
round whose interior is put a piece of moist blotting-paper to
prevent evaporation from the blood. The drug is applied as
with Stricker’s stage. Solutions of corrosive sublimate and
veratria, even in very minute quantity, stop the movements of
the white blood-corpuscles, but neither is so active as quinine.
Strychnia is rather less powerful than any of these, and many
other alkaloids much less so.

Action on Inflammation—During inflammation, the white
blood-corpuscles are very active, and crawl through the walls
of the capillaries in much greater numbers than usual. It is,
therefore, interesting to inquire what will be the effect on this
of any drug that stops their motions. For this purpose we
curarise a frog, and lay it on a large plate of cork with a hole
at one side and another piece of cork 4 inch high at the
other. We fix the body of the frog to the raised piece, open its
abdomen with a pair of scissors, draw out the intestines, and
fasten the mesentery with very fine pins over the hole. In an
hour and a half or two hours afterwards white corpuscles come
rapidly out of the vessels and wander over the field. We may
then inject our drug into the circulation or apply it locally to
the mesentery.

Binz states that, when he injected quinine into the circula-
tion, the number of corpuscles in the vessels became diminished,
and they ceased to wander out, while those already out con-
tinued to wander further, so that, instead of being evenly
distributed over the field, they left a clear space round the
outside of the vessel, in which few were to be seen. If, on the
other hand, it be applied locally, the corpuscles which are
already out stop moving, while those in the vessel continue to
migrate, and thus, instead of a clear space, a dense accumula-
tion of corpuscles forms round the vessel. In order to produce
this effect, ss 55th to sptg pth of the animal’s weight of quinine

— -
pean Wah GAS) By back aa Lda? ual i ih Bh be a

STEPS OF AN INVESTIGATION. 249

is necessary ; and, if it were given to a man weighing 150 lbs.,
in order to stop the exit of corpuscles from the vessels in such
a disease as peritonitis, 3 or 4 drachms of the medicine would
require to be given within a short time. Binz’s observations as
to the effect of quinine on the white corpuscles have been con-
firmed by Martin, but have been denied by Schwalbe, so that
further investigations on this point are very desirable.

Action of Gases.—This is examined by putting the cells to be
examined on Stricker’s warm stage, and bringing the gas into
contact with them in the manner described by him.*

Steps of an Investigation—The animals which we chiefly
use in experiments are frogs, rabbits, guinea-pigs, and dogs.
In investigating the action of a drug, we examine—

1, What the symptoms are which a large dose produces.

2. Taking the most prominent symptom, we inquire (a) On
what organ does the production of this symptom depend? (0)
How has it been affected by the drug? (c) Has this affection
been primary or secondary ?

3. We examine other organs which we think may have been
also affected.

Administration of Drugs——To examine the general effect of
a drug, we weigh the animal and then give it a large dose in
-our first experiment, in order to get exaggerated symptoms. It
may be given by the mouth or by subcutaneous injection. In
frogs, the substance may be injected either under the skin of
the back or into the abdominal cavity. In rabbits, &., it is
most conveniently injected under the skin of the flank. In
guinea-pigs, the abdominal parietes are very thin; and, if we
wish to compare experiments with different doses, care must be
taken not to push the point of the syringe into the abdominal
cavity, as the absorption will be then more rapid, and the same
dose produce a greater effect. If we wish to give the medicine
‘by the mouth, we either put it well back on the root of the
tongue and then hold the animal’s jaws together till we think it
has swallowed it, or we put a perforated cork between its teeth,
push an elastic catheter through the hole in the cork down the
cesophagus into the stomach, and inject the drug in solution

* Stricker’s Histology, Sydenham Society's edition, p. 8.

250 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

through the catheter. Orfila used to introduce the drug into
an opening in the cesophagus, which he then ligatured to pre-
vent vomiting; but since subcutaneous injection was introduced
this method is rarely employed.

Observation of Hffects.— After the drug has been administered,
we allow the animal to move freely about, but prevent frogs
from escaping by covering them with a large bell-jar. We then
see whether the animal is restless or disinclined to move;
whether its movements are perfectly performed or unsteady ;
whether or not its legs seem weak and paralysed, or convulsive
movements or involuntary twitchings be present; whether its
heart-beats or pulse, and respirations, are quick or slow, strong
or weak, regular or irregular; whether there is vomiting or
purging, diuresis, salivation, dryness of the mouth, flow of
tears, or dry conjunctiva, and whether the pupil be contracted
or dilated. If the animal seems asleep, we pinch it to ascertain
if reflex action continue after voluntary motion is gone; and if
respiration cease, we ascertain if the heart still continue to beat.
As soon as possible after death, we open the animal and see if
the heart still be beating. If it have stopped we note whether
its cavities are full or empty, its walls flaccid or firm, and try
whether it will contract or not on pinching or scratching it, or
on irritating it by an electric current. We observe whether the
veins are turgid or empty, the lungs pale or congested, the
stomach and intestines quiet or in active peristaltic movement,
the spleen large or contracted, the bladder full or empty; and
the urine may be tested for sugar. .

Interpretation of Results—If we find in the course of these
experiments that voluntary motion is increased or lessened, we
may naturally conclude that the activity of the cerebrum is
increased or diminished, unless the increase of motion should’
depend on pain, or its diminution on impairment of the motor
apparatus. Unsteady movements, paralysis or convulsions,
impaired reflex action on pinching, or stoppage of respiration
before the heart, point to the spinal cord, to the nerves, or to
the muscles; while quick or slow, strong or weak pulse, or
stoppage of the heart before the respiration, point to the vaso--
- motor system or cardiac nerves; increased or diminished secre-

LETHAL DOSE—ADMINISTRATION-—EXCRETION. 251

tion, to secreting nerves; and full or empty bladder, and
diminished or increased peristalsis, to the motor nerves of the
bladder or intestine. We then try the effect of a small dose
and note in what respect it differs from that of a large one.
We thus ascertain in a general way what the organ is, which
is chiefly acted on by any drug, and afterwards proceed to
investigate the nature of the action by a farther series of
experiments.

Minimum Fatal Dose.—If the drug be poisonous, we then try
to ascertain the minimum fatal dose. For this purpose we
weigh an animal and inject into it a dose which we think will
not prove fatal, wait a short while, and then inject more till
death is produced. We then reckon how much of the drug has
been injected for every pound weight of the animal. We take
another animal, and inject into it a¢ once a quantity which will
be somewhat smaller for its body-weight than that given to the
first. The reason why a somewhat smaller quantity should be
taken is, that some time was allowed in the former experiment
for the excretion of part of the poison between each dose. If
this amount prove fatal, we must give a still smaller quantity
to another animal; but, if not, we must give more till we find
the smallest quantity which will kill.

Various Channels of Administration—The next point to be
determined is, whether the effects are the same when given by
the mouth or rectum, or other-~mucous surfaces, as by sub-
cutaneous injection. If we should tind, as Bernard did with
curare, that a substance which is active when injected sub-
cutaneously or into a vein, has no effect when introduced into
the mouth, rectum, eye, or bladder, we must determine whether
this is due to want of absorption or to decomposition of the
drug by the secretions with which it becomes mixed. This is
done by mixing it with these secretions, such as urine or gastric
juice, allowing it to stand some time at the temperature of the
body, and then injecting the mixture subcutaneously, and
observing whether the usual effect is produced or not; or by
ligaturing the ureters to prevent excretion.

_ Excretion—Lastly, we examine in what manner it is excreted
from the body. As most solids are excreted by the kidney, we

252 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

generally restrict this process to evaporating the urine, or
testing it either chemically or by injecting some of the extract —
into another animal.

Mode of Securing Animals.—In order to determine in an
exact manner what organs or parts are affected, we are obliged
to make use of apparatus of various kinds; and, before these
can be applied to an animal, it must be prevented from moving.
Frogs are fastened to a frog-board by a piece of cord with a
noose at the end, slipped over each elbow and ankle. The frog-
board may consist of a piece of mill-board about 9 inches long by
3 inches broad, with four slits at the sides to keep the cords in
position, or of a piece of wood the same size, and from a quarter
to half an inch thick, with holes, through which the cords are
passed. ‘They may be fastened by simply tying them together
or by sticking a small wooden pin into each hole, or by four
screws, such as are used by fastening the wires of galvanic
batteries, placed in the edges of the board. The last way is, I
think, the most convenient. Rabbits are best secured by
Czermak’s holder and board (shown in Fig. 126). The best cord
is strong window-cord. The one end should be flattened with a
hammer, and turned over so as to make a small loop, whose
two sides are then firmly bound together with waxed thread.
Through this loop the other end is passed, and the noose thus
made is ready to be drawn tight at any moment. The other
end of the cord should be cut to a point and also bound with
waxed thread to prevent the strands unravelling. The rabbit is
placed on the board, the nooses slipped over the legs and drawn
tight, and the ends of each cord passed through the screw which
will be nearest it when the animal lies on its back. The rabbit
is then turned over, and the cords drawn through the screws
and fastened. The bar / is then put between its teeth, and the
screw / turned till g and g’ fit tightly over its muzzle, and the
projecting ends of g fixed into the ends of f Dogs may be
fastened by Bernard’s holder (Fig. 1274), or by a simple bar of
iron put behind their canine teeth. <A piece of cord is first tied
round the upper jaw, the bar put into the mouth, and the two
jaws tied firmly over it. A split trap may be used instead of
the cord. J have had a bar made with a hole at each end, into

METHOD OF SECURING ANIMALS. 253

Fie. 126.

Czermak’s Rabbit Holder and Board. A, The board. zB, A bent piece of
iron forming the upper part of the board. c, An open space through which
instruments can be introduced from below to divide the spinal cord. It is
generally covered by an iron plate. Dis an upright rod fixed by a screw into
aslitinB. jf is a forked rod, which can be moved back or forward, up or
down, by the nut e. The forks are hollow, so that the ends of the holder can
be passed into them and fastened by the screw j. & is a bar which passes
behind the incisor teeth of the rabbit. g and g’ are two bent bars which ,pass
under the chin and over the nose of the animal, and are brought together by
the screw &. From the upper end of g’ hangs a screw, which passes between
two projections on g, and has a mother-screw k, The screw & works against
the projections on g, and draws the ends of g’ and g together. These press on
the rabbit’s nose and under jaw and keep the teeth firmly locked over the
rod h. m mare screws for fixing the cords which confine the legs. They are
a remarkably convenient sort, consisting of an outer part with a horizontal
hole, and an inner ring with a stalk on which a milled screw plays. When the
milled head is at the top of the stalk, the inner ring and outer holes corre-
spond, and the cord can then be easily pushed through; but when the milled
head is turned, the stalk and ring are drawn up and the cord nipped between
it and the outer part. The cords may either be fastened directly in the screw
or passed first through one of the holes in the edge of the board. The board
should be covered with a large pad of india-rubber stuffed with horse hair, and
there should be another round pillow to put under the animal’s neck.

which a fork of steel passes, and is secured by a screw. The
fork may then be fastened by a nut to an upright rod, as in
Czermak’s holder (Fig. 127s). Cats and guinea-pigs may be fast-
ened by Czermak’s holder. For guinea-pigs, a little padding
must be placed between g and g’ in order to make them catch
the head. A simple bar and cord may also be ‘used for rabbits,
cats, and guinea-pigs, as well as for dogs.

Instruments required.—The instruments which we generally
require for operations are—sponges, one pair of large scissors

»

254 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

Fic. 127.

Ais Bernard’s dog-holder. ais a metal ring, within which a bent piece of
metal, d, is moved up and down by the screw c. h is a straight piece, which is
Keiened by a screw to a, and can be moved nearer to or farther from a corre-
sponding piece at b. These two pieces lie under the lower jaw of the dog; the
bent piece 6 is screwed down on its nose, and the strap 7 buckled behind its
head, which is thus firmly fixed. It may be moved back or forward by sliding
the rod d through the nut e, or up and down by moving e on f, which is a
strong iron rod fastened to a table or board by the screw g.

B, Brunton’s holder for dogs or rabbits. A loop of cord is tied round the
upper jaw, the bar 7 passed behind the canine teeth of the dog or cat or
incisors of the rabbit, and the two jaws then tied together to prevent its
slipping out. This mode of fastening animals has been long used, and my
modification simply consists in the addition of the forked bar %. After 7 is
fastened in the mouth, the forked ends of # are pushed through holes in /, and
fastened by the screws m. & may then be fastened to an upright bar by means
of a nut in the same way as Bernard’s or Czermak’s holder.

and one small pair, cutting well at the points, scalpels, forceps,
small bull-dog forceps with smooth points, blunt hooks, a small
aneurism-needle, flattened sidewise and with a rounded point
(Fig. 128c), ligatures, finder (a kind of probe set in a handle to
open up the lumen of a divided vessel), syringe, cannule, a
piece of card, small whalebone-probe, and one or two swine’s
bristles. As these are very apt to be mislaid during an opera-
tion, I find it convenient to have a small wooden tray about
three-quarters of an- inch deep,’ with thin upright sides, and

az

INSTRUMENTS. 255

divided into compartments, one for each kind of instrument.
It is advisable, also, to have an extra instrument or two of each
sort.

Way of Making Cannule.—Cannule for injecting into vessels
may be made of metal (Fig. 128c) or of glass. Glass ones can
be easily made of any size required by heating a piece of glass-

‘

Fie. 128.

‘A is a metal cannula with an ear e, by which it can be fastened to any tube
connected with its large end. B is an instrumeut for introducing into a
vessel. It consists of a piece of metal tubing, with a pointed piece of wood at
one end, over which Ais put. The point projects through the small opening
in A, so as to enter the lumen of the vessel readily. c is a metal cannula
which fits on the end of a syringe for injecting fluids into vessels. D is a glass
cannula, The dotted line shows the original tube drawn out in the blow-pipe
flame; the darker line shows the finished cannula. £ and F are two pieces of
glass tubing drawn out to make pens. They may be attached by pieces of cork
to any writing apparatus. G is an aneurism-needle.

tubing over the flame of a blow-pipe, and drawing it out in the
middle, as represented by the dotted line (Fig. 128p). It is then
heated at a and slightly drawn out, so that a bulging piece is
left between a and ¢c; it may then be heated and very slightly
drawn out at d, then cut with a three-cornered file at ¢, and the
point ground obliquely off ona hone. If the point be at all
sharp, its edges may be rounded in a gas-flame. When the
cannula is introduced into a vessel, a ligature at a prevents it
from coming out: it may be connected with a syringe or with
any piece of apparatus by a piece of india-rubber slipped over

256 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

the other end and tied at 4, A cannula for connecting an artery
with a kymographion may either be of this sort, or may be
made of metal of the shape shown in Fig. 1284. As itis difficult
to hold it with forceps, it should be put on a piece of wood or
whalebone of the shape shown at B. This both hoids it firmly,
and the point entering the vessel allows the cannula to be more
readily pushed on into the lumen. A few notches on the side
of the cannula prevent the vessel and ligature with which it has
been tied from slipping off the end. By means of the little ear
at.e, it can be tied to the tube, on to which it is fitted.

Mode of Making Cannule, T-tubes, and Pens —Cannule for
the trachea are made by closing one end of a tube, directing a
small blow-pipe flame against a point in its side till it is quite
soft, and then suddenly blowing into it. The soft part expands
into a thin bulb, which is scraped off, and a hole remains in the
side of the tube. The object of this hole is to allow the air to
escape during expiration. Instead of a hole in the cannula,
one may be cut in the side of the india-rubber tube to which it
is connected; but this is more apt to be accidentally closed.
The tube is then drawn out into the form seen at Fig. 1294,
p. 262, cut off at both ends, and one end ground obliquely off
on a sandstone with some water.

A knob may be made at the ends of other cannule for
various purposes, by heating the end and s‘riking it against a
piece of glass or iron, or by heating the end in a flame, continu-
ing to blow steadily through the tube while you do so.

T-tubes are made by blowing a hole in the side of one tube,
in the same way as for a respiration-cannula; and then putting
the heated end of another tube over it while the first is still
hot, so that the two stick together. The joint must then be
annealed by heating it in an ordinary gas-flame, reducing the
size of the flame gradually, so that the glass may cool very
slowly.

Pens for use with a kymographion are made by drawing
tubes to a point, as shown in Fig. 128, and F, and grinding the
point on a fine hone, and rounding it, if necessary, in the
flame. |

Narcotising Animals—Narcotics cannot be given in all cases

ADMINISTRATION OF NARCOTICS. 257

to animals on whic’: we experiment, as their action must to a
certain extent complicate that of the drug which we wish to
investigate. We cannot use them when we are observing what
are the general symptoms which a medicine produces. But,
when we are investigating its action on particular organs, we
may often use them, not only with safety, but with advantage,
when they have no action on the particular organ which we are
studying, or so little that its disturbing influence is more than
ecmpensated by the diminished muscular action, and conse-
quent ease in performing the experiment, which narcotics
produce.

It is almost unnecessary to say that, in all cases which adrhit
of it, narcotics should be used, as we have no right to inflict
any unnecessary pain, although we may be justified in taking
the lives of the lower animals in order to preserve the more
valuable life of man, either by supplying him with food by
means of those killed in the slaughter-house, or by obtaining
the knowledge which shall enable us to cure disease by means
of those killed in our experiments. The narcotics which we
use are opium and chloral. Chloroform is inadmissible, as its
administration generally seems to cause dogs more pain than
the experiment itself, and rabbits are very easily killed by it.*

A convenient form of giving chloral is a solution containing
half a grain in 1 minim or 1 gram in 2 cc. of water. The
dose for a frog is 2 to 5 centigrams, or about 1 to 5 drops.
The dose for guinea-pigs is about 12 minims of this solution
for an animal half a pound weight; and more or less may
be given, according to the weight of the animal, 18 minims
being given to one weighing three-quarters of a pound, and 24
to one weighing a pound. About the same proportion of dose
to weight may be employed for rabbits.

Opium may be given in the form of laudanum, or of solution
of acetate or hydrochlorate of morphia. Much as it is used,
the proper dose for different animals has not been exactly de-
termined. We do not often employ it to’ narcotise guinea-pigs
or rabbits, but frequently for dogs. The dose for a medium-
sized dog is about 40 minims or 2} cc. of laudanum, or

* This statement is erroneous, vide p. 336.
8

258 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

2 drachms of liquor morphiz, which is equal to 1 grain or
5 centigrams of morphia. This dose is for injection into a
vein: when injected subcutaneously, rather more should be
given. If the dog be above or below middle size, the dose must
‘be proportionately increased or diminished. We must be care-
ful not to give too much opium to old dogs, or they will die.
Opium is preferred by some to morphia, as producing more
certain narcosis, and being less likely to produce the excitement
and hypereesthesia which sometimes follow the administration
-of morphia.

When we wish to render the animal absolutely motionless, or
to observe what effect any drug will produce after the motor
nerves have been paralysed, we give curare. Small doses of
this remarkable substance paralyse the motor nerves of muscles,
but leave the vagi and vaso-motor nerves unaffected. Large
doses of it seem also to cause paralysis of the vagi. It affects
the blood-pressure to a certain extent, moderate doses contract-
ing the vessels and raising the pressure, while large ones lower
it. The dose of curare for a frog is about 1 to 5 drops or more
of a solution of 1 part in 1000. The dose varies with the size
of the frog and the purpose for which we wish it. If we wish
to observe the circulation microscopically, we must not give too
large a dose, or the heart may stop. To rabbits, $ to 1 cc. or 8
to 15 minims, and to dogs, 4 to 6 cc. or 1 to 2 drachms, of such
a solution, may be given.*

Definite rules cannot be laid down as to the experiments in
which narcotics may or may not be used. The experimenter
himself must judge in each case whether their action is likely
to disturb that of the drug to be experimented on or not. For
this purpose, he must know the action which the narcotics them-
selves produce; and I will, therefore, mention in a few words
what that of each is.

Action of Narcotics—Chloral acts on the brain, producing
deep sleep, during which there is no sensation or voluntary
motion. The reflex function of the spinal cord is first increased
and then diminished in frogs; in guinea-pigs and rabbits, it is

* Curare may be obtained from Messrs. Hopkin and Williams, New Caven-
dish Street, London; or from Briickner and Lampe, Leipzig.

INTRODUCTION OF CANNULA. 259

diminished for thermal irritations, but not for tactile ones—
pinching producing reflex action, but burning or pricking: none.
It leaves the motor nerves, vagus, and muscles unaffected; but
diminishes the activity of the respiratory nervous centre,
rendering the breathing slow, and of the cardiac ganglia,
somewhat weakening the heart. It lessens the blood-pressure
and temperature, probably by dilating the vessels at the surface,
as the ear of a rabbit becomes hot and its vessels dilated, while
the general temperature is falling.

Opium is a mixture of several alkaloids, some of which are
purely narcotic, while others produce tetanic spasms just like
strychnia, and others partake of both characters. This is the
case with morphia, in which, however, the narcotic qualities
predominate. In small doses it first slightly imercases, and
then diminishes the irritability of motor and sensory nerves,
the reflex action of the cord, the irritability of the vagus (ends
and central roots), the musculo-motor apparatus of the heart,
and the temperature. If the dose be large, those functions
may be at once lessened. The blood-pressure varies, but is
generally raised.

The advantage of giving either a narcotic or the drug to be
investigated by injection into a vein rather than subcutaneously
is, that the «ction is immediate, and we know that the whole of
the dose has taken effect; whereas, after subcutaneous injec-
tion, a part may remain for some time in the cellular tissue
before it enters the blood and becomes active. The most con-
venient vein is the external jugular. In dogs, however, it is
sometimes more convenient to inject the narcotic into a vein
which runs obliquely across the outside of the hind knee-joint.
Before injecting, we must introduce a cannula into the vein;
and the introduction of a cannula into a vessel is an operation
on the proper performance of which the success of many an
experiment depends.

Introduction of Cannule into Vessels—First the hair must
be cleanly clipped or shaved away, and loose hairs removed by
a moist sponge. The skin, subcutaneous cellular tissue, and
cutaneous muscles, are divided with a scalpel, and any bleeding
vessels are twisted or ligatured. If the vessel lie deep, the

S$ 2

2°60 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

muscles are separated from each other by the finger of the
operator, or by a blunt ancurism-needle, and any unyielding
connective-tissue may be cut by a pair of scissors. That sur-
rounding the vessel itself should be separated from it by the
aneurism-needle. A closed pair of foreeps may be pushed
under the vessel and then opened. This both raises it from its
bed, and lays bare a considerable part of its course. A couple
of ligatures are now caught between the jaws of the forceps and.
drawn through. The proximal end of the exposed part of the
vessel is now compressed by a pair of smooth-pointed bull-dog
forceps, or a ligature laid in a simple slip-knot; one ligature is.
firmly tied round the distal end, and the second ligature is tied
in a loop round the middle, but is not drawn tight. A small
piece of calling card, about an eighth of an inch broad, is then
slipped under the vessel, so that it may rest on it and remain
steady: its walls are then snipped by a sharp-pointed pair of
scissors just on the distal side of the loop. The finder, or
aneurism-needle, may be introduced so as to make the opening
more distinct, and, if necessary, this may be enlarged by the
points of the forceps being introduced, and then separated.
One lip of the divided vessel is seized by the forceps, the
cannula introduced, and the loop drawn tight over it so as to tie
it firmly into the vessel. The cannula is then filled by a small
' glass pipette with the fluid to be injected, the syringe is fitted
on, the bull-dog forceps removed, and the requisite amount in-
jected. The bulldogs are again put on, and the syringe removed.

Injection of Fluids into Vessels—First, we prepare the solution
to be injected in a test or a watch-glass, and see that the syringe
is in working order. The most convenient is one for sub-
cutaneous injection, with a glass barrel and a graduated piston.
On the piston-rod a small nut screws up and down, so that it
can be set to any figure on the rod, and thus prevents it from
being any further pushed in, so as to allow the exact amount
required to be given at once, but prevent the accidental injec-
tion of more than this amount. The end of the barrel must
either fit directly into a cannula of the shape shown in Fig. 128,
Cc, or it may be adapted to a glass cannula by tying a small piece
of india-rubber tubing to the cannula, The cannula is then

a

STIMULATION OF NERVES. 261

introduced into the vessel as already described. A fine pipette
must be at hand, made by drawing a piece of glass tubing to a
point, and by this the cannula, or cannule with the attached
india-rubber tubing, must be carefully filled with the fluid, so
that no air-bubbles remain. The syringe is then connected to
it, the slip-knot of the ligature untied, or the bulldogs com-
pressing the vessel in front of the cannula removed, and the
necessary amount injected. The slip-knot is then re-tied, or the
bulldogs replaced, if a second dose is to be given. If no more
is to be injected, the vessel may be firmly ligatured.

Division and Irritation of Nerves——The nerve must. be laid
bare, and separated from the surrounding connective tissue in
the same way as a vessel, especial care being taken never to
seize the nerve itself with the forceps. Blood must be removed
by a sponge squeezed quite dry, and the nerve must on no
account be touched with water. If we wish to remove any
adhering clot; or if the nerve happen to get dry through long
exposure, it may be moistened with a little saliva or serum. A
director is then pushed under the nerve, or we. raise it up by a
ligature passed below it, so as to secure the adjoining vessels
from injury, and we then divide it by a pair of scissors. Very
often we wish to have the nerve prepared for section some time
before we actually divide it. We then pass the ligature under
it and tie the two ends together, so as to prevent the ligature
from being pulled from below the nerve, and thus form a loose
loop by which we can at any mcment raise and divide the
nerve.

Nerves may be irritated by pinching, the application of strong
saline solutions, or heat; but more generally we use Pulver-
macher’s galvanic forceps, which are made of alternate wires of
copper and zinc, and dipped in acetic acid, or, still oftener, the
interrupted current from Du Bois Raymond’s induction coil.
The most convenient electrodes for this purpose consist of two
wire points, about a quarter to half an inch long, and an eighth
toa quarter of an inch apart. They may either be set in an ivory
handle, or they may be simply fixed in a piece of glass tubing
by means of cement or sealing-wax, or simply pushed through a
piece of cork.

262 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

. Artificial Respiration in Mammals.—Artificial respiration is
chiefly used to keep an animal alive after it has been poisoned
with curare, for the purpose of rendering it perfectly still during
an experiment: or after the thoracic cavity has been opened for
observation or experiment on the viscera it contains. It is per-.
formed by introducing a cannula into the trachea, and inflating
the lungs by means of a bellows connected with it by india-:
rubber tubing.

Fia. 129.

A is a glass cannula for artificial respiration, large enough for a small dog.
A hole for the exit of expired air is seen in the side. Ba metal one fora
rabbit. The hole for expiration is at the top, and not visible in the figure.
The lower part of the cannula can be turned round upon the upper at a joint
about one-third of the way from the top, not marked in the figure. The tube
which conveys air can thus be brought from the side instead of the front.

To introduce the cannula, an incision is made in the middle
line below the cricoid cartilage through the skin and cutaneous
muscles; the larger muscles lying along the side of the trachea
are separated from it by an aneurism-needle or the handle of
the knife, and a strong ligature is passed under it by an
aneurism-needle or forceps, care being taken to avoid the veins
which lie close to its posterior wall. A round or oval piece
must then be cut out of the front of it by the scissors er knife,
and the cannula introduced, and tied firmly in by the ligature.

When the knee-shaped metal cannula is used, it is advisable
to push the heel of the cannula into the trachea, so that tht
tube lies quite in its lumen. After the cannula has been tied.

ARTIFICIAL RESPIRATION. 263

into the trachea, the ends of the ligature may be fastened round
the upright bend of the knee, to ensure that it do not slip out.
The bellows may be simply held in the hand, or fastened to the
under side of a table by means of a piece of board screwed to
its upper side and larger than the bellows itself, so that there is
a rim of board all round. A few screws passed through this
projecting rim into the under side of the table hold the bellows
fast. A small pulley (one used for window-blinds will do) is
then screwed into the under side of the table, and a cord passed
over it. One end of the cord is fastened to a piece of board a
foot and a half or two feet long, which serves as a treadle; and
the other end to the under board of the bellows, so that it may
be drawn up when the treadle is pressed down by the foot. A
weight must be attached to the under board of the bellows, in
order to draw it down again after it has been raised. The
respiration is kept regular by depressing the treadle in accord-
ance with the beat of a metronome set to beat the proper
number in a minute.

The apparatus may be rendered more complete by the intro-
duction between the bellows and trachea of a valve which will
allow the air to pass readily towards the trachea, but hinder its
return. Such a valve may be readily made by passing two
pieces of glass tubing through the cork of a wide-mouthed
bottle, and partially filling it with mercury or water. The tube
nearest the bellows must descend nearly to the bottom of the
bottle, while the other just passes through the cork. The air
from the bellows passes easily through the mercury or water in
which the end of one tube dips; but any attempt to return
simply raises the mercury in the tube. If water be used, the
tube must be longer, so that it may contain a column of water
sufficiently high to afford the necessary resistance to the return
of the air. This sort of valve is termed Miiller’s valve.
(Fig. 130, v.)

Artificial Respiration. in the Frog— Although the frog can
live perfectly well for some time without breathing, it may be
desirable in some experiments to employ artificial respiration.
A cannula for this purpose is best made by heating the end of
a glass tube about one-eighth of an inch in diameter (more or

264 EXPERIMENTAL INVESTIGATION OF TIIE ACTION OF MEDICINES.

less, acco: ding to the size of the frog), and then suddenly pres-
sing it down on a metal plate, so that a broad rim is formed
round the end, The sides of the larynx are seized by two
artery forceps, the cannula introduced, and tied firmly in. A
Richardson’s spray-producer, from which the tubes have been
removed, is then connected with it and used as a bellows.

Introduction of Gases or Vapours into the Lungs.—Gases or
vapours may be introduced into the lungs either by simple
inhalation or by artificial respiration. For the inhalation of a
gas, a conical bag of oilskin, india-rubber, or bladder, must be
made to fit the snout of the animal, and connected with a bag,
bladder, or gas-holder containing the gas. Or a tube may be
put into the trachea and connected with the gas-holder.

For the inhalation of a vapour, a cone of strong paper or
cardboard may be used, the wide end being put over the muzzle,
and the liquid, the vapour of which is to be inhaled, dropped on
a piece of blotting-paper and put on the small end. Or the
whole cone may be made of blotting-paper. |

Many different kinds of apparatus have been used for the
artificial respiration of gases, among which may be men-
tioned the ingenious instrument of Thiry and the beautiful
respiration-pump of Ludwig. The simplest method probably is
to have the gas in a bag, connected by means of the bottle or
Miiller’s valve with the tracheal cannula. The gas may then
be forced into the lung at intervals, by alternately oe
and relaxing the bag.

Air may be loaded with the vapour of any kind of fluid hefond
it is sent into the lungs, either by mixing the fluid with the
water in the bottle-valve, or by emptying out the water and
putting a little of the fluid alone on the bottom of the bottle.
Pure air or air loaded with vapour may be sent into the lungs
alternately by the arrangement shown in Fig. 130. A stream of
air is sent from the bellows through the india-rubber tube s,
and divided into two by the T-tube 1’. When the clip x is
removed, and x’ put on, the air passes straight through to the
tracheal cannula z. If x be now put on, and x’ rouge the
air passes through v (Miiller’s valve), and becomes loaded with
the vapour of any fluid placed in the bottle.

MULLER’S VALVE—BRUNTON’S STOPCOCK. 265

The alternation may be effected still more rapidly and con-
veniently by a stopcock which I have had made for this pur-
pose. Two tubes, c and c’, pass from its sides, and two others
p and vb’, from its bottom. The interior is perforated with
three holes. Two cf these, E and xk’, are L-shaped, and one (F)
passes straight through from side to side. When the handle B
is in a line with c and c’, their lumen corresponds with that of

Fia. 180.

A. Brunton’s stopcock. v. Miiller’s valve.

the hole F, and air passes straight through. When B is trans-
verse, the hole E corresponds with © and D, and £’ with ¢ or D’,
so that air passing in through c’ passes down through bD’, and
may pass up through Dp and out at c. When B is neither in a
line with c nor yet transverse, but half-way between, the holes
in the interior do not correspond with those on the exterior of
the stopcock, and no air can pass at all, and it may thus be
used for experiments on asphyxia. When such experiments
are made, the hole in the tracheal cannula must be carefully

266 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

stopped with white wax. By means of the screw G the stop-
cock may be fastened to the rod E of the rabbit-hold in Fig. 1.
The tubes D and D’ may either be attached by pieces of india-
rubber tubing to tubes of a bottle such as Vv, or they may be
themselves passed through the cork and a small piece of glass
tubing long enough to reach the bottom of the bottle attached
to D’. By then simply turning the stopcock, pure air may be
passed direct to the lungs through c’, F, and ¢, or it may be
loaded with vapour by passing it through D’ into the bottle, and
then up through D and ¢ to the lungs.

III. ARTIFICIAL CIRCULATION: INVESTIGATION OF BLOOD-
PRESSURE.

(British Medical Journal, 1871, Tune 8, p. 881.)

Artificial Circulation of Blood.—Circulation of Wazm and of Cold. Blood.—
Fever.—Mode of Conducting Artificial Circulation.—Application of this
Method to Pharmacological Investigations.—Schema of the Circulation.—
Circulation in the Living Body.—Importance of the Arterial Elasticity.—

Arterial Tension or Blood-Pressure.—Oscillations in it produced by the~

Heart and Respiration—Causes of Variation in the Blood-Pressure.—
Influence of Nerves upon it.—Cardiac Ganglia.—Inhibitory Nerves of Heart.
—Quickening Nerves of Heart.—Vaso-motor Nerves. — Vaso-inhibitory
Nerves.—Action of Counter-irritants.—Tabular View of the Causes of altered
Pulse-Rate and Blood-Pressure.—Application of this to Pathology.—Experi-
mental Examination of Blood-Pressure.—Forms of Manometer.—Kymogra-
phion.—Mode of using the Kymographion.—Reduction of the Kymo-
graphion Tracings.—-Mode of recording -eiaapeaginge —Graphie Method of
representing Experiments.

Artificial Circulation of Blood.—A constant supply of arterial
blood to all parts of the body is necessary to preserve their
vitality ; and if the supply to any part be cut off by stopping its
circulation, that part will die. Thus, if the circulation be
stopped in an arm or leg by tying its arteries, or through
their becoming plugged by emboli, mortification, or death of
the part, ensues; and if the heart cease to beat, and the circu-
lation be thus stopped in all parts of the body, they all die.
But, if we supply arterial blood artificially to any one part, we
may keep it alive at least for a certain time after the rest of
the animal is dead ; and the muscles may be made to contract,

the lungs to excrete carbonic acid, the lymphatics to pour forth.

OO ———

ARTIFICIAL CIRCULATION, 267

lymph, and the excised liver to secrete bile, for hours after the
rest of the animal has been consigned to the dust-bin.
Circulation of Warm and Cold Blood.—For this purpose,

blood may be used either at the temperature of the room or of

the body ; but these have not exactly the same effect, and experi-
ments made with blood at one temperature must not be com-
pared indiscriminately with those made with blood at another.
Professor Ludwig, to whom we owe this method, has discovered

by its means the curious fact that the muscles of a warm-

blooded animal may be artificially endowed with the pro-
perties of those of a cold-blooded one. Those of a frog or other
cold-blooded animal retain their irritability, and contract,
when stimulated, for a long time after they have been removed
from the body ; while those of warm-blooded animals quickly
lose theirs, and will no longer contract on the application of a
stimulus, no matter how powerful it may be. But if the
muscle of the warm-blooded animal be quickly cooled by pass-
ing a stream of cold blood through its vessels immediately after
it has been excised from the body, and before it is stimulated,
it will retain its irritability for a long time, and respond to
stimuli again and again, like that of the cold-blooded frog.

Fever.—In the same way, by supplying the heart of a mammal
with cold blood, it may be made to resemble that of a frog or
turtle; while, on the other hand, if the heart of a frog be
supplied with warm blood, it will become like that of a mammal ;
and if the temperature be still further raised the quick and
weak beats of fever are produced.

Mode of Conducting Artificial Circulation—When we wish to
pass blood, at the ordinary temperature of the room in which
we are working, through any organ, we defibrinate the blood of
the animal itself from which the organ has been obtained, or
the blood of an animal of the same species; dilute it some-
what with salt solution of 1 per cent.; and put it into a flask
with two necks, one of which is near the bottom of the flask,
as seen at A, Fig. 131. We then introduce a cannula into the
principal. artery of the organ, and ligature, if necessary, the
smaller arteries and branches ; fill it carefully with blood by
means of a fine pipette, so that no air-bubble remains in it, and

268 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

connect it with the lower neck of the flask. By then simply
raising the flask, the blood flows out of it through the
cannula into the vessels, and out again by the veins, from
which it may be collected, shaken with air, and used over again.
As the lips of the divided veins are sometimes apt to fall
together and hinder the exit of blood, it is advisable to put a
cannula into them as well; and great care must be paid to the
adjustment of these, in order that they may be fairly in a line
with the lumen of the vein, and not form an angle with it,
which would present an obstruction to the flow of blood from it.
For the purpose of passing a stream of blood at the tempera-
ture of the body, we use the same apparatus ; but the flask con-
taining blood (£, Fig. 131) is then placed in a water-bath, kept
constantly heated to 98° F. As this prevents us from con-
veniently raising the flask high enough to obtain the pressure
required to carry on the circulation, we supply the want by
-compressing the air in the upper half of the flask, £, by. means
of two other bottles, A and C, containing mercury or water. On
raising A, the fluid which it contains runs into Cc, and compresses
the air in its upper half; and as this communicates with & by
an india-rubber tube, the pressure is freely transmitted to it,
and exerted on the surface of the blood which it contains.
Applicution of this Method to Pharmacological Investigations.
— Besides its use in the experiments of Ludwig and his pupils
on the secretion of bile and the formation of lymph, this method
has been used by Cyon to show that urea is formed in the
liver; but, so far as I know, no experiments on the actidn
of medicines have yet been made by its means. It may seem,
then, a strange thing that I should mention, in a ccurse of
experimental pharmacology, a mode of research which as yet
has only been tried in physiology; but the good service it has
already done the physiologist, and the splendid promise it gives
to us, are, I think, a sufficient excuse. For we can thus take
two similar. organs, or two parts of the same organ, and supply
them with the same blood, at the same temperature and the
same pressure—in short, we may put them under exactly the
same external conditions; but to the blood supplying the one
we may add any drug whose action on the organ we wish to

PHARMACOLOGICAL USES OF ARTIFICIAL CIRCULATION. )

bo
o>

Fic. 181.

ee ng) ey Nat
| ¥ PFE: ‘a
a) mt I H — sea
¢ on G ¥ a :
2 a : 22
oS ae AL Zz = AN
Rm SS B
— ~ —_—-
3 YW ui ————
. J

Aand c, Bottles containing mercury or water. 3B, Wooden blocks, by which
A may be raised to the required height. If water be used, it is easier to suspend
it from a pulley in the ceiling, so as to get sufficient pressure. D is a manometer,
to estimate the pressure in C and E. Eis a bottle containing blood, F is a small
stand to raise the bottle E from the bottom of @, as it is otherwise apt to become
too warm, and the bottom of the bottle cracks, or the blood is decomposed. G, a
tin water-bath. At one side of it is a trough with hollow sides, into which the
warm water freely passes, and in which the organ to be experimented on may be
laid. His an iron stand supporting @. J is a Mitscherlich’s burner. kK isa
thermometer, by which the temperature of the water-bath is examined.
L, Bunsen’s gas regulator, as modified by Geissler. This apparatus consists of a.
wide glass tube, w, divided into two parts by a septum, from the middle of
which a tube runs down nearly to the end of w. The upper part is filled with
mercury, which, of ‘course, runs Gown the inner tube and fills the bottom of w,
compressing the air in it. A perforated cork, z, is then put into the upper part.
of w, and the tube y pushed through the hole in its centre. Inside y, and
shorter than it, isa second tube x, and the two are sealed to one another at their
upper ends. The tube y is then connected to a gas-pipe, and x to Mitscherlich’s
burner, by india-rubber tubing. So long as ¥ is not pushed so deeply into w
that the point of x dips into the mercury, the gas enters through Y, passes down
between y and X, comes up again through x, and goes to the burner. The
apparatus is now set by dipping it into the water-bath, and heating the water to
98°, or any other temperature desired, and then pushing y down till the point of
X is just covered by the mercury. The passage of gas through it is at once
stopped, and the flume would go out were it not that a very small hole in the
side of x admits just enough gas to keep it alive. As the flame gets low, the
temperature of the water-bath above it diminishes, the air and mercury in Ww
contract and leave the end of x open, so that the gas again passes freely to the
burner, and the flame becomes larger. The water-bath now regains its former
temperature, the air and mercury expand, the end of X is again closed, and
again the flame becomes small. By this apparatus a water-bath may be kept for
avery long time without varying more than half a degree.

test. We can analyse the blood flowing into, and that flowing
from, the substance of the organs before and after the experi-

270 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

ment, the lymph produced, or the secretion poured forth;
and by comparing the results when the drug was added with
those obtained when it was withheld, we may, I think, gain
such a knowledge of its action as could be got in no other
way.

Schema of the Circulation.—In the living body, a constant
stream of blood is kept up in the vessels, in exactly the same
way that a constant current of air is produced in Richardson’s
spray-apparatus. By removing the glass or metal tube from

Fria. 132.

Simple schema of the circulation, consisting of a spray-producer, bladder, and
mercurial manometer. The elastic ball represents the leart; the elastic
bag, covered with netting to prevent too great distension, represents the
aorta and arterial system ; and the bladder represents the venous system.

one of these, and attaching a nozzle with a small stopcock to
the india-rubber tube in its stead, we obtain a very good schema
of the circulation ; and, by imitating on it the changes which
occur in the heart and vessels, we may form a much clearer
idea of them than we could otherwise do. The india-rubber
bail will represent the heart; the elastic bag, surrounded by
netting, will represent the elastic aorta and larger arteries; and
the stopcock, which regulates the size of the aperture through
which the air escapes, will represent the small arteries and
capillaries, whose contraction or dilatation regulates the flow of
blood from the arteries into the veins. If we turn the stop-

AUTHOR’S SCHEMA OF THE CIRCULATION. 271

cock so as to present some resistance to the escape of air, and
then compress the india-rubber ball, very little air will issue
from the stopcock even while we are squeezing the ball; the
greater part of it goes to distend the bag; and, when we cease
to compress the ball, no air at all comes out from the stopcock.
At the next squeeze, the bag becomes a little more distended ;
and a little air issues from the stopcock, not only while we are
compressing the ball, but even when we relax our grasp. <At
each squeeze of the ball, the elastic bag becomes tighter,
till it is so tense and contracts so strongly on the air inside,
that it can press all the extra amount of air forced into it when
the ball was compressed, out through the stopcock, during the
time when the ball is relaxed. When this is the case, every
time we squeeze the ball we see the bag become a little fuller,
and air issue more quickly from the nozzle. At each relaxation,
while the ball is refilling, the bag gets a little slacker, and the
air passes out of the nozzle a little more slowly, but never stops
entirely. During the time the ball is filling, the valves between
it and the bag and nozzle are closed, and cut it off from any
connexion with them. All this time, then, the stream of air
from the nozzle must be entirely independent of the ball; it is
produced by the contraction of the elastic bag, and by it alone.
The bag may be stretched, and the tension of its walls increased
in consequence, in two ways: first, by working the ball more
quickly ; second, by lessening the opening of the nozzle, and
thus hindering the passage of air through it. One trial will, I
think, be enough to show you how much easier it is to alter the
pressure by changing the size of the nozzle than by any alteration
in the working of the ball, and thus convince you that altera-
tions in blood-pressure probably depend much more on altera-
tions in the lumen of the small arteries than on changes in the
action of the heart.

But our schema, as it at present exists, is not a perfect repre-
sentation of the heart and vessels; for it draws its air from an
inexhaustible reservoir, the atmosphere, and is not obliged each
time to use that amount alone which it had previously driven
through the nozzle; while the heart can only use the blood
which has been forced by it through the capillaries and returned

272 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES,

to it by the veins. In order to make our schema complete, we
must connect its two ends by tying them into a bladder or large
thin caoutchouc bag (such as is used, after inflation, as a toy for
childreu:), so that the air shall pass into it from the nozzle and
be sucked out of it by the elastic ball. This will represent the
veins. If we then repeat the experiment just described, we
shall find that, when we begin to work the ball and stretch the
elastic bag representing the arteries, the bladder, representing
the veins, becomes empty and collapsed; and just in proportion
as we fill the bag do we empty the bladder. If we now stop,
the air will gradually escape from the bag to the bladder, till
both are equally filled as they were at first.

Circulation in the Living Body.—The phenomena of the cir
culation in the heart and vessels are very much the same as in
the spray-producer. When the heart stands still (as when the
vagus is strongly galvanised), the blood flows from the arteries
into the veins till they are nearly full and the pressure inside
both is about the same. If the heart now begin to beat, it
forces blood into the elastic aorta and arteries at each systole,
and distends. them, just like the elastic bag of the spray-
producer ; while at the same time it takes blood from the veins,
and they become empty in proportion as the arteries become
full. At every diastole, the elasticity of the distended aorta
causes it to contract on the blood it contains, and keeps it
flowing on through the capillaries till another systole occurs.
During the diastole, the leart is completely shut off from the
aorta by the sigmoid valves (just as the ball of the schema was
shut off from the elastic bag), and the blood is kept flowing
during this time by the elastic contraction cf the aorta and
large arteries. In general, the diastole is longer than the
systole; so that for the greater part the circulation is carried on
by the elasticity of the arteries, and not directly by the heart..
The arteries become distended by the heart, just as the elastic
bag was by the ball, and press more and more on the blood in
them (so that it would spout higher and higher, if one of them
were cut), till they are able during the diastole to press the
same amount of blood through the capillaries into the veins as.
had been pumped into them during the systole. The more

ARTERIAL TENSION OR BLOOD PRESSURE. pie

these are stretched, the greater is the pressure they exert on the
blood they contain; and the amount of this is termed the
arterial tension or blood-pressure. These two terms mean the
same thing, and we use one or other just as the fancy strikes us.
At each systole, the fresh supply of blood pumped in by the
heart stretches them more; that is, the arterial tension rises.
During each diastole, the blood escapes into the wide and
dilatable veins, and the arteries become relaxed; that is, the
arterial tension falls.

Besides the osgillations which take place in the blood-pres-
sure at each beat of the heart, a rise and fall in the form of a
long wave occurs at each respiration. The wave begins to rise
just after inspiration has begun, reaches its maximum just after
the beginning of expiration, and then begins to fall again till a
new wave succeeds it. The heart-beats are generally quicker
during inspiration, and slower during expiration.

The blood-pressure thus oscillates up and down at each heart-
beat and rises and falls with each respiration, and the average
between the highest and lowest points is called the mean
arterial tension or mean blood-pressure.

Causes of Variation in the blood-Pressure.—The pressure of
blood in the arteries depends on two circumstances: first, the
amount of blood pumped into them in a given time; and
second, the amount that flows out of them into the veins in the
same time. If more be pumped in, or if less flow out, it will
rise; if less be pumped in, or if more flow out, it will fall.
It may, therefore, be raised—1. By the heart beating more
quickly ; 2. By a larger amount of blood being sent into the
aorta at each beat; 3. By contraction of the small vessels. It
may be lowered—1. By the heart beating more slowly; 2. By
the heart sending out less blood at each beat; 3. By dilatation
of the small vessels, allowing the blood to flow more quickly
into the veins; 4. By contraction of the pulmonary vessels, or
obstruction to the passage of blood through them.

The influence on the pressure exerted by the amount of blood
sent out by the heart at each beat, and by the number of beats,
to a certain extent, though by no means completely, counteract
eacn other; for, when the heart is going quickly, it has not

T

274 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

time to fill completely, and so sends out little blood at each’

beat; but, when going slowly, it becomes quite full during each
diastole; and sends out a larger quantity of blood at each
contraction.

It must be remembered that we measure the blood-pressure.
in the systemic arteries; and, before the blood can get into
them from the veins, it must come through the pulmonary

vessels. Any contraction of the lumen of these vessels, by
lessening the entrance of blood into the systemic arteries, will
cause the pressure in them to fall. 7 ¢

_ INFLUENCE OF NERVES ON BLoop-PRESSURE.—-Both the quick-
ness of the heart’s beat and the contraction of the arteries are

regulated by the nervous system; and it is generally by acting
on different parts of it that drugs alter the blood pressure,

though they may also do so by acting on the muscular walls of

the heart and arteries themselves. The parts of the nervous
system chiefly concerned in regulating the circulation are :
I. The cardiae ganglia which le in the walls of the heart,
and are, in all probability, the cause of its rhythmical action.
Il. Inhibitory nerves, which render the heart’s action slow,
and, if irritated very strongly, may stop its beating altogether,

and produce still-stand in diastole. The inhibitory fibres have

their origin or roots in the medulla, and proceed in the vagi to

the heart. Im man and in dogs, they are normally in constant

action ; and, after they are cut or paralysed, the heart beats in
the dog three or four times as quickly, and in man twice as
quickly, as before. In rabbits and cats they act less, and their
division only makes the heart go one-half or one-fourth
faster. A drug may irritate them, and render the heart's action
slow— ,

1. By acting directly on (a) their roots in the medulla,
(b) their fibres, (¢) their ends in the heart ;

2. Indirectly, through its action on other. parts, producing
(a) increased blood-pressure, or (0) accumulation of carbonic
acid in the blood, both of which act as irritants to the vagus-
roots ;

3. Reflealy, (a) through irritation of sensory nerves, (0) irrita-
tion of the intestines, (c) of the sympathetic nerve, (d) of the

—-- —— ~

CARDIAC AND VASO-MOTOR NERVES. Zi

depressor, or (e) of the vagus of the other side. Reflex irritation
is only likely to be caused by drugs having a powerful local
action.

Drugs may also paralyse the inhibitory fibres, and thus
quicken the heart.

III. Quickening Nerves. These belong to the sympathetic
system. They have their origin in the brain or medulla, pass
down through the cervical part of the spinal cord to the last
cervical and first dorsal ganglion (which are often united), and
thence through the third branch of the ganglion to the heart.
Quickening fibres are said by some to run also in the cervical
part of the sympathetic cord. Unlike the vagus, the quick-
ening nerves are not normally in constant action. They may
be irritated—

1. By the direct action of drugs upon them.

2. Indirectly by the drugs producing a diminished blood-
pressure, which acts as a stitndles to them.

IV. Vaso-motor Nerves, which cause the smaller arteries, and
probably also the capillaries, to contract. These belong to the
sympathetic system; and the most impertant of them are the
splanchnics, which produce contraction of the intestinal vessels.
As these vessels can, under certain circumstances, hold all the
blood in the body, the influence of the splanchnics over the
blood pressure is very great; and division of these can lower
it, or stimulation of them increase it very much. The centre
for the whole vaso-motor system, however, seems to be in
the medulla oblongata; and it is generally in constant action,
keeping up a certain amount of contraction or tone in these
vessels. Its activity may be increased, and the vessels made
to contract—

1. By direct irritation of the centre.

2. By reflex irritation through (a) the cervical sympathetic
(6) the vagus, when the brain is intact, and the animal not
narcotised, (¢) sensory nerves. When the medulla is separated
from the rest of the body by dividing the spinal cord at the
atlas, it can, of course, no longer exert any influence over the
vessels; and they consequently become dilated throughout the
- whole body, and the blood pressure sinks very low. If the
T 2

276 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

lower end of the divided cord be then irritated, the vaso-motor
nerves which pass through it from the medulla to the body are
stimulated, and the blood-pressure rises.

V. Vaso-inhibitory Nerves. Irritation. of these nerves is con-
ducted to the vaso-motor centres, and acts on them in sucha
way as to cause a reflex dilatation of the small vessels, either
(1) throughout the whole body, or (2) in one particular part
of it.

1. The chief nerve which causes dilatation throughout the
whole body is one which runs from the heart to the medulla,
and is called, from its power of diminishing blood-pressure,
the depressor nerve. Its fibres seem to be included in the
vagus in the dog; but in the rabbit it generally runs separate
from the heart to the level of the thyroid cartilage; here it
divides into two so-called roots, one root going to the superior
laryngeal, and the other to the vagus nerve. These are generally
called roots, though, as the nerve conveys impressions from the
heart ¢o the brain, they are, physiologically, really branches,
There seem to be also depressor fibres in the vagus itself;
but this nerve contagns fibres of many kinds, and, among
others, some which cause contraction of the vessels and rise
of blood-pressure —hence called pressor-fibres. The former
seem to act on the vaso-motor system through the medulla
itself, while the latter affect it through a centre in the brain, so
that, when the brain is perfect, irritation of the central end of
the vagus causes increased contraction of the vessels and raised
blood-pressure ; but, when the brain is removed or its functions
abolished by opium, it causes dilatation of vessels and
diminished pressure.

2. When a sensory nerve is irritated, the action of the vaso-
motor centre is suspended in the part supplied by the nerve,
and in those which immediately adjoin it, so that their vessels
become dilated, while at the same time contraction of the vessels
in other parts of the body is produced. The blood-pressure is
thus increased generally, and produces in the locally dilated
vessels a very rapid stream of blood. This fact was first dis-
covered, and its importance in therapeutics indicated, by
Ludwig and Loven.

COUNTER-IRRITANTS—PATIIOLOGY OF CIRCULATION. 277

Action of Counter-irritants—The application of an irritant,
whether mechanical, chemical, or thermal, injures the tissues
of the part to which it is applied; and what better means of
removing the injury and restoring health could be imagined
than a copious supply of blood, and the removal of every
hindrance to its free flow which contraction of the vessels might
present ?

Experiments are still wanting to decide how far the vascular
dilatation will extend in the neighbourhood of the irritated part
when more or less powerful irritants are applied, or which the
vessels are (if any) that especially contract, when certain others
dilate ; so that at present, when we apply a mustard plaster to
the chest to relieve bronchitis, we are unable to say with
certainty whether the relief is due to a more full flow of blood
through the vessels of the bronchi, or to contraction of their
lumen diminishing congestion, or (though this is unlikely) to
some unknown action independent of the vessels altogether.
The experiments of Sinitzin, however, (detailed by a recent
writer in the British Medical Journal, 1871, p. 535) which
show that ulcers of the cornea, eyelids and lips, occurring after
division of the fifth nerve, rapidly heal when. dilatation of the
vessels of these parts is produced by extirpation of the superior
cervical ganglion, render it in the highest degree probable that.
it is to the increased flow of blood that healing is due. As
a general rule, too, the vascular-dilatation seems to extend more
widely the stronger the irritant applied; and we may thus see
1cw a strong irritant, or one applied over a large extent of
surface, may prove beneficial in a deep-seated inflammation
when a weak one or one applied to a simall surface has no
effect.

For convenience of reference, I have put together the causes
of alteration in the blood-pressure in the following table
(p. 278). .

Application to Pathology.—The brief sketch of the circulation
which I have given, will enable you to understand and appre-
ciate the meaning of the changes produced in our circulation by
any drug, and to explain the facts we may meet with in the
course of an investigation, I may remind you that the altera-

EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

278

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BLOOD PRESSURE AND PULSE RATE. 279

tions in the pulse-rate and blood-pressure which we meet with
in disease, as well as those produced by drugs, are due to some
one or other of the causes mentioned in the previous table; and
whenever you meet with a quick, slow, weak, or irregular pulse,
you must try to find out to which of these causes it is due, in order
that vou may be able to apply scientifically the proper remedy.
Experimental Examination of Blood Pressure: Forms of
_Manometer.—As the life and health of the body and of the
organs comprising it depend on the supply of blood to them—
and this, as we have already seen, is closely associated with the
arterial pressure—the observation of the effects of drugs on it
naturally forms one of the most important parts of an investi-
gation into theiraction. The first to measure the blood-pressure
was Hales, who simply connected a glass-tube with an artery,
and noted the height to which the blood rose in it. Poiseuille
improved upon this method by substituting a bent tube, par-
tially filled with mercury, for the straight tube, and estimating
the pressure from the difference in the level of the mercury in
_the two limbs. A solution of carbonate or bicarbonate of soda
was introduced into the tube between the mercury and the
blood in order to prevent its coagulation. The bent tube,
partly filled with mercury, is called a hemadynamometer, or,
more generally,a manometer. The height of the mercury is
read off froma scale fixed behind the tube. Usually both limbs
of the tube are of equal diameter, and the blood-pressure is
then ascertained by doubling the height of the mercury above
- zero in one limb and subtracting a fraction, which varies with
the specific gravity of the solution of soda used. The height
-must be doubied, because the mercury descends as much below
zero in the one limb as it rises above it in the other; anda
fraction of the whole is subtracted for the additional weight of
the column of soda solution, which enters one limb as the
_ mercury rises in the other.

A very simple manometer, which will show the mean blood-
pressure as well as the maximum and minimum between which
it oscillates, may be made by passing two straight glass-tubes
about 16 inches long through the cork or india-rubber stopper
of a small wide-mouthed bottle, and fixing behind them a

280 EXPERIMENTAL INVESTIGATION OF THE ACTION CF MEDICINE

graduated cardboard scale. Tlie lower end of one tube must
be nearly closed in the blow-pipe flame, and both pushed dewn
till they almost touch the bottom of the bottle. A third bent
tube is inserted into the stopper, reaching only to its under
surface, and a piece of india-rubber tubing is attached to its
upper end for the purpose of connecting it with the artery.
Some mercury is then poured into the bottle, so as to stand a
little above the ends of the tubes, and both it and the india-
rubber tube are filled with a saturated solution of bicarbonate
of soda and connected with the artery. The mercury rises and
falls in the open tube with every pulsation; but in the one
with the constricted end the resistance to its movement is so
great that it can only rise and fall slowly, so that, before its
upward oscillation has had time to show itself, its descent has
begun, and vice versd. The upward and downward oscillations
thus balancing each other, the mean pressure only is shown
(vide pp. 103 and 104). :
The oscillations in the unconstricted tube are so rapid that it
is impossible for the eye to follow them exactly; and this difii-
culty led Ludwig to conceive the idea of making them register
themselves by means of a slender rod swimming on the surface
of the mercury, and bearing at its upper end a pen which
moved up and down on a piece of paper fixed on a revolving
cylinder. The vertical height of the tracing thus produced
showed the blood-pressure, while the horizontal distance from
one point to another on it indicated the time between them.
This instrument is called a kymographion ; and, in devising
it, Ludwig introduced for the first time into physiology that
method of self-registratiun which is now generally applied to
all kinds of vital phenomena, and has already done much
49 render our knowledge exact. That form of it which is used
by Traube, and made by Sauerwald, of Berlin, is shown in
Fig. 153. It consists of a metal cylinder (p) supported on a
wooden frame (7), and caused to revolve at a steady rate by
clockwork and pendulum (J and w). The manometer is fixed to
the wooden frame and connected with the artery by tubing of
lead and india-rubber. On the mercury in one limb floats a rod
or swimmer of glass, to whose upper end is attached a glass

LUDWIG’S KYMOGRAPHION, 28T

Fra. 133,

A, Ludwig's Kymographion. a’, the manometer. Instead of one simple bent
giass tubo, is consists of two tubes fixed on a piece of wood and joined by a piece
of metal 6, which may be unscrewed for cleaning the tubes. c¢ is a tube of soft
lead, for connecting the manometer with the artery. One end of it is screwed
to the manometer and the other is attached to a stopcock d. d is a stopeock

282 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

attached to e, and may be connected with the tube B in the artery by a piece of
india-rubber tubing. It is bored in a T-shape, and is perforated in the centre
by an additional perpendicular hole, into which is put a hollow pluge. f isa
flask containing saturated solution of bicarbonate of soda, and connected by
india-rubber tubing with e. When the clip on the india-rubber tube just above
e is removed, and the stopcock turned longitudinally, soda solution will flow into
eas well as out of d. By turning it transversely, the opening towards ¢ may be
closed, and soda will then only run out through d. This is done when we wish
to wash out the cannula with soda without altering the level of the mercury in a.
g isa glass pen attached to the top of a glass rod or swimmer, which rests on the
surface of the mercury ina. isa thread of unspun silk, with a small weight
attached to it. It rests against the pen g, and keeps it constantly applied to the
paper without impeding its movements. 7 is an iron wire, from which the
thread h is suspended. j is the wooden frame bearicg the clockwork and
revolving cylinder. & are three screws to level the frame. J is the clockwork.
mis an upright, and 2 a horizontal bar, which support a pivot 0. p is a metal
cylinder, which carries the paper. g is a small metal bar for holding the paper
on theeylinder. It is hinged to the lower edge of the cylinder, and caught by a
spring at its upper edge. It lies in a hollow in the cylinder, so that its outer
surface does rot project above it. When a new paper is to be put on, the spring
catch at tle upper end of g is raised, g pulled out, the old paper removed, and
the edges of the new one plaved underg. It is then pushed down, its upper
end is caught by the spring, and the paper is securely held. + is a catch for
stopping the movement of the clockwork. s and s’ are two weights to drive the
clockwork. ¢is a rack for winding up the weight s’. w is a pendulum, with a
movable bob, to regulate the motion of the clockwork and cylinder. By moving
the bob up or down, the motion may be made quicker or slower. v is a pencil
stuck through a piece of cork and fastened to the upright m; so as to draw a
line on the paper at the same level as g, when there is no, pressure on the
mercury in the tube. The blood-pressure is estimated by the height of the
curve traced by g above the zero line thus drawn. y is one of Marey’s tympana,
which is supported on a movable rod z, and may be sed for registering either
the respiration or the form of the pulse-wave. It consists of a shallow cup of
metal, over whose top a piece of india-rubber is tightly stretched. A metal
tube passes into the interior of the cup, and a light lever lies over the upper
surface of the india-rubber and is firmly connected with it. When air is blown
into the interior of the cup, the india-rubber bulges and raises the lever; when
air is sucked out, it becomes depressed and draws the lever down. When used
to register the respirations, it is simply connected with a tube in the trachea of
the animal, or with a mask fitted before its nose. As the piece of india-rubber
stretched over y is thin, it would be blown out, and perhaps burst, by the
pressure, if we were to connect it directly with the artery. One of Marey’s
sphygmoscopes is, therefore, introduced between them when we wish to measure
the blood-pressure. The sphygmoscope consists of a little bag of strong india-
rubber, enciosed in a piece of glass tubing, connected with the tympanum. The
bag is filled with soda solution and connected with the artery. Each time that
the pressure rises in the artery, the bag becomes distended and forces some of
the air out of the glass tube into the tympanum, and raises the lever; and when
the pressure diminishes, the bag collapses again and the lever falls. «# is a
modification of this, designed by my friend Dr. Burdon Sanderson. Instead of

DOUBLE REGISTRATION. 283

a bag enclosed in a tube, it consists of a metal box, across the interior of which
a septum of strong india-rubber is stretched. One side of the box is filled with
soda solution and connected with the artery ; the other with air and connected
with the tympanum. w is a piece of lead-tubing for connecting the sphygmo-
scope x with the tube in the artery.

B is a forked tube of German silver or brass for connecting the artery with the
kymographion. a@ is a cannula, which is inserted into an artery (see fig. 34).
6 is a small ring, soldered to it, by which it may be tied to the rings e on B, to
iprevent it from slipping off. e and e are two rings soldered to B. By means of
ligatures passed through these, B may be fastened to the skin or hair of the
animal, to prevent its being displaced by any sudden movement. The oblique
limb of B may be connected to a d alone by a piece of india-rubber tubing, or to
both a d and A w at the same time by means of a Y glas3 tube and india-rubber
tubing. Another piece of india-rubber tubing is attachecl to the straight limb d,
and closed by aclamp or clip. Whena clot forms, the clip is taken off and
the clot removed, the tube washed out by a stream of soda solution, and the
clip again replaced.

c is the tracing-pen (see fig. 32). It is stuek horizontally through a piece of
cork; another small piece of giass tubing, about three-fourths of an inch long,
closed at its upper end, and about one-twelfth of an inch in diameter, or just
wide enough to admit the end of the swimmer, is stuck vertically into the same
piece of cork.*

pen (9g), which registers the movements of the mercury on the
revolving cylinder.

The disadvautage of the mercurial nanometer is, that it does
not give the true form or extent of the variations of blood-pres-
sure, the inertia of the mercury causing it to oscillate above
and below the true value. We may, however, obtain the true
form of each oscillation along with the mean pressure by con-
necting the artery at the same time with the manometer and
one of Marey’s sphygmoscopes and levers (Fig. 133, z and y) by
means of a Y-tube, oue end of which is connected to d and the
other to w. In order to obtain the mean pressure, we turn the
stopcock (eé) till, on blowing through it, only a slow rise and fall
of the mercury can be produced, but no sudden oscillation. On

then connecting it with the artery the mercurial column shows
the mean pressure, while the sphygmoscopic lever registers each
oscillation (¢f: Brunton and Cash, Phil. Trans., vol. clxxxii (1891)
B, pp. 547-550 and 601-632).

Besides this form there are various others on the same prin-
ciple, some of which have cylinders which wind off a con-

* The instrument figured here was made by Sauerwald for Von Bezold, but
as Von Bezold did not require it on account of illness it was sold to the author
by Sauerwald in 1867.

2814 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

tinuous roll of paper from a bobbin, so that a tracing may be
taken uninte:rruptedly for an hour or two without renewing the
paper. In order to avoid the inconveniences of the mercurial
manometer, Fick has constructed one (Fig. 134) in which the
pressure is not measured by the movements of a column of
mercury, but by those of a bent hollow tube (A) fixed at one
end and free at the other. The tube is filled with alcohol, and

Fie. 134,

E

Fick’s spring kymographion. A is a flat tube of German silver, fixed at one
end B to a piece of board Dp. The other end c is freely movable. £ is a tube
connecting A with the artery. Fis a lever made of reed, connected toc. @G is
the writing point, moved up and down by F, and kept perpendicular by another
short lever above. The tube a is filled with alcohol, and the tube E with a soda
solution, and B is then connected with the artery. Whenever the pressure rises,
the tube a tends to straighten itself, but it is firmly fixed at the end B, and so
the end c alone moves upwards, and pushes up the lever F and the writing-
point G. Whenever the pressure relaxes, the tube bends pack again to its*
original shape, and the point G consequently again descends. The tracing is
taken by allowing G to rest aguinst a revolving cylinder, covered with a piece of
p-per, which has been smoked either over a gas flame or a paraffin lamp.

its fixed end connected with an artery. At every rise of
pressure this tube tends to straighten itself, and this motion of
the free end is communicated by it to a lever (F) and writing-
point (G), which records it on a smoked cylinder.

The advantage of this form of kymographion is that it gives

MODE OF USING THE KYMOGRAPIIION. 285

the exact form, duration and extent of each pressure-variation.
Its disadvantage is that the tracings it gives are on a small
scale, so that it is not so well adapted for showing small oscilla-
tions of pressure like those at each heart-beat in the rabbit,
although it answers admirably for dogs. Another disadvantage
is that the tracing must be taken on smoked paper, and this is
more troublesome to manage than white paper and ink.

Mode of using the Kymographion—The kymographion must
first be rendered perfectly level by the screws K kK (Fig. 133).
The upper part of the outer tube of @ and the tube e¢, the india-
rubber tube connecting it with B, and B itself, are then filled
with soda solution and the clip ate put on. A fresh sheet of
paper is put on p, the pen (g) filled with ink, and the pencil (v)
adjusted at the same level, A piece of cotton-thread should be
drawn through the pen, so that the end projects just beyond
the pen’s point; this makes the pen write better. The animal
is next fixed, a vein exposed for injecting, the cannula (a)
introduced into an artery in the way already described, the
blood being prevented from entering the cannula by a clip
placed on the artery. A drop of carbonate of soda solution is
placed in the cannula (a), the tube (B) fitted into it and tied to
it by a thread through the ears 6 and ¢« Two other threads
through e and e fasten the tube (B) to the skin or hair of the
animal. The flask (/) is raised several feet above the appa-
yatus, and the clip at e opened, so-as to make the pressure in
the manometer and tubes nearly equal to that of the blood in
the vessels so as to prevent the blood from filling the tubes. It
must not be greater, or the carbonate of soda will pass into the
vessels and produce convulsions. The clip at eis then replaced
and that on the artery removed, the cylinder set in motion, and
6 tracing of the normal blood-pressure taken.

The drug in solution is now injected into a vein and a fresh
tracing taken. At the time the injection is begun, a cross
should be made on the tracing opposite the pen of the kymo-
eraphion, and a o should be made when the injection is finished.
The time at which these were made should be noted on a sepa-
rate piece of paper, and afterwards copied on to the tracing
itself. Instead of putting on a fresh piece of paper each item,

286. EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

two or three may often be taken on one paper by having two or’

three exactly similar glass pens of the form shown filled with
inks of different colours. Each is stuck through a small piece
of cork, and into the under side of the cork a small glass tube

is put, which will just fit the top of the swimmer. By simply:
dropping the glass tube on the end of the swimmer, the pen is
in its place at once, and can be changed with great facility. A

small sable brush may also be substituted for the glass pen.

After the experiment has gone on for some little time, a clot
is apt to form in the cannula. When this is the case, the clip

must be replaced on the artery, the stopcock (d) turned trans-

versely, so as to keep the mercury at the same height, the clip

on the india-rubber tube at dB and at eA removed, and the
tube washed out by a stream of carbonate of soda. Any clot in

the cannula is removed by a spill of twisted paper, by a hog’s’
bristle, or by a piece of whalebone. The whalebone-probes are
most convenient, as they can be made of any size. <A single

jet of blood should now be allowed to escape from the artery, so
as to make sure that there is no clot in it, the tube again
washed out with carbonate of soda, the clips at ¢ B and eA

replaced, that on the artery removed, and the stopcock turned

and tracings taken as before.

Reduction of the Kymographion Tracings.—lt is not only im-
possible to publish the tracings as they are taken from the
kymographion for the benefit of others, but it is extremely
difficult to draw any except very general conclusions from them
for one’s self. Before they can be of much use they must be
reduced to tables, or, what is still better, the tables themselves
may be graphically represented. In making the tables, we
must first fix the time at which the different parts of the tracing
were made. The time when the tracing was begun and when the’
injection was made must be noted down at the time ina separate

note-book, or, still better, on the tracing itself. In the first tracing ~

it is convenient to take the time when the injection was made,
as a starting-point from which to reckon the other periods.
Beginning at this point, then, we divide the abscissa or zero
line into parts corresponding to five seconds each, or any other
period we think convenient. If the circumference of the

REDUCTION OF KYMOGRAPHIC TRACINGS, 287

cylinder be 60 millimétres, and it revolve once in a minute,
each 5 millimetres of paper will correspond to five seconds’
revolution. .

Secondly, we must ascertain the blood-pressure at different
times. At the point where the injection took place, we draw
from the tracing a perpendicular to the abscissa, and another,
5, 10, or 15 seconds further back. The mean pressure is most
readily and exactly got by means of a planimeter; but, as this
is an expensive instrument and possessed by few, we usually
employ ruder methods. The first is to determine the square
superficies of the irregular figure contained by the abscissa, the
two perpendiculars and the curve, and then divide it by the
length of the abscissa; this gives the mean height of the
pressure-curve. The size of the figure is ascertained by placing
over it a piece of tracing-paper or glass ruled in square mdlli-
metres, and counting the number of squares contained in it.
Volkmann cuts the figure exactly out in paper of uniform
texture and weighs it. By then comparing its weight with that
of a square of given size, the superficies of the figure is easily
ascertained. The second method is still simpler, and, though
not so exact, takes much less time, and is, therefore, frequently
employed. It consists in drawing a straight line from one per- |
pendicular to the other along the curve, so as to cut the pulse-
and respiration-waves as nearly as possible in their middle, and
leave as much of their surface above as below it. We then
measure the height of this line above the abscissa, double it,
and subtract from it the fraction of the whole, which represents
the column of carbonate or bicarbonate of soda solution which
entered one limb of the manometer and pressed on the mercury
in it as the mercury rose in the other limb. For a solution of
carbonate of specific gravity 1018, this fraction will be about ;!,
of the whole. s 3

Passing along the curve taken after the drug has been
injected, we note the place where any change in pressure has
occurred, and here we draw another perpendicular and proceed
as before.

Thirdly, we obtain the number of pulsations and. respirations
in a minute by counting the pulse- and respiration-waves,

288 EXPERIMENTAL INVESTIGATION OF TIIE ACTION OF MEDICINES.

between each two perpendiculars, and reckoning from the time
petween them what the rate of pulse or respiration will be in a
minute. As the rate of both may change several times in a
minute, and a calculation of this sort would lead to consider-
able error, we not unfrequently take 15 seconds as the unit of
time instead of a minute.

The way in which the numbers thus obtained may be
tabulated, is shown by the following examples of supposititious
experiments. These examples have been made by piecing
together several experiments of Von Bezold, and show generally
the action of atropine, but must not be regarded as accurate
descriptions of any one experiment.

Even when a continuous roll of paper is employed, instead of
several separate pieces, it is often convenient to divide it by
lines, and tabulate each pari separately, just as when separate
pieces of paper are used,

MoprE or RecorDiInc EXPERIMENTS,
Experiment I, November 5, 18—.

Young rabbit. Weight 1540 grammes. Jugular vein
exposed and 1 cubic centimetre of tincture of opium, contain-
ing 2 grammes in 25 cubic centimétres, injected into it.
Cannula in the left carotid. Animal otherwise uninjured.

n
a
5 Score
= Ba Remarks,
25/82] 3 | ‘Bs
&o2|/ 22} 3 6
S.A |, Ra} & |
Tractne I.
Tracing begun 2.39 P.M...| o- 78 60 23 | 2) milligrammes of
Injection begun 2.39.15 ..| .. 78 60 23 sulphate of atropine,
" ended 2.39.25 ..| .. 80 63 18 dissolved in 2 cubic
At O.S90: 86 esas ev eatecs] 2087 8S 65 19 centimetres of water,
At 2.400 0666.45 45 vanes ys] OO 86} ST 70 20 injected into the
jugular vein towards
Tracine IT. the heart.
At 2.40.30 eeeeeveeve eee 15 92 92 22,

a a

GRAPHIC REPRESENTATION OF EXPERIMENTS. 289

Experiment IT, November 9, 18—.

Old rabbit. Weight, 1764 grammes. Jugular vein exposed.
Animal not narcotised. Cannula in the left carotid. Animal
otherwise uninjured.

a
1 ot
8 ff ee
© o
B2|.8 |] 5 3 Remarks,
ee) Ss ].8 [gaa
Ad a a ad
Aes | Aa | A 6.5

Tracrne I.

Tracing begun 3.50.0 P.M. | + 92 64 26 | 2 centigrammes of
Injection begun 3.50.10..| 92 64 26 sulphate of atropine,
At 3.50.13... .0cececesees ee dissolved in 2 cubic
Injection ended 3.50.15..| .. 73 70 24, centimetres of water,
MEBOLO gescctccdécces |, 408. [EZ 70 26 injected into the
jugular vein towards
Tracine II. the heart,

At 3.58.0 eeeeeveee ee eee 7.40 78 68 25

Graphic Method of Representing Experiments.—In looking
over a coluinn of figures such as the tables we have now
obtained, it is by no means easy to see at once what it really
indicates ; and it is still more difficult when we have to com-
pare several tables together. For this reason it is of great
advantage to convert the tables into curves, from which the
result of any experiment can be learned at a glance, and the
points of resemblance, or difference in the results of a whole
series compared with the greatest ease.

To obtain these graphic curves, we reverse the process by
which we formed our tables. We first take a piece of paper
ruled in squares, and on it we draw a horizontal line or abscissa,
and then a perpendicular to one or both ends, and number the
spaces along both the abscissa and the perpendicular or ordinate.
Those along the abscissa represent periods of time to which we
may assign any value which is convenient, seconds, minutes,
hours, or multiples of these. The numbers along the ordinate
may represent blood-pressure, pulse-rate, number of respirations,
or degrees of temperature ; and we may describe curves repre-
senting all of these on the same paper, distinguishing them from

U

290 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

one another by the use of different coloured inks. Fig. 135 repre-
sents graphically the tables of blood-pressure and pulse-rate in
Experiments I and II. We begin the pressure-curve by making
a dot on the first perpendicular, at a height corresponding to
the number 78. Passing along horizontally from this for a
space corresponding to 15 seconds to the abscissa, we make
another dot ; and at 10 seconds further, at a height correspond-
ing to 80, we make a third dot, and soon. We then connect
the dots by lines, and thus obtain the curves we wish.

Fra. 135.

millimetres.

HAG HG + Sees Seeao! po SSeS SSRS8 SSSkS SRS ee ese! ue Cau
! tut snes ome bi} ft) 11h. fi) —tiiitiiijitit eee i

Exp. 1. The straight line shows the blood-pressure, and the dotted line the
pulse-rate.

millimetres.

Exp. 2.

LTV .— DETERMINATION OF THE EXACT STRUCTURES TITROUGH
WHICH DRUGS AFFECT THE HEART AND VESSELS.

(British Medical Journa!, 1871, December 9, p. 659, December 16, p. 687,
and December 30, p. 749.)

Comparison of the Effects of Drugs on different Animals in different Doses.—
Mode of determining the exact Cause of Symptoms.—Mode of raising Blocd-
pressure.—Modes of counting the Beats of the Heart.—Causes of Quickened
Pulse.—Direct Stimulation of the Sympathetic.—Stimulation of Cardiac
Ganglia.— Paralysis of the Vagus-roots and Fibres, and of its Ends in the
Heart.—Causes of Slow Pulse.—Irritation of Vagus-roots.—Mode of sup-
plving the Head and Body with different kinds of Blood.-—Indirect Irrita-
tion of Vagus-roots through the Blood-pressure: mode of lowering and
raising it.—Reflex Irritation of Vagus-roots.—-Indirect Irritation through
the Respiration.- Irritation of Vagus-fibres.—Increased Conducting Power
of Fibres.—Stimulation of Vagus-ends.—Paralysis of the Sympathetic.—

COMPARISON OF EFFECTS OF DRUGS. 291

Paralysis of the Cardiac Ganglia.—Part of the Ganglionic Apparatus
affected.—Nervous System in the Heart.—Motor Ganglia.—Stimulating
Ganglia.—Inhibitory Ganglia.—Connecting Apparatus.—-Action of Drugs
on the Inhibitory Apparatus.—Nicotia, Muscaria.—Antagonism of Atropia
and Physostigma ; bearing of this on Therapeutics.—Paralysis of Co-ordina-
ting Apparatus.—Paralysis of the Muscular Fibres of the Heart.—Blood-
pressure: mode of determining whether Changes in it are due to Alterations
in the Heart or Vessels.—Elimination of the Action of the Heart: Division
of its Nerves.—lIrritation of Vagus.—Ligature of Aorta.—Artificial Cireu-
lation ; in Mammals, in the Frog.—Observation of Vessels.—Action on

Vaso-motor Centre; on Vascular Walls.—Influence of the Action of Parts

surrounding the Vessels upon them.—Action of the Pulmonary Circulation

on the Blood-pressure.—Use of the Sphygmograph.

Comparison of the Effects of Drugs—Before proceeding to
examine separately the different structures through which a
drug may act on the blood-pressure, it is advisable to compare
the effects which it produces on animals of different kinds, such
as dogs and rabbits, as well as the action of larger and smaller
doses on animals of the same kind. Continuing to take as an
example the action of atropia, admirably investigated by Von
Bezold, we find the following results.

With a small dose of atropia injected into the jugular vein
towards the heart :

The blood-pressure rises in both rabbits and dogs:

The pulse becomes quick, rising in rabbits from 256 to
288 ; in dogs, from 80 to 240.

With a Se dose :

The blood-pressure, in both rabbits and dogs, falls at first
and afterwards rises to the normal.

The pulse becomes quick in both.

With an additional dose :

The blood-pressure in rabbits falls very low as the poison
reaches the heart; afterwards rises; and falls again
below the normal.

The pulse becomes slower, and then quicker.

With a very large dose:

The blood-pressure sinks instantly in both rabbits and
dogs.

The pulse in rabbits becomes slower and weaker, and
then stops ; in dogs it becomes quick.

u 2

292 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

This comparison between the effects which atropia produces in
different animals, and in large and small doses in the same
animal, shows us that it sometimes raises and sometimes lowers.
the blood-pressure, but that it always quickens the pulse,
except when a large quantity of the poison is introduced at
once into the heart of the rabbit. On consulting the table
already given (p. 278),* it will be seen that quickening of the |
heart may be due to stimulation of the sympathetic, either
directly by the drug or indirectly by diminution of the blood-
pressure ; to stimulation of the cardiac ganglia; or to weaken-
ing or paralysis of the vagus. Any one of these conditions may
cause quickened pulsation ; and, in order to determine which of
them really does it, we must test each one of them separately
by farther experiment.

Mode of determining the exact cause of Symptoms.—The plan
which we follow is this: we suppose for the time being that the
cause which we are testing is the true one, and consider what.
effects it will produce under certain conditions. We then
supply these conditions experimentally, and see whether or not.
the results we obtain correspond with those which we should
find if our supposition were correct. So in the present instance
we first ask, Is the quickening of the pulse due to indirect
stimulation of the sympathetic roots by diminished blood-
pressure or not? We suppose for the moment that it really is.
so, and we consider that if we raise the blood-pressure we shall
remove the cause of quickening and bring the pulse down again
to its normal rate. We then proceed to raise the pressure, and.
see whether or not the pulse is rendered slow, as we expect it to.
be. In the case of atropia, a special experiment is not neces-.
sary for this purpose, as we have seen that small doses do not.
lower but raise the blood-pressure, at the same time that they
quicken the pulse ; consequently the quickening cannot be due:
to indirect stimulation of the sympathetic. Other drugs, how-
ever, such as nitrite of amyl, even in small doses, lower the
blood-pressure at the same time that they quicken the pulse,
and in their case we must raise the blood-pressure artificially.

* Brilish Medical Journal, June 3rd, page 538.

RAISING BLOOD PRESSURE—COUNTING PULSE. 293

Mode of Raising Blood-pressure-—This may be done either by
injecting a sufficient quantity of the defibrinated blood of
another animal of the same species, warmed to 98° Fahr.,
into the carotid or crural artery towards the heart, or by com-
pressing the aorta. The aorta may be either compressed by the
thumb of the operator, or by a narrow pad of cork laid over it
and pressed upon it by a tourniquet, of which the strap has been
passed round the animal’s body.

Mode of Counting the Beats of the Heart.—Now, if we wish to
determine the blood-pressure at the same time with the pulse-
rate, we may count the latter from the oscillations which each
beat of the heart produces in the tracing of the kymographion,
or from the sphygmoscope attached to it; but thisis not always
necessary, and we may wish to ascertain the pulse-rate without
going to the trouble of opening an artery and using a manometer.
We may do this in three ways:—l! By feeling the pulse in one
of the large arteries, such as the crural, with the finger; 2. By
listening to the beats of the heart with a stethoscope; 3. By the
motion of a needle stuck into the ventricles. For this purpose
a fine harelip-needle is inserted at the point where the apex
beats, and is pushed upwards into the substance of the ven-
tricle. At its upper end it may have either a knob, or a loop to
which a thread can be attached, and a barb at the point will
prevent it from changing its position in the heart when traction
is made upon it. In rabbits, the-point where the needle should
be inserted is in about half an inch to the left of the sternum
in the third intercostal space, and the length of the needle used
should be about 3 inches. Various means have been proposed
for counting the oscillations more readily than can be done by
simply watching the movements of the needle itself. The
knob of the needle may be allowed to strike against a wine-
glass, and the pulsations may thus be counted by the ear; ora
needle without a knob may be used, and a rice-straw with a
piece of bright-coloured paper attached to it may be slipped
over it, so that its vibrations, amplified by the long straw, and
made more visible by the bright-coloured paper, may be readily
counted by the eye.

A couvenient way of registering the oscillations on an upright

294. EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

cylinder is one devised by Professor Stricker. One of Marey’s
cardiographic levers is fixed on a rod close to the side of the
animal and some distance above. it, and a small piece of cork
attached to the lever. One end of a fine thread is then fastened
to the needle, and its other end pulled through a slit in the cork
till it is sufficiently tight to make the lever vibrate with each
movement of the needle; it is then fastened by twisting it
round the lever, or by a little sealing-wax. If the lever be not
raised several inches above the needle, it is pulled too much to
a side and not sufficiently downwards to give a good tracing,
The tracing may be taken either on plain paper with a glass pen
or camel’s-hair brush attached to the lever by a piece of cork, or
with a dry point on smoked paper. Instead of a vertical
cylinder a horizontal one may be used, and is perhaps still
better. In this case the lever should be nearly on a level with
the needle, and not raised much above it (¢f/. antea, p. 208).

Is the Quickening of the Pulse due to direct Stimulation of the
Synvpathetic 2—If so, the injection of the drug should cause an
increase in the pulse-rate after the vagi have been divided as
well as when they are intact. We therefore divide the vagi,
inject the drug into the veins, and see whether or not the pulse-
rate is increased. On doing this with atropia it is found that
the pulse becomes slower rather than quicker, showing that the
drug does not stimulate the quickening nerves of the heart.
The increased rapidity of the pulse which it produces when the
vagi are intact is, therefore, not due to this cause.

Is the Quickening due to Stumulation of the Cardiac Ganglia! ?
—The experiment just mentioned shows that it is not, for, if it
were, injection of atropia should cause quickening after division
of thevagi. Supposing, however, that it had caused quickening, the
question whether the acceleration was due to the ganglia or the
sympathetic would have to be decided by dividing all the nerves
going to the heart with a platinum-wire heated by electricity,
and then injecting the drug, or by applying it to the heart
of the frog in a way which I shall afterwards describe. If’ it
quickened the beats of a heart thus separated from all other
nerves, it could only do so by acting on the cardiac ganglia
themselves.

TO WHAT CAUSE IS A QUICK PULSE DUE? 295

Is the Quichkening due to Paralysis of the Vagi ?—The exclu-
sion of the other causes leads us to believe that it is due to this ;
but, in order to avoid the possibility of error, we must try to
confirm our conclusion by other experiments ; and, moreover, we
have still to find out, which part of the vagus is affected—its
roots, its fibres, or its ends in the heart.

Are the Vayus-roots Paralysed by the Drug ?—We are enabled
to answer this. question by our knowledge of the fact, that
poisons only act on the parts to which they are carried by the
blood, and that when introduced into the circulation they do not
reach every part of the body at once, but are carried on with
the blood-stream first to one part and then to another, and will
reach a part near the point where they were introduced before
one which is farther off. Thus, if we inject a drug into the
carotid it will be carried direct to the head, and will act on the
medulla oblongata and the roots of the vagus before it reaches
the heart; but if we inject it into the jugular vein it will reach
the heart and act on the vagus-ends in it before it reaches the
roots in the medulla. If atropia paralyse the vagus-roots, then
its injection into the carotid towards the head should be fol-
lowed by rapidity of the pulse more quickly than its injection
into the jugular; but if it act on the vagus-ends in the heart,
the pulse should become rapid more quickly after injection into
the jugular vein towards the heart than after injection into the
carotid. On testing this experimentally, it is found that, when
atropia is injected into the jugular vein towards the heart, the
pulse at once becomes quick, even before the. injection is
finished ; but, when it is injected into the carotid towards the
head, the pulse is not quickened for a quarter of a minute or
more, or, in other words, till the poison has had time to pass
through the capillaries of the head and go through the veins to
the heart. This, then, shows that it is the vagus-ends in the
heart, and not the roots in the medulla, that are paralysed
by it.

Are the Vagus-fibres Paralysed ?—From the rapidity with
which paralysis of the vagus occurs after atropia reaches its
ends, we have already come to the conclusion that the ends are
the part affected rather than the roots or fibres; but it is well to

296 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

substantiate our conclusion by further experiment. We divide
the vagus and galvanise its peripheral extremity. If we do this
to a normal vagus, the heart will beat more slowly or stand still
altogether ; but if either the fibres or ends of the nerve have
been paralysed, no change will be produced in the heart’s rhythm
by the application of galvanism to its trunk, and this we find to
be the case after the administration of atropia. But this ex-
periment does not enable us to decide which part of the nerve
is paralysed—the fibres or the ends, for in either case the effect
would be the same. We may do this, however, by observing
the effect which irritation of the vagus-trunk produces on such
of its fibres as do not go to the heart. If it were the fibres which
were paralysed, we should expect that those which go to the
heart would not be the only ones affected, but that those going
to other parts would be paralysed likewise.

I have hitherto spoken of the vagus as if it were a simple
nerve containing only inhibitory fibres for the heart, but it is
really a most complicated bundle, containing centripetal fibres
having probably no fewer than eleven different functions, and
centrifugal ones having nine or ten; soit is little wonder that
it has long been a puzzle to physiologists, and even yet its
functions are not completely investigated. Among these fibres
are some which produce contraction of the cesophagus and
muscles of the larynx; and if we find that irritaticn of the
vagus continues to produce contractions in these parts after it
nas ceased to render the heart’s action slow, as is the case after
injection of atropia, we conclude that its fibres are not paralysed.
Dr. Rutherford has shown that the best mode of observing
the effects of irritation of the vagus on the muscles of the
larynx, is to open it in frent and place the animal in such a
position that the light may be reflected from the inner surface
of the arytenoid cartilage, as the slightest movements can then
be readily detected. In this way it is found that atropia pro-
duces complete paralysis of the cardiac branches of the vagus,
while the motor fibres supplying the muscles of the larynx
remain unaffected ; and we are therefore forced to conclude that
it acts not on the fibres but on the ends in the heart. A more
direct method is to apply the drug dissolved in an indifferent

COMPLEX FUNCTIONS OF THE VAGUS. 297

fluid, such as half per cent. solution of chloride of sodium, to
the vagus itself, and then to irritate the nerve about this point.
This may be done by dropping the solution on the nerve after
‘placing a piece of gutta-percha tissue below it, so as to keep the
fluid from reaching the tissue below and being absorbed. If the
drug paralyse the fibres, the irritation which is applied to the
nerve above the part which is moistened by the solution will
not be conveyed by the paralysed part of the nerve, and will
consequently have no effect on the heart.

How does a Drug vender the Heart's Action Slow ?—We have
now gone over the experiments which are necessary to deter-
mine what the structure is through which a drug quickens the
heart’s action, and we have now to consider those which we
require when investigating the action of a drug which renders
it slow. It may do so by irritating the vagus-roots, fibres, or
ends; by increasing their excitability, so that they act more
strongly when stimulated; or by paralysing the sympathetic,
the cardiac ganglia, or the muscular substance of the heart
itself.

Does it act by irritating the Vagus roots ?—In order to answer
this question, we divide both vagi and then inject the drug.
We thus separate the heart from the vagus-roots and deprive
them of any influence over it, so that, if they have been the
cause of slowness of the pulse in previous experiments, it will
_ not occur in this; but if the slowness have been due to other
causes it will, with one or perhaps two exceptions, be noticed in
this experiment, just as it would had the vagi been intact.
These exceptions, which we will consider afterwards, are in-
creased excitability of the vagus-fibres and ends. The vagus-
roots can enly act on the heart through the medium of the fibres
and ends; if the drug itself should affect these structures, its
action on the heart may be much altered or even destroyed. If
the vagus-ends be paralysed, the roots can exert no more action
on the heart than they can after we have cut through the
trunks; and if the excitability of the ends be increased, the
power of the roots over the heart will be greatly augmented, so
that the heart’s action may be made slow without there being
any actual irritation either of the roots or ends. In order, then,

298 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

to find out what effect the drug has on the vagus-roots them-
selves, we must inject it into the carotid, so that it may reach
them before it reaches the fibres or ends ; and note what change
occurs in the pulsations of the heart immediately after the
injection. Any change which occurs immediately is due to the
effect of the drug on the roots themselves ; and, by comparing
the number of pulsations at this time with that which is found
a quarter of a minute or so afterwards, when the drug has.
reached the vagus-ends, we may discover whether their excita-
bility has been inereased or diminished. Thus, in the experi-
ment already mentioned for ascertaining whether or not the.
vagus roots are paralysed by atropia, we find that, when we
inject it into the carotid, we get immediate slowness of the
pulse, showing that the vagus-roots are irritated by the drug;
but whenever it gets round to the heart it paralyses the vagus-
ends, and the slowness at,once disappears. If we were to keep
the head alive by supplying it with an artificial stream of blood
containing atropia, and prevent any of the poisoned blood from
reaching the heart, the slowness might be continued in-
definitely.

Mode of supplying the Head and Body with different kinds
of Blood.—In his researches on respiration Hering employed
a method of this sort, at one time supplying the brain with
blood loaded with carbonic acid while the blood of the body was
richly arterialised, and at another sending arterial blood to the
brain while respiration was stopped and the blood circulating
in the body was intensely venous. For this purpose he opened
the thorax and tied the left carotid and innominate close to the
aorta, and the vena cava superior close to the heart in a cat; he
then introduced one cannula into the innominate artery, and
another into the vena cava, and injected doe’s blood, defi-
brinated and warmed, into the innominate ertery, while he
allowed it to flow out by the vein.

In airopia we have an example of a drug which acts on more
than one part at once, and whose action on one part completely
neutralises the effect which its action on the other would pro-
duce. In the case of others, however, we have the action on
the different parts strengthening each other, as in veratria

ACTION OF DRUGS ON THE VAGUS-ROOTS. 299

which, like atropia, stimulates the vagus-roots, but, instead
of paralysing the ends, increases their sensibility, and thus
‘greatly augments the effect which the excited roots would have
exercised over the heart, even had the ends remained unaltered.

Are the Vagus-roots Irritated directly by the Drug or indirectly
through inereased Blood-pressure ?— Along with the slow pulse,
produced by the injection of atropia into the carotid, a rise occurs.
in the blood-pressure ; and how are we to determine whether
the irritation of the vagus-roots is due to this increase, ar to
the direct action of the drug«tself? This is a question very
difficult to solve in the case of atropia, on account of the
rapidity with which the vagus-ends are paralysed and all influence
of the root over the heart destroyed. In the case of other drugs,
however, where time is allowed, the question might be settled
by diminishing the blood-pressure and seeing whether or not.
the slow pulse returned to its normal rate, and then raising it.
again and observing whether the pulse again became slow.

Mode of Lowering and Raising the Blood-pressure—The blood-
pressure may be lowered by opening a large artery, such as the
carotid or crural, and allowing the blood to flow out into-a.
vessel warmed to 98° Fahrenheit, and again raised by injecting
the warm blood back into the artery. Or we may adopt Ludwig
and Asp’s plan, of inserting into the central end of the carotid
a straight tube with a stopcock in its middle, and the moist.
bladder of a small animal, well emptied of air, tied to its free
end. When the stopcock is opened, the blood rushes from
the carotid into the bladder, and the tension in the arteries is.
diminished; but, when we press the blood out of the bladder
back into the arteries, the tension on them is again increased.

Are the Vagus-roots Irritated Reflealy from some other part of
the Nervous System ?@—There are two ways of deciding this:
the first is to inject the poison in such a manner that it shall
reach the vagus-roots before it reaches the other nervous struc-
tures through which we suspect it to act reflexly ; the second is
to remove these nervous structures themselves, or to destroy
their function by means of some other poison. Thus,if we think
that atropia, when injected into the carotid, acts on the medulla
through the cerebrum, we may either remove the latter, or

200 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

abolish its function by opium or chloral, The application of
irritating vapours, such’ as ammonia or tobacco-smoke, to the
nasal mucous membrane of a rabbit, produces still-stand of the
heart. We ascertain that this is due to irritation of the vagus
by cutting it and finding that the vapour then has no effect’;
and we next decide that the irritation is conducted to the
nervous centres through the trigeminus and not through the
olfactory nerve, by observing that section of the former like-
wise prevents the action of the vapour on the heart, while
‘section of the latter does not affect it.

Ave the Vagus-roots Irritated indirectly by the Drug impairing
Respiration, and thus allowing Carbonic Acid to accumulate im the
Blood ?—In the experiment just mentioned, we have ascertained
that the vagus is irritated, and that irritation is conducted to
ithe nerve-centres through the trigeminus, but we do not know
that the irritation is directly reflected from the trigeminus to
the vagus. It might be due to irritation of the vagus-roots by
carbonic acid, which has accumulated in the blood from im-
peded respiration; for the irritating vapour applied to its nose
causes the rabbit to close its nostrils and stop breathing for a
while if the trigeminus be intact, but when it is cut no irritating
impression can be conveyed to the brain, and so no closure of
the nostrils takes place, either voluntarily or reflexly. The
rabbit, therefore, continues to breathe freely: no carbonic acid
accumulates in the blood, and no irritation of the vagus occurs.
‘Other drugs, such as strychnia and curare, &c., impede respira-
¢tion—not by causing closure of the nostrils and consequent
obstruction to the passage of air to the lungs, out by acting on
the muscles and nerves and diminishing the respiratory move-
ments. Strychnia does this by producing tetanic contraction of
the respiratory muscles, curare by paralysing them, and chloral
by diminishing the excitability of the respiratory nervous
centre. In all such cases, in order to ascertain that indirect
irritation of the vagus from impeded respiration is not the cause
of the slowing of the pulse, we insert a cannula into the trachea
and begin artificial respiration; we then note the rate of the
pulse and blow the irritating vapour into the nostrils, or inject
ithe drug into the veins, and see whether or not the pulse is

VAGUS-FIBRES—VAGUS-ENDS. 302

rendered slow, taking care to keep up artificial respiration al?
the time. If the drug cause convulsive movements which
interfere with the proper performance of artificial respiration,
curare should be given so as to prevent their occurrence, and
the experiment should be again repeated.

Are the Vagus-fibres Irritated ?—To ascertain this we apply
the drug dissolved in an indifferent fluid, such as a solution of
half per cent. of chloride of sodium, or serum, to the nerve,
and notice whether any change occur in the heart-beats. Care
must be taken that the solution of the drug be not applied in
too concentrated a solution, as false conclusions might thus be
arrived at, for it might then have an irritant action, which it.
could not have if it reached the part through the circulation
and became diluted by the blood before reaching the nerve.

Is their Conducting Power Increased, so that the Roots can act
through them on the Heart more readily and powerfully ?—If
their conducting power be increased, other stimuli as well as.
those from the roots will act more powerfully on the heart. We
therefore divide the vagi and apply a stimulus to the peripheral
end of one or both by irritating them with one of Du Bois
Reymond’s induction-coils, and note at what distance from the
primary coil the secondary one must stand in order to produce
stoppage or slowness of the heart; we then apply the drug to
the nerve below it and again irritate. If the excitability of the
nerve be increased, stoppage or>slowness should be produced
when the distance between the primary and secondary coils is.
greater—that is, when the current is weaker than before. It is
generally assumed that the fibres are not likely to be affected,
and these experiments are rarely performed.

Are the Vagus-ends Excited ?—-We may test this in the same
way as the action on the roots, by injecting the drug at one time
into the jugular and at another into the carotid. If it increase
the excitability of the ends without affecting the roots, we should
find it produce, when injected into the jugular vein, an imme-
diate slowing of the pulse, which does not become greater in a
quarter of a minute afterwards, when the drug has reached the
roots. When injected into the carotid, no slowness should occur
till sufficient time has elapsed for it to pass round to the heart.

302 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

If it increase the excitability of both roots and ends, immediate
slowness should occur, whether it be injected into the jugular
or carotid, and this should become more marked after 15 or
20 seconds. If, like physostigma, it increase not only the
excitability of the vagus-ends, but that of the quickening centre
in the head, injection into the jugular should be followed by
immediate slowing, which would become less marked when the
drug reached the head, and injection into the carotid by an
immediate quickening, which would become less or give place
to slowness when the drug reached the heart.

At first sight one might think that, after time had been
allowed for the drug to pass rcund the circulation and be applied
both to the vagus-roots and ends, its action on the heart would be
the same whether it had been originally injected into the jugular
or into the carotid; but this is not the case, for that organ
towards which the drug was injected gets a larger dose, and its
action is more strongly excited than that of the other. Thus
when physostigma is injected into the carotid, the quickening
centres are stimulated and the pulse-rate rises; and, although
the pulse falls somewhat after the vagus-ends have also been
acted on, it nevertheless continues above the normal, the stimu-
lation of the vagus-ends not being able to counteract the still
more excited quickening centres. When it is injected into the
jugular, the vagus-ends get the largest dose; and although the
pulse, which is at first made very slow, may afterwards become
quicker when the drug reaches the brain, it nevertheless does
not reach the normal rate, the quickening centres being unable
to counteract the more strongly excited vagus. If the vagus be
then cut, however, the pulse becomes quicker than it would
have done had no physostigma been given; or, if the vagi be
first cut and the drug injected, the pulse is quickened at
once. One might think that, since the drug acts on the vagus-
ends, its action should remain after the nerves themselves
have been divided; but since it is by increasing the excita-
bility of the ends that it acts, if we separate these ends
from the roots, and thus remove their normal stimulus, their
increased excitability can have but little effect. In order
to measure the amount of increase in the excitability of

SYMPATHETIC NERVES—CARDIAC GANGLIA. _ 305

the nerves, we divide the vagi and irritate them by an induc-
tion-coil, noting the strength of current required to produce
still-stand or slowness of the heart before and after injection of
the drug into the veins.

Is the Sympathetic Paralysed ?—This is tested by cutting the
vagi and dividing the spinal cord between the first and second
cervical vertebrae, so as to exclude the action of those centres
in the head which quicken the heart and raise the blood-pressure ;
the drug is then injected, and the sympathetic irritated by an
induced current and the pulse counted. If it be quickened by
the irritation, the sympathetic is not paralysed.

Are the Cardiac Ganglia Paralysed ?—To see whether or not
the nervous structures contained in the heart itself are acted on
by a drug, we must separate it from all other nerves passing to
it from without, and prevent its being acted on by anything
other than the drug, such as altered blood-pressure or tempera-
ture. This is done in mammals by dividing the vagi, the
sympathetic cord, the depressor, and the spinal cord between
the first and second cervical vertebrae. The heart is thus sepa-
rated from the quickening and retarding centres, so that any
alteration in its beats must be due to the nerves contained in its
walls, or the muscular fibre of these walls themselves: at the
same time the vessels are separated from the vaso-motor centre,
and the heart is thus protected from the effects of any change
in the blood-pressure, except the generally unimportant ones
produced by the action of the drug on the vascular walls. The
number and amplitude of the heart’s contractions are then
registered by a needle placed in the ventricle, and the blood-
pressure by the manometer ; poison is injected into the jugular,
and the tracings taken afterwards are compared with those
taken before: If we find that the heart-beats have become
slower and weaker, while the pressure they have to overcome
has not been increased, we may conclude that the motor nerves
or the muscular substance of the heart have become paralysed.
If the blood-pressure have risen, blood should be allowed to
flow from an artery till it falls to its previous level, and then
tracings should be taken with the needle for comparison with

the previous ones.

304 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

The action of drugs on the heart can be studied still better in
the frog than in mammals, as the heart of the former can be
completely separated from the body, so that the drug can be

applied to it alone. After its removal it continues to pulsate .

just as before, and, consequently, any action of the drug on the
rhythm or force of its beats can be very easily noticed. The
usual way of making experiments on this subject formerly was
to take out the heart and lay it in a solution of the poison, or,

what was better, to take two glasses containing solution of chlo- ~

ride of sodium (half per cent.) and.add a little of the drug to one
of them. A frog’s heart was then laid in each, and the beats of
the poisoned compared with those of the unpoisoned one. Both
of these plans are inferior to that of Ludwig, who supplies the
heart with serum so as to keep it as nearly as possible in a nor-
mal condition, and attaches to it a manometer, so that it may
itself register the number and form of its beats, and give more
exact indications than could be obtained by merely looking at
it. The apparatus which he and Cyon first used, and which is
figured in his Arbeiten for 1866, has been considerably modified
by Dr. H. P. Bowditch, and is shown in Fig. 136. It consists of
a bent glass tube (c c’ 0”), which is supported by a glass plate
(p). The frog’s heart (A) is connected to the ends of this tube
by means of india-rubber tubing and two glass cannule, one of
which (B) is tied into the vena cava and the other (B’) into the
aortic bulb. The tube has three openings, each of which is
furnished with a three-way glass stopcock. By means of one of
these (v) it can be filled with serum from a reservoir (K or K’),
and the stopcock may be so turned as to allow serum to enter
the part of the tube above it, the part below it, or both together,
or the communication with K may be shut off while the lumen
of the tube remains open. By c’, the serum which has been
already uséd is allowed to escape, when a fresh supply is giyen,
and oc’ allows the tube to communicate with a manometer (M),
- on the mercury in which a fine pen floats and registers its oscil-
lations on a revolving cylinder (Q). Each time the heart con-
tracts it drives the serum with which it is filled out of the
ventricle, round the tube, and back through the vena cava into
the auricle, and at the same time raises the mercurial column in M.

a7
hie ial aes

=: a Se ag
ital. fo ed madd bated S$ ih f

bel te bleh bold thai ele ee meee ee Tie had ea el

a eS i 2 =
rTy

oes ie ee ed oe

BOWDITCH’S APPARATUS. 305

Fie. 186.—Dr. H. P. Bowditch’s Apparatus for Experiments on the Heart

of the Frog.
K 4
Byt ca
: fe
a ’
N ~ | &
Joa cl y [
ow
S
D
é : Pe ei 3
B Bom

A is the frog’s heart. B is a cannula tied into the vena cava, and B’ one into
the aortic bulb. o, oc’ and o” are three glass stopeocks. By c fresh serum is
supplied, by oc’ old serum is let out, and 0” allows the communication between
the bent tube B 0’ B’ and the manometer M to be opened or shut at will. Disa
glass plate, through which the bent tube B 0’ B’ passes. E isa rod ending ina
ring into which p is fitted. ¥F isa nut by which the whole apparatus can be
moved up and down on the standg@. H is a T-tube. J and J’ are two clips to stop
the flow of serum from K ork’. K and XK’ are two fountain-bottles for supplying
serum to the heart. K contains pure, and x’ poisoned serum. 1 and L’ are bent
tubes which convey the serum out of K and K’. Misasmall manometer. N is
the pen or point which swims on the mercury. The horizontal part is made of
glass; the vertical rod of esparto grass, with a small piece of sealing-wax at its
iower end. The tracing may be made with ink, or with a dry point on smoked
paper. P isasmall weight which hangs by a piece of unspun silk from a bent
wire, and keeps the pen resting on the paper. Q is the revolving cylinder. 8 is
the clockwork, which is provided with one of Foucault’s regulators. s is a table,
which can be raised or lowered at pleasure, and fixed at any height by the
screw T. Vis an india-rubber tube, through which the serum is emptied from x,
x is a graduated tube, into which the serum is allowed to pass after it has circu-
lated some time. yY is an india-rubber tube, which is generally closed by a clip,
but is opened when the apparatus is to be filled, or when we wish to let down
the mercury to zero, in order to draw an abscissa. wW is a glass vessel, which
fits tightly to the under side of p, and protects the heart from external irrita-
tion. Into the two holes seen in p tubes may be fitted air-tight, and the heart
made to pulsate in an atmosphere of any sort of gas.*

* This apparatus is made by Geisler, Blume’s Hof, Berlin. Mr. Hawksley,
x

306 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

The height of the curve traced by the pen depends very much
on the amount of serum which the heart contains, being
very much higher when the heart is full; and it must, there-
fore, be equally filled each time, or very different tracings will
be obtained. For this purpose I use, as reservoirs for the serum,
fountain-bottles, in the mouth of which it always stands at the
same level, and, consequently, always fills the heart at the same
pressure. One of them (kK) is filled with pure serum, and the
other (K’) with serum to which a certain amount of the drug to
be tested has been added.

For the purpose of introducing the cannula into the heart,
the brain and. cord of the frog are destroyed by a piece of wire,
and the animal fixed on its back to a board. A V-shaped in-
cision, with its apex at the lower end of the sternum, and its
limbs extending upwards and outwards towards the forearms, is
then made in the skin, and the flap turned back or cut off. The
sternum is then removed in a similar way. The pericardium is
next opened, the cut being made while the heart is contracted,
so as to avoid injuring it. The apex of the heart itself is then
turned upwards, and two ligatures are passed underneath a
small vein which runs from its posterior surface to the pericar-
dium. The ligatures are tied, and the vein is cut between them.
The pericardium must now be removed entirely from the heart,
and the vena cava superior and the right branch of the aorta
tied. The vena cava inferior is carefully isolated; a ligature is
passed under it, a short and wide cannula tied into it, and
another into the left branch of the aorta. The heart is then cut
‘away from the body. Both cannule are filled with serum, and
connected by india-rubber tubing to the ends of the tube cc’ co”,
care being taken to exclude air-bubbles. The end of the mano-
meter nearest C is filled with serum by opening the clip at y,
and allowing all the air and a little serum to escape. The clip
is then replaced, and the heart allowed to beat once or twice,
with the stopcock c and the clip J freely open, so that it may
of Blenheim Street, Oxford Street, has adapted a bobbin and rollers to the
revolving cylinder figured above, so that it will carry a continuous roll of paper,
and may be conveniently used instead of the kymographion shown in fig. 133.

The instruments which I have already described as necessary for experiments
may be obtained from him or from Oswald Hornn, Schiller Strasse, Leipzig.

LUDWIG AND COATS’ APPARATUS. 307

become full of fresh serum. The stopcock c is then turned so
as to cut off the tube c c’ c” from all communication with kK ;.
and tracings are then taken, an abscissa or zero-line being drawn
under each. The heart is next supplied with poisoned serum
from Kk’, and the tracings which it gives are compared with the
normal ones. By slightly turning the stopcock c, a greater or
less resistance may be opposed to the circulation of fluid, and
the effects thus imitated which contraction or relaxation of the
vessels would produce in the living animal.

Another apparatus has been invented by Ludwig, and used
by Coats in his research on the vagus, in which there is no
circulation, the serum being simply forced out of the ventricle
at each systole, aud falling back at each diastole. It gives,
however, very good tracings of the number and form of the
heart-beats, and is extremely well adapied for observations on
the effects of drugs on the vagus. It consists of a manometer,
E, and a reservoir, A, with which the frog’s heart is connected by
two cannule, D and p’. The frog’s heart is prepared by destroy-
ing the brain and spinal cord, removing the sternum and fore-
legs, but leaving a large flap of skin, s, to cover the heart with,
and then introducing a cannula into the vena cava and aorta, as
in the former experiment. Instead of then cutting out the
heart, the liver and lungs are removed, and the stomach is cut
through the middle ; and a glass tube, sealed at both ends, and
as thick as the cesophagus will admit, is pushed through it till
one end projects at the mouth and the other from the cut end
of the stomach. The vagus is thus clearly displayed; and, in
order to isolate it more perfectly, all other nerves should be cut
away, as well as a part of the pharynx, so that no soft parts
may touch it from its exit from the bone to the place where it
crosses the aorta. From this point to the heart, it should be
left untouched; and the jugular vein should not be tied, so as
to Jeave it undisturbed. The glass tube J is then fixed firmly
in a holder L, and the cannule, pD and pb’, connected with the
reservoir A, and the manometer Er. Instead of the reservoir A
shown in the figure, it is perhaps better to use two fountain-
bottles. The apparatus is used just like that shown in Fig. 136;
and the heart should in this case also be filled so full that a

x 2

Fie. 137.—Ludwig and Coats’ Frog-heart Apparatus.

|
AY

Te in

: L i i l

NYT
| i iF

lt

: lt

NC i
et fi

Ais a reservoir for serum. B, a stopcock to regulate the supply to the heart.
Cc, a piece of caoutchouc tubing connecting A and D. D, a giass cannula in the
vena cava inferior. oD’, another in the aorta. £E,a manometer. F, a piece of
tubing closed by a clip, to allow of the escape of serum. 4, a fine pen, floating
on the mercury in E. H, the frog’s heart. J, a sealed glass tube, passed through
the cesophagus kK, and firmly held by a holder t. M, anut which allows L to be
moved upand down. N, a second holder to support A. p,a stand with upright
rod. §, a flap of skin to cover the heart and prevent drying. v, the vagus.

GANGLIONIC APPARATUS IN HEART. 309

certain tension exists within it even during diastole. The
amount of this is shown by the height of the diastolic curve
above the zero-line. When the vagus is irritated, the tension
during the diastole sinks; but, if its inhibitory fibres be para-
lysed by atropia, which leaves its quickening ones unhutt, irri-
tation has then the opposite effect, and the tension during the
diastole becomes greater and greater till the heart may stand
still in firm contractions.

What Part of the Ganglionic Apparatus in the Heart is
affected ?—In dealing with this part of the subject, we tread on
very unstable ground, for here pharmacology has almost run
ahead of physiology ; and even with our physiological know-
ledge of the nervous structures of the heart a great deal of
speculation is mixed. We know that the heart contains ganglia
scattered through its substance, but found in the greatest num-
bers in the septum between the auricles and in the auriculo-
ventricular groove of the frog’s heart, in which they have
been chiefly investigated. As the heart, long after it has been
separated from the body, or the apex after it has been cut off
from the ventricle, will still continue to beat rhythmically, the
cause of the contractisns must be contained in itself; and we
assuine the cause in each part to be the cardiac ganglia, and
suppose that they are connected by some apparatus which keeps
them working harmoniously together, as the different parts of
the heart all contract in a definite order so long as it is unin-
jured. Their action may be rendered slow or quick by nerves
passing to them from Without, both the retarding and the
quickening nerves being contained in the vagus in the frog
while in mammals the retarding ones are found in the vagus,
and the quickening ones chiefly in the third branch of the
ganglion stellatum (or first dorsal generally joined to the last
cervical), although some may also be found in the vagus.

Some physiologists consider that the function of all the
ganglia is simply to keep up rhythmical movements in the
heart. Others hold that only some of them, found chiefly
in the venous sinus and ventricle, have this function:
while others are inhibitory, and restrain the action of the
former. Thcse inhibitory ones exist chiefly in the septum

310 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES

between the two auricles. The reason of this supposition
is that, when the venous sinus is separated from the rest of
the heart, it continues to pulsate; but the auricles and ven-
tricles stand still. When the ventricle is cut off from the
auricles, it begins to beat again, but the auricles do not; so that
it would seem as if the motor apparatus in the venous sinus and
ventricles together could overcome the inhibitory apparatus in
the auricles, and keep the heart going; but that this is too
strone for the motor ganglia in the ventricle alone, and will not
let them go on till they are separated from it, or till it becomes
exhausted, which it seems to do after a little, and then both
auricles and ventricles begin anew. The physiologists who
hold the simpler view, say that this stoppage is only due to the
irritation of the vagus-fibres which run along the venous sinus,
and that the renewed cardiac contractions are simply due to
the irritation passing off. ‘The pharmacologist, however, is not
contented even with the more complicated of these mechanisms,
but demands a still more elaborate nervous apparatus in order to
explain the action of poisons on the heart. The necessity for this
has been clearly shown and a plan of the nerves drawn up by
Professor Schmiedeberg. I have endeavoured to represent the
supposed nature of this apparatus in the accompanying diagram.
(Fig. 138.) It consists of a ganglion M, which keeps up a rhyth-
mical contraction of those muscular fibres of the heart to which
it is connected by the fine nervous filaments E. This ganglion
is connected by an intermediate apparatus, B, with an inhibitory
ganglion I, which can retard or stop the muscular contractions
which M produces; and by another apparatus c, with another
canglion Q, which quickens the contractions. I is connected by
an intermediate apparatus, A, with the retarding fibres v, of the
vacus, and Q by A’ with the quickening nerves s, of the heart.
Inhibitory Gunglia of Heart—We have hitherto included
under the terms vagus-ends all the inhibitory apparatus in
the heart; but, when we begin to experiment with the heart
alone, we find that poisons which such experiments as have
already been described would lead us to class together as acting
on the vagus ends, really act on very different parts of the
cardiac nervous system. Thus nicotia, when injected into the

AUTHORS DIAGRAM OF CARDIAC GANGLIA, oll

blood after the vagi and cord have been divided, renders the
pulse slow; but this soon gives way to quickening; or, if the
dose be large, quickening may occur at once; and, if we then
irritate the vagus, we find that we cannot render the heart
beats slow any more than we can after poisoning by atropia.
We thus see that, after the irritation which nicotia first occa-
sions in the vagus-ends has passed off, it paralyses them; and
we might thus be inclined to think that they acted on the same

structures. But, if we give nicotia to a frog, and instead of

Fia. 138.—Diagram of the hypothetical Nervous Apparatus in the Heart,

M, motor ganglion. 1, inhibitory ganglion. Q, quickening ganglia. v, inhi-
bitory fibres ; and s, quickening fibres from the medulla. A, a’, B and ©, inter-
mediate apparatus. &, fibres passing from the moter ganglia E, to the muscular
substance F. For simplicity’s sake, only one set of motor ganglia has been
represented, but other similar ones are to be supposed to be present in other
parts of the heart, and so connected with this set that they all work in unison.
It must be remembered that this diagram is purely hypothetical; but if this be
carefully borne in mind, the sketch will be found of service in remembering and
comparing the action of different poisons on the heart.

irritating the vagus, we irritate the venous sinus, still-stand of
the heart is at once produced; while, if atropia be given, and
the venous sinus then be irritated, the pulsations are not slowed
at all—showing us that there is some inhibitory apparatus in the
venous sinus which has been paralysed by atropia, but left
untouched by nicotia. We may substantiate this conclusion by
another and extremely useful method of investigation—viz., by
administering another poison, and seeing how its action is
affected by each of the other two. If we allow a little muscaria

312 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

to reach a frog’s heart, its beats become slower and slower, and
at last cease altogether, the ventricles remaining widely dis-
tended, just as they would do if the vagus were strongly
galvanised. If nicotia be then injected into the frog or mixed
with the serum supplying an excised heart, no alteration is
observed ; and if nicotia be injected before the muscaria, the
latter poison stops the heart just as usual, although the nicotia
may have so paralysed the vagus that no irritation whatever
applied to its trunk could act on the heart. But, if atropia be
used instead of nicotia, the effect of the muscaria is at once
destroyed, and the heart, which was standing quite still, imme-
diately begins to beat. If the atropia be applied first, and
muscaria given afterwards, it has no effect. Hence we see that
nicotia has paralysed some part of the inhibitory apparatus
farther away from the motor ganglia than that on which mus-
caria acts, while atropia has acted either on the same part as
muscaria, or on some other one which lies between it and the
motor ganglia.

Now, as the inhibitory effect produced by muscaria,is net
developed all at once, but goes on slowly increasing till it makes
the heart stand still in diastole, it seems probable that its
stimulating action is exerted on a ganglion, rather than on a
nerve-fibre, and we therefore suppose that it acts on the inhibi-
tory ganglion I. As the action of nicotia is exerted on some-
thing farther from the heart than I, our first idea is that it
must be the nerve-fibres v. But on applying nicotia to the
trunk of the vagus, after fixing the heart in Coats’ apparatus,
we find, on irritating the nerve above the point, that it still
conducts impressions and causes stoppage of the heart. We are
thus led to suppose the existence of an intermediate apparatus
on which nicotia acts; but, whether or not this intermediate
part simply consists of nerve-fibres less protected from tle
poison than those in the trunk, we cannot say. As atropia
destroys the action of muscaria, it may act like muscaria on 1;
but the fact that muscaria does not destroy that of atropia
would lead me to refer the action of the latter to a part between
I and M, which is represented by B. Of what nature this part
is we know nothing; but that such a part exists is rendered

ANTAGONISM IN ZYMOTIC DISEASES. 313

all the more probable by the mutual antagonism of atropia and
physostigma. Although this latter poison renders the vagus
very sensitive, so that the power of any irritation applied to its
trunk to stop the heart is immensely increased, yet it has not
the extraordinary power of producing still-stand of the heart
possessed by muscaria. Unlike mvscaria, however, it has the
power of removing the paralysis of the vagus produced by
atropia, and, though an additional dose of atropia will again
cause paralysis, a second dose of physostigma will again remove
it. This difference of action between muscaria and physo-
stigma seems to show that they act on different nervous struc-
tures; while the mutual power that atropia and physostigma
possess to neutralise each other's effects, indicates that atropia
acts on the same structure as physostigma, and consequently on
a different one from muscaria.

Antagonism of Atropia and Physostigma.—Atropia and physo-
stigma are thus physiclogical antidotes to each other; and
Fraser has shown that a dose of physostigma large exough to
kill an animal may be given to it with impunity if atropia be
administered along with it, and that the animal may be after-
wards destroyed by a small dose given alone. It is true,
they do not completely counteract each other’s action, each
one seeming to produce several effects, some of which, and these
the most deadly, are neutralised by those of the other drug,
while others are not so neutralised; and, if enormous doses be
administered, those active effects which are not neutralised may
become so powerful as to cause death, although they are com-
paratively unimportant when the dose is small.

Importance of this in Therapeutics—Nevertheless, within
certain limits these poisons do antagonise each other most suc-
cessfully ; and this observation seems to me to have a most
important bearing on the treatment of such diseases as have
their origin in morbid matter introduced into the system, for it
shows that it is not always necessary to eliminate a poison in
order to remove its effects, but that it may be neutralised and
rendered innocuous while still present in the organism; and
seems to indicate that, for the treatment of zymotic diseases, we
should seek to discover such remedies as will counteract the

314 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES,

effects of the poisons on which they depend, and not merely
endeavour to quicken their elimination.

Action of Various Drugs on the Inhibitory Apparatus—From
experiments which he has made on the excised hearts of frogs
with Ludwig and Coats’ apparatus, Boehm has come to the
conclusion that conia paralyses the terminal filaments of the
vagus ; nicotia the intermediate structure between them and the
inhibitory ganglia ; and that others, such as atropia, hyoscyamia,
daturia, physostigma, aconitia, delphinia and veratria, diminish
or destroy the irritability of the inhibitory ganglia themselves.
It is rather extraordinary to find physostigma in this list; and
it would thus seem that the pure alkaloid which Boehm used
had a different action from the tincture used by Von Bezold,
unless it be that the result depends simply on a difference in
the amount of the poison used.

Accelerating Ganglia in the Heart—We infer the presence of
quickening ganglia in the heart from the effects produced by
irritating the vagus after its inhibitory power has been destroyed
by the administration of nicotia or atropia. When irritation is
then applied to the nerve, it no longer produces retardation,
but, on the contrary, a decided acceleration of the cardiac pulsa-
tions. This shows that the vagus contains fibres which quicken
the heart, and that these are unaffected by the drugs which
have paralysed the others. The quickening, however, does not
take place till some time after the application of the irritant,
and, if it be applied only for a short time, no acceleration may
take place till after its removal; but, after it does occur, it
remains for a considerable time. If we irritate the heart
directly, instead of irritating the nerve, its beats are quickened
at once, and the acceleration does not last long after the irrita-
tion is discontinued. This shows that, when we stimulate the
quickening nerves, we do not act directly on the motor ganglia M
(Fig. 158), as we do when we irritate the heart itself, or as we
should do if the quickening fibres ended directly in them;
and we therefore infer the existence of the accelerating ganglia
Q between the quickening nerves s and the motor ganglia M.
The accelerating apparatus seems to be stimulated by veratria,
for we find that the cardiac pulsations are increased by its

CARDIAC GANGLIA AND CARDIAC MUSCLE. 315

administration to mammals in which the spinal cord, vagi,
sympatheties and depressors have all been divided, or when it
is applied to the excised heart of a frog.

Is Quickening of the Excised Heart due to Paralysis of Inhibi-
tory or Stimulation of Accelerating Ganglia ?—It is possible that
the quickening may be due to paralysis of the inhibitory
ganglia in the heart, and not to stimulation of the quickening
ganglia. This can be decided by paralysing the inhibitory
ganglia by means of atropia, before applying the poison to be
tested—e.g., veratria. If the latter poison exercise a stimulating
action on the quickening ganglia, it will quicken the heart after
atropia has been applied. If it simply paralyse the inhibitory
ganglia, it will have no further effect after their power bas been
destroyed by atropia. In the diagram, I have figured inter-
mediate structures C and D between the quickening nerves and
ganglia, so as to correspond with those of the inhibitory appa-
ratus; but whether they really exist or not, we cannot at
present say.

Is the Co-ordinating Apparatus of the Cardiac Ganglia Para-
lysed ?—Regarding this apparatus we know almost nothing.
When the heart is dying its rhythm is often disturbed, and two
or three contractions of the auricles may occur for every con-
traction of the ventricle. When laudanum is poured into the
heart, the rhythm is quite reversed; for after each pause the
ventricle contracts first, and contraction of the auricle follows
it. Digitalis and some other poisons cause peristaltic move-
ments in the ventricle; and occasionally some spots in the
ventricle continue to pulsate while the rest of it remains firmly
contracted and motionless. These effects are probably due
to disturbance of the apparatus which connects the different
motor ganglia in the heart and causes them to work in unison.

Are the Muscular Fibres of the Heart Paralysed ?—We test
this by applying an irritant to them directly, and seeing whether
or not they contract. If the motor ganglia be uninjured, the
application of an irritant generally produces a rhythmic contrac-
tion of the whole heart; but, if they be paralysed while the
muscular fibre is healthy, the irritation only causes a local con-
traction of the part to which it is applied.

316 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES,

Blood-Pressure.

The blood-pressure depends on two things—1, the activity
with which the heart pumps the blood into one end of the
arterial system; 2, the rate at which it flows out at the other
end into the veins. The rate is regulated by the small arteries
and capillaries, which dilate and contract so as to quicken or
slow it. The power of contraction is denied to the capillaries
by many physiologists; but Stricker has, I think, conclusively
shown that they do possess it.

The rapidity with which the blood flows through them dees
not depend entirely on the width of the capillaries, but also on
the pressure in the arteries which is forcing the blood into
them. The higher this is, the more rapidly does the blood flow ;
and in proportion as it diminishes does the current become
slower. From this circumstance we can judge of the force of
the heart-beats from the form of the curve which we obtain
with the sphygmoscope. When the heart contracts with great
force, it drives the blood out of the ventricle into the arteries so
quickly that there is no time for much to escape from the capil-
laries while the systole lasts, and so the tension rises high,
This increased tension makes the blood run quickly out of the
capillaries, and we have a fall of pressure, rapid at first, but
gradually becoming slower as the tension diminishes. This is
shown in Fig. 139. When the heart contracts less forcibly, it

Fie. 189.

sends in the blood more slowly, and there is time for a greater
quantity to escape by the capillaries during the systole; and
the tension does not rise so high. From the tension being
lower, the outflow of blood is not so quick, and the pressure
therefore sinks more gradually than in the former case. This
is represented in Fig. 140. Both of these figures were obtained

EXAMINATION OF CAPILLARIES, 317

Fie. 140.

by connecting a sphygmoscope with a schema of the circulation
such as I have already described, and compressing the india-
rubber ball which represented the heart with greater or less
force and suddenness, care being taken, however, to empty it
completely each time, so that the amount of air sent out should
always be alike.

As variations in the blood-pressure may be due to alterations
in the activity of the heart or the size of the capillaries, or to
both together, we cannot say when it is due to the one and
when to the other, unless we can keep one of them constant
while we allow the other to alter, or unless we examine them
both separately.

Elimination of the Action of the Heart.—We may keep the
action of the heart tolerably constant, and thus ascertain with
considerable exactitude the action of any drug on the exit-tubes
—whether they be arterioles or capillaries matters not—by
separating the heart from the nerve-centres, and then injecting
the drug into the circulation.

Division of Cardiac Nerves.—This separation can be effected
to a considerable extent by dividing the sympathetics, vagi and
depressors in the neck; but it is done much more effectually by
dividing the nerves near their entrance into the heart by a fine
wire heated by means of a galvanic battery.

As poisons generally produce their most marked effects on
the heart of mammals through the nervous centres whose con-
nexion with the heart we have thus severed, alterations in the
blood-pressure will be due to changes in the vessels, except in
so far as the drug may have affected the cardiac muscle or
ganglia. But, just as we obtained the most exact results when
we examined the heart altogether apart from the blood-vessels,
so we shall probably come to the most satisfactory conclusions
regarding the vessels by observing them apart from the heart.

318 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

You will remember that, during the diastole, the circulation is
carried on entirely independently of the heart by the pressure
of the blood in the arteries ; and, if we can prolong the diastole
sufficiently, we shall be able to tell whether the vessels are
dilated or contracted by simply seeing whether the pressure
sinks quickly or slowly.

If we prevent any blood from being pumped into the aorta
by the heart, the arterial system will come to resemble a bottle
with a hole in it, from which the fluid which it contains is
running. The larger the hole, the more quickly will it run out
and the bottle become empty, and vice versdé ; and, in the same
way, the more dilated the capillaries are, the quicker will the
blood run out of them into the vein, and the pressure sink in
the arteries; the more contracted the capillaries are, the more
slowly will the blood flow through them, and the more gradual
will be the fall of pressure. In the case of many poisons, we
may do this by irritating the vagi' before poisoning, and seeing
how quickly the pressure falls while the heart is standing still;
and then repeating the experiment after injecting the poison.
If the pressure fall more quickly in the second case, we know
that the vessels have become dilated; and if more slowly, that
they have contracted. Of course, only those parts of the
tracings in which the pressure has been the same are to be
compared with each other; but, if we stop the heart long
enough, we can always get parts in both which are capable of
comparison.

When the poison paralyses the vagus, as atropia does, this
method fails; and then we must open the thorax, perform arti-
ficial respiration, and put a ligature round the aorta.

Artificial Circulation in Mammals—As an animal quickly
dies when the aorta is ligatured, it is better to carry on artificial
circulation by a syringe through a cannula inserted into the
aorta, as Hering has done in his researches on the ‘con-
nexion between arterial movement and respiration. After the
blood has circulated once, it may be defibrinated, shaker with
air, warmed to 40° Cent., and re-injected. Instead of using a
syringe, the cannula in the aorta may be connected with the
nozzle M, Fig. 141, and the blood put in the flask z. It can thus

ee

™ ia teen ne

ARTIFICIAL CIRCULATION. 319

Fig. 141.
te

be kept at a constant temperature more easily than when a
syringe is employed. The pressure may be alternately increased
and diminished so as to imitate the beats of the heart by raising
and depressing the flask a. This may be done by passing a
string over a pulley, and attaching one end to the flask and the
other to a treadle worked by the foot. Warm blood has the
disadvantage, that it undergoes change and becomes decomposed
quickly; and cold blood may, therefore, be sometimes preferred.
When cold blood is employed, only the flask which contains the
blood is necessary ; and it may be raised or lowered in the same
way as the other.

Artificial Circulation in Frogs.—Artificial circulation may be
kept up in frogs by simply inserting a cannula into the aorta»
and allowing blood to flow into it from a raised reservoir, as
done by Rollett. By using two, as in the experiments on
the frog’s heart, normal blood may be allowed first to circu-
late through the vessels; and, the web being put under the
microscope, their diameter may be measured; and then
poisoned blood may be allowed to flow through them, and any
change in their diameter noticed.

Observation of Vessels—The parts best adapted for observing
changes in the size of vessels in mammals are the ear in rabbits
and the mesentery. When the mesentery is chosen for observa-
tion, the abdominal parietes should be divided ; but the peri-
toneum should not be opened, as changes in the diameter of the
mesenteric vessels may be observed through it, and they are
thus protected from the disturbing element which the irritation

320 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

produced by the access of air to them would introduce into the
experiment. ‘The vessels in the rabbit’s ear are readily measured
by a micrometer used with one of Briicke’s magnifiers, which is
simply a telescope with an extremely short focus. The ear
should be held up so as to allow the light to shine directly
through it, and the magnifier placed horizontally.

The area of the capillaries may be lessened, and the flow of
blood through them retarded in two ways: 1, by contraction of
their walls; 2, by pressure exerted on them from without.
They may be made to contract by irritation, 1, of the vaso-
motor centres, 2, of the vaso-motor nerves, or, 3, of their mus-
cular walls ; and pressure may be exerted from without by the
motions of muscles or of organs composed of involuntary mus-
cular fibre such as the intestines. The movements of respira-
tion also, as already mentioned, exercise an important influence
on the pressure.

Elimination of Respiration and Muscular Movement.—The
influence both of respiration and of muscular movement may be
eliminated by giving the animal curare, and keeping up artificial
respiration, before beginning to experiment with the drug whose
action we wish to examine.

Elimination of Vaso-motor Centre-—For the purpose of ascer-
taining whether the drug has acted on the vascular walls or on
the vaso-motor centre, we divide the vaso-motor nerves going to
a part before injecting it, and see whether it acts as it would
have done had they been undivided. Thus, when we are
observing the rabbit’s ear, we divide the sympathetic in the
neck; and, when looking at the mesentery, we cut the
splanchnics before the injection, and see whether the vessels
contract or dilate as we have previously seen them do under
influence of the poison in animals in whom the nerves were
intact.

For the purpose of ascertaining whether the drug acts on all
the vessels in the body in the same way that it does on those of
the ear or mesentery, we first cut the vagi, sympathetics and
depressors, and then divide the spinal cord between the occiput
and atlas. or atlas and axis, so as to sever the connexion between

PULMONARY CAPILLARIES—SPHYGMOGRAPH. 321
the vaso-motor centre and vessels, and begin artificial respira-
tion. We next note the blood-pressure, inject the poison, and
see what alterations it produces. Experiments may also be
made by irritating the vagus or ligaturing the aorta,

Action of Surrounding Paris.—It sometimes happens, as in
the case of physostigma, that the drug produces no contraction
in the vessels of the ear or mesentery when their nerves are cut
—a fact which shows that it acts on them through the vaso-
motor nerves, and not directly on their walls; and nevertheless,
when injected into a vein after the cord has been cut, it may
cause the blood-pressure to rise very considerably. At first
signt, this would seem to indicate that the drug acted on the
walls of some vessels in the body, if not on those of the ear or
mesentery, directly, and not through their vaso-motor nerves.
On examination, however, it is found that the obstruction to
the flow of blood through the capillaries does not depend on
their contraction, but on the occlusion of a large number of
them in the intestine by spasmodic contraction of the intestinal
walls in which they are imbedded.

Influence of the Pulmonary Capillaries—It has lately been
pointed out by Holmes that when a drug such as ergot,
which acts on the walls of the vessels and causes them to con-
tract, is injected into the jugular vein, it has to pass through
the pulmonary capillaries before it reaches the systemic ones ;
and, by contracting them, it will lessen the amount of blood
sent into the aorta from the left ventricle, and will at first pro-
duce a fall in the arterial pressure, succeeded by a great rise
when time has elapsed for the drug to reach the systemic
capillaries and cause them likewise to contract.

Use of the Sphygmograph.—For a description of the sphygmo-
graph and the mode of applying it, we must refer to the special
works on that subject, such as those of Marey and Sanderson.
The indications which it gives are the following: 1. The greater
or less pressure which is requisite to compress an artery and stop
its pulsations enables us to estimate approximately the amount
of pressure within it. 2. The amount of pressure and the
rapidity of the pulse help us to form conclusions regarding the
motor and inhibitory apparatus of the heart, in the same way as

-

322 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

in the experiments already mentioned, though, of course, to a
much more limited extent and with much less. certainty.
3. The form of the curve, like those in Figs. 13 and 14, shows,
in the same way as those of the sphygmoscope, Figs. 13 and 14,
the rapidity with which the pressure falls during the diastole,
and from this curve and the amount of blood-pressure we can
judge of the size of the capillaries.

LEcTURE V,—See APPENDIX, p. 643.

VI.— RESPIRATION.
(Reprinted from the British Medical Journal, Feb. 13, 1875, p. 201.)

Position of the Respiratory Centre; chiefly situated in the Mecdulla Oblongata,
but extends also to the Spinal Cord.—Effect of Strychnia upon it.—In-
. fluence of Nerves upon it.—Influence of Vagus.—Vagus contains two sets of
Fibres, Accelerating or Inspiratory, and Retarding or Expiratory.—Cause
of Rapid Breathing in Pneumonia.—Influence of the Superior and In-
ferior Laryngeal Nerves.—Nasal and Cutaneous Nerves.—Local Action of
Vapours when inhaled.—Action of Ammonia.—Methods of Registering
Respiratory Movements.—Acceleration of Respiration by Drugs.—Is it due
to (1) Excitement of the Voluntary Nerve-centres, (2) Increased Tempera-
ture, (3) Increased Venosity of the Blood p—Increased Venosity may be due
to (A) Prevention of Blood from reaching the Air; (B) Prevention of Air
from reaching the Blood. Blood may be prevented from reaching Air—
_ a) By Stoppage of the Heart: Action of Quinine——(s) By Embolism of
the Pulmonary Vessels ; Action of Condurango.—(c) By Contraction of the
' Pulmonary Capillaries; Action of Muscarine.—Observation of the Pulmo-
nary Capillaries in the Frog under the Microscope.—Effect of Heat and
Cold upon them.

Ir used to be supposed that the respiratory centre was not only
situated in the medulla oblongata, but was confined to it.
Legallois found that the cerebral hemispheres, cerebellum, and
even a part of the medulla itself, could be removed without
arresting respiration; and thus showed that the respiratory
centre was either in the medulla or in the spinal cord. (Aa-
périences sur la Principe de la Vie. Paris, 1830, tome i)
Flourens noticed that injury to a point named by him neud
vital, at the lower end of the calamus scriptorius, instantly
arrested respiration, and thus caused death (Comptes Rendus,
vol. xxxili, page 437); and all experimenters have found that
division of the cord just below the medulla also arrested
breathing. These experiments seem to show most conclusively
that the respiratory centre is situated in the medulla, and does

RESPIRATORY CENTRE IN THE SPINAL CORD. 323

not extend to the spinal cord; but the rce2nt researches of
Prokop Rokitansky (Stricker’s Medicinische Jahrbiicher, 1874,
p. 30) on this subject show how careful we must be in drawing
conclusions from experiments. Like all others, he has found that,
under normal conditions, breathing ceases as soon as the influence
of the medulla is destroyed by division of the cord just below
it. But if strychnia be given to the animal, so as greatly to
increase the excitability of its respiratory centre as well as of
other reflex centres before the cord is divided, respiration will
go on after the section has been made; and strychnia injected
into the veins after the section will restore the respiratory
movements, which the cut had arrested. This shows that the
respiratory centre is not confined to the medulla, but extends
into the spinal cord. The part contained in the cord is, how-
ever, too weak to keep up respiration alone under ordinary
circumstances, though it can do so when its power is increased
by strychnia. These remarkable effects of this poison give
promise of future benefit from its use as a restorative in cases
of death from drowning, &c.; but further experiments on
animals are necessary before we dare employ such a power-
ful remedy in man.

Rokitansky’s experiments enable us to demonstrate the
presence of a respiratory centre in the spinal cord, as well
as in the medulla of adult animals; but it is only fair to say
that this was shown long ago by Brown-Séquard in the case of
young ones. In young mammals and adult birds, he found that
the thorax continued to execute rhythmical respiratory move-
ments for a short time after the cord had been divided trans-
versely at the level of the first or second pairs of cervical
nerves, so that there must needs be a part of the respiratory
centre in the cord below that level (Journal de la Physiologie,
vol. i, 1858, p. 223, and vol. iii, 1860, p. 153). Besides this,
he considers that there are what we may term peripheral
respiratory centres—viz., ganglia in the substance of the
diaphragm itself analogous to those in the heart, which enable
it to contract rhythmically after its connections both with the
medulla oblongata and with the spinal cord have been destroyed
(op. cit., vol. ii, 1859, p. 115).

Y¥2

324 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

Although the excitement of the respiratory centre and the
amount of work done by the respiratory muscles depend on
the venosity of the blood in the medulla oblongata, yet this
; work may be differently distributed by the respirations becom-
ing quicker but shallower, or slower but deeper, without the
quantity of air respired being at all altered. This is effected
by the action of various afferent nerves, of which the chief are
the vagus, the superior laryngeal, and the nasal nerves; though
others, such as the cutaneous nerves generally, have consider-
able influence.

Irritation of the vagus, or of its central end when divided,
lessens the resistance in the respiratory centre, and quickens
the respiration, but makes it shallower. Stronger irritation
causes prolongation of inspiration. A very strong excitation
annihilates the resistance in the centre, and causes inspiration
to be almost indefinitely prolonged, so that the breathing is
completely arrested.

The ends of the vagi in the lung are normally in a state of
constant excitation, and therefore division of these nerves
renders the respiration slow.

Irritation of the vagi, on the contrary, causes, as we have
said, considerable acceleration of the respiration; and the
quick breathing which we observe in pneumonia is probably
due to the irritation of the pulmonary branches of the vagus
which the inflammation produces. It can hardly be caused by
the venous condition of the blood alone, nor yet by increased
temperature; for the blood may be very much more venous in
bad bronchitis, and the temperature higher in fever, without
the respiration becoming anything like so rapid as in a case of
pneumonia. But, although I thus speak of the vagus as an
inspiratory or accelerating nerve alone, I do this only for the
sake of simplicity, as this is its chief function. It really con-
tains, however, both inspiratory and expiratory fibres, although
the former predominate. (Hering and Breuer, Wiener Acad.
Sitzungs-ber. Math.-Naturwiss. Cl., vol. lvii, Ab. 2, page 672.)
The inspiratory fibres are excited by collapse, and the expira-
tory fibres by distension, of the lung. Thus, these nerves form
a sort of regulating mechanism for the respiratory movements,

RESPIRATORY CENTRE AND RESPIRATORY NERVES. 325

As soon as a deep inspiration is taken, the distension of the
lungs excites the expiratory fibres, and leads to the consequent
expulsion of the air; as soon as expiration takes place, the
collapse of the lungs excites the inspiratory fibres, and thus
leads to renewed inspiration.

Fie. 142.—Diagram showing the position of Respiratory Centre, and the Afferent

@aryag

. Superior I aryngeal Nerve.
. Infer or Laryngeal Nerve.
. Cutaneous Nerves of the Chest.

Nerves which influence it. Inspiratory Nerves are indicated by plain,
and Expiratory by dotted, lines.

. In piratory and Expiratory Fibres F. Larynx.
for voluntary alterations in Re- H. Expiratory Fibres of Vagus ex-
spiration. cited by distension of Lung.

. Cutaneous Nerves of Face. 1. Inspiratory Fibres of Vagus ex-

Nasal Branch of Fifth Nerve. | cited by collapse of Lung.
K. Respiratcry Centre in Medulla
and Cord.

L. Spinal Cord.

chiefly ex-
piratory

-_-—_—wT

As the effect of irritating other nerves as well as the vagus

is not always alike (Bert, Lecons sur la Respiration, page 490),
it is probable that the laryngeal, nasal, and cutaneous nerves |

326 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

may also contain both inspiratory and expiratory fibres. It has
already been mentioned, that the accelerating fibres of the
vagus in the lungs are probably irritated in pneumonia, but in
bronchitis the expiratory ones are chiefly irritated, and give
rise to the expiratory efforts in coughing, which serve to expel
any irritating substance in the bronchi. When these fibres are
exhausted, or the respiratory centre is feeble or irresponsive,
the mucus will remain, and consequently strychnia suggests
itself as an auxiliary in such cases. If the irritation depend
on something which cannot be removed by coughing, such as
miliary tubercle, we employ opium, chloral, &c., which lessen
the excitability of the respiratory centre.

Moderate irritation of the superior laryngeal nerve renders
the respirations slower but deeper; a stronger irritation pro-
longs. expiration; anda very strong one causes the respiration
to stop entirely in the state of expiration (Rosenthal, Athembe-
wegungen, p. 244) until the increasing venosity of the blood
greatly stimulates the respiratory centre, and causes respiration
again to commence.

Irritation of the inferior laryngeal nerve (Burkart, Pfltiger’s
Arch., vol. i, p. 107), and of the supramaxillary (Kratschmer,
Sitzwnges-ber. der Wien. Acad., Math.-Nat. Cl. 1870, vol. xii,
Abt. 2, p. 24), and nasal branches of the fifth nerve, acts in a
similar way to irritation of the superior laryngeal nerve, as
well as irritation of the cutaneous nerves generally, and
especially of those of the face and chest. (Schiff, Compt.
ftend., 1861.)

We have then to find out hotter the alteration in respira-
tion produced by any drug is due to its action on the respiratory
centre, or on some of the nerves which influence it; and the
following table may help us to do so more readily, by showing
at a glance the chief ways in which the respirations may be
accelerated or retarded. ;

: ( Excitement of Increased irritation of the vagus.
The respiratory

nerves. By action of voluntary centre.
or ee Great it z { Increased temperature of blood.
may be quick- | Greater exci seine °" 4 Increased venosity of blood.
ened by - resp. centre. Action of drugs, )

CAUSES OF QUICK AND SLOW RESPIRATION. 327

ment of respiratory 4 Action of drugs.

Diminished ratory} Action of venosity of blood.
The respiratory centre.

movements (Slight irritation of cutanetus
may be ren- nerves.
dered slow by Action of voluntary centre.

Paralysis of vagi.

Nervous influences. 4 Irritation of superior laryngeal
nerves.

Irritation of inferior laryngeal
nerves.

| Irritation of nasal nerves,

If the drug to be experimented on be injected subcutaneously
or into the veins, the actions on the respiratory centre and -
on the vagi are the chief points which require attention;
but if we are experimenting with a vapour, its local action
on the nasal, laryngeal, and possibly, also, on the pharyngeal
nerves (Brown-Séquard, Archives of Scientific and Practical
Medicine, p. 94) must be carefully attended to, as it may
greatly modify its general action on the respiratory centres.
Thus Kratschmer has found (op. cit.) that tobacco smoke
inhaled by a rabbit through its nostrils, or blown upwards
into the nasal cavity from an aperture in the trachea, will
cause arrest of breathing in a state of expiration from the
irritating effect of the vapour on the nasal branches of the fifth,
while it has no such effect when blown into the lungs.
Ammonia, when inhaled, also arrests the respiratory move-
ments in the same way; but Knoll (Sitzwngs-ber. der Wien.
Acad., vol. lxviii, Abt. 3, p. 255) has observed that, if it be
blown into the lungs, while the nostrils are carefully protected
from its influence, it causes accelerated and shallow breathing,
alternating with slow and deep respirations, and occasional
stoppages in the position of expiration, obviously from its
action on the different fibres of the vagi. When injected into
the blood, it causes, according to Funke (Pfliiger’s Archiv.,
vol, ix, p. 436), various alterations in the respiration, which are
not easy to analyse, but it certainly seems to excite the respira-
tory centre; but the use of carbonate of ammonia in bronchitis
has long been familiar to the medical profession.

The movements of respiration are not only more easily
counted than in any other way, but their depth, and the —

‘328 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

relation of inspiration to expiration, best noted by causing
them to register themselves on a revolving cylinder. Various
.means of doing this have been suggested by different authors.

One of the simplest consists of a needle pushed into the dia--

phragm, and connected by a thread with one of Marey’s levers
‘(see I, Fig. 143). Marey’s pneumograph consists of a cylinder

/

Fig. 113.— Methods of Registering Re-piration.

Ais the lever of Marey’s registering apparatus; B is a hollow drum, with
open tube below, and covered at the top with a piece of thin caoutchoue, on
which rests a tin plate connected with the lever 4. When the air is blown
into B, the caoutchouc is lifted, and the lever rises. When air is drawn out,
the caoutchoue sinks, and the lever falls. The tube of B may be connected
by india-rubber tubing with the respiratory passages in several ways. © is a
“T-tube, open at one end and connected at the other with a cannula (p), which
is placed in the trachea of the animal and brought into communication by its
upright limb with B. Instead of D, an india-rubber catheter may be placed in
the animal’s nostril. E is a caoutchoue bag, which is tied over the animal’s
muzzle and used instead of the tracheal cannula. F is a large vessel, from
which two tubes (4 and H) proceec. @ is connected with the lever B, and H
with the respiratory passages of the animal. I is a needle, which is simply
connected with the lever by a thread: when pushed into the diaphragm, it
registers the respirations.

of soft india-rubber, enclosing a spiral spring, whose extremities
are connected with two pieces of metal which form the ends
of the cylinder. A band is passed round the thorax of the
animal, and attached to the ends of the cylinder. The interior
of the cylinder is brought into communication with one of

CAUSES OF QUICK RESPIRATION. 329

Marey’s levers; and as each respiratory movement draws the
ends of the cylinders wider apart, or allows them to approach,
the air is rarefied or compressed, and a corresponding movement
is transmitted to the lever. Bert has modified this, and made
it more sensitive by making the cylinder itself of metal, and
its ends of india-rubber. Another method—one more ordinarily
employed—is to introduce one limb of a T-tube into the
nostril or trachea of an animal, or to connect it with a tracheal
cannula. The respired air passes through the other end, and
the third limb is connected with one of Marey’s levers.

Ts Quickening of Respiration due to Irritation of the Vagi ?—
When the respiratory movements become quickened by the
injection of a drug into the circulation, the first cause to which
it may be due, mentioned in the preceding table, is irritation of
the ends of the vagus in the lung. In order to discover
whether this be the cause or not, the vagi must first be divided
and the drug injected. If it acts only on the ends of the vagus,
the respiration which was quickened by injection when the
yagi were intact, will not be quickened by it when these nerves
are divided.

Is the Quickening due to Excitement of the Voluntary Nervous
Centres ?—This cause of quickening is eliminated by narcotis-
ing the animal with opium or chloral, or by removing the
cerebrum. For the method of doing this, see Sanderson,
Handbook for the Physiological Laboratory, p. 295.

Is it due to Incréased Temperature ?—lf tbe temperature of
the animal has risen above the normal—the fact can readily
be ascertained by the thermometer—it may then be reduced
by the application of cold water or ice, or by a stream of cold
air directed on the surface of the skin. Unless the cooling be
effected very gradually, these applications cause reflex disturb-
ance of the respiratory movements through the cutaneous
nerves.

Is it due to Increased Venosity of the Blood ?—The drug may
produce this by its action on the blood; and this is to be deter-
mined by the means already described. Generally we let a little
blood issue from an artery ; and if its colour be of normal bright-
ness, we conclude that the gases it contains are also normal.

330 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

But external respiration may be arrested or diminished, the
blood rendered venous, the respiratory movements consequently
increased, and dyspnoea and asphyxia produced by preventing
the blocd from reaching the air, as well as by preventing the
air from reaching the blood. The blood may be prevented from
coming into relation with the air: (a) By stoppage of the
heart; (0) By embolism of the pulmonary artery; (c) By con-
traction of the capillaries of the lung.

(a) By Stoppage of the Heart.—When respiration is suddenly
impeded in any of these ways, the breathing becomes panting;
and when it is suddenly stopped altogether, asphyxial convul-
sions occur. When the jugular vein is chosen for the introduc-
tion of drugs into the circulation, they come very quickly and
without much previous dilution with blood nto contact with
the heart and pulmonary vessels, and thus affect them more
strongly than they would do if injected subcutaneously, vr into
one of the veins of the extremities. When a large dose of
quinine is thus injected, the heart may be stopped at once, and
convulsions ensue. Any alteration of the heart’s action pro-
duced by a drug is easily noted by means of a needle fixed in
the ventricle.

(6) By Embolism of the Pulmonary Artery.—This cause of
interrupted respiration may easily lead an inexperienced
observer to very erroneous conclusions regarding the action of
a drug. Supposing him to inject an unfiltered solution of some
extract into the jugular vein, he may-find the respiration
almost immediately afterwards become panting; the eyes start
from their orbits, the limbs become convulsed, the head drawn
back, and after one or two quivering contractions, life becomes

extinct. He at once concludes that the substance he has:

injected is one of extreme activity, whereas it may be really
quite inert; the violent symptoms which followed its injection
being due to the extract being imperfectly dissolved, and the
suspended particles producing embola in the pulmonary vessels.

In some experiments which I made on condurango, I was at
first misled by this circumstance, and believed that the drug
had a tetanising action, like that of strychnia, as convulsions

came on immediately after injecting a solution of the extract

wef Aa) cal i tl

a ‘ —— :
pe ee el en ee

CONTRACTION OF PULMONARY CAPILLARIES. 331

into the jugular vein. The same mistake has probably beem
made by Gianuzzi,* who attributes a convulsive action to the
drug. By injecting the solution into the peritoneal cavity,
however, I found that it had no action whatever even when
used in large quantities, while a solution of strychnia applied
in the same manner would have acted nearly as strongly as
when injected into a vein.

(c) By Contraction of the Pulmonary Capillaries—When
contraction of the pulmonary capillaries is produced by a drug
injected into the veins, the venous blood is hindered from
reaching the left side of the heart, and the left ventricle and
arterial system become empty, and the arterial pressure sinks
while the right ventricle and venous system become swollen
and turgid. The alteration of the blood-pressure in the
arterial and venous systems may be measured by manome-
ters connected with them; but while the arterial fall in the
pressure is easily observed, there is considerable difficulty in
measuring that in the veins, due to the rapid formation of
coagula in the tube which is pushed down the jugular vein
into the vena cava.

Another method is, to open the thorax and note the colour
of the lungs and the comparative fulness of the right and left.
sides of the heart, and of the venous trunks, before and after
injection of the diug. The animal is first narcotised, and a
cannula placed in the trachea. The skin and cellular tissue are
then divided along the middle of the sternum and reflected on
each side. The muscles are then divided along the line of the
costal cartilages, and artificial respiration is begun. The
abdominal muscles are then separated from their attachment
to the sternum and costal cartilages; the latter are cut through,
except the first, which is left untouched in order to avoid
wounding the internal mammary artery, and the sternum is
bent upwards and retained in its position by a hook. In the.
rabbit, it is generally unnecessary to tie any vessels, as the
bleeding stops quickly of itself; but if any one should bleed

* Gianuzzi and Bufalini, Ricerche eseguite nel Gabinetto di Fisiolegia della
Universita di Siena, pp. 71-86; abstracted in the Centralblatt fiir die Med.
Wiss., 1873, p. 824.

232 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

much, it ought to be iaid hold of and ligatured. Artificial
respiration being carefully and regularly kept up by means of
a metronome, the colour of the lungs, the size of each ventricle,
and the number of cardiac pulsations is observed, the drug
injected, and the observation repeated. The pulsations must
be counted, because slowness of the heart’s action, by affording
time for the accumulation of venous blood in the right ventricle,
would cause it to become distended, although there were no
obstruction to the pulmonary circulation. When the drug to
be experimented on is not a solution but a vapour, it must be
passed into the lungs by the method already described (British
Medical Journal, May 20, 1871).

In this way, I have found that muscarin causes contraction

of the pulmonary vessels, and produces dyspnoea (see British
Medical Journal, November 14, 1874), although the heart con-
tinues to beat, and artificial respiration is vigorously kept up.
The lungs hecome pale, the right side of the heart swells up,
and the left side and arteries become empty, as represented
diagrammatically in Fig.145. The vapour of chloroform blown

Tia. 144. Tia. 145.

Fia. 144.—Diagram representing the normal condition of the circulation.
Both the veins and arteries are moderately full; the two sides of the heart are
of much the same size, and the circulation through the lungs is free.

Fia. 145.—Diagram representing the condition of the circulation after the
administration of muscarine. The veins are distended, the arteries empty ; the
right side of the heart is much enlarged, the left side collapsed, and the
circulation through the lungs almost entirely arrested.

into the lungs causes a similar appearance, but it arrests the
cardiac pulsations more or less completely at the same time.

— ee oe

ad a bah) eh de

EFFECT OF HEAT AND COLD ON PULMONARY CAPILLARIES. 333

The action of the drugs on the pulmonary capillaries in the
frog may be observed directly by means of the microscope. <A
frog is curarised, and a glass cannula, to which a short piece of
india-rubber tubing is attached, is tied into its larynx. An
incision is then made into the side of the frog a little below the
arm, care being taken not to injure the lung in dividing the
thoracic wall; and, the lungs being inflated through the
eannula, one of them protrudes through the opening. The
piece of india-rubber at the end of the cannula must then be
clamped, so as to prevent the air from escaping and the lung
from collapsing (Fig. 146). The whole froy is then placed cn a

Fig. 146.—Form of Tube for insertion into the Larynx of the Frog.

It is made by drawing out a piece of tubing to the size marked a, heating the
_ end and pressing it against a piece of metal, so that it assumes the shape db.
eis a piece of india-rubber tubing, which must be closed, cither by a ligature,
as shown in the drawing, or, what is still better, by a clip, so as to prevent the
escape of air from the lung.

glass plate, which is fixed with a clip to the stage of the
microscope. The lung is brought under the objective, and
supported, if necessary, by a cork ring fixed to the glass plate
with sealing-wax. Any changes in the calibre of the pulmo-
nary vessels are then readily observed by means of a micrometer
placed in the eye-piece.

Four years ago I attempted to ascertain by this method
(Fig. 147) the effect of sudden changes from heat to cold on the
lungs; and I have found that, if a stream of warm moist air be
first directed on the lung, and immediately afterwards a stream of
cold moist air, the capillaries sometimes contract as much as
one-third of their diameter under the influence of the cold.

Dr. Sharpey informs me that the lung of the toad, unlike
that of the frog, does not collapse even when no obstruction is
offered to the escape of air; and therefore, if toads be used,
the india-rubber tube and clamp on the cannula are unnecessary-

334 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

_¥Fi¢. 147.—Apparatus mentioned on preceding page, and which I employed in my

experiments made in 1871 for ascertaining the effect of heat and cold on the
vessels of the frog’s lungs. A,a piece of cork to which the frog is fastened,
is laid on B, the stage of a microscope, and attached by an india-rubber strap,
©. Disasmall ring of cork covered with a thin circle of glass. E is the
inflated frog’s lung. F is a tube by which a current of air can be directed on
the frog’s lung. It is held in position by a piece of wire, @, which can be
bent to any position. I is a flask containing ice and water. 4, a flask con-
taining hot water. Kis a three-way stopcock, by which a current of air may
be sent from the spray-producer, L and M, through either 1 or H at will, and
thus cold or hot air may be applied alternately to the lung. (Reprinted from
‘my Text Book of Pharmacology, §c. London: Macmillan & Co.)

Pe ee OT ey PN Lire

ARTIFICIAL CIRCULATION. 335

APPENDIX

Artificial Circulation through Isolated Organs.—In order to
study the effects of alterations in the blood, and the action of
various poisons upon the walls of the vessels themselves, with
entire exclusion of the nervous system, Ludwig and Mosso have
kept up artificial circulation in the kidney and the liver. In
removing these organs great care is taken not to wound them,
and the diaphragm is removed along with the liver. In
experimenting on the kidney large dogs were employed. The
earotids were first opened, and blood allowed to flow until
convulsions began. The artery was then closed for some time,
during which the blood was defibrinated and part of it put into
a flask, so as to be ready to wash out all the coagulable blood
from the kidney. The carotids were now opened a second time,
and as much blood as possible got from them by pressure on
the abdomen, &c. As soon as the animal became insensible
the abdomen was opened, the renal artery was then compressed
just above its bification, so as to prevent any air getting into it,
and a glass cannula was introduced into the main artery;
another cannula was put into the. renal vein. All the small
vessels which communicate with adjacent parts were ligatured,
and the kidney was then removed. Before connecting the
cannula in the renal artery with the apparatus for artificial
circulation, it was carefully filled. by means of a fine pipette
with defibrinated blood, and the utmost care employed to
prevent any air bubbles from getting into the vessel. After the
communication between the renal artery and the flask has been
opened, it sometimes happens that blood does not flow until a
considerable time has elapsed, owing, apparently, to a tetanic
contraction of the vessels in the kidney.

After the blood has begun to flow it does not do so in an
equable stream, as it would do through glass tubes, but its
velocity is alternately greater and less, owing to periodic con-
tractions of the walls of the renal vessels, independently of any
nervous influence. If the circulation is arrested for some time
and then allowed to go on, the rapidity is much greater after
than before the stoppage, but it gradually falls again to normal.

336 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

Blood containing much carbonic acid and little oxygen (erstick-
wngsblut), causes the vessels to contract and the stream to
become slow, while blood containing much oxygen and little
carbonic acid causes them to dilate. When different sorts of
blood are allowed to circulate after each other through the
kidney, and each successive kind contains less CO, than the
one preceding it, the rapidity of the flow from the vein goes on
increasing ; or, a3 it might be expressed, each kind of blood in
this series seems to diminish the amount of contraction of the
vascular walls which the greater amount of CO, in the preceding
kind had occasioned. ‘The order would be this—suffocation—
blood—venous—arterial—apneeic, 2.¢., saturated with oxygen
by agitation with air, This dilatation, however, was only
temporary.

When nicotine was mixed with blood in the proportion of
1 to 10,000 it seemed, at first, to cause contraction of the vessels,
for it produced a diminution in the flow of blood, and also in
the size of the kidney; but both soon returned to the normal.
One per cent. of nicotine, on the contrary, seems to cause
immediate dilatation of these vessels, for it immediately causes
an increase in the velocity of the current and the size of the
kidney. The increased velocity is not to be entirely ascribed
to contraction of the vessels, for a solution of nicotine of this
strength alters the blood, and will diminish the friction in the
vessels.

Atropia has a powerful action, and different doses of it produce
different effects. In the proportion of 1 in 100,000 it causes
diminished rapidity in the flow of blood and in the volume of
the kidney, but both soon return to their normal. One in
10,000 causes diminished, followed by increased rapidity, but
this soon disappears. One in 5,000 soon kills the kidney, but
before doing so causes first diminution, and then acceleration of
the current through it. Chloral hydrate first causes diminished
and then greatly increased velocity, but it also has a very
peculiar action on the vessels, increasing the rhythmical con-
tractions in them when they are present, and causing them to
appear when they were previously absent.

The shocks of an induction coil, or Faradaic currents, do not

INDUCTION OF ANAUISTHESIA, 337

alter the velocity of the circulation, but constant currents do.
During the time they are passing, both the rapidity of the
current and the size of the kidney increase, and after the
irritation ceases they diminish. When the circulating blood
contains a small quantity of chloral, this action is altered. At
first, when the chloral has not altered the current much, it
becomes slightly diminished during the irritation, and slightly
increased after its removal. When the chloral has acted
longer and increased the velocity of the current to five or six
times its normal, no alteration is noticed during the application
of the current, but a still further increase occurs after its
removal.

After the kidney has been removed from the body for 24
hours, and kept in a cool place, its vessels still retain their
irritability, but small doses of chloral in such a kidney only
cause contraction, and larger doses of 0°3 to 0°5 per cent. are
requisite to induce dilatation. The effect is not due to the
action of the chloral on the blood, for it is produced when the
blood is replaced by serum. One of the most extraordinary
things about the action of chloral is that, in the dead kidney,
instead of increasing the rapidity of the current, or leaving it
unaltered, chloral greatly diminishes it—exactly the opposite to
its effect on the living organ. When the blood used in the
artificial circulation is saturated with carbonic acid, chloral no
longer produces any effect on the vessels, so its action would
seem to be abolished by this gas.

Induction of Anesthesia.—At p. 257 I have stated that
chloroform is inadmissible as a narcotic, as its administration
seemed to cause dogs so much pain, but farther experience has
shown me that this statement is incorrect. Chloroform can be
readily administered to all animals by placing them under a
glass bell-jar, along with a sponge or piece of blotting-paper,
saturated with the anesthetic. The advantage of the glass jar
is that the movements of the animals can be distinctly seen,
and they can be removed immediately on their becoming
insensible, thus avoiding the danger to which they would be
exposed by longer inhalation of air saturated with the vapour.
The vapour being heavier than air sinks to the bottom of the

Z

338 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

jar, and, when the animal falls unconscious, the air it then
respires is much more heavily charged with the vapour than
that which it breathed while still erect. On account of the
density of chloroform vapour, anesthesia is more quickly pro-
duced when the bell-jar has an opening at the top which can be
plugged with cotton-wool saturated with chloroform, than when
the sponge is laid at the bottom of the jar; as in the former
case, the vapour falling down is more rapidly diffused through
the air of the jar than in the latter. Instead of a bell-jar a
deep milk pan may be used, the rabbit or cat being placed in it
and the top covered by a towel stretched tightly over it. The
chloroform is sprinkled on the towel. Anesthesia is thus
rapidly induced, but care must be taken not to allow the animal
to remain too long in the vessel. For large dogs an inverted
packing-case, without the lid, may be used instead of a
bell-jar.

After the animals have been rendered insensible and the
operation has been begun, the anesthesia may be kept up by
putting a piece of cloth round the animal’s nose and pouring
chloroform upon it, a drop or two at a time, as often as is neces-
sary. In this way less chloroform is required, and there is not
so much danger of killing the animal by giving it the vapour
in too concentrated a form.

Instead of keeping up the anesthesia by the continued ad-
ministration of chloroform, it is often more convenient to open
a vein and inject opium or chloral.

_In operations on the abdominal viscera in dogs, eg.,in making
a gastric fistula, death sometimes occurs from shock, although the
animals are completely under the influence of chloroform. For
such operations ether is preferable, as it increases rather than
diminishes the power of the heart. If given in the same way
as chloroform, however, much time and a very large quantity of
ether are required to produce anesthesia. Professor Schiff has
found,* however, that it can be readily done by pouring a
quantity of ether into a bladder, and holding this tightly around
the dog’s muzzle, so that it respires ether vapour almost pure.
As dogs do not like to be tied down, the muzzle shown at fig. 127,

. * Professor Schiff, verbal communication to the author.

nee eed) Pete

USE OF ETHER. 339

p. 254, should be put on, and the operator, sitting on a low
stool, should put the dog’s fore paws on his knee and hold
them with one hand, while with the other arm passed round the
dog’s body he restrains its movements, and an assistant holds
the bladder with ether over the dog’s nose.

Zz 2

PHYSIOLOGICAL ACTION OF CONDURANGO,

(From Journal of Physiology, vol. v, pp. 17—34.)

ALL the experiments which I have performed for the purpose
of ascertaining the physiological action of Condurango were
made with a watery extract prepared for me by Mr. Jeffs,
Dispenser to St. Bartholomew’s Hospital.*

Characters of the Extract of Condurango.

One ounce of the extract was obtained from one pound of the
root. It was of a dark brown, almost black colour, slightly
aromatic odour, and a bitter taste. It was very soluble in
water, and formed a dark brown opaque solution.

General Action of the Extract on Frogs.

Some of the experiments here detailed were made with the
double purpose of ascertaining the influence of Condurango on
reflex action as well as its general action, and the animals
were therefore in these experiments suspended, instead of
being allowed to move freely on a level surface.

Experiment —Five grains of the extract of Condurango
were suspended in six minims of water and Zths of the mixture
(4% grains) injected under the skin of the back of a large frog,
tolerably strong but not so active as most of the others. It.
was then covered by a glassjar. The frog remained quiet when
left to itself, but moved actively when touched. No effect.
seemed to be produced by the Condurango for an hour after-
wards.

Twenty-four hours after the frog was again examined and
seemed totally unaffected. Four days afterwards it was found

* The experiments recorded in this paper were all made in the autumn of
1871,

id oe tereek OAL © imme tty ae f |

ACTION OF CONDURANGO ON FROGS. 341

to be somewhat languid, and five days after the injection it was
dead.

Experiment II.—A strong frog was suspended by the fore
legs and two grains of solid extract were introduced under the
skin of the abdomen. Immediately afterwards the frog seemed
somewhat more restless than before, and drew up its legs more
quickly when they were touched. Its movements were per-
formed in the same way after the injection as before it. When
placed on a level surface it seemed quite unaffected by the
Condurango, and continued to be so for the next ten days
during which it was observed.

Experiment JJI.—One grain of extract mixed with a few
drops of water was injected under the skin of the back of a
strong frog suspended in the same way as the other. Imme-
diately afterwards it became restless, and seemed also uneasy
when touched. Otherwise it remained unaffected, and no effect
of the Condurango could be observed during the next ten days.

Experiment IV.—Two grains of the extract mixed with a few

drops of water were injected under the skin of the back of a

frog suspended like the others. The result was the same as in
Experiment ITI.

Experiment V.—Five grains of the extract were suspended in
water and injected under the skin of the back of a strong frog.
The frog was suspended by the head. It seemed somewhat
restless after the injection, but no other effect could be observed.
Next day it seemed in its normal condition, and on the third
day also.

Laperiment VI—The same experiment as in V was repeated
with a like result.

Experiment VIJ—The same as in V and VI. No result was
observed at first. Next day the frog seemed weak, and when
laid on its back could not turn over so readily as the others.
It was a smaller frog than the others. On the third day it
seemed well.

These experiments show that the extract of Condurango when
injected under the skin of frogs produces no effect even when
such a large dose as 5 grains is administered.

The restlessness which is noted in those hung up was in all

342 PHYSIOLOGICAL ACTION OF CONDURANGO.

probability due to the injection of the fluid, and not to the
action of the drug, as it occurred immediately after the opera-
tion and before there had been time for much to be absorbed.

The death of one frog after the injection can hardly be

attributed to the Condurango, as the animal was observed to be

less active than the others previous to the injection, and death

did not occur till several days afterwards.

General Action on Mammals.

The experiments on this point were made exclusively on
rabbits. ;

Experiment VIII—One gramme (15:4 gers.) of the extract
was dissolved in 20 cub. cent. of a solution of one part NaCl in
200 of water. It was dissolved in 4 per cent. NaCl solution in
preference to water, in order to avoid the irritation which water
itself produces when brought in contact with the tissues of the
body. Ten cubic centimetres of this solution were injected
into the peritoneal cavity of the body weighing 936 grammes
(2 lb. 1 0z.).

No effect whatever was observed. 3

Thirty-four minutes afterwards the remaining 10 cub. cent.
were injected. No effect was produced. The solution had not
been filtered.

In order to test the effect of the injection of saline solution
itself, 10 cub. cent. were injected into the peritoneal cavity of a
rabbit weighing 425 grammes (1 lb. 15 0z.).

It produced no effect.

Next day both animals were perfectly well and lively. They
seemed to have passed a good deal of water during the night,
but as they were both in the same cage it was impossible to
say how much had been passed by each. Both animals were
kept under observation for several days, but no further effect
of the injection was noticed. The increased urination was
probably only due to the water which had been injected.

Experiment IX.—One gramme (15°4 gers.) of extract was
mixed with 10 cub. cent. of water. The solution was not
filtered, and contained little particles. A cannula was placed

ACTION OF CONDURANGO ON MAMMALS, 343

in the jugular vein of a rabbit weighing 1,030 grammes (2 lb.
4 oz.), and 14 cub. cent. of the solution were injected into it.
No apparent effect was produced.

Fifteen minutes afterwards 1 cub. cent. more was injected ;
three minutes after the second injection the respiration was
much quicker; and five minutes afterwards 1 cub. cent. more
was injected.

One minute after the last injection the animal’s hind legs
spread out laterally, and it sank down on its fore paws.

In half a minute more it turned on its side, its head became
drawn backwards on its shoulders so as to form almost a right
angle with the body, and it gave one or two convulsive kicks.
Its eyes then became very prominent and the cornea insensible
to the touch.

Post-mortem Examination.—The body was immediately
opened. When the abdominal muscles were divided the legs
gave a twitch. The heart was still found pulsating, though
only feebly. The right cavities were full, but the left cavities
were empty

In this experiment the injection of about one-third of a
gramme (5 grs.) of the extract into the jugular vein was fol-
lowed by death, whereas in Experiment VIII the injection of
three times this dose into the peritoneal cavity of a smaller
rabbit produced no effect. As drugs are generally absorbed
with great rapidity from the peritoneal cavity the difference
between the results of the two experiments could hardly be due
to non-absorption of the Condurango in Experiment VIII, and
it was therefore in all probability due to something not con-
nected with the action of the drug.

The hurried breathing, convulsions, and death which followed
the injection of the unfiltered solution of the extract into the
jugular vein, as well as the distension of the cavities on the
right side of the heart and the emptiness of those on its left,
seemed to indicate that the death of the rabbit in Experi-
ment IX was due to the production of emboli in the pulmonary
artery by the undissolved particles of extract.

In order to test this conclusion the following exper iment was.
made :—

344 PHYSIOLOGICAL ACTION OF CONDURANGO.

KHaperiment X.—One gramme (15°4 grs.) of the extract was
dissolved in 20 cub. cent. of warm water and filtered. When
first thrown on the filter it passed rapidly through, but in the
course of a minute or two it began to pass through very slowly.
As soon as it began to do this the fluid was emptied out of the
first filter and thrown upon a fresh one. In this way the
filtrate was obtained quickly, but might contain very fine
particles which had passed through the filter and might have
been removed by it afterwards.

A cannula was placed in the jugular vein of a rabbit weigh-
ing 680 grammes (14 lb.), and 10 cub. cent. of the filtrate were
slowly injected into it. During the injection the respiration

became hurried, and occasionally a convulsive twitch of the

limbs occurred. A few minutes afterwards 5 cub. cent. more
were injected. The animal was then released. It tumbled
much and seemed weak, but could move about perfectly well.
Its respiration was laboured. Twenty hours afterwards it
seemed weak and languid and its respiration somewhat hurried.

In this experiment nearly ? of a gramme were injected into
the jugular vein of a rabbit weighing 680 grammes with the
effect of producing hurried respiration and weakness. In
Experiment IX the injection of 4 of a gramme was followed by
the death of a rabbit weighing 1,030 grammes.

The difference between these experiments consisted in the
solution of Condurango being filtered in Experiment X and not
in Experiment LX, and we must therefore conclude that the
fatal result in the latter case was due to the presence of large
particles in the fluid.

The hurried breathing in Experiment X might be due to the
small particles which had passed through the filter but were
yet large enough to become impacted in the pulmonary capil-
laries.

Results of Experiments on the General Action of the Extract of
Condurango.
Condurango has no poisonous action.
The extract produced no apparent effect on frogs when given
in doses of 4 of a gramme (5 grs.), or on a rabbit in a dose of 1

-

—

PP ae

EFFECT ON REFLEX ACTION. 345

gramme (154 grs.), an amount which is equivalent to 72 grammes
(23 oz.) of the extract, or 24 1b. of the root for a man weighing
150 lb. The convulsions which occurred in Experiment IX were
in all probability due to embolism of the pulmonary artery and
not to the action of the Condurango, The statement of Gianuzzi
and Bufalini* that Condurango has a convulsant action like
strychnia probably depends on a mistaken misinterpretation of
the results of experiments like that of Experiment IX, although
I cannot be certain on this point, as I have never been able to
see their original paper.

It has no paralysing action, and apparently no action of any
kind on voluntary muscles or motor nerves, as the movements
of the animals were unaffected by its administration.

Effect of Condurango on Reflex Action.

As Condurango produces no apparent effect, and as Dr. Joseph
Xavier Eguigusen states that “it cannot be administered many
days in succession because in some persons nervous phenomena
of importance supervene,” it seemed possible that its action
might resemble that of quinine.

The following experiments were therefore undertaken in order
to ascertain whether it had, like quinine, the power of diminish-
ing reflex action.

They were performed in the usual way, by suspending a frog
by the fore-arms or head and noting by the aid of a metronome
the time which elapsed before it drew its foot out of a very
dilute mixture of sulphuric acid and water. Extract of Condu-
rango was then injected under the skin, the foot again dipped
in dilute acid, and the time till it was pulled out compared with
that which had been noted before the injection.

To show that the mere suspension of the frog and the succes-
sive irritations applied to the feet: had no effect on the time
required for reflex action, a frog into which nothing was injected
was suspended at the same time as the others.

* Ricerche eseguite nel Gabinetto di Fisiologia della Universita di Siena,
pp. 71—86, abstracted in the Centralblatt de Med. Wissenschaften, 1873,
p. 824,

\

346 PHYSIOLOGICAL ACTION OF CONDURANGO.

Experiment XI.—Four frogs were suspended by their arms,
and their feet irritated by a very dilute sulphuric acid. After
each application of the acid the foot was carefully washed.

In the following account & stands for right foot, Z for left
foot, and the numbers under each indicate the number of
seconds before the foot was drawn out of the dilute sulphuric
acid.

Time. | Frog I. | Frog II. | Frog III. | Frog IV. Remarks,

RK LL. | KR L| KR %L.| R. LL. | FrogI was tested first,
but on dipping its
right foot into the
acid, it became ap-
parent that it was
too strong. It was
therefore diluted
and again applied.

8p, 90’ 12” 5 15” ee 6” 5/’ BY
*: 35/ 197 10” .o 12” 19” 16” 6” 6”
S 88’ 1Or% 10°" ] gr 6” 13” 20” Ag Bg”
5p OS FSIS 1S 18 i ee ee ee Ve,
1 5’ 95” Ra 12” 20” 20" 8” LO”

45, 0’ Two grains of extract
se ‘ of Condurango were
ae uneasy suspended in a few
ae | quiet uneasy quiet quiet drops of ¢ per cent.

NaCl solution, and

injected under the

skin of the back of

Vrog IV.

ee ty uneasy uneasy

On touching the feet
of Frogs II, III, and’
IV, they drew them
away much more
readily than Frog I.

26” 28” | 12” 380” | 18” 46” | 4” 8” | Reflex action again

B20 AO 10" 18 68) 8" 4 BF tested by acid.

46” 34/’ 8” 8” cB be 99" 9” bd =

Frog I was not so lively as the others, and it will be seen
from the next experiments that the diminution. of reflex action
which occurred in it during this experiment is not a general
rule but due to an individual peculiarity. |

Experiment XIT.—Two frogs were suspended by the head and
reflex action tested by dilute sulphuric acid (one part acid te
250 of water). 7

EXPERIMENTS ON REFLEX ACTION,

347

During the experiment both frogs struggled a good deal, and
when a severe struggle occurred just before the acid was
applied to the foot reflex action seemed to be somewhat di-

minished.
Time. Frog I. | Frog. II. Remarks.
tems RS es: ae
15, 33’ 10” 49” | 26’ 42” | Acid of 1 in 300 was here used.
Frog I struggled much after acid had
been applied to the right foot.
8” 14” | 10” 11” | Acid of 1 in 250 here used.
5am © cs 1 as a
14/’ 14” 4" 7 fhe
25, 57’ Five grains of extract of Condurango
- suspended in water was injected
under the skin of the back of
abt, 35 B° 217.1 63" 26” Frog II.
5h. 53’ I 2S Ye" SO"
Twenty hours 4” 10” | 36” 62”
afterwards } 20” 16” | 41” 35”
Frog II very restless.
tar AEE Oem

During the night they were taken down and had rested.
Experiment XIII—Two frogs suspended, and reflex action
tested with sulphuric acid (1 to 250 water).

Time. Frog I. | Frog II. Remarks.
Ra. BD. i ae i
1” 3 Th rd 6”
Q" 3g 9” ge
on 5 5” 6”
=. is" a Five grains of the extract of Condu-
rango suspended in a few drops of
water were injected under the skin
Frog of the back of Frog II.
uneasy
abt. 3, 5’ as" 8” 10” | Frog I remained untouched.
5h, 58’ a hdd 1 As 5” 6”
They were taken down at night and
Twenty hours Se £5 ORY i not left suspended.
afterwards eee Le Ee”

348

PHYSIOLOGICAL ACTION OF CONDURANGO.

“

Experiment XIV.—Two frogs were suspended by the head,
and reflex action tested by applying dilute sulphuric acid
(1 part acid in 250 of water) to the feet.

Time. Frog I. | Frog II. Remarks.
R, «lL. |} Re Te
Qh, 26/ she te 8” i 5”
a 32’ ot 8” iY 1" 7
- 52’ 10” 6” 6” ae
+ toe Five gruins extract of Condurango,
suspended in a few drops of water,
were injected under the skin of the
back of Frog II.
Frog I was untouched.
Frog II became uneasy and restless
3, 10’ Ww Ae oe” Se immediately after the injection.
abt. 6". 8” 10” | Frog I had escaped and could not be
Twenty hours toate: iad found.
afterwards } 12": 1B"

For greater convenience in comparing the results of these ex-
periments I subjoin the mean number of seconds required for
reflex action in each of the frogs during the time they were
suspended before Condurango was injected into some of them,

and the number of seconds required during the time they hung

after the injection had been made.

fe]

Experiment XT.

Frog I. | Frog II. | Frog III. | Frog IV.
2 had 23 grs. | had 2 grs. | had 2 grg
Uninjured./ extract. extract. extract.
+ OES RS ies ees RS ae hee eS Re
In the time before injection | 12 14 | 103 113 |13 152| 54 74
After 342 34/10 16% | 153 31 | 6§ 7

Difference | 2144 20 2 55] 23 1534] +
more more} less more | more less | more less

EXPERIMENTS ON REFLEX ACTION,

Lxperiment XII.

d49

Frog I. Frog IT.
ee 5 grs.
Uninjured. Peon
RR Tt a ee
In the time before injection 11% 14 8: 92
After 10 113 | 323 39
Difference ii 28 24% 293
less less | more. more
Experiment XIII.
Frog I. Frog, II,
Se Got 5 grs. of
Uninjured. the extract.
|: ieee oe R. L.
In the time before injection 1 2} 33 53
After 24 28 % 8683
Difference is wv 345 3%
more more| more more

Experiment XIV

Frog I. Frog II.
ree Got: 5 grs,
Uninjured. | o¢ extract.
Rm TL. R. L.
In the time before injection 10.8 83 53
10 103
13 15
‘more more

Difference between the number of seconds required for reflex
action during the time the frogs were suspended before the
injection of Condurango, and in the time after the injection.

350 PHYSIOLOGICAL ACTION OF CONDURANGO.

Uninjured Frogs.

R. L.
Frog I, Expt. XI... ». 2143 more 20 more

In the time after injection

Frog I, Expt. XII... is 41 less 23 less
oer: re hee LS cs +’s more 35 more

Frogs which received Condurango.

R. L.
2 less 5, more Frog II Expt. XI 2 grs. solid extract
2% more 151 more Soo es BAIA mt 2 grs. in water
+= more +" less fying omregy 2 BTS. 5,
24.4, more 29} more ae I 9) = RAD Sees es
33% more 3/5 more Tags Oi ys eho GPU ee
13 more 538; more ee 4} ome. Gage Sys Pager

In only one of these experiments (Experiment XII) does
any marked diminution of reflex excitability occur after the
injection of Condurango. Nearly as great a diminution is to be
observed in Experiment XI, Frog I, where nothing had been
injected, and it is therefore probable that the exceptional
diminution in Experiment XII as well as in Experiment XI,
Frog I, is to be ascribed to an individual peculiarity of the frog
and not to the action of the Condurango.

In most of the other experiments we find a slight diminution
of reflex excitability, but it is very slight and might be due to
the exhaustion produced by the struggles of the animal after the
injection of the drug.

Conclusions regarding the Effect of Condurango on Reflex Action.

Unlike. quinine Condurango has very little effect on reflex
action. A slight diminution of reflex excitability was observed
after the injection of the extract into frogs in doses of 2 or 5
grains, but the number of experiments is insufficient to show
whether or not this was due to the exhaustion produced by the
struggles of the frog.

Effect of Condurango on Circulation and Respiration.

Experiment XV.—A cannula was placed in the trachea of a
rabbit and connected by india-rubber tubing with a ‘T-tube, to

EFFECT ON CIRCULATION AND RESPIRATION, ooL

one limb of which was attached a stopcock, which allowed of
more or less free communication with the atmosphere and the
other limb of which was in connection with one of Marey’s
cardiographic levers which registered the respirations on a
revolving cylinder. By increasing or diminishing the resistance
which the stopcock opposed to the entrance of air into the
tracheal cannula the amplitude of the excursions of the lever
could be altered at will,

The blood-pressure was registered by a kymographion con-
nected with a cannula in the left carotid of the rabbit. The
number of cardiac pulsations was estimated from the undula-
tions produced by them in the blood-pressure tracings,

Blood- ey oe Respi-
pressure. | rations.

Time.

Remarks.

in millimetres| - Fea) fe
of mercury. in 74" | in 74
abt. 4%, 15’ 120 21 6% | Each 6th respiration became larger
than the others when the injec-
tion was made.

5 cub. cent. of a suspension of
4 grammes extract in water was
injected into the peritoneal
cavity.

120 18 63 | The respirations decame deeper and
the undulation in the tracing of
the blood-pressure corresponding
to every 6th respiration becomes
very distinct, while previously it
was very slight.

This seems due to the pain of the
injection and the excitement of
the animal after it.

abt. 44, 23’ 120 17 6
Injected about 23 cub. cent. more.
The undulations in the pressure
curve again became more distinct
and the respirations much more
forced.
4>, 32’ 114 20 63
5 — 108 p 7

Attempted to inject more solution
into the peritoneum, but the tube
seemed stopped up and the solu-
tion would not enter. <A clot
now formed in the cannula in the
carotid, so it was cleaned out. in
order to prevent the blood from

382 PHYSIOLOGICAL ACTION OF CONDURANGO.
: Blood- Respi-
Time. pressure. Pulse. patione: Remarks.

in millimetres | . wis ”
of mercury. in 74" | in 74
passing too far into it after re-
adjustment, the bicarbonate solu-
tion of soda was passed into it at
a pressure nearly equal to that
at which the blood had formerly
stood.

When the artery was again con-
nected with the manometer it
was found that the blood-pres-
sure had fallen, and therefore
some of the bicarbonate of soda
in all probability passed into the

artery.
5», 21’ 86
70 16 8
66
55, 21’ 45” Injected 4 cub. cent. of saturated
solution of extract of Condurango
in $ per cent. solution which had
been filtered while hot into the
jugular vein.
5B, 22! 60 14, 8}
55. 22’ 15” - 650 123 8 Cardiac pulsation larger.
55, 22’ 30” 56 13 8
55, 23’ 64 8
5», 24’ 30” 64 14
55, 30’ 48 153 9

The animal was then killed.

Experiment XVI.—A cannula was placed in the trachea of a
rabbit and connected as in the previous experiment with one of
Marey’s levers by a T-tube and a stopcock,

The movements of the registering lever were increased or
diminished according to the greater or less resistance which the
stopcock opposed to the entrance of air into the J -tube.

A second cannula was placed in the left carotid and connected
with a kymographion which registered the blood-pressure. The
number of cardiac pulsations was ascertained by counting the
undulations which they produced in the blood-pressure.

The Condurango was injected through a cannula in the
jugular vein.

ACTION ON CIRCULATION AND RESPIRATION. 353

|
: Blood- Respi-
Time. pres:ure, Pulse. mary el Remarks,
/
in milli-
metres of | in 73”.| in 73”
mercury. :
Tracing I. 102 35 7%
Rizht vagus irritated by
an interrupted cur-
is ; rent,
After ot 73! 46 7? | 15? | Respiration trembling
tion and imperfect. Irri-
tation stopped after
continuing for 7}".
The pulse immedi-
ately became quick
y and the blood-pres-
sure rose,
15° 122 113?
223! 1U7 12?
30’ 106 30 145
375" 98 36 11}
Tracing Il.
Some |
minutes 104 9} |5 cub. cent. of a cold
after J saturated solution of
Tracing I Condurango were fil-
tered and injected into
VES PRA :
After injec- \ sey bys a st the right jugular vein.
ata 96 33 yk
Tracing III. 87
after
beginning
of tracing
15’ 83 33 10
224! 54 10
30’ 77 30 10
371 75 95
45! 75 30 93
523’ 78 10
60’ 75 10
ts , 75 93
15’ 75 9 |) Right vagus irritated.
223/ 63 —'The nerve was not
30’ 73 14 5 divided.
37%’ 83 12} 7? | $TIrritation continuing.
45’ &8 13 12?
523’ 93 13 15
25, 95 13 14 |) Irritation stopped.
73! 122 #0 13}
15’ 124 28 1l
224’ 113 1]

354 . PHYSIOLOGICAL ACTION. OF CONDURANGO.
‘ Blood- Respi-
Time. pressure, Pulse. Bevin a Remarks,
in milti-
metres of | in 7}” | in 7}
mercury.
Tracing III 30’ 106 30 11}
(continw). 373’ 101 10}
45’ 99 11
523’ 98 113
Tracing IV. 93
73! 94
15’ 102 12 Right vagus irritated.
222’ 102 103 Irritation continuing.
30’ 102 104 Respiration very weak.
Irritation stopped.
Tracing V.. 73’ 99 Both vagi divided.

The pressure curve
shows large undula-
tions which do not
correspond with the
respiratory or pulse
wave, but extend over
a period nearly equal
to that occupied by
23 respirations,

15’ 103 5
223’ 102 4
803’ 101 b
373’ 100 34? 5
Peripheral extremity
45’ 95 43 of the right vagus
523’ 94 11 4s irritated.
a. 98 5 Irritation stopped.
Bh 9 94 43

The animal was now killed.

Experrment XVII.—A strong rabbit weighing 6 lb. was ex-

perimented on.

The respirations, pulse, and blood-pressure

were recorded as in the previous experiments,

Pe ————— —

ACTION ON CIRCULATION AND RESPIRATION. 355

: Blood- Respi-
Time. pressure, Pulse. vais a Romarks.
in milli-
metres of | in 7}” | in 73’
mercury.
Tracing I. 7%! 131
15’ 181 30 8
223’ 131 30 8}
Tracing Il. Both vagi cut.
oe 128 34 6
15’ 129 34 5
30’ 128 33 5
373’ 128 33 5
45’ 126 5}
52’ 127 343 53
Tracing III. | 1*. 129 53
7%! 128 . 53
15’ 127 33 43
153’ Vagus irritated and
heart stopped.

Blood pressure fell
during the first stop-
page 388 mm. in = of

, a second.
183’ 46
223’ 150 The electrodes were then
less closely applied to.
the nerve, and the
pressure rose.
30’ 142 343 6

After the irritation:
ceased three respira-.
tions succeeding it
were much smaller
than the others.

$3’ Vagus again irritated..
The blood-pressure
sank 48 mm. in ,% of
a second.
373! 47 2? 7
394 36 0 Irritation stopped.
433’ 0 7%
45’ 92
47’ 186 Respiration very small,
524’ 162 6
2, 160 323 53
73! 126
15’ 123 36 6
Tracing IV. 7%’ 123
15’ 122 35 5}
223’ 124 53
30’ 120 27 53
Tracing V. vi 120 28 6

PHYSIOLOGICAL ACTION OF CONDURANGO.

. Blood- Respi-
Time. pressure. Pulse. mpi e: Remarks.
in milli- |
metres of | in 7)” | in 732”
mercury.
Tracing V rh be ‘ Began to inject a sola-
(continued). 15’ 122 31 7 tion of Condurango
223! 127 6 (filtered into the jug-
30’ 125 31 5} ular vein. Injected
373’ 123 32 5h 10 ¢.c. containing 2
45’ 123 6 grammes of extract.
52}! 123 323 6
55’ Injection finished.
7, 123 333 5}
5 122 6
15’ 119 32 53
16}' | Left vagus irritated.
Blood-pressure fell
38 mm. in 3 ths of
21/ 61 4 a-second.
1», 223/| 99 | eels |
27' 106 8} 6 |) Irritation stopped.
3u' 136
37%! 118 55

At this time peculiar curves began to appear in the blood-

pressure tracing.

I could not understand in the very least

what their cause was at the time, but when the experiment was
finished I found that a clot of blood had formed in the tracheal
cannula, which would obstruct the breathing, and was in all

probability the occasion of these curves.

As this would com-

plicate to a great extent the effects observed I have not noted
this part of the experiment.

Results of Experiments XV, XVI, and XVII.

Pane: Pulse. Bernie, Remarks.
pressure. tion,
Expt. XV. unaitered | slightly | slightly | Injection of 1 gramme of ex-
slower slower tract into the peritoneum.
somewhat | quickened | quickened | } gramme more.
less to normal | to normal
less slower | no effect | Injection into the jugular.
Expt. XVI. less no effect | quicker do. do.
Expt. XVII.| uraltered | quicker quicker |4 gramme into jugular;—

vagi cut.

ACTION ON ARTERIOLES. 357

These experiments show that Condurango has no action on
the pressure of the blood when it is injected into the peri-
toneum in large doses. The diminished blood-pressure noticed
in some instances might be due to the animal’s strength being
diminished by its position on the board and the effects of the
operations. Its effect on the pulse and respiration is not con-
stant, the injection being sometimes followed by quickening
and sometimes by slowing, and moreover the results which .
followed its injection into the jugular might in some degree be
due to the presence of fine particles in it having a mechanical
effect.

The whole subject of the pulmonary circulation, the action of
drugs upon it and the effect which changes in it produces upon
other parts of the body, is at present very imperfectly known,
and it is therefore extremely difficult or impossible to say what
the effect of such fine particles as were contained in the solu-
tion of extract might be when they once enter the pulmonary
vessels.

For the purpose of ascertaining whether Condurango had
any effect in contracting or dilating the arterioles and capil-
laries, the vagus was irritated so as to stop the heart, and the
rapidity with which the blood-pressure fell during the stoppage
of the heart before the injection was compared with that which
was found after it.

Experiment X VII. Tracing LI.

; 8
Blood-pressure fell os mm. in aaths of a second | Safire tnieatiod
” ” ” B4 ay: ”? of i gramme.
43 4 24 ,, ths in one pulse wave +
* 38 , x;ths of a second
K Pe 18 ,, ;ths in one pulse wave hap ih

These numbers show that with the instrument employed no
definite conclusion can be drawn regarding the state of contrac-
tion of the arterioles, but indicate that no extensive alteration
was produced in them by the Condurango.

It may seem strange that I have not made any experiments
on the effect of Condurango on tissue change as indicated by
the amount of urea and salts in the urine more especially, as it

358 PHYSIOLOGICAL ACTION OF CONDURANGO,

has been recommended especially in cases where a drug posséss-
ing an influence over tissue change would be likely to be
serviceable. The experiments of Boeck have, however, shown
that those drugs, such as iodine, morphine, and quinine, which
have some effect upon tissue change, produce but very slight
alterations compared with those which result from variations in
food, and Toldt and Nowak have found that the amount of
nitrogen varies even in the flesh of the same animal, so that it
would be almost necessary to analyse the flesh eaten every day
as well as rigorously to fix its amount, and this would be more
than anyone could well undertake who could not devote his
whole time to the work.

General Summary.

Watery extract of Condurango has no action on frogs even
when injected into the dorsal lymph-sac in doses of 5 grains.
On rabbits it has no poisonous action when injected into the
peritoneal cavity. When a solution containing fine particles in
suspension is injected into the jugular vein the animal dies with
symptoms of opisthotonos. When the coarser particles are
removed this does not occur although the breathing is quickened.
It is not improbable that the quickening of the breathing is
due to the lodgments of fine particles in the pulmonary capil-
laries, and that the opisthotonos which I noticed in one experi-
ment (Exp. 1X) and which has been supposed by Gianuzzi and
Bufalini to be due to the direct action of Condurango on the
nerve centres was really due to asphyxia caused by pulmonary
embolism.

Unlike quinine Condurango has very little effect on shi
action.*

Condurango when injected into the peritoneum even in large
doses has no action on the blood-pressure.

It does not exert any definite action on the arterioles nor
does it paralyse the peripheral terminations of the vagus. |

* Since the preceding experiments were made Mr. Pardington and I have
found that the diminution in reflex excitability which Chaperon described as
caused by the injection of quinine into the lymph-sac of the frog probably
depends on the local irritation produced by the acid in which the quinine is
dissolved.

5
:
°
i
}
4
‘

“

ON THE EMPLOYMENT OF NITRITE OF
AMYL IN THE COLLAPSE OF CHOLERA
[WITH EXPERIMENTS UPON THE PUL-
MONARY CIRCULATION].

(Reprinted from the British Medical Journal, January 13th, 1872; with
references.)

_In two papers which have recently appeared in this Journal,*
and in the Practitioner,t Dr. Talfourd Jones very ably advocates
the use of nitrite of amyl asa remedy in the collapsed stage of
cholera. His proposal is, however, by no means a new one; for
it was made by Dr. Chapman in 1866, as he mentions ina letter
to this Journal,f and also by Dr. Gamgee about the same time.
At the time that I mentioned the suggestion of the latter in a
paper on the “ Action of Nitrite of Amyl in Angina Pectoris,”
in the Lancet for July, 1867, I was unaware that this medicine
had been already tried unsuccessfully by Drs. Hayden and
Cruise of Dublin. Shortly after the publication of my paper, I
obtained, through the kindness of those gentlemen, a copy of
their Report of the Cholera Epidemic of 1866, as treated in the
Mater Misericordize Hospital, Dublin; and from this§ I now
extract the following notices of the action of nitrite of amyl in
_ that disease.

“When inhaled for a few minutes, he (Dr. Richardson) showed
that it is capable of so exciting the circulation, that the face
becomes flushed, accompanied by a thrilling sensation. It
occurred to us that, in virtue of this remarkable property, the
nitrite of amyl might be useful in re-establishing the circulation
in the collapse of cholera. In one case, that of a man forty-two
years of age, admitted in incipient collapse, the pulse rose from

* British Medical Journal, September 30th, 1871, p. 378.
+ Practitioner, October 1871, p. 213.

{ British Medical Journal, October 7th, 1871, p. 426.
§ Report of the Cholera Epidemic, p. 56.

360 NITRITE OF AMYL IN THE COLLAPSE OF CHOLERA.

102 to 114, and the temperature in the axilla rose from 954° to
962° F., after inhalation of the nitrite of amyl for three minutes.
The inhglation appeared to aggravate his thirst. In another
case, that of a woman aged thirty-four, also in collapse, the
pulse became perceptible after inhalation for a few minutes ;
and the patient seemed otherwise improved. Thirst seemed
ageravated by the inhalation in this case also. A boy aged
four, in collapse, inhaled the amyl for a few minutes, after which
there was a slight appearance of colour in the face. The boy
strenuously resisted its further administration, owing to the
obstruction to free respiration which it occasioned. In several
other cases the amyl was tried; but although, when inhaled for
a few minutes, it usually heightened in some degree the colour
of the face and surface-temperature, the difficulty of inducing
patients to continue the experiment for a sufficient length of
time, owing to its interference with respiration and the increased
thirst which it occasioned, caused it to be abandoned.”

As the results of theix trial of oxygen are very interesting, I
subjoin them also.

“ Inhalation of oxygen by means of Dr. Richardson’s apparatus
was also made trial of. In one case, that of a woman in collapse,
the pulse became perceptible for a few minutes. A woman aged
forty-four, in collapse, inhaled oxygen for eighteen minutes.

The pulse, previously all but imperceptible, increased in strength ; _

and the temperature of the surface was slightly elevated. Ina
third case, that of a girl aged twenty-four, oxygen was adminis-
tered on three several occasions. The temperature rose slightly
after the first administration, and the patient requested that she
might have it again, as it gave her relief. The oxygen, like the
amyl, though of temporary advantage, was found to produce no
permanent benefit, and was therefore abandoned.”

Both these remedies seem to offer fair promise of success, and
their use is certainly indicated by the symptoms; that of nitrite
of amyl by the contracted state of the vessels which is almost
certainly present in the collapse of cholera; and that of oxygen
by the cyanotic appearance of the patient, and by the diminished
combustion in the body, which is indicated by the small amount
of carbonic acid given off from the lungs during this state. It

SYMPTOMS OF CHOLERA. 361

is, therefore, rather disheartening to find from this Report that
they produced no permanent benefit; and that the use of the
nitrite of amyl, from which one would have been inclined to
expect still more advantage than from that of oxygen, had to be
abandoned, because it increased the distress of the patient by
impeding still more the already ditficult respiration, and render-
ing more intense the tormenting thirst. It is, however, better
to know that they have been tried and found unsuceessful, than
to cherish a false hope in their efficacy, only to be undeceived
and disappointed when we come to try them; and a careful
consideration of the cause of their failure may possibly help
towards a more successful plan of treatment. In order to under-
stand why the oxygen and amyl did not fulfil the expectations
which had been formed regarding them, it will be necessary to
take a glance at the conditions which are found in the collapse
of cholera, their probable causes, and the mode of action of the
remedies employed. |

The most striking symptoms in the collapse of cholera are
generally the excessive purging; the peculiar nature of the
stools, which are liquid and colourless, resembling rice-water in
appearance; and the large amount of fluid which is evacuated
from the bowels. The extreme thirst of the patient, and his
urgent calls for water; the shrivelled and pinched look of the
surface, and its bluish colour and coldness; the cramps in the
muscles ; the husky voice; and occasionally the difficult respira-
tion, also attract immediate attention. A closer examination
shows that the pulse is small, or even imperceptible ; and that
the proportion of carbonic acid excreted by the lungs is not
more than a third of that given off in health.*

In attempting to trace each of these symptoms back to its
origin, we do not deal with certainties, but only with probabilities
more or less strong. We cannot say with any approach to cer-
tainty what the cholera-poison is, by which all these symptoms
are occasioned ; but we may assign a proximate cause to each
one of them—to some with a probability almost amounting to
certainty ; to others, only with hesitancy and doubt.

The rice-water stools, which form so prominent and charac-

* Davy, quoted by Rayer, Gazette Médicale, 1832, p. 278.

362 NITRITE OF AMYL IN THE COLLAPSE OF CHOLERA.

teristic a symptom, have naturally attracted much attention ;
and numerous analyses of them have been made by Kiihne,*

Parkest and others, with a view to ascertain their nature and
probable origin. It has thus been found that their composition
is like that of the intestinal juice, except that they contain a
much larger proportion of water than it does. Under ordinary
circumstances, the secretion from the mucous membrane of the
intestine is never so dilute as the stools of cholera; but a very
dilute juice, which is almost identical in composition with the
rice-water stools,t is secreted by the intestine when the nerves
going to it are paralysed, as in the well-known experiment of
Motean. § This gentleman took a large dog, which had not been
fed for at least twenty-four hours, and, after putting it under
chloroform, made an incision through the abdominal walls, and
drew out a loop of intestine. Round this he put two ligatures,

Fig. 148.—Diagram showing the effect of section of nerves on secretion from
the intestine. The nerves going to the middle loop have been divided, and
it is distended with the fluid secreted.

NERVES
’ .

=.
we \.
== SSS: z A
SS SSSSSaeaeesessesssaees
—— = 5
LSS A

about 4 or 5 inches apart from one another, so that the
piece of bowel between them was completely tied off from the
rest of the intestine; he then cut all the nerves going to this

* Kiihne. Paper read before the Medical Society of Amsterdam in the winter
of 1868-9. Unpublished.

+ Parkes, London Journal of Medicine, vol. i, p. 134.

{ Kihne, op. cit. . )

§ Moreau, Comptes Rendus, 1858, p. 554.

eS ee ee

MOREAU’S EXPERIMENT. 363

part, but took care to leave all the blood-vessels uninjured. He
next tied off in the same way a piece of intestine about the same
Jength as the tirst on each side of it, but did not cut the nerves
going to them. All the three parts were thus completely
empty; they were all equally isolated from the rest of the
intestine, and were all in exactly the same condition in regard
to their vascular supply; but the nerves of the middle piece
were cut, and therefore paralysed, while:those of the pieces at
each side of it were not. He then put the intestine back into
the abdomen, and sewed up the wound. After four or five
hours, he killed the dog, and examined the intestine. The two
pieces which had been ligatured off from the rest, but whose
nerves had not been cut, were found empty, just as they were
when they were put into the abdomen: but the third piece,
which lay between the two others, and whose nerves had all
been divided, was found distended like a sausage with a fluid
whose composition, as I have already said, was almost identical
with that of cholera-stools. Now, in this experiment, all the
nerves going to the intestine were cut, and therefore paralysed ;
but we do not know whether or not the same effects would have
been produced if only some of them had been paralysed, and it
is not improbable that it might have been so.

We have, then, in cholera, the same profuse secretion as in
Moreau’s experiment; and from identity of effect we may fairly
infer identity of cause, and are, therefore. justified in concluding
that the great outpouring of fluid into the bowel is due in both
cases to paralysis of some, at least, of the nerves of the intestine.
The probability that only some of the nerves, and not all of them,
are paralysed in cholera, is strengthened by a consideration of
the circumstances which induce a paralytic secretion of saliva in
the submaxillary gland. Whenever a difficult question regard-
ing secretion arises, we are always obliged to refer to this gland,
because in it the process of secretion hasbeen most fully investi-
gated, and the conditions under which it takes place are best
understood. When some of the nerves connected with the sub-
maxillary gland* are paralysed by dividing them, a continuous
and profuse secretion is poured out by it. When some addi-

* The fibres connecting the submaxillary ganglion and the lingual nerve.

364 NITRITE OF AMYL IN THE COLLAPSE OF CIIOLERA.

tional nerve-fibres,* however, are divided, instead of the secretion
becoming still more profuse, it becomes diminisiied. We do
not possess sufficient knowledge regarding secretion from the
intestine to be certain that it can be modified in the same way
as that from the submaxillary gland; but if, as seems very
probable, this analogy subsists between them, we can easily
understand that, while a profuse flow of liquid into the intestine
indicates a certain amount of paralysis of its nerves, a more
moderate flow might be due to two opposite causes—viz., either
to a less degree of paralysis or to a still greater one. When I
speak of the choleraic discharges as a consequence of nervous
paralysis, I refer only to the rice-water stools, and do not at all
include the preliminary diarrhcea; for that may depend only on
irritation of the intestinal nerves without paralysis, just as an
abundant: secretion of saliva may be obtained from the sub-
maxillary gland by irritating some of the nerves connected with
it,f without division or paralysis of any one of them.

In consequence of such a large amount of water being ab-
stracted from the blood by the intestinal glands in order to
form the rice-water stools, the blood itself becomes much thicker,
and the proportion of solid matter it contains much greater.t
The intense thirst during life, and the dryness of the tissues
which is found after death, appear to be directly due to the
loss of water from the blood.

The other symptoms have also been ascribed by some
persons to the effect of the thickened blood; while others
attribute them partly to this, and partly to the reflex action of
the intestinal lesions on the nervous system; and yet others to
the direct action of the cholera-poison itself.

As Dr. Parkes§ and Dr. George Johnson have clearly pointed
out, all the other symptoms can be referred to the blood being

* The fibres connecting the ganglion and the chorda tympani. Kiihne,
Lehrbuch der Physiologischen Chemie, p. 4.

+ E.g., as by irritation of the chorda tympani, either directly by irritation
applied to its trunk, or reflexly through the lingual by acids applied to the
tongue. .

t Herrmann, Wittstock, Dittel, Thomson, &c., quoted by Griesinger. Vir-
chow’s Patho’ogie, Bd. ii, Abt. 2, p. 334.

§ Parkes on Cholera, London, 1847, p. 105.

ARRESTED PULMONARY CIRCULATION 565

hindered from passing through the lungs. In consequence of
the obstruction in front, the biood accumulates in the right side
of the heart, and distends the large veins. It passes so slowly
through the pulmonary vessels, that, although it is laden with
earbonic acid, and is quite able to give off this gas and to take
up oxygen,* the air which is expired contains but a small pro-
portion of the carbonic acid which it would do in health.f So
little blood reaches the left ventricle, that all that it can send
out at each ‘systole hardly causes a wave in the arteries. The
pulse therefore becomes weak and imperceptible, not only in
the radial, but in large vessels like the brachial; and the
arteries, when cut across, hardly bleed at all.{ The arterioles,
and probably the capillaries, become empty; or, as some term
it, the vital turgor disappears; and this empty state of the
vessels, along with the drying of the tissues already alluded to,
eauses the face to become pinched and shrunken, the fingers
shrivelled, and the skin to lose its wonted elasticity.§ From
the want of any fresh blood from behind to force it on, rather
than from the obstruction in front, the blood stagnates in the
venous radicles, and becomes almost completely deoxygenated,
giving a livid hue to the surface ;]] and when a vein is opened,

* T have not been able to find direct experiments on the amount of carbonic
acid contained in the venous blood in cholera, nor on its power to give off this
gas and absorb oxygen, but I infer that it contains much carbonic acid, from its
extremely dark colour ; and that its power of undergoing respiratory changes is
not destroyed, from the fact that it becomes red on exposure to air. See Parkes
on Cholera, p. 113.

+ Rayer, Gazette Médicale, 1832, p. 278, and several authors quoted by him.

t Dieffenbach, quoted by Griesinger, Virchow’s Handbuch der Pathologie und
Therapie, Bd. ii, Abth. 2, p. 327, and by Magendie, Gazette Médicale, 1832,
p. 253. Magendie attributes the emptiness of the arteries, and Griesinger the
slow passage of blood through the lungs, to weakness of the heart ; but it seems
much more probable that they are due to obstruction of the pulmonary circula-
tion, as Parkes has shown that the heart sometimes continues to beat with
considerable vigour during collapse, and the second sound of the heart becomes
inaudible while the first can still be heard. Now the first sound is caused
almost entirely by the contraction of the muscular walls of the heart (Ludwig
and Dogiel, Ludwig’s Arbeiten, 1869, p. 78), and it disappears first in cases of
weakness of the organ, as in fever; but the second sound is caused by the closure
of the sigmoid valves,

§ Niemeyer, Practice of Medicine ; translation. London, 1871, vol. ii, p. 637.

|| Griesinger, op. cit., p. 328.

iid

366 NITRITE OF AMYL IN THE COLLAPSE OF CHOLERA.

and the thick blood which distended it is emptied out, no more
will flow. From the blood, which in health acts as the diffuser
of heat to the extremities, and the equaliser of temperature in
the body, being thus pent up in its interior, and no longer
circulating through the skin or lungs, and becoming itself cooled
as it warms them, the surface and the expired air both become
cold, while a thermometer in the rectum may show a tem-
perature higher than any observed even in the most intense
fever.”

All the symptoms are thus easily and satisfactorily explained
by the hypothesis of Parkes and Johnson, that the circulation
is obstructed in the lungs; and even cases which at first sight
might seem to militate against it, on closer examination serve,
I think, only to confirm it. Such cases are those observed by
Mackinnon,t where, after a check had been put to the vomiting
and purging, the voice, breathing, and warmth of the skin
became natural ; the face had none of the peculiar character of
the disease; the patients walked about and called for food,
saying that they felt well; but their pulse was imperceptible,
and in one or two days they died of coma. In these cases, it is
true, the imperceptible nature of the pulse might be partly due
to feeble action of the heart; but it seems not improbable that
it was owing in great measure to persistent obstruction in the
pulmonary circulation. It would appear almost impossible for
men to live in such a condition ; but Sir James Paget has shownt
that persons may have their pulmonary circulation obstructed
to an enormous extent, and yet hardly present a symptom of
anything wrong, so long as the systemic vessels contract in
unison with the pulmonary ones, and do not allow any more
blood to pass through them in a given time than is able to flow
through the obstructed arteries in the lungs during a similar
period.

While the hypothesis of obstruction to the pulmonary cireu-
lation readily explains the symptoms in collapse, it is not easy
to ascertain how this obstruction is occasioned, and several

* Giiterbock, Virch. Arche, vol. xxxviii, p. 30.
+ Reynolds’ System of Medicine, vol. i, p. 163.
{ Medico-Chirurgical Transactions, 1845, p. 359.

THE BLOOD IN CHOLERA. © 367

causes might be assigned to it, and much might be said in
favour of each of them. It might be due only to the thickened
condition of the blood, which hindered it from passing through the
pulmonary capillaries, although they were not contracted beyond
their normal calibre, or the thickened blood itself may act as
an irritant to them and cause them to contract. It is very
probable that the thickened state of the blood is one cause, and
by no means an unimportant one, of the retarded flow of the
blood; but it appears also likely that contraction of the pul-
monary capillaries is present in addition, and also that it does
not depend on the condition of the blood, for, as Niemeyer and
others have pointed out, the symptoms of collapse may dis-
appear so quickly that it can hardly be supposed that time
enough has elapsed to allow of the absorption of sufficient fluid
to restore to the blood its normal amount of water.*

The blood in cholera has the colour of bilberry juice, and this
might be supposed to indicate changes in it which would cause
it to act as an irritant to the pulmonary vessels, and cause them to
contract independently of any change in the amount of water it
contained. This, however, can hardly be the case, as Kruken-
bergt has found this condition continue for weeks. This pecu-
liar colour of the blood is probably due to some of it having
become so completely deoxidised in the capillaries, that the
hemoglobin has passed out of the corpuscles into the plasma,
and this view is confirmed by the dark red colour which the
serum sometimes presents (Parkes on Cholera, p. 124). When
blood has undergone deoxidation to such an extent that this
occurrence takes place, it ceases to become red when exposed to
air, but it nevertheless takes up oxygen and gives off carbonic
acid in the usual way. This fact explains the statement made
by Rayer, that blood in cholera does not become red when
exposed to air; and the observation of Searle (Searle on Cholera,
p. 62), that the blood drawn from the arteries in cholera is often
dark coloured.

Besides the causes already mentioned, there are two others to
which the contraction of the pulmonary vessels might readily be

* Niemeyer, Symptomatische Behandlung der Cholera, p. 14,
t Niemeyer, op. cit., p. 13,

368 NITRITE OF AMYL IN THE COLLAPSE OF CHOLERA.

attributed ; viz., reflex action from the intestines, and the direct
action of the cholera poison, whatever that may be, on the vessels
themselves. The occurrence of symptoms almost exactly resem-
bling those of cholera-collapse in cases of perforation of the
intestines, or of intense gastro-intestinal irritation by arsenical
poisoning, would seem tu favour the first view. On the other
hand, the fact that there is no great lesion of the intestinal tube
in cholera during life—the denudation of epithelium, on which
Niemeyer laid much stress, being chiefly, if not entirely, a post-
mortem phenomenon—as well as the occurrence of symptoms of
collapse after intense malaria poisoning, as mentioned by
Goodeve,* is in favour of the second view, and between them I
cannot pretend to decide. Whatever be the cause of the con-
traction of the pulmonary vessels in cholera, we may, I think,
assume that the obstruction to the circulation is due partly to
it and partly to the thickened condition of the blood.

The indications for treatment in cholera-collapse, then, ie
1. To remove the paralysis of the intestinal nerves. 2. To
dilute the thickened blood. 3. To dilate the pulmonary ge
laries. 4. To oxygenate the blood passing through them.

How the paralysis is to be removed I for one do not know.
That the copious secretion from the bowel eliminates the poison
from the blood is, I think, doubtful, and any benefit that may
result from it in this way is, I believe, more than counteracted
by the alteration which it produces in the condition of the
blood. That many cases in which the discharge has been pro-
fuse have ended in recovery, and that others in which it has
been scanty have terminated fatally, may simply show (if the
analogy between the secretion in the intestine and the sub-
maxillary gland be correct) that the nervous paralysis has been
more complete in the latter than in the former case, while the
accumulation of fluid in the intestine without purging, in the
so-called cholera sicca, would indicate paralysis not merely of
the secreting, but also of the motor, nerves of the bowel. What
I have just said, however, is no argument against the use of
eastor-oil in the treatment of collapse. When we know so
little of the pathology of the disease, or of the action of the

* Reynolds’ System of Medicine, vol. i, p. 17.

ee ee ee eee ”Dl eee ee

=

ACTION OF AMYL NITRITE ON PULMONARY CAPPILLARIES. 369

remedies we employ, our treatment must be empirical, and suc-
cessful results must be our warrant for employing one method
rather than another. The second indication, viz., to dilute the
blood, is generally fulfilled by giving ice and ice-cold water by
the stomach. The wonderful effects which immediately follow
injection of salt solutions into the veins show what an important
share the loss of water from the blood has in the production of
collapse. The ultimate benefit resulting from this mode of treat-
ment has hitherto not been commensurate with the immediate
relief to the symptoms which it affords, but this should only
lead us to try whether we cannot, by employing different pro-
portions of salts, or using medicines in addition to them, find
some method of rendering the immediate effects of the injection
permanent.

For the purpose of relaxing the contraction of the pulmonary
capillaries, nitrite of amyl would seem, as Dr. Jones says, to be
the very remedy. In this Journal for October 14th (1871), Dr.
George Johnson observes that nitrite of amyl may not act on the
pulmonary capillaries as it does on the systemic ones. I have,
however, tried it on animals, and find that it does. When given
to rabbits, it causes the systemic capillaries to dilate enormously,
the blood flows rapidly into the veins, and the pressure on the
arterial system sinks in a corresponding degree. If it did not
produce dilatation of the pulmonary as well as of the systemic
capillaries, the blood which pours rapidly into the veins could
not pass with equal rapidity out of them through the pulmonary
vessels, and it would consequently accumulate in, and distend
the right side of the heart. In order to see whether this was
the case or not, I thoroughly narcotised a rabbit with chloral,
put a cannula into its trachea, and kept up artificial respiration.
I then opened the thorax, and, after carefully noting the appear-
ance of the heart, passed the vapour of nitrite of amyl, mixed
with air, into the lungs. When this was done, the cardiac pul-
sations became a little quicker, but not the slightest distension
of the right side of the heart or of the jugular vein could be
observed. I repeated the experiment several times with the
same result. There is no reason to suppose that the chloral
with which the animal was narcotised altered in any way the

2B

370 NITRITE OF AMYL IN THE COLLAPSE OF CHOLERA.

action of the nitrite of amyl on the pulmonary vessels, for I
have found that other vapours, as well as certain poisons,
injected into the jugular vein, cause accumulation of blood in
the right side of the heart after the animal has been completely
narcotised. I have also observed that this accumulation of
blood, which I believe to be due to contraction of the pulmo-
nary vessels caused by the poison or vapour, has disappeared in
the case of one poison at least,* after the injection of another
drug which had been previously found to be an antidote to it
in other respects. With the prosecution of these experiments
I am at present engaged; and I take this opportunity of thank-
ing Dr. Burdon Sanderson for his kindness in allowing me the
use of his laboratory and apparatus.

Dr. Johnson also says that, even if nitrite of amyl were
shown to possess the power of relaxing the pulmonary capil-
laries in health, it might not do so in disease, or at any rate not
to the same extent. Some observations which I have made on
its action in angina pectoris lend probability to this idea. In
the paper already referred to, which I published in 1867, I
mentioned my belief that angina was due to spasmodic contrac-
tion of the capillaries; and in a paper in the Clinical Society's
Transactions for 1870, I gave copies of one or two of the
sphygmographic tracings which led me to form this belief. In
it I noticed that occasionally after the anginal pain had dis-
appeared from every other part of the cardiac region, it remained
persistently at a spot two inches inside the right nipple. This -
local persistence of the pain was accompanied by a peculiar
condition of the pulse, which seemed to me to indicate that the
pulmonary capillaries had not become relaxed to the same
extent as the systemic ones. As sphygmographic tracings,
especially when taken with an instrument like the one I used,
in which the pressure exerted by the spring could not be esii-
mated, sometimes admit of different interpretations, I append
copies of-some of them. J may mention, however, that these
tracings are strictly comparable with each other, although they

* Muscarin, the active principle of amanita muscaria, discovered by Professor
Schmiedeberg, seems to produce contraction of the pulmonary capillaries, and
this is at once removed by atropla.

PULMONARY AND SYSTEMIC CAPILLARIES. 371

may not be so with tracings taken at a different time ; for while
these were being taken, the instrument remained attached to
the arm of the patient, and the pressure of the spring which
rested upon the artery remained unaltered. In the normal con-
dition of the patient, his pulse presented the characters seen in

Fig. 149.

Fia. 149.

During the attack of angina, the capillaries become con-
tracted, and the arterial tension rose as seen in Fig. 150. When

Fra. 150.

the nitrite was inhaled, the pulse in most cases quickly regained
its normal character; but when the pain remained in the region
of the right nipple after the inhalation, the arterial tension fell
as usual, indicating dilatation of the systemic capillaries, but the
volume of the pulse remained small, as shown in Fig. 151. The

Fie. 151.

small volume is, I think, due to the pulmonary capillaries not
dilating, or only imperfectly, under the action of the nitrite;

and if I discontinued the inhalation before the volume of the
232

372 NITRITE OF AMYL IN THE COLLAPSE OF CHOLERA.

pulse became normal, as well as its character, I felt nearly
certain that the spasmodic pain would speedily return with all
its former intensity.

The observation of Drs. Hayden and Cruise that the pulse
became perceptible in their patients after the inhalation, seems
to show, however, that the nitrite did relax the pulmonary
vessels during the collapse, and allowed a fuller stream of blood
to pass into the left ventricle, and thence to the body. Why,
then, did it increase the difficulty of breathing? One would
have thought that by allowing more blood to flow through the
lungs, it would at least have alleviated this symptom, if it did
not remove it altogether. The experiments of Dr. Arthur
Gamgee at once enable us to answer this question. In a paper
in the Royal Society's Transactions,* he showed that nitrite of
amyl combines with hemoglobin, the oxygen-carrier of the
blood, and prevents it from giving off oxygen after it has taken
it up. When the blood is exposed to the vapour of the drug as
it passes through the lungs, the oxygen becomes locked up in it,
and cannot be given off to the tissues for their use, so that
however much oxygen the blood in the arteries may contain, it
acts very much as if it were venous. In consequence of this, I
have found that when the vapour of the nitrite is passed into
the lungs of rabbits, they are seized with suffocative convul-
sions. The greater part of the blood which passed through the
lungs having been acted on by the vapour, it affects the brain
just as it would have done if the trachea had been closed, and
no air allowed to come near it during its passage through the
pulmonary vessels, and therefore convulsions occur as soon as it
reaches the brain. Professor H. C. Wood, of Philadelphia,t
who has lately written a valuable paper on the action of the
nitrite, found no convulsions after injecting it subcutaneously.
By giving it in this way, the blood was not acted on during its
passage through the lungs, and asphyxia was prevented. This,
I think, shows that if nitrite of amyl is to be used at all as a
remedy in cholera, it must be given internally or by subcu-
taneous injection, and not by inhalation. This mode of admini-

* Philosophical Transactions, 1868, p. 589.
+ American Journal of Medical Sciences, July, 1871.

CAPILLARY DILATATION AND INTERNAL RESPIRATION. 373

stration seems to me to be indicated also in spasmodic asthma,
when the arterialisation of the blood is also impaired. In angina
pectoris it will act when given internally, but a larger dose is
required than when inhaled; and it remains to be seen whether
it can be given in cholera in sufficient doses to relax the capil-
laries without, at the same time, injuriously impairing the re-
spiratory changes in the blood and tissues.

ON THE USE OF ARTIFICIAL RESPIRATION
AND TRANSFUSION AS A MEANS. OF
PRESERVING LIFE. |

(Reprinted from the British Medical Journal, May 17, 1873.)

IN his admirable Lessons in Physiology, Huxley says that “the
brain, the lungs, and the heart, have been fancifully termed the
tripod of life; but, in ultimate analysis, life has but two legs to
stand upon, the lungs and the heart, for death through the
brain is always the effect of the secondary action of the injury
to that organ upon the lungs or the heart.” This conclusion is
founded on the experiments of many observers, among the most
interesting of which are those of the Abbé Fontana and
Legallois.* The former found that the brain was not necessary
to life; for he could cut off the heads of rabbits and guinea-pigs,
and yet keep their bodies alive by connecting a pair of bellows
with the trachea, and keeping up artificial respiration. As he
himself says, an animal can live quite well without a head:
artificial respiration and the circulation of the humours in the
various parts are quite sufficient. ‘The headless trunks evi-
denced their vitality by displaying sensitiveness to impressions,
and executing what the Abbé considered to be voluntary
movements, but which we would now term simply reflex
actions. Legallois went even further than Fontana; for, not
content with cutting off the rabbit’s head, he tied the aorta and
vena cava, and then cut away the whole of the posterior part of
the body, leaving only the headless thorax. This fragment of
the body, mutilated as it was, still remained alive; the fore
paws showed sensibility when irritated, and the thorax twisted
when the skin over it was pinched, or more distinctly still if

* Fontana, T'raité sur le vénin de la vipére, sur les poisons Américains, sur le
laurier cerise, et sur quelques autres poisons végétaux, Florence, 1781, tome 1,

page 317; Legallois, Hxpériences sur le principe de la vie, Paris, 1830, tome 1,
p 130,

¢

LIVING HEAD AND DEAD BODY. 375

the lower end of the spinal cord were touched. Even when the
experiment was carried farther, and the whole of the cervical
with part of the dorsal spinal cord was destroyed, evidences of
life could be observed in the posterior two-thirds of the thorax.
These experiments demonstrated beyond doubt that, if the lungs
and heart could perform their functions with any other fragment
of the body as they do with the thorax, it might be kept alive.
As Legallois himself says, “if the place of the heart could be
supplied by a sort of injection, and if at the same time a supply
of arterial blood, either natural or artificial, if such a formation
of blood were possible, could be obtained, life might be main-
tained indetinitely in any fragment of the body whatever; and
consequently a severed head might be kept alive and in pos-
session of all the faculties pertaining to the brain. Not only
could life be maintained in this manner, either in the head or
in any other isolated part of an animal’s body, but it might be
recalled after its entire extinction ; it might even be recalled to
the whole body, and a veritable resurrection, in every sense of
the word, might be effected.” Perhaps it may seem that the
success of his experiments rendered Legallois too sanguine ; but
his anticipations have already in great part been fulfilled, and a
severed head has been partially at least restored to life by
M. Brown-Séquard. His experiment, as related by M. Vulpian,*
consisted in cutting off the head of a dog immediately after it
had been killed, and connecting the carotid and vertebral
arteries with an apparatus for artificial circulation. After eight
or ten minutes had elapsed, and all signs of excitability in the
medulla oblongata and the rest of the encephalon had been gone
for several minutes, defibrinated and arterialised blood was
injected simultaneously into the vertebrals and carotids. Ina
few seconds, signs of life began to appear, and the muscles of
the eyes, in fine, acted in such a way as seemed to prove that
the cerebral functions were re-established.

Hardly less astonishing than Brown-Séquard’s experiments
are those of Preyer,t who has succeeded in restoring their vital
properties to a frog’s muscles after they have been brought into

* Revue de Cours Scientifiques, 1864-65, tome 2, p. 217.
t Centralblatt fiir die Med. Wissenschaft., 1864, p. 769.

376 USE OF ARTIFICIAL RESPIRATION AND TRANSFUSION.

the state of rigor mortis by dipping them into warm water.
This condition depends on coagulation of the muscular substance
or myosin ; and circulation of blood alone through muscles in
this state is of no use, for it cannot soften the hardened myosin.
Something more is therefore necessary. Coagulated myosin is
soluble in a solution of common salt; but, though a muscle
dipped in such a solution may lose its hardness and again
become soft and pliable, it does not regain its vitality. By
combining the two methods, however, the difficulty has been
overcome ; and, by first dipping the rigid muscle in a solution of
salt, and then allowing blood to stream through it, Preyer has
had the satisfaction of seeing frogs jump and swim by the aid
of muscles which had been almost as hard and stiff as a piece of
wood only a short while before.

Nor are nerves and muscles the only parts which can be kept
alive by artificial circulation. Glands also preserve their
vitality ; and Ludwig and his pupils,* by maintaining artificial
circulation in them, have succeeded in making livers secrete
bile, and lungs excrete carbonic acid, for hours after they have
been excised from the body.

More examples might be given, but the above are sufficient to
show the power of artificial circulation to keep any part of the
bedy alive after the death of the rest. The converse of this is
also true; and, if blood be prevented from circulating through
any part of the body, that part will die, although the rest may
remain healthy. So generally known is this, that no one ever
thinks of tying a bandage so tightly as to stop the circulation,
and leaving it thus, as he well knows that death, or, as we
usually term it, mortification of the ligatured part would be the
result. It is easy for any one, indeed, to observe for himself
the destructive effects of want of blood and the vivifying power
of renewed circulation, by repeating the experiment devised by
the Danish physiologist Steno, or Stenson, more than 200
years ago. A gentle steady pressure with the thumb on the
abdominal aorta of a rabbit, so as to stop the circulation for a
couple of minutes, is all that is necessary to produce complete
paralysis of the hind legs of the animal; and a few minutes

* Ludwig’s Arbeiten, 1868, p. 113, and 1870, p. 38.

TRIPOD OF LIFE. 377

more of renewed circulation suffice to restore them to their
normal state. It might almost seem that the tripod of life had
been reduced to one leg—viz., a circulating apparatus or heart ;
but this is not the case, for it must be remembered that the
blood which circulates. must be oxygenated or arterial; and if,
as in the case of artificial circulation, there be no lungs to effect
its oxygenation, their place must be supplied by agitation with
air, though this is at best but a poor substitute. Indeed, it is
rather because the blood carries oxygen than nutriment to the
_ tissues that arrest of circulation causes them to die so speedily ;
for Kronecker found* that, after he had exhausted the muscles
of a frog by constant irritation, he could restore their contrac-
tility by passing through their vessels a solution of permanganate
of potash, which, like the blood, could supply them with oxygen,
although it could yield them no nourishment.

The body is made up of a number of parts ; and if the heart
stop, the circulation ceases; or, if the lungs fail to perform
their duty, so that the circulating blood is no longer arterial-
ised, all the parts, and therefore the whole body, will die. But
the parts will not all die at the same time ; and this is a point
of great practical importance. The brain and spinal cord
generally die first, and the heart may be pulsating as regularly
as ever when all respiratory movements have ceased, and no
irritation, however intense, will evoke the faintest indication
of consciousness, or excite the slightest reflex action. The
muscles retain their irritability still longer than the heart, and
they continue to possess their power of contraction, and the
lungs their ability to oxygenate the blood, even after the cardiac
pulsations have entirely ceased. Here, then, we come to the
third leg of the tripod of life—viz., the brain—for want of which
the other two cannot stand. The whole body, in fact, may be,
and often is, alive, with the exception of the nervous centres.
The heart is alive, the lungs are alive, but the brain is dead,
and, without it, the respiratory muscles will not work. The
want of oxygen weakens the heart ; it gradually stops, and then
the other parts of the body die, each in its turn. But, if the
respiration can only be kept up artificially, the heart will go on

* Ludwig’s Arbeiten, 1872, p. 182.

378 USE OF ARTIFICIAL RESPIRATION AND TRANSFUSION,

beating; the circulation of arterial blood through the brain
may gradually restore its power ; the rhythmical movements of
natural respiration will again begin, and the life of the animal once
more be securely established. This is no mere fanciful dream,
but sober fact, as the successful efforts of the Humane Society
to resuscitate persons apparently dead abundantly prove. It
has, moreover, been lately demonstrated in a striking manner
in some experiments of Schiff.* These were made for the pur-
pose of ascertaining what the use of artificial respiration would
be in concussion or compression of the brain, or in cases of
apoplexy where a clot has formed in the medulla oblongata, and,
by pressing upon that part of it which presides over the inner-
vation of the muscles of respiration, has pnt a stop to these
movements. In order to imitate the effect of an apoplectic
extravasation, Schiff anzesthetised a dog with ether, and, after
exposing the medulla oblongata, destroyed a considerable part
of it with a scalpel or sound, though he always left one lateral
column at least intact. Immediately after the injury the respi-
ration ceased, the tongue became swollen and livid, convulsions
occurred, and the animal appeared to be dying. The heart
became weaker and weaker; but, when it had almost ceased to
beat, artificial respiration was begun. Very shortly the pulsa-
tions regained their normal strength, and the death-like lividity
of the tongue gave place to the rosy hue of health. After
respiration had been kept up for a few hours it was discon-
tinued, and then, if the injury to the medulla had not been too
great, spontaneous respiratory movements commenced, but they
were still feeble. They became much stronger if artificial
respiration were again renewed for half an hour longer—strong
enough, indeed, to keep the animal alive without any artificial
assistance. It is true that, when the lesion had destroyed the
one side of the medulla, only one-half of the thorax took part
in the respiratory movements; but this was in many cases
quite sufficient for the wants of the animal. In the only case
in which Schiff attempted to keep the animal alive permanently
he was perfectly successful. The beneficial effects of artificial
respiration were equally encouraging when natural respiration
* La Nazione, 1872, No. 102.

ARTIFICIAL RESPIRATION IN APOPLEXY, 379

was arrested by compression of the brain through the injection
of tepid water under high pressure into the cranial cavity.
From these experiments it is evident that we may hope for the
best results from the use of artificial respiration in some of
those cases of apoplexy where an extravasation almost instantly
arrests the respiratory movements, either directly by destroying
a part of the medulla, or indirectly by causing compression of
the brain. It may be thought that there is a considerable
difference between the compression produced by the injection of
tepid water and that which is due to an extravasation of blood,
inasmuch as the water will be rapidly absorbed, while the blood
will not. To a great extent this is true, and we can hardly
expect very much good from artificial respiration in cases of
apoplexy where the clot is large and the affection of the respi-
ration is gradual. In those cases, however, where a small extra-
vasation only has taken place in or near the medulla, the respi-
ratory movements are abolished, just as in Schiff’s experiments,
by what may be termed the shock, although the medulla could
carry on respiration well enough if time were given it to
recover from the immediate effects of the injury. The em-
ployment of artificial respiration for a few hours would give the
time required.

In another class of cases—that of poisoning by weorara,
hydrocyanic acid, &c.—artificial respiration is invaluable. In
his 7ravels* Waterton tells a melancholy story of a poor Indian
who, when shooting at a monkey sitting in a tree straight above
him, was wounded near the elbow by his own arrow as it fell
down. He immediately became convinced that it was all over
with him. “I shall never,’ said he to his companion in a
faltering voice, and looking at his bow as he said it, “I shall
never bend this bow again.” Having said this, he took oft the
little bamboo poison-box which hung across his shoulder, and
putting it, together with his bow and arrows, on the ground, he
laid himself down beside them, bade his companion farewell,
and never spoke again.

It is not true, as some persons formerly supposed, that the
minutest quantity of woorara in the blood is sufficient to cause

* Travels in South America, 1825, p. 71.

380 USE OF ARTIFICIAL RESPIRATION AND TRANSFUSION.

death. It is a very powerful poison, certainly; but there is a
limit to its virulence; and, if there be too little of it in the
blood, it will have no action. On this account it is not usually
poisonous when swallowed, for it is excreted by the kidneys as
quickly as it is absorbed from the stomach, and so there is
never enough in the blood at any one time to produce any effect
whatever on the body. The result is very different, however,
when the kidneys are prevented from acting, by ligatures
applied to the ureters. Then the poison, which is gradually
absorbed from the stomach, goes on accumulating in the blood,
and by-and-by, when it has reached the necessary amount, it
produces exactly the same effects as if it had been injected
directly into the veins. When the poison is applied toa wound,
it is usually absorbed more quickly than the kidneys can
excrete it, and so poisoning occurs. But, if a ligature be applied
above the wound so as nearly to stop the circulation, the
absorption of the poison may be hindered so much that it is not
taken up from the wound any faster than the kidneys can
excrete it. Thus the whole of it may be got rid of, without its
ever being able to produce any toxic effects whatever. If the
circulation be allowed to go on at all in the wounded part, it is
rather difficult to regulate it exactly enough to ensure that too
much poison shall not be absorbed at once. It is, therefore,
better to apply the ligature so tightly as to stop the circulation
altogether, and only remove it occasionally for a few seconds at
atime. In this way it is easy to control the absorption of the
poison by removing the ligature with more or less frequency,
and leaving it off for a longer or shorter period, as seems
advisable. But it is not by regulating the absorption of woorara
only that we are able to prevent its toxic action. Even when a
large quantity is circulating in the blood, and the animal seems
pertectly dead, recovery is still possible. ,

The woorara, curare, or ticunas poison—for it has all these
names and several more—has little or no action on either the
brain or the muscles; but, as Bernard has shown, it paralyses
the motor nerves; and so the rhythmical nervous impulses
which the medulla usually sends to the muscles of respiration
cannot be transmitted, and breathing ceases. Many years before

HYDROCYANIC ACID AND COBRA POISON. 81

Bernard’s experiments, however, Sir Benjamin Brodie* observed
that, in animals apparently killed by this poison, the heart con-
tinued to beat for a long time; and the idea occurred to him
that, if he could keep up respiration for a sufficient length of
time, the poison would be eliminated, and the animal com-
pletely restored. His first attempts were unsuccessful, but after
a little while he succeeded completely; and since then his
experiment has been so frequently repeated, that no physiolo-
gist can doubt that the complete restoration of an animal
poisoned in this way is merely a matter of time, unless the dose
has been so overwhelmingly great as to paralyse the heart. I
have myself twice restored to life rabbits which a dose of
-woorara had apparently completely killed, by keeping up arti-
ficial respiration in the one case for one, and in the other for
four hours; and in foreign laboratories I have seen them par-
tially restored, and only rendered motionless by repeated doses
of woorara, oftener than I can well recollect. Hydrocyanic acid
is amuch more dangerous poison than woorara; for it seems
not only to arrest respiration by paralysing the brain, spinal
cord, nerves and muscles, but also to stop the circulation by
destroying the power of the heart. The heart, however, is not
so soon affected as the respiratory organs ; and Brodie succeeded
in restoring animals poisoned by small doses of it given in the
form of oil of almonds.

The poison of the cobra di eapello resembles prussic acid
rather than woorara in the universality of its action ; for some
experiments which I made about a year ago in the laboratory of
Dr. Burdon Sanderson seem to show that it paralyses the spinal
cord, the motor nerves and the muscles themselves. The heart
also, as Dr. Fayrer and I have found, seems to be paralysed if
the dose be very large, as it may be also by an excessive dose
of woorara; but it almost always continues to beat for a long
time after respiration has ceased. To this fact I have drawn
particular attention in my appendix to Dr. Fayrer’s admirable
work on the Zhanatephidia of India. The same thing was
observed by Fontana (op. cit., tom. i, p. 80) in poisoning by the
bite of the viper, and by Weir Mitchell in poisoning by the

* Phil. Trans., 1812.

382 USE OF ARTIFICIAL RESPIRATION AND TRANSFUSION.

rattlesnake. Weir Mitchell* found that the heart might be
kept pulsating for a long time by means of artificial respiration ;
but his results do not seem to have been so encouraging as to
lead him to propose it as a means of saving life. Dr. Fayrer
and I have been more fortunate, and on one occasion we have
succeeded in keeping the heart of a rabbit beating for eight
hours after the animal was apparently dead. Nor had the heart
eeased to pulsate even then; but the hour was late, the room
was cold, the assistant was no doubt tired, and the experiment
was consequently given up. Although respiration had been
continued for a much longer time than is usually necessary with
woorara, the animal gave no signs of returning sensibility. This
seems to indicate a difference between the poisons. On the
probable cause of this, I shall have something to say in a later
part of this paper.

The service which artificial respiration renders in cases where
breathing has ceased in consequence of asphyxia, whether due
to drowning, strangling, or poisoning by carbonic acid in brewer's
vats or close rooms, is so generally recognised, that it is un-
necessary to say anything about it here. Its use in poisoning
by strychnia is not so well known, and, so far as I am aware,
has only been tested upon animals. Before I proceed to speak
of this, it may be well to say a few words in explanation of the
term apncea, which I shall have to use, as it is employed by
physiologists in a different sense from that which is attached to
it by many physicians. On the meaning of dyspnea, both
physicians and physiologists are agreed; and both apply it to
the violent respiratory efforts which occur when the blood is
imperfectly aérated. Apnoea, however, is not unfrequently used
by physicians in the sense of extreme dyspnea, where there is
excessive difficulty of respiration. Physiologists apply it to a
very different condition—viz., that in which the blood is so
excessively aérated that there is no need for breathing at all.
This will be much better understood by the reader if he will
try a simple experiment on himself. Let him note how many
seconds he can hold his breath, and he will find that he can
only do so for a very short time. Let him then quickly take

* Researches on the Venom of the Rattlesnake, 1861, p. 81.

STRYCHNINE—CARBONIC OXIDE. 383

several deep breaths, and repeat the experiment. He will now
notice that for several seconds more than on the first trial he
does not feel any inclination to breathe at all. This is the state
of apnoea as understood by physiologists. A few years ago, .
Rosenthal and Leube* discovered that, when rabbits were kept
in this condition by means of artificial respiration, a fatal dose
of strychnia might be injected subcutaneously without producing
any effect. When the respiration was discontinued, and the
animal was allowed to pass from the state of apnoea, convul-
sions came on even after the respiration had been kept up for
as much as three hours, If it were continued for three and a
half or four hours, however, the strychnia seemed to have
been destroyed or excreted, and respiration might be discon-
tinued without the occurrence of any convulsion whatever.
That the lives of the animals had really been saved by artificial
respiration was shown by the fact that they died when a similar
dose of strychnia was given to them some time afterwards, and
respiration was not used. A year afterwards, another of Rosen-
thal’s pupils—Uspensky—showedf that strychnia was not the
only poison the action of which could be prevented by artificial
respiration. The convulsive action of brucia, thebaia, and
caffeine was abolished in an exactly similar manner; but no
influence could be observed upon that of picrotoxin and nicotia.

The examples already given are sufficient to prove that life
may often be preserved by means of artificial respiration alone,
both in injury and in poisoning. If a man be found lying
insensible in a close room, poisoned by the fumes of a charcoal
fire, he can generally be restored by respiration if his heart be
still beating. But this is not always the case ; for the charcoal-
fumes contain carbonic oxide, which unites with the colouring
matter of the blood, and prevents it from taking up oxygen;
so that it may pass time after time through the lungs, and yet
remain venous. Itis true, that after a while the carbonic oxide
will be expelled from the blood, which then will become capable
of taking up oxygen as usual; but the heart may stop, and
all hope of recovery be lost before this can be effected, if the

* Reichert and Du Bois Reymond’s Archiv., 1867, p. 629.
t Op. cit., 1868, p. 522.

384 USE OF ARTIFICIAL RESPIRATION AND TRANSFUSION.

blood have been much changed by the deadly gas. In such eases,
the only hope lies in removing the poisoned blood, and replacing
it by healthy.

This does not by any means always succeed ; but occasionally
the recovery from impending death is almost miraculous, as ina
case where it was employed by Dr. Hueter (Berlin. Klin.
Wochensch., 1870, p. 341). The patient, who was a strong
young man, was living in a hotel, and one night had a fire
lighted in the stove of his room. Next morning he was found
perfectly unconscious, his iris and cornea quite insensible, and
his pulse small andrapid. His respiration was weak and inter-
mitting. Just as everthing was ready, and transfusion of blood
was begun, it failed altogether. Notwithstanding this, fresh
blood was allowed to stream into the patient’s radial artery;
the poisoned blood was drawn from a vein, and respiration was
kept up artificially. Gradually the pulse became stronger,
spontaneous respiratory movements again began, and the cornea
became sensitive. In about five hours consciousness returned,
and in a few days health was completely restored. Except-
ing the veritable resurrection of which Legallois speaks,
what can be more wonderful than the recovery from impending
death just related? Aud, if the joint use of artificial respira-
tion and transfusion is so successful in one case of poisoning,
there seems to be no reason why it should:not be so in all. In
strychnia-poisoning, for instance, where the quantity absorbed
has been too great, and death is impending, notwithstanding
the use either of chloroform or of artificial respiration, part of
the poison might be removed by abstracting some of the blood
in which it was circulating, and fresh blood supplied. If con-
vulsions were occurring constantly, transfusion would be nearly
impossible, but they might be stopped either by much chloro-
form or by woorara. I have already mentioned that woorara is
excreted rather quickly by the kidneys; and, consequently,
artificial respiration for a few hours is usually sufficient to
restore animals which have been poisoned by it.

Let us suppose it, however, to be slowly excreted. Many
hours, or even days might then elapse before the whole of it
could be got rid of ; and the maintenance of artificial respiration

_— =~

a

USES IN SNAKE BITE, 385

for such a length of time might be impossible. In such a case
as this, the obvious plan of treatment would be, of course, to
remove the poison along with the blood in which it was circu-
lating, instead of waiting for its slow removal by the emunc-
tories.

Now, it appears to me that this is the case in poisoning by
the bites of snakes, and this the treatment which must be
adopted. We must combine artificial respiration with trans-
fusion. The experiments of Dr. Fayrer show that the poison of
the cobra is circulating in the blood of an animal which has
been bitten by it; for this blood will kill another animal when
injected into it. From those of Fontana, it would seem that
the poison of the viper is eliminated from the body; for pigeons
did not die if a ligature were placed on the bitten limb, above
the place where the wound had been inflicted, and removed
after some time. Fontana thought that the poison had been
destroyed in the limb, but was evidently puzzled about it, for
some of his other experiments had shown him that mixing it
with blood did not destroy its virulence. He imagined that he
had completely stopped the circulation in the injured limb; but
_ it is more probable that he had only partially done so, and that
the poison was thus slowly absorbed from the limb, and, being
excreted equally quickly, did the creature no harm. If this expla-
nation of his experiments be not correct, it is difficult to under-
stand why poisoning did not occur when the ligature was removed,
as Waterton found to be the case in some similar experiments
which he had tried with woorara. So long as the ligature was.
tight, the woorara remained confined to the limb ; but as soon as
the circulation was allowed to go on, the poison was absorbed,
and the animal died. This may seem to be in direct contradic-
tion to what I have already said regarding the probable com-
parative slowness of the excretion of snake-poison to that of
woorara; but it must be observed that Fontana waited a much.
longer time before he untied the ligatures than Waterton did,
and would thus allow a much larger proportion of the poison
to be excreted. It must be noted also that the poison with
which he experimented was that of the viper and not of the
cobra, and there may be considerable differences in the facility

20

386 USE OF ARTIFICIAL RESPIRATION AND TRANSFUSION,

with which they are excreted. It is, however, possible that I
am mistaken in supposing that cobra-poison is more slowly.
excreted than woorara, as the facts on which I base the suppo-
sition are simply that the poison of the cobra, introduced into the
- stomach, seems to produce death more readily than woorara
would do, and that animals poisoned by it may be kept alive
for a longer time by artificial respiration without ultimately
recovering. The poison of the viper, on the other hand,
according to Fontana, may be swallowed, in moderate quantity
at least, with impunity, though it also occasionally kills when
taken in this manner, as woorara likewise does when the
quantity is great and the stomach empty, so that absorption is
rapid. | | a
Enough has now been said to show the possible use of trans-
fusion, combined with artificial respiration, not only in poisoning
by carbonic oxide, but by strychnia and other poisons, Its |
employment in collapse from hemorrhage requires no remarks
at present. But, in order to make such a method serviceable, ;
it must be easily performed, and a supply of blood easily got.
Now, I believe that a very simple apparatus indeed will serve
‘the purpose of transfusing defibrinated blood. But how is a
sufficient supply to be got ? for it is evident that a considerable
quantity may be required. The requisite quantity of human
blood in most cases can hardly be obtained; but it has been
experimentally shown that the blood of lambs and calves may
be transfused into the blood-vessels of man without doing him .
any harm. |

Two hundred years ago, an objection was raised to this
method of proceeding by Laury (Revue des Deux Mondes,
January, 1870, p. 393), who said that, as the blood of a calf or
of any other animal whatever is composed of several different
particles fitted to nourish the different parts of the body, what
is to become of the particles which were destined to produce
horns? And, if the blood of a calf be transfused into the veins .
of a man, as the disposition and habits usually accord with the \
temperament, will the blood of the calf not give the man the )
stupidity and brutal inclinations of this animal? Here we
almost seem to have Darwin’s theory of pangenesis; and, if

Pa ee

OBJECTIONS TO TRANSFUSION 387

____ this theory be true, are not Laury’s objections well founded?
_ As far as man is concerned, it may be difficult to give a positive
answer either in the affirmative or the negative ; but the experi-
= ments which Mr. Galton has made on rabbits, for the express
__ purpose of testing Darwin’s theory, show that in these animals
| 4 | transfusion has no effect either on the animals themselves or on
| their progeny. We may therefore, I think, safely conclude
that the risk of injuring a man’s character, or that of his
| descendants, by transfusion of an animal’s blood, is not for an
instant to. be weighed in the balance against the chance of
saving his life in those cases where alone the operation would
be performed. |

2c 2

VERANDERTE WIRKUNG ZWEIER ARZNEI-
MITTEL, WENN SIE GLEICHZEITIG IN DEN
ORGANISMUS EINGEFUHRT WERDEN.

(From the Centralblaté der medicenischen Wissenschaften, September 27,
1873, p. 689.)

DIE ausgezeichneten Untersuchungen von Crum Brown und
Fraser haben dargethan, dass ein Alcaloid, welches vor seiner
Einfiihrung in den thierischen Organismus eine Verbindung
mit einem anderen Korper eingegangen ist, eine veriinderte

Wirkung aussert. So weit mir bekannt, ist bis jetzt von einer

ahnlichen Modification, hervorgebracht durch die vereinigte
Wirkung zweier Arzneimittel innerhalb des Organismus, Nichts
veroffentlicht worden.

Ich habe eine solche in letzter Zeit an salpetrigsaurem Amyl-
oxyd und Strychnin beobachtet. Diese 2 Arzneimittel bringen,
wenn sie gleichzeitig wirken, Lahmung der motorischen Nerven
hervor. Das betreffende Experiment wird in folgender Weise
ausgefiihrt. Ein Frosch, in dessen Riickenlymphsack Strych-
ninlésung injicirt worden, wird, sobald Tetanus eingetreten, in
ein mit Diaimpfen des salpetersauren Amyloxyds gefiilltes
Gefiiss gebracht. In dasselbe Gefiiss wird ein gesunder Frosch
als Vergleichsthier eingefiihrt. Beide Frésche verbleiben
daselbst, bis sie bewegungslos sind. Wenn hierauf der Nv.
ischiadicus blosgelegt und gereizt wird, so treten in dem nur
durch salpetrigsaures Amyloxyd vergifteten Frosche heftige
Contractionen der Extremitit ein, waihrend in dem anderen
. Frosche dies nicht der Fall ist, obgleich seine Muskeln auf
-directe Reize sich contrahiren. Ein ahnliches Resultat wird
' beobachtet, wenn vor der Vergiftung mit Strychnin und salpe-
trigsaurem Amyloxyd die Circulation der Extremitit durch eine
oberhalb des Kniegelenks angebrachte Ligatur, mit Ausschluss.
des Ny. ischiadicus, aufgehoben wird.

Obgleich nach Paralyse der motorisuhen Nerven die Muskeln

i A

SALPLTRIGSAURES AMYLOXYD UND STRYCHNIN. 389

ihre Reizbarkeit be:behalten, so waren se dennoch sehr rasch
todtenstarr, sowohl nach der gleichzeitigen Anwendung beider
Arzneimittel, als auch, wenn salpetrigsaures Amyloxyd allein
angewendet wurde. Salpetrigsaures Amyloxyd sowie andere
salpetrigsaure Verbindungen sind deshalb als Muskelgifte zu
betrachten. Es ist nicht leicht zu entscheiden, wie viel von der
Paralyse der directen Wirkung auf das Ende der motorischeo
Nerven und wie viel der Abnahme an Irritabilitiit der Muskel-
substanz zuzuschreiben ist. Ich hoffe binnen Kurzem in der
Lage zu sein, meine Experimente iiber die Wirkung des Strych-
nins in Verbindung mit anderen Kérpern sowie iiber die
Wirkung der salpetrigsauren Verbindungen zu veroffentlichen.

ON THE APPARENT PRODUCTION OF A
| NEW EFFECT BY THE JOINT ACTION OF ©
DRUGS WITHIN THE ANIMAL ORGANISM. |

(From the Journal of Anatomy and Physiology, November, 1873, vol. viii,
». 94.)

THE admirable researches of Crum Brown and Fraser have
demonstrated that the physiological action of several alkaloids |
may be completly altered by their union with such bodies as
iodide of methyl. The compounds thus produced sometimes :
act on. organs which do not appear to be affected by either of j
the, components separately, the ends of the motor nerves for
example being paralysed by iodide-of-methyl-strychnia, though
neither iodide, of methyl alone, nor strychnia alone, seems to
have much influence over them. Although chemical action
outside the body alters in this way the action. of alkaloids, I
am not aware that any instance has been noticed in which a
similar modification appears to be produced by the joint action
of two drugs after their introdaction into the animal organism.
I have lately observed an example of this sort in the case ot
strychnia and nitrite of amyl. The experiments which I made
on this subject were performed in several ways, but I will only
describe the two most important. In the first series of experi-
ments a solution of strychnia was injected into the dorsal
lymph sac of.a frog, and as soon as tetanus came on the
animal was put into a vessel filled with the vapour of nitrite q
of amyl. A second healthy frog was also introduced along

with it for the purpose of comparison. They were left in the

vessel till both were motionless, when they were removed and

the sciatic nerves of both were exposed. On irritating these

nerves by the application of a Faradic current, vigorous con-

tractions occurred in the limbs of the frog poisoned by nitrite

of amyl alone, but those of the animal poisoned by strychnia —
and nitrite of amyl together remained motionless. The skin

a

ey

See

NITRITES AND STRYCIININE. 391

was then removed from the legs of both and the muscles
irritated by the application of the current directly to them.
In many instances, those of the frog poisoned by the nitrite and
the strychnia together contracted nearly as strongly and readily
as those poisoned by the nitrite alone. It is therefore evident
that their failure to contract when the nerves were stimulated
must have been due to paralysis of the nerves themselves, just
as it is in poisoning by woorara. The second series of experi-
ments was made by ligaturing the artery supplying one leg of
a frog before injecting strychnia into the lymph sac. The
poison was thus carried by the blood to every part of the
body except the leg whose artery had been tied. The animal
was then placed in a vessel filled with the vapour of nitrite
of amyl as before, and after motion had ceased the sciatic
nerves were exposed and irritated. It was then found that
the muscles of the ligatured leg which had been exposed to
the nitrite of amyl, but preserved from the strychnia, con-
tracted vigorously when the corresponding sciatic was irritated,
while those of the other leg did not respond at all. When the
skin was stripped off, however, and the muscles irritated directly,
in many instances no great difference could be noted between
their irritability.

The muscles of frogs which had been poisoned either with
strychnia and nitrite of amyl, or with nitrite of amyl alone,
passed more quickly than usual into a state of rigor mortis;
and I therefore regard nitrite of amyl as a muscular poison.
It is not improbable that the apparent paralysis of the motor
nerves may be partly due to diminution of the irritability of
the muscle itself, but the results of direct stimulation show
that this is not sufficient to explain it entirely, and we must
therefore believe that the nerves themselves are also paralysed: °
Besides nitrite of amyl, I have tried the nitrites of sodium,
ethyl, butyl and capryl; but my researches on these are not
yet completed. They seem, however, to show that the nitrites
are muscular poisons, but their actions differ according to the
bases which they contain.

ON THE PATHOLOGY AND TREATMENT OF
SHOCK AND SYNCOPE.

(Address read before the Abernethian Society, St. Bartholomew’s Hospital.
Reprinted from the Practitioner, vol. xi, p. 246, Oct. 1873.)

THE assemblage of phenomena which we designate by the term
“shock” is so much more frequently met with in surgical than
in medical practice that it may almost seem that in writing a
paper on this subject I have left the proper domain of the
physician, and trespassed on that which the surgeon claims as
his own. We shall hereafter see, however, that shock may
occur in the course of diseases for which the physician alone is
called into consultation, and it is intimately connected with
fainting or syncope, a condition which is usually treated of in
medical rather than in surgical text-books. So closely, indeed,
are syncope and shock connected that they were considered by
the celebrated surgeon, Travers,* to differ in degree rather than
in kind, and we shall find it convenient to take a glance at the
conditions which we find in syncope, before we proceed to
examine those of shock.

I shall divide this paper into three parts. First, the injuries
or impressions on the nervous system which occasion syncope
and shock, and the symptoms which are observed in these con-
ditions ; Secondly, the causes of each symptom ; and Thirdly, the
remedies used and their mode of action. To put them shortly,
these three heads are: 1. Zhe symptoms and causes; 2. The
pathology ; and 3. The treatment of shock and syncope.

As I have already said, it will be convenient to consider the
symptoms of syncope before those of shock. Having had little
surgical experience myself, I shall quote very freely from the
works of others ; and the first case I shall give is one taken,
not from a scientific work, but from the pages of a popular
religious periodical. I cannot even vouch for the historical

* Treatise on Constitutional [rritation, 1826, p. 466.

,
tee, vi bil ali Gielen a ee ee

_

TERT ORS Te ee

SYNCOPE AND DEATH FROM PAIN. 393

truth of the narrative, and yet I choose this case because we

have records of numerous other ones which resemble it so much
in one or more particulars, that we can hardly doubt the sub-
stantial accuracy of the description ; and owing to the peculiar
circumstances under which the events are said to have taken
place, we find in this one instance all the phenomena which we
would otherwise have to seek for, some in one case, some in
another.

During the reign of Charles or James the Second, one of the
Scottish Covenanters, named John Bruce, concealed himself from
the dragoons who were in search of him at some little distance
from his cottage, and his little daughter Alice was accustomed
daily to visit him with a supply of provisions. One day, while
on this errand, she was unhappily discovered and seized by the
dragoons, who at once guessed her purpose from the food she
was carrying, and declared that unless she informed them of the
place of her father’s concealment they would torture her with
thumb-screws. She refused, and the instruments were accord-
invly applied. Scarcely, however, had a few turns of the screw
been made, when her face became deadly pale, and she féll back
insensible. The screw was at once undone, water from a neigh-
bouring rivulet was dashed in her face, and after a deep sigh
or two the paleness disappeared and consciousness returned.
Again the dragoons demanded her secret, adding the threat that
they would not let her off so-easily this time. Again she

refused, and the dragoons, irritated by her obstinacy, by a few

rapid turns of the screw nearly crushed her thumbs between

the jaws of the instrument. A second time the deadly pallor
-overspread her face, and unconsciousness relieved her pain.

This did not suit the purpose of the dragoons, and they again
sought to restore her as before. But this time all their efforts
were unavailing; the heart had ceased to beat, and the poor
child was dead.

Here we have a typical instance, first of fainting, then of
death by syncope, following the infliction of intense pain alone,

without any injury whatever to the vital organs. Sometimes

death may occur from an impression on the nervous system
without even pain being felt, as in a case recorded by Sir Astley

394 PATHOLOGY AND TREATMENT OF SHOCK AND SYNCOPE.

Cooper in his lectures on surgery.* “A healthy labourer be-
longing to the India House was attempting to lift a heavy weight,
when another labourer came up and said, ‘ Stand on one side;
let an abler man try.’ At the same time he gave the former a
slight blow on the region of the stomach, when the poor fellow
immediately dropped down and expired. On examination of
his body there was not any mark of violence discovered.”
This may be regarded as a typical instance of instant death
from shock, but cases like it are comparatively rare. Usually
the injury is succeeded by a period of depression of all the
vital functions, and this may either end in death, pass into a
state of excitement, or gradually disappear and give place at
once to health without any intervening excitement.

The symptoms ordinarily observed in shock are well illus-
trated by a case which Professor Fischer has described in a
clinical lecture on this subject.— From this I have made the
following extracts:—‘The patient, a strong and perfectly
healthy young man, was struck in the abdomen by the pole of
a carriage drawn by runaway horses. No serious injury was
done to any of the internal organs, at least we have not been
able after a careful examination to find any trace of one.
Nevertheless, the grave symptoms and the alarming look which
he still presents made their appearance immediately after the
accident. He lies as we see perfectly quiet, and pays no atten-
tion whatever to anything going on around him. His coun-
tenance is sunk and peculiarly elongated, his forehead is wrinkled,
and his nostrils dilated. His weary, lustreless eyes are deeply
sunk in their sockets, half-covered by his drooping eyelids, and
surrounded, by broad, dark rings. The pupils are dilated, and re-
act slowly to the light. He stares purposelessly and apathetically,
straight before him. His skin and such parts of the mucous
membranes as are visible are pale as marble, and his hands and
lips have a bluish tinge. Large drops of sweat hang on his
forehead and eyebrows. His whole body feels cold to the hand,
and a diminution in temperature is readily detected by the
thermometer, which indicates a degree and a half in the axilla,

* Lectures on Surgery, from notes by Tyrrell, 1824, vol. i, p. 10.
t Volkmann’s Sammlung Klinischer Vourtrdge, No. 10.

—— ee he eS ve

SYMPTOMS OF SHOCK. 395

and a degree centigrade in the rectum, below the normal.
Sensibility is much blunted over the whole body, and only
when a very painful impression is made on the patient does he
fretfully pull a wry face and make a languid defensive movement.
He does not move a single limb spontaneously, but after being
repeatedly and urgently requested, he shows that he can still
execute limited and brief movements with his extremities.
If the limbs are lifted and then let go, they immediately fall as
if dead. The sphincters remain closed in our patient, at least
passage of urine and feces has not been noticed since he came
into the hospital. When drawn off with the catheter, the urine .
is found to be scanty and dense, but free from any traces of
sugaror albumen. ‘The pulse is almost imperceptible, irregular,
unequal, and very rapid. ‘The arteries are small, and the tension
very low While the patient was being brought to the hospital
the pulse became quite imperceptible, and the cardiac sounds
very irregular and intermittent. The patient is perfectly con-
scious: he replies very slowly and only when repeatedly and
importunately questioned, but his answers are quite to the point.
You heard how he gave the details of the accident reluctantly
and imperfectly, but in the main correctly Only while he was
being brought to the hospital did he refuse to answer at all.
His voice is hoarse and weak, but his articulation is good. On
being repeatedly questioned the patient complains of cold,
faintness, formication and deadness of the extremities. When
he shuts his eyes he becomes sick and giddy. THis senses are
perfectly acute. His respiration appears to be irregular, and
abnormally long, deep and sighing inspirations alternate with
very superficial ones, which are scarcely visible or audible.
While being brought to the hospital he vomited several times,
and nausea and hiccup still remain. Anyone who knew the
patient, or had seen him shortly before the accident, could hardly
recognise him now. His appearance, cold skin, and hoarse voice
immediately recall the appearance of a cholera patient to the
memory of the attentive observer ; the characteristic dejections
are alone wanting to make the resemblance complete.”

But cases of shock do not always present these appearances.
If we call the form just described the torpid one, we can readily

395 . PATIIOLOGY AND TREATMENT OF SHOCK AND SYNCOPE.

distinguish from it another erethismic form which Travers terms
“prostration with excitement.’* The countenances of patients
suffering from it are distorted, and express a nameless anxiety
and excruciating agony. They toss wildly about, groan and
scream, and complain of a fearful oppression and want of breath,
oppressive presentiments of death, and a feeling of total anni-
hilation. No encouragement is of any use; they lament and
behave themselves like madmen. The consciousness of these
sleepless and restless patients is unclouded, but seems to be
completely engaged by the frightful anguish. On this account
they answer no questions, but only sigh and moan. They mur-
mur to themselves, and pay no attention to what is going on
around them. Such parts of the mucous membranes*as are
visible are pale, but the countenance, on the contrary, is slightly
flushed, and the forehead hot; the eyes are sunk, but have a
peculiar lustre, and the pupils are contracted. The skin of the
extremities is generally cool and insensible, but not to the same
degree as in the torpid form of shock seen in the case of the
patient already described. Occasionally no coldness is percep-
tible. Vomiting of quantities of mucus and painful retching are
constant and very obstinate symptoms of this form of shock.
Burning thirst is present, and liquids are greedily swallowed,
but no sooner are they down than they are again rejected.
Every movement is made hastily and accompanied by a remark-
able trembling. Occasionally all the limbs shiver as in a rigor,
and the patient has no power to control the movement. A
wounded officer in this condition repeatedly requested me, says
Professor Fischer, not to consider it as a sign that he was afraid.
Convulsive movements, and fibrillary twitchings of the muscles,
and especially of those in the face, are observable. The respira-
tion is frequent and superficial, the pulse small, and cannot be
counted.

Both these forms of shock may occur independently, but
there is a certain connection between them. Patients recovering
from the torpid form may come gradually to present the symp-
toms of the erethismic, and vice versd, when the condition

becomes worse, the torpid may be developed from the
* Travers, op. cit., p. 407.

<a

oe oe

a

CAUSES OF SIIOCX. 397

erethismic form. The latter is then to be regarded sometimes
as an independent condition, and sometimes as a second stage
of the torpid form.

Both forms of shock sometimes terminate in death, while at
other times, according to Mr. Travers,* instead of the continu-
ance and fatal increase of the symptoms of prostration, they
may gradually give place to a partial and defective reaction,
protracting life but scarcely improving the prospect of restera-
tion, which remains doubtful for several days in succession ;
or, on the contrary, an efficient and healthy degree of reaction
may be quickly established consequent upon symptoms threat-
ening the most unfavourable issue. “ Again and again,” he
continues, “I have left the bedsides of patients brought into the
hospital pulseless, and apparently moribund without any exter-
nal injury, having suffered falls or blows so serious as to have
induced the symptoms of prostration to an alarming extent,
and have found them on the succeeding day, to my great
surprise, restored-to the tone and tranquillity, comparatively
speaking, of health. Reaction has in these cases been spon-
taneous, or nearly so, although gradual enough to occupy a
period of many hours.” “Now, had such persons suffered
topical injuries of a severe though reparable description, it
is to my mind more than probable that reaction would have
failed altogether ; but had it, by favour of circumstances, been
established, it is at least equally probable that it would have
taken the form of excitement. In other cases days have
elapsed before a perfect reaction and complete relief have been
obtained.”

Having said so much regarding the symptoms of shock, let
us shortly run over its causes. The cases already related
show us that it readily follows a blow on the abdomen, some-
times even when the blow is by no means severe. Injury to
the genitals is another important cause of shock. Hardly
anyone finishes his school days without receiving a blow on
the testicies, either at cricket or during the struggles at foot-
ball, and ever afterwards he bears vividly in mind the dreadful
depression, weakness and sickness which instantly overpowered.

* Travers, op. cit., p. 409.

398 PATHOLOGY AND TREATMENT OF SIIOCK AND SYNCOPE.

him. The same thing takes place in operations, and Mr.
Erichsen* has observed that at the moment of division of the
spermatic cord in castration the pulse sinks, even though
the patient has been fully anesthetised. Still more striking are
the effects occasionally observed on the passage of a catheter
or bougie. They are thus described by Sir Astley Cooper :f “A
person has a bougie passed into his urethra for the first time;
the urethra is irritated by it; he says, I feel faint,’ becomes
sick, looks pale, and, without care, he drops at your feet. His
pulse has nearly ceased, and his body is covered with a cold
perspiration. You place him on a sofa with his head a little
lower than his body, and as soon as the blood freely enters the
brain all his functions are restored. Thus, by irritating the
urethra the stomach is influenced, the actions of the head and
heart are suspended, and the powers of the mind vanish.”

Injuries to bones have a peculiar power to induce shock.
It is, perhaps, more frequently observed as a consequence of
the crushing of bones in railway accidents than of any other
cause whatever. It may be said that in such cases all the
textures of the limb, skin, fascia, muscles, vessels and nerves are
injured as much as the bones, but two cases of Pirogoff’st seem
to show that it is to injury of the latter rather than of the
former structures that the effect is to be attributed.

In two amputations of the thigh which he performed, before
the introduction of chloroform, death occurred on the operating
table. One case was for severe traumatic injury, the other for
chronic disease of the knee-joint, which had greatly weakened
the patient. In both cases the pain and loss of blood during
the operation were only a little greater than usual, yet in both,
immediately after the bone had been sawn through, the face
became pale, the eyes staring, the pupils dilated, a peculiar
rigidity of the body occurred and death immediately took place.

Extensive burns frequently cause shock in a marked degree,
and such, says Mr. Travers,§ is the effect of the transient bodily

* Science and Art of Surgery, 4th edit., p. 6.

+ Lectures on Surgery, from notes by Tyrrell, 1824, vol. i, p. 9.
+ Quoted by Fischer, op. cit., p. 10.

§ Travers, op. ctt., p. 74

i i i

PEATH FROM FRIGUT. 399

pain experienced in the extraction of a tooth, or the extirpa-
tion of a wart or corn, as in some persons to produce syncope,
retching, or convulsions. Nor must the effect of mental
emotion be left out of account, as this is sometimes sufficient
of itself to cause death without any injury to the body what-
ever. Many years ago the janitor of King’s College, Aberdeen,
had rendered himself in some way obnoxious to the students,
and they determined to punish him. They accordingly pre-
pared a block and axe, which they conveyed to a lonely place,
and having dressed themselves in black, some of them prepared
to act as judges, and sent others of their company to bring him
before them. When he saw the preparations which had been
made he at first affected to treat the whole thing as a joke,
but was solemnly assured by the students that they meant it
in real earnest. They proceeded to try him, found him guilty,
and told him to prepare for immediate death, for they were
going to behead him then and there. The trembling janitor
looked all round in the vain hope of seeing some indication
that nothing was really meant, but stern looks everywhere
met him, and one of the students proceeded to blindfold him.
The poor man was made to kneel before the block, the execu-
tioner’s axe was raised, but instead of the sharp edge a wet
towel was brought smartly down on the back of the culprit’s
neck. This was all the students meant to do, and thinking that
they had now frightened the janitor sufficiently, they undid the
bandage which covered his eyes. TJ’o their astonishment and
horror they found that he was dead.

Another case is related by Mr. Travers,* who saw a man
suffering from strangulated hernia expire suddenly on the table
during the steps preliminary to the operation which, from the
state of the symptoms and of the bowel as ascertained by
examination after death, might be said to afford the fairest
prospect of relief.

The cases of shock of which we have so far spoken are
perhaps more likely to come under the notice of the surgeon
than of the physician. The state of shock, or collapse as it is
more frequently called in medical practice, occurs when the

# ‘Travers, up. cit., p. 23.

400 PATIIOLOGY AND TREATMENT OF SHOCK AND SYNCOPE,

abdominal viscera are injured from within, just as when they

receive a blow from without. Thus the intense irritation which
corrosive poisons, such as sulphuric and other mineral acids,
or large doses of arsenic, occasion in the stomach, produces, in
addition to local pain, coldness and pallor of the surface,
sighing respiration and weak or imperceptible pulse. The
same thing occurs when perioration takes place in the stomach
or intestines, and their contents escape into the peritoneal
cavity. The occurrence of shock after parturition, especially in
cases of twins, is probably partly due to nervous influence and
partly to the removal of pressure from the abdominal vessels
by the loss of such a large portion of the abdominal contents,
which must almost unavoidably occasion more or less relaxa-
tion of the vessels.

To recapitulate shortly what we have said under this head,
the symptoms of shock are: pallor and coldness of the skin,
weak pulse, oppressed and sighing respiration, dilated pupils
and sickness.

The causes of shock are: painful impressions—more espe-
cially extensive burns—injuries to bones, and, above all, injuries
to the abdominal viscera and genitals.

We have now to consider our second head, viz.: Zhe pathology
of shock; or, the causes of each symptom. I ought properly to
take up every one and trace it back to-its cause, but I shall
not attempt to do this, because it would occupy toc much time,
and I am not sure I could at present succeed in the attempt.
I shall, therefore, be content to glance at a few of the principal
symptoms only.

And first :—Why should the pulse be small and weak and
the tension in the artery low, so that a slight pressure with the
finger is sufficient to compress its walls and completely arrest
its pulsations? The smallness of the pulse wave under such
conditions at once informs us that only a little blood is sent
into the arteries at each contraction of the heart. This may be
owing to the heart acting so feebly and imperfectly that it only
sends out a small portion of the blood with which its cavity
was filled, or it may be that it is doing its duty perfectly but
has no blood to send out, It would be very hard to say which

SS ey

GOLTZ’S EXPERIMENTS. 40}

of these two causes is the true one, or whether they do not
both share in the production of shock, if we had not experi-
ments on the lower animals to give us some clue to the true
solution. Several years‘ago Professor Goltz, now of Strassburg,
found that on striking the abdomen of a frog several times
the heart stopped altogether.* After a short pause it again
went on, but instead of becoming completely full during each
diastole, and sending a large volume of blood into the arteries
at each systole, it remained pale and empty; no blood at all,
or hardly any, flowed into it during the diastole, and conse-
quently it could not send any into the vessels when it did
contract, and it might just as well have remained motionless.
On looking for the blood that ought to have been supplying
the heart, he found that it was stagnating in the vessels of the
abdomen, and especially in the veins. The intestinal vessels
are so capacious that when they are fully dilated they can
h:old all the blood in the body. Normally, however, they are
kept in a state of partial contraction by the influence of the
vaso-motor nerves which supply them. It used to be supposed
that these nerves only went to the arteries, and that these alone
were capable of contraction and relaxation, but Goltz found
that the veins also were supplied by vaso-motor nerves, and
that they too could contract and dilate, though to a less extent
than the arteries. Whenever the power of the vaso-motor
nerves was destroyed, both arteries and veins dilated and held
so much blood that there was not sufficient left to keep up the
circulation in the rest of the body. If the frog was held in the
upright position no blood at all reached the heart, but if it was
laid horizontally a little blood trickled into the heart, and the
circulation was thus kept up, though very weakly.
Here, then, we have in the frog the same effects produced by
a blow on the abdomen as in the case of the young man who
was struck by the carriage pole, with this difference, that in the
man we could only feel the weakness of the pulse, while in the
frog we can see why it is weak. Professor Fischer says that
the best and shortest definition of shock which has yet been
given is that of Mr. Savory :—“Shock is the paralysing influ-
* Virchow’s Archiv, vol. xxvi, 1863, p. 11, and vol. xxix, 1864, p. 394,
2D

402 PATHOLOGY AND TREATMENT OF SHOCK AND SYNCOPE,

' ence of a sudden and violent injury to nerves over the activity
of the heart.” The experiments of Goltz show that this defini-
tion is perfectly correct, but you must not forget that there are
the two factors in shock as seen in the frog. First, the stoppage

Fie. 152.—Diagram to illustrate the Effects of the Horizontal and Vertical
Positions on the Circulation of the Frog in Shock.

ase

= c

a. Normal circulation in the upright position. 6. Circulation after dilatation of
the veins has been produced by a blow on the intestines. The blood does
not reach the heart, and it beats empty, so that the circulation stops.
e shows the circulation in a horizontal position after the veins have been
dilated, as in 6. The veins are still dilated, but the blood reaches the heart,
and the circulation is carried on. Fig. ¢ is perhaps too diagrammatic, as is
appears to show an empty space in the veins. In reality the veins, being
very thin-walled, collapse. Fig. is open to the same objection, but if we
suppose ourselves to be looking at the vein from the front instead of in
section, 6 represents almost exactly what I have seen myself in repeating
Goltz’s experiment. This diagram was not in the original paper, but is
taken from my Teat-Book of Pharmacology, &c.

of the heart; and second, dilatation of the vessels. Zhese are
quite distinct, and I have frequently observed that blows of
moderate severity will produce in some frogs stoppage of the heart
without dilatation of the vessels, in others vascular dilatation
without arrest of the cardiac pulsations, although severe blows
generally produce both.*

The pallor of the surface and the coldness of the skin are the
next symptoms which engage our attention, and what we have

just learned regarding the circulation will render their explana-

tion easy. The rosy flush of health is due simply to the red
colour of the blood shining through the skin as it courses
through the capillaries, and whenever the circulation is stopped,
either by the vessels contracting as after exposure to coid, or by
the blood stagnating in the abdomen as in shock, pallor over-
spreads the surface. The warmth of the external parts of the
body is due to the warm blood from the interior, which heats

* Results of a series of unpublished experiments.—T. L. B.

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AV TOR a ee

PATHOLOGY OF FAINTING. 403

them in the same way that rooms are warmed by hot-water
pipes, and whenever the circulation ceases there is nothing
to prevent the surface of the body being cooled down to the
temperature of the surrounding medium, and such, in fact, does
take place. The lividity or blueness which is occasionally
observed is due to the biood in the capillaries becoming dark
and venous as it flows sluggishly through them, or even stag-
nates in them altogether when the circulation is very weak. I
shall at present say nothing about the respiration or sickness,
but pass on to consider the insensibility which we find in
syncope though not in shock, and which distinguishes the
former from the latter. |

The functions of the brain, on whose failure insensibility
depends, require for their performance a constant supply of
blood, and when this is cut off they at once cease. A year or
two ago Dr. Waller proposed to produce temporary anesthesia
for short operations by compressing both carotids, or, in fact,
earotting the patient; and I have been informed by my friend
Mr. Image, of Bury St. Edmunds, that in Baron Larrey’s
H6pital du gros Caillou, in Paris, it was the usual custom, before
the introduction of chloroform, to lay a patient on his back and
then to lift him up very suddenly to the standing posture, when-
ever they wished to induce fainting for the purpose of relaxing
muscles in cases of dislocation. The vessels of the patient were
carrying on the circulation all right while he was in the hori-
zontal position, but they had not time to adapt themselves to
the altered conditions when the man was placed upright, and so.
the blood ran to the depending parts of the body, and the brain
was left without it.

But why should a fainting fit, which, apparently, is more
severe than shock, inasmuch as the brain also has ceased to act,
and the patient is thus rendered more deathlike, be quickly
recovered from, while shock lasts for many hours? This is a
question difficult to answer, inasmuch as the necessary data fail,
and we are forced to fall back on hypothesis. In attempting to
answer it we must remember that it is not really the heart’s
action which keeps up the circulation directly. It is the
pressure of the blood inside the arteries forcing it on through

2D %

404 PATHOLOGY AND TREATMENT OF SHOCK AND SYNCOPE.

them, and, es Goltz’s experiment shows, the heart may be pul-
sating and yet the circulation be at a standstill. Now, the
arterial tension may be lessened (1) by the heart stopping, or
(2) sending little blood into the arteries at each beat, or (3) by
the arterioles dilating so as to let the blood easily out from the
arteries into the veins, where it may stagnate and be useless.
Another point we must remember is that it is the circulation in
the brain which is the important factor in producing insen-
sibility. In the patient who was suddenly lifted on his feet the
circulation in the rest of the body was going on perfectly well ;
it only failed in the brain.

Now, it is very easy to bring down the blood-pressure very
much by stopping the heart for a few instants, and it may take
a little while before it rises to its normal condition. A second
way is to dilate the arterioles, and if the arterioles be dilated at
the same time that the heart is stopped, the pressure will fall
with great rapidity, and, when the heart again begins to beat, it
will take a much longer time to raise the pressure sufficiently to
carry on the circulation than it would otherwise do. Now,
when a painful impression is made on a sensory nerve, it is not
unfrequently carried up to the medulla oblongata, where it is
transferred to the vagus nerve, which, as you know, has the
power of stopping the heart, and by setting this nerve into
action arrests the cardiac pulsations. If the arterioles should
happen to be dilated, as they almost always are in a warm
room, the pressure of blood in the arteries immediately sinks,
the brain getting an insufficient supply ceases to act, and the
patient falls down unconscious. The very fact of the head being
lowered induces more blood to pass to it, and the normal con-
dition is at once in many cases restored.

The condition of the vessels in fainting has not been ascer-
tained, and the only observation bearing on the subject that I
can find is one by John Hunter.* While engaged in bleeding
a lady she fainted, and during the continuance of the faint he
observed that the blood which flowed from the vein, instead of
being dark and venous, was of a bright scarlet colour, like that
of arterial biood. Now, the only condition in which we know

* Works of John Hunter, edited by Palmer, 1837, vol. iii, p. 91.

:
|
.

DILATATION OF ARTERIES IN MUSCLES. 405

this to take place is when the arterioles are greatly dilated, and
the blood flows so quickly through them that there is no time
for it to be deprived of oxygen during its passage. This 1s seen
in the submaxillary gland during irritation of the chorda
tympani nerve,and it was observed by Meyer,* the celebrated pro-
pounder of the doctrine of conservation of energy, in persons
whom he bled in the tropics, and who had their vessels dilated
in consequence of the heat ; and it was also noticed by Crawfordt
in animals bled during immersion in a warm bath. It would
therefore seem that in fainting the vessels of the external parts
of the body are occasionally, at least, widely dilated, and this
explains the frequency with which persons faint in warm rooms
and crowded churches. I am inclined then to suppose, that in
fainting there is dilatation of the vessels in the external parts of
the body, although the data on which I found my opinion are
too imperfect to allow of my speaking very positively on the
subject. If you examine the veins on the back of your hand
in a crowded assembly, such as people often faint in, you will
probably find them very full, indicating that blood is flowing
rapidly into them from the arteries, and that their colour
is of a lighter blue than usual, showing that the blood
they contain is lighter coloured or less venous than usual.
This indicates that the cutaneous arterioles are dilated, and
this dilatation has doubtless a great deal to do in many

* R. Meyer, Die organische Bewegung in ihrem Zusammenhang mit dem
Stoffwechsel, 1845, p. 84. _Meyer’s explanation of the occasional red colour of
venous blood is difierent from the one I have given above. We both agree that
the slightness of the alteration it has undergone in its passage from the arteries
into the veins is due to the fact that but little oxygen has been taken from it by
the tissues as it flowed through the capillaries. Meyer considers that the tissues
adapt themselves to the wants of the body, and take little oxygen from the blood
when the external air is warm. The oxidation which usually goes on within the
body is thus diminished, the production of the heat lessened, and the tempera-
ture of the animal prevented from rising too high. This hypothesis, though very
plausible, is rendered improbable by the experiments of Bernard (Revue
Scientifique, 1871-72, pp. 183 and 182), which show that the tissues of animals
which have been exposed to a high temperature absorb oxygen (after death at
least) much more quickly than usual. Itherefore attribute the florid cvlour of
the blood to dilatation of the arteries and capillaries, allowing it to flow so
quickly through them that the tissues have not time to abstiact much oxygen
however great their avidity for it may be.

+ Crawford, Experiments and Observations on Animal Heat, 1788, p. 308.

406 PATHOLOGY AND TREATMENT OF SHOCK AND SYNCOPE.

instances with the reduction of the blood-pressure and the in-
duction of syncope. As the skin is usually pallid during the
fainting fit itself, we can hardly suppose that the blood is
then flowing very rapidly through the cutaneous vessels.
If the hypothesis I have just advanced be correct, we are
driven to the conclusion that it is the blood-vessels of the
muscles which undergo dilatation during syncope. This idea
likewise receives confirmation from the observation made by
‘Thackrah,* that it is in muscular men that venous blood most
frequently presents a florid colour. Such of you as have seen a
living muscle cut across, however, know that when it is at rest
very little blood indeed flows from the divided ends of the
vessels which permeate its substance, and you may be inclined
‘to doubt the possibility of these vessels ever being able to dilate
so much as to drain, as it were, the blood from the arteries into
‘the veins and produce syncope. That they can dilate and drain
‘the blood out of the arteries very quickly has been shown by
Ludwig and Hafiz,t who found that when the vessels of the
‘intestines and skin were made to contract, the blood which
could no longer flow through them poured through the vessels
of the muscles, and, notwithstanding the fact that these vessels
were at that very time excited to contraction by irritation of
their vaso-motor nerves, the blood flowed from the arteries into
the veins, and the pressure in the arteries sank nearly as quickly
as when the cutaneous and intestinal vessels were patent. If
such be the effect of the muscular arteries on the blood-pressure
when they are trying to contract, what must it be when they are
ready to dilate? Dilatation of the vessels alone may sometimes
be sufficient of itself to lower the blood-pressure to such an
extent that fainting occurs; but at other times this is combined
with the depressing effect of sudden stoppage of the heart. - In
shock there is great dilatation of the vessels in the ¢ntertor of
the body, especially of the veins of the intestine. If this state
should be associated with sudden stoppage of the heart, instant
death will occur, as in the case of the labourer in the India
Docks. In short, then, I consider syncope to depend chiefly on

* Thackrah, Inquiry into the Nature and Proverties of the Blood, p. 88.
{ Ludwig's Arbeiten, 1871, p. 107.

—"

svete eee

eum “es Aik os

ACTION OF SMELLING SALTS. 407

dilatation of the arterioles, especially of those near the surface,
though in cases like that of Alice Bruce it may be due entirely
to stoppage of the heart; while the chief factor in shock is dila-
tation of the abdominal veins. The longer duration of shock
than of syncope is probably due to the veins recovering their
contractility more slowly than the arterioles,

Having thus formed some sort of idea regarding the pathology
of syncope ancl shock, we come to our third head, viz., the ques-
tion of treatment. In syncope, our first idea is to restore the
circulation to the brain, and this we do by laying the head
level with the body, or perhaps, still better, as recommended
by Sir Astley Cooper, on a level somewhat lower than that of

the body.

The next thing is to raise the blood-pressure. Now, this is
most easily done by causing the arterioles to contract. We

therefore hurry a person who has fainted from the warm room

to the cold air, and dash cold water on the face, in order to
cause contraction of the vessels on the surface of the body.
We also give draughts of cold water to cause contraction of
those of the stomach. Besides this we apply ammonia or aro-
matic vinegar, which is strong acetic acid, to the nose. Why do
we do this? Many of you know that when ammonia is applied
to the nose of a rabbit it causes the heart to stop instantaneously,
and one would therefore think that to hold it before a fainting
person’s nose was to do the very worst possible thing. But we
all know that this is not the case. Some time ago a member
of this Society asked me this question, and I could at that time
give him no satisfactory answer. I have since made some ex-
periments on the subject,and I find (what has indeed been already
noticed by Kratschmer*) that when ammonia or strong acetic
acid is held before the rabbit’s nose, it causes contraction of the
arterioles. Consequently it prevents the blood-pressure from
falling quickly, even should the heart become feeble or stop,
and is thus useful in preventing syncope. When the blood-
pressure has already become lowered by the occurrence of syncope,
contraction of the arterioles causes it to rise, and it is by causing

this that acetic acid or ammonia are useful as restoratives,

* Wiener Sitz. Bericht, 1870, Abt. II, vol. lxii, p. 24.

408 PATHOLOGY AND TREATMENT OF SHOCK AND SYNCOPE.

In shock we have two conditions to remove. The first of
these is the feebleness of the heart itself, which is due to the
action of the vagus. To counteract this we apply stimulants.
Now, one of the most powerful stimulants to the heart is. heat.
It is true that it dilates the vessels, but in shock we have nothing
to fear from dilatation of the vessels near the surface of the body,
where circulation is hardly going on at all, nor is it likely that
it will increase the dilatation of those in the interior. We
therefore pursue a. plan of treatment directly the opposite of
that which we employ in fainting, and apply warmth instead of
cold to the surface, especially to the cardiac region, over which
a hot poultice or india-rubber bottle filled with hot water should
be placed. At the same time, and for a similar purpose, we give
brandy and ether internally. The second and most important
indication for treatment is to cause contraction of the great
vessels, especially the veins in the abdominal and thoracic cavi-
ties, so that the blood, instead of stagnating uselessly in them,
may be sent onwards to the heart, and thence to the rest of the
body. I have already described the effect of acetic acid and
ammonia held before the nose, but this is only one example of
the general rule that all powerful impressions on sensory nerves
cause contraction of the blood-vessels. Painful impressions
made upon the skin, for example, bave this effect, and Goltz has
shown that pinching the toes of a frog, or irritating them by
acetic acid, prevents the vessels from dilating when the abdomen
is struck, or causes them to contract and propel the blood to the
heart if dilatation has already taken place. If I may judge
from my own experience, persons not unfrequently take uncon-
scious advantage of this effect of pain, and medical students
occasionally prevent themselves from fainting, when witnessing
an operation, by biting their lips or pinching their fingers. Its
beneficial action in shock is very great,and my friend Dr. Fayrer
informs me that he has succeeded in recovering. a patient from
a state of collapse by thrashing his feet and the calves of his
legs with switches after other means had failed. Mustard plas-
ters are often applied for a similar purpose. Sometimes the
performance of. an operation during shock is attended by a
marked improvement in the patient’s condition, and it seems to

DIGITALIS IN SHOCK. 499

me not improbable that this is due to the stimulus thus given
to the vaso-moter nerves. At other times, however, the addi-
tional injury seems to produce an injurious effect either on the
heart or vessels, and the patient succumbs. It is possible that the
different effects of operations performed during shock may depend
to some extent on the greater or less amount of irritation which
is occasioned to the nerves of bones as compared with those of
the soft parts; for, as we have already mentioned, injuries to bones
tend to cause syncope, while irritation of other nerves, unless it
be excessive, tends to prevent it by raising the blood-pressure.
This, however, is a question which pertains more especially to
surgeons, and with them I will leave it. -I must not conclude
without mentioning another valuable remedy in cases of shock,
viz., digitalis. It has, I think, been conclusively proved by Dr.
Adolf B. Meyer and myself,* that this drug possesses the power
of contracting the arterioles, and I have shownf that it greatly
strengthens the pulsations of the heart. We would therefore
expect it to prove useful in shock, and experience does not dis-
appoint our anticipations. ‘This is well shown by a case of shock
following parturition, in which it was employed by Dr. Wilkst
some years ago. My attention was drawn to this by my fiiend
Dr. Milner Fothergill, and I quote the following from his admir-
able essay on digitalis.§ “ The patient was apparently in articulo
mortis; her limbs were cold, her body in a state of deathly
clammy sweat; the face was livid, no pulse could be felt at
the wrist, and a mere fluttering was heard when the ear was
placed over the region of the heart. Brandy and ether had
been tried without any good effect, and as dissolution was
imminent, it was determined to try digitalis. Half-drachm
doses were given every hour; after four doses a reaction
took place, and after seven doses complete recovery occurred.”
Such a case as this needs no comment, and a consideration
of the encouraging results here obtained can hardly fail «to
vain for digitalis a much more extensive application in cases of
shock than it has hitherto received.

* Journal of Anatomy and Physiology, Nov., 1872, p. 134, vide antea, p. 151.
+ On Digitalis, London, 1868, p. 28, vide antea, p. 62.

t Medical Times and Gazette, Jan. 16, 1864.

§ Digitalis: its Mode of Action and its Use, London, 1871, p. 63.

DIURETISCHE WIRKUNG DER DIGITALIS

In Verbindung mit H. POWER, M.B.

(From the Centralblatt der medicinischen Wissenschaften, July 4, 1874,
p. 497.) ,

Max Hermann und Ludwig haben gezeigt, dass die Geschwin-
digkeit der Harnabsonderung von dem Unterschied des Blut-
druckes in den Nierenglomerulis und dem Druck des Harnes
in den Harncanalchen abhanet.

Gegenwirtig nimmt man allgemein an, dass die diuretische
Wirkung der Digitalis nicht von einer specifisch diuretischen
Wirkung dieses Arzneimittels, sondern ausschliesslich von
seiner Fahigkeit, den Blutdruck im arteriellen Gefisssystem zu
steigern, bedingt ist.

Die Resultate von Experimenten, die wir vor ungefihr einem
Jahre angestellt haben, beweisen, dass dies nicht der Fall ist.

Nach Injection einer bedeutenden Dosis von Digitalin in die
Venen eines catheterisirten Hundes fanden wir die Harnsecre-
tion bedeutend vermindert und. selbst vollkommen schwinden,
wiahrend gleichzeitig der Blutdruck zuweilen bedeutend gestei-
gert war. Nach einiger Zeit fiel der Blutdruck wieder und in
einigen Experimenten trat die Harnsecretion gerade wieder ein,
als der Blutdruck zu sinken begann, wahrend in anderen Fallen
dieselbe nicht vor dem Sinken des Blutdrucks unter die Norm
auftrat. In einigen Experimenten war die Geschwindigkeit,
mit der der Harn abfloss, geringer, in anderen floss er sehr
reichlich, obgleich der Blutdruck bedeutend unter die Norm
gésunken war. Wiirde Digitalis seine diuretische Wirkung
einzig und allein der Fahigkeit, eine Steigerung des Blutdruckes
zu bewirken, verdanken, dann hatte das Fliessen des Harnes
bedeutend vermehrt sein miissen unmittelbar nach der Injection
und hitte wieder abnehmen miissen, so wie der Blutdruck fiel.
Statt dessen fanden wir die Secretion am geringsten wihrend

So.

HARNSTOCKUNG UND ALBUMINURIE DURCH DIGITALIS. 411

des héchsten Standes des Blutdruckes, sehr reichlich hingegen,
als der Blutdruck unter die Norm gesunken war. Zur Erkla-
rung dieser Erscheinungen sind wir geneigt, anzunehmen, dass
Digitalis eine erregende Wirkung auf das vasomotorische
Nervensystem im Allgemeinen und auf die vasomotorische
Nerven der Niere im Besonderen ausiibt. Gleichzeitig miissen
wir annehmen, dass es eine massige Contraction der Gefiisse des
Korperkreislaufes und eine Steigerung des Blutdruckes in
denselben, so wie eine iibermissige Contraction der Nieren-
arterien bedingt, deren nichste Folge eben das Aufhéren des
Fliessens des Harnes ist. So wie die excitirende Wirkung auf
das vasomotorische Nervensystem nachlisst und voribergeht,
erschlaffen die Gefiisse der Niere schneller und bedeutender als
die tibrigen Gefiisse, so dass der Blutdruck in den Nierenglome-
rulis noch tiber die Norm gesteigert ist, obgleich die Spannung
der Gefiisse im Allgemeinen unterhalb der Norm ist.

Unterstiitzt wird diese Annahme noch durch die Thatsache,
dass der nach dem Wiedereintreten der Secretion gesammelte
Harn Eiweiss enthielt, gerade wie Hermann nach mechanischer
Absperrung des Kreislaufes in den Nierenarterien gefunden,
Wir wollen. die Méglichkeit, dass das Variiren der Secretion
theilweise auch von der directen EKinwirkung des Arzneimittels
auf die secernirenden Elemente der Niere abhangen mag, nicht
tibersehen; wir sind gegenwirtig mit diesbeztiglichen Experi-
menten beschiftigt, die wir nach deren Abschluss veroffent-
lichen werden.

ON THE DIURETIC ACTION OF DIGITALIS.
In conjunction with HENRY POWER, M.B., F.R.CS.

(Reprinted from the Proceedings of the Royal Society, No. 153, 1874.)

It has been shown, by Max Herrmann and Ludwig, that the
rapidity of the urinary secretion depends on the difference in
pressure between the blood in the renal glomeruli and the urine
in the urinary tubules.

At present, it is generally assumed that the diuretic action of
Digitalis is not caused by any specific influence of the drug
upon the kidney, but is due exclusively to its power of increasing
the blood-pressure in the arterial system.

The results of some experiments made by us nearly a year
ago show that this is not the fact. On injecting a considerable
dose of digitalin (1—2 centigrammes) into the veins of an
etherized dog, we have observed that the secretion of urine was
either greatly diminished or ceased altogether, while the blood-
pressure rose, occasionally to a considerable extent. After some
time the blood-pressure again fell; and in sonie of the experi-
ments the secretion of urine recommenced at the instant the
fall began. In other instances it did not recommence till the
blood-pressure had sunk below the normal. Occasionally the
secretion did not flow with its original rapidity, but in others it
was poured forth copiously, even although the blood-pressure
had sunk considerably below the normal.

If Digitalis acted as a diuretic only by raising the blood-
pressure, the flow of urine should have been greatly increased
immediately after the injection, and should have. diminished
with the fall of arterial tension. Instead of this the secretion
was least when the blood-pressure was highest, and most copious
when the tension had fallen below the normal.

The explanation we would offer of these phenomena is, that
Digitalis probably stimulates the vaso-motcr nerves generally,

ANURIA AND ALBUMINURIA FROM DIGITALIS. 413

but affects those of the kidney more powerfully than those of
other parts of the body. Thus, it causes a moderate contraction
of the systemic vessels, and raises the blood-pressure in them,
but, at the same time, produces excessive contraction of the
renal vessels, so as to stop the circulation in the kidneys and
arrest the secretion of urine.

As the action of the drug on the systemic vessels passes off,
they relax, and the blood-pressure falls; but the renal arteries
probably dilate more quickly and to a greater extent than the
others. The pressure of blood in the glomeruli may thus be
increased above that normally present in them, although the
tension in the arterial system generally may have fallen below
the normal.

Additional evidence in favour of this explanation is afforded
by the fact that the urine collected after the re-establishment
of secretion contams albumen, just as Herrmann found it to do
after mechanical arrest of the circulation through the renal
arteries.

We do not overlook the possibility that the alteration in
secretion may be partly due to the direct action of the drug on
the secreting elements of the kidneys, and we are still engaged
in experiments on this subject. *

i

CASES OF EXOPHTHALMIC GOITRE.

(Reprinted from St. Bartholomew’s Hospital Reports, vol. x, 1875.)

Tus disease is characterised by three prominent symptoms—
viz., palpitation of the heart, enlargement of the thyroid gland,
and protrusion of the eyeballs. It was first observed by Parry,
and described by him in a paper on “Enlargement of the
Thyroid Gland in connection with Enlargement and Palpitation
of the Heart,” published in 1825. Parry’s work, however, seems
to have been little known, and the disease was again noticed by
Graves of Dublin, and described by him under the title of
“Newly observed Affection of the Thyroid Gland in Females,”
in his System of Clinical Medicine, published in 1843. The
attention of the profession having been attracted to the disease
by Dr. Graves, it is generally called Graves’ disease in this
country, and “maladie de Graves” by Trousseau in France.
Both Parry and Graves observed the protrusion of the eyeballs,
as well as the other symptoms, but they seem to have regarded
it as quite subsidiary to the other two symptoms, and perhaps
looked upon it as an accidental complication. The equal im-
portance of the exophthalmic with the other symptoms was
first insisted upon by Basedow, a practitioner in the German
town of Merseburg. He is therefore considered by the Germans
to have been the first to give a complete picture of the disease,
and they call it after him “die Basedow’sche Krankheit,’ or
Basedow’s disease.

In most of the cases described by Graves the paroxysmal
nature of the palpitation, and of the increased enlargement of
the thyroid, forms a prominent symptom, and appears to have
specially attracted his attention. In these cases the protrusion
of the eyeballs does not seem to have been at all noticeable;
while in most cases where this symptom is prominent, the
thyroid gland, although subject to occasional variations in size,
generally remains more or less obviously enlarged. The follow-

ee ee a eee é

bi etal een, ee ne

eS See

a ay ne

EPILEPSY AND EXOPHTHALMOS. 413

ing case is one of purely spasmodic exophthalmos, in the inter-
vals of which the symptoms entirely disappeared. Not having
witnessed one of the fits myself, I am obliged to rely solely
on the testimony of the mother for the accuracy of my facts.

M. M.,a girl aged 13, first seen on Wednesday, August 26,
1874, middle height, fair, well nourished, slightly strumous-
looking ; has a somewhat vacant expression. The eyes are not
prominent, nor is the thyroid gland larger than usual. Mammee ~
not developed. There is a loud systolic murmur at the apex of
the heart, faintly audible over the base.

About 20 months ago a large weight fell from a window
and slightly grazed her nose. Three days afterwards she had a
fit. According to her mother’s account, this fit was not pre-
ceded by any warning. The first thing noticed was that the
eyes became very prominent, or in the mother’s own words,
“ stood out shocking.” The hands were clenched, and the arms.
drawn up towards the head. The body was drawn somewhat.
to the right side, and the mouth also to the right. This lasted
for 4 hours and 20 minutes. She then fell asleep, and slept.
for four hours more, only awakening once during that time.
During this sleep her eyes returned to their ordinary size.
About 14 months afterwards she had another fit; a third one
on June 21; a fourth one about four weeks ago;. and a fifth
one last Monday, August 24. During the fit she foams at the
mouth: there is also some bleeding from the mouth; in the last
fit from the ears also. After the fit she complains of pain in all
her limbs; and a fortnight before the fit comes on she complains
of being very tired, and of aching in her back and sides. She
has never menstruated, the appetite is good, the tongue covered
with a thin white fur. Bowels open two or three times a
week,

Ordered—Ferri et ammonie citrat., gr. viii.; ammon. carb., gr. ii; spt. chloro-

form, 1 x.; tinct. nuc. vom., 1 x. ; infus. quassiew,ad 3i.: ter die sumend..
Pil. aloes et myrrh, gr. v.: omni nocte sumend.

August 31.—Jn statu quo. Has had no more fits.
Rpt. haust et pil.

October 9.—The same treatment has been continued. There

416 CASES OF EXOPHTHALMIC GOfTRE.

has been no return of the fits; but the mother says that she
thinks one is now coming on, as she sees premonitory symp-
toms.

Ordered—Potass. bromid, gr. xxv.; spt. chloroform, 1 xx.; aque, 3 i.: ter
die sum,

The next one was admitted into Mary Ward, under the care
of Dr. Andrew, in June last. It is a most interesting case,
presenting in a typical manner most of the symptoms of exoph-
thalmic goitre, although neither the enlargement of the thyroid
nor the protrusion of the eyeballs is present to any great extent.
It is also remarkable in being complicated by diabetes, a dis-
ease which has been shown by the researches of Cyon, Eckhard,
Pavy, and others to be closely associated with the third cervical
ganglion, and the nerves passing through it; the very part, in-
deed, to which the nervous disturbances in exophthalmie goitre
have already been attributed.

Dr. Andrew has not only kindly placed this case at my dis- ;
posal for publication, but has afforded me every assistance and
facility for observing it myself. I have also to acknowledge my
obligations to Dr. Andrew’s house-physician, Mr. Strugnell, to
whom I owe the observations with the ophthalmoscope, and to
Mr, Wharry, to whom I am indebted for the analysis of urea.
In recording the case here, I have inserted some observations
which were made some time after the patient’s admission: eg., |
the ophthalmoscopie observations, which were made about the :
end of August. Most of these, however, I have distinguished
by brackets from those made at the time of admission. | :

S. P., aged 43, lady’s maid. Patient is of the middle height, |
and very thin and nervous-looking. Hair thin. 4

History—Her mother’s family is very rheumatic, but they |
are all long-lived. Father's family not so rheumatic, and they |
live generally above middle age. There are none of either
family who have suffered from fits, nor is there any history of
either diabetes or phthisis. When 17 years of age, she had
rheumatic fever. At the age of 25 she became a lady’s maid. :
About 10 years ago she had some family trouble, and some |
more five or six years ago. About 13 years ago she went to a ‘

—_

el ee) i, tae ,

COMMENCEMENT OF ILLNESS. 417

family where one of the members was fidgety, and gave her a

good deal to do. She remained in this situation for ten years.
About five years ago she began to lose flesh, but she grew
stronger again. Three years ago she went to a situation where
the Jadies were very kind, but were often out at balls, so that
she was often kept up at night. When she did not get sleep at
night, she lost it altogether ; for she never could sleep in the
day. About two years ago she noticed a pulsation in the epi-
eastrium. About that time she had a severe fall on the back of
the head. She was unconscious for some minutes, and did not
recover from its effects for several hours. About this time, also,
she began to notice that her stools became occasionally very
pale. They continued so for about five weeks at a time, and a
similar attack has come on every three months since. About
six months ago she became very thirsty, felt pain in the back,
and began to lose flesh. Two months ago she had diarrhea
and sickness. About three weeks ago one of the ladies whom
she served noticed that her right eye was looking strange, and
asked if she had a cold in it. Before that time it was natural.

On Admission—The patient is very thin. There is some
eedema of the feet and ankles. The thyroid gland is more pro-
minent than usual: the right lobe is larger than the left. The
patient never noticed the enlargement of the gland until it was
pointed out to her in the hospital.

Hyes.—Both eyes somewhat prominent; the right eye more
prominent than the left. [On pressure, the eyes retreat in the
sockets. There is very slight tenderness to pressure on the
right eye, more on the left. There is a brown patch on the right
side of the right conjunctiva. This has been there ever since
she remembers. On making the patient look up and down, the
right upper eyelid does not follow the movements of the eye as
quickly as normal; so that on looking down, the conjunctiva is
exposed, forming a white ring above the cornea. The patient
states that she feels as if the right eyelid caught. The left eye-
lid moves normally.

The pupils are normal in size. The right pupil does not act
quite so readily as the left. She is presbyopic, focus being 16
inches.. She has noticed that she required to hold objects

25

415 CASES OF EXOPHTHALMIC GOITRE.

further off only since she came into hospital, but the presbyopia
may have come on some weeks before, as she had no work, and
therefore no opportunity of observing it. The vision of the left
eye is +2 of Snellen’s types. That of the right eye is 14, with
a —48 lens it becomes +2. Her eyes ache if she looks long at
any object. They did not use to do so. She is often troubled
with musce volitantes. She has some subjective visions when
her eyes are closed. These are in the form of stars flying
about; they are usually of a red colour. On ophthalmoscopic
examination, the media are found to be a little hazy. Nothing
abnormal in the dises, except that the right disc seems a
little smaller than the left. The fundus of both eyes is fairly
natural.
Circulatory System.—The heart’s apex beats two inches below
and half an inch outside of the left nipple. There is a systolic
murmur. The abdomen is retracted, and there is strongly-
marked epigastric pulsation. The veins on the armis, legs, and
neck are very large, full, and light blue, not dark blue, in colour.
When emptied, they fill very rapidly from behind. The face is
not flushed, nor are the ears red. The temporal arteries are
prominent and tortuous. The pulse is 120, full and regular.
The sphygmographic tracing shows a flat plateau and mode-
rately slow descent. This seems to indicate that the arteries
have undergone senile degeneratieu, and that they do not empty
with any very great rapidity. There is no marked pulsation in
the thyroid gland, nor is there any very obvious increase in the
pulsations of the carotid arteries.

Respiratory System.—The voice is soft and pleasant. (She
has lately noticed it change, and become weaker and more
“elinky.” She has only noticed this since she began to recover
in hospital. She sometiines has a little pain in her throat when
she speaks.) The lungs are normal.

Muscular and Nervous Systems.—The muscles are very small.
The thumbs are drawn in upon the palms. She finds difficulty
in rising from a sitting posture. She is very neat in her habits,
is not quick-tempered, but the contrary. She is very emotional,
and is in either very high or very low spirits. When well, she
is high-spirited and full of fun; but for three weeks before

CONDITION OF PATIENT 419

admission she has been liable to fits of crying, during which
she is miserable without knowing why. These fits are relieved
by cold water to the face, ether internally, or ammonia to the
nose. She feels very hot, and cannot bear many clothes on
during either day or night. She has always had this feeling,
and always liked cold weather best. Temperature on admis-
sion, 101°9 .

Digestive System.—Tongue very dry and furred. She is very
thirsty, and her appetite is bad. Bowels irregular.

Secretions.—Verspires very inuch in warm weather, or on the
slightest exertion. Urine very abundant, sp. gr. 1038, acid.
Contains much sugar.

June 2, Ordered—Bran cakes; beef-tea, 1 pint; brandy, 2 fluid oz.; eggs, 2.
Pil. col. c. hyoscyam., gr. x. statim; hst. sode citrat. efferv.,
6tis horis.

3. Feels rather better; ordered fresh greens.

4, Urine, 3} pints; sp. gr. 1C30.

Ns a. »” 24 ” ” 1028.
» 6 5 3b » » 1025.
» 7 5s 8 oy wi 20Ra.
OE oe ee ae iF
De ee: dae » 1024. Seems better. Temperature, 99°;

pulse, 114. Ordered—Esseuce of
meat, 3 v. (spt. rect, 3 i.; aq.,
3 i.), instead of brandy.

re) 10. ” t ” %”> 1024.

> ll. ” 45 ” ” 1022.

3 a2. ” 44 ” ” 1025. ~

aay + os — = 1023.

» 14, i ORR ue i ee

»j De » “45's ., 1023. Is rather uysterical ; adde hat. tinct,

opii, nL v. Temp., 99°,

= Rib ee. Cae ~». “2038.

Ly aor ie » : 1028.

ee OS ORE he » 1022.

Oe eae, ee Wane

ety eS » 1018.

oe Diarrhea.

23. » 2) pints; sp.gr.1013. Still some diarrhea; otherwise
, seems better: less sugar in urine.
Ordered—Bismuth subnit., gr.
xv.; tinct. catechv., 5 ss. ; decoct
hematoxyli, 3 i. p r.n.

5) 20» % oa a | 202.
eff » & pints; ~~. AGE.
9 206 PS at a pi toon | EAE

E 2

b>

420 CASES OF EXCPHTHALMIC GOITRE.

June 30. Urine, 4 pints; sp. gr.1027, alk. Temp., 99° No diarrhea;
appetite good; sleeps well; less.
cdemxz of, fect; seems better.
Ordered—Acid, nitrohydrochlor..
dil., mW x.3 lig. strychniae, my iii. ;
tinct. opii, NL v.; aq. menth. pip,,
3 i., ter die.

is » 1013.

» 4% pints; ,, 1013. .General.condition improved ; sugar
rather diminished; feet still a
little swollen. Ordered — Hst.
sodee cit. efferv. 6tis hors.

ey
acl
i)
ah ae

FOUN 1) Rea: 1089,

5, 16. Ordered—Lig. strychnie, my iii.; tinct. opii, my v.;.acid phosph..
dil., NL xxv.; aque, 3 ii. 6tishoris.

, 28. Urine, 5-pints; sp. gr. 1028. Rather hysterical. Weight, 5st. 8lbs..

Urine. Percentige Totalurea.
c.c, Sp. gr. Reaction. of urea, Grammes.
August 25. .. 2565 1u3 ) Acid. ‘73 13°7245
» 22 « 2280 1030 Acid. "85 18°96
3 23> ee 6200 1025 Faintly acid. *825 22°275

September 1.—Urine, 4 pints, sp. gr. 1030. Nothing ab-
normal in fundu: of eyes.

September 8.—Gained 3}1bs. during the last few weeks.

September 23.—Not quite so well last night.

October 4—Had not been quite so well during the day.
Hysterical, and crying a great deal. About seven o’clock she
went to bed, and took some beef-tea ; about nine she spoke to:
the nurse; at 10 the sister saw that she was lying quiet, with
the curtains of the bed slightly drawn ; and at 11 p.m. she was
found to be dead. No dyspnoea whatever was observed. The:
friends of the patient would not allow a post-mortem examina-
ticn in the hospital, and after some difficulty permission was.
obtained to examine the body at their house. Owing to the
circumstances under which it was made it was exceedingly
imperfect and unsatisfactory. The lungs were much con-
gested and cedematous. ‘There was no consolidation, and they
were singularly free from pleuritic adhesions. No vegetations
were observed on the cardiac valves. The left ventricle was
contracted and empty; the right ventricle contained a little
blood. The liver was normal. The thyroid gland was enlarged

CAUSES OF PALPITATION, 4?1

and hard, and it was firmly attached to the trachea, The eyes
were sunken, but not greatly.

The cause of death here has evidently been cedema of the
lungs, which has come on rapidly and insidiously,

In this case, the three prominent symptoms of exophthalmic
goitre, although present, are not so noticeable as in many others ;
but the collateral symptoms, such as the imperfect consensus
between the movements of the upper eyelid and visual plane,
ou which Von Griife laid particular stress, the emotional cha-
racter, the feelings of heat, the actual high temperature noticed
by Teissier, are particularly well marked, To trace the
symptoms back to their origin is exceedingly difficult, and,
indeed, impossible, in the present state of physiological know-
ledge. All that we can hope to do at present is to put together
the facts already ascertained, so that we may gain a clearer
idea of the possible origin of the symptoms, and see more
readily what points remain for investigation,

Palpitation.— Three causes of palpitation at once suggest
themselves to the mind, and these three are undoubtedly the
chief, although there may be, and probably are, others which
occasionally come into play, These three are—1. Paralysis of
the vagus; 2. Relaxation of the arterioles ; 3, Stimulation of the
accelerating nerves of the heart. The vagus acts as the regu-
lating nerve of the heart, not only by diminishing the number
of its pulsations, but by moderating their strength. Paralysis
of this nerve, therefore, causes palpitation of the heart, as well
as quickness of the pulse, Palpitation depending on this cause
may be compared to the excessive work done by a steam-engine
from which the governor-balls have been removed. But a
steam-engine may also work with excessive and injurious
violence if the resistance it has to overcome is much diminished,
especially if this occur suddenly, and the governor-balls,
~ although present, work imperfectly. The same is the case with
the heart, which is very liable to palpitate violently when the
arterioles become relaxed from weakness of the vaso-motor
system, and allow the blood to pour readily through them into
the veins, instead of opposing a moderate amount of resistance
to its passage,

422 CASES OF EXOPHTHALMIC GOITRE.

In anzemic persons, for example, where the vaso-mctor system
is weak and the arteries relaxed, the heart often beats violently,
especially when any additional relaxation is produced in the
arteries by some slight exertion. Here, no doubt, there is a
disproportion between the action of the heart and the work it
has to do. This implies a weakness or disturbance of the
nervous arrangement, which ought to regulate the one to the
other. The part of this arrangement which is in fault, how-
ever, seems to be the vaso-motor system, which allows the vessels
to dilate too much, rather than the vagi, whose function is to
restrain the heart. Both kinds of palpitation which I have
mentioned, depending as they do on a weak or paralysed con-
dition of the vagi or vaso-motor nerves, ought to be relieved by
the use of tonics; and in fact we do find that such remedies,
and more especially iron, are of the utmost service in the palpi-
tations of anemia. But the third cause of palpitation, viz.
stimulation of the accelerating nerves of the heart, depends
not on weakness, but on over-action of that part of the nervous
system, and anything that will increase its power will prove
injurious rather than beneficial.. Now this is exactly the con-
dition which is found in exophthalmic goitre. Although’
persons suffering from this disease are not unfrequently anemic,
the administration of iron is not followed by its usual good
effects. On the contrary, Trousseau states that it increases the
palpitation to such an extent that its employment can rarely
be continued. This is exactly what we should expect on the
supposition that the palpitation depended on stimulation of the
accelerating nerves of the heart, and I am therefore inclined to
believe that the palpitation in exophthalmic goitre is due to
irritation of these nerves. Their deep crigin has not been
exactly determined, but they pass out from the spinal cord along
the vertebral artery to the third cervical ganglion, and thence’
to the heart. They might be excited by an irritation applied
to either, at their origin or during their course, and thus we
might expect them to be called into action by changes in the
brain, medulla, spinal cord, third cervical ganglion, the branches:
accompanying the vertebral artery, or those going to the heart.
In order to ascertain where the source of irritation’ is,.we must’

CAUSES OF EXOPHTHALMOS. 428

discover what other nerves appear to be irritated in exoph-
thalmic goitre, and consider what points exist at which applica-
tion of an irritant might affect all the nerves at once.
Enlargement of the Thyroid Gland.—The great variations
which occur in the size of the thyroid gland in exophthalinic
goitre, and its remarkable pulsation, which has sometimes
caused it to be mistaken for aneurism, have led nearly all
observers to ascribe its enlargement, in the first instance at
least, to dilatation of its vessels and engorgement of the gland
with blood, in a manner similar to that which occurs in erectile
tissues. After this has continued some time, increased growth
may occur in the glandular elements. This dilatation may
depend on direct paralysis of the vasomotor nerves of the
glandular vessels, or on inhibition of these nerves by others, in
the same way as the vaso-motor nerves of the penis cease to act
and allow the vessels te become full when the nervi erigentes
are irritated. The vasomotor nerves of the thyroid vessels
proceed from the second cervical ganglion, but I am not
acquainted with any experiment showing whether they pass
from the spinal cord to the ganglion through its communicating
branches, or pass upwards through the third cervical ganglion.
Neither do I know whether these vaso-motor nerves may be
inhibited, and the vessels dilated, by irritation of the third
cervical ganglion, or other parts of the nervous system.
Protrusion of the Eyeball.—In-a case recorded by Laqueur*
the protrusion of the eyeballs seems to have been partly due to
an increased amount of fat within the orbit, but this may have
been only consequent on long-continued congestion. In many
eases the protrusion varies at different times, and in the case of
M. M. it is only temporary, disappearing in the intervals
between the fits. It is therefore usually ascribed, and in all
probability correctly, to increased fulness of the blood-vessels,
or of the blood-vessels and lymphatics, in the orbit. It may be
also due, however, as suggested by Professor Laycock, to con-
traction of the involuntary muscular fibres stretching across
the back of the orbit, which were described by Professor
Turner of Edinburgh some years ago. Whatever be the cause

* Dissertation: Berlin, 1861; Canstatt’s Jahresbericht.

494 CASES OF EXOPHTHALMIC GOITRE

of it, however, Claude Bernard has found that protrusion of the
eyeball may be produced by irritating the branches connecting
the first and second dorsal ganglia with the spinal cord,

Impaired Movement of the Hyelid—The loss of consensus
between the movement of the eyeballs and the upper eyelid is
ascribed by Von Grafe to disturbed innervation of the lids, and
especially of the levator of the upper eyelid, which is partly
supplied by the sympathetic.

Diabetes.—The diabetes in this case can hardly be due to
imperfect destruction of sugar in the body, as the temperature
was higher than normal. It must therefore be due to increased
formation. Increased formation depends, according to Bernard,
on dilatation of the hepatic vessels, and a quicker flow of blood
through the liver, According to Cyon, the vaso-motor nerves of
the liver pass from the vaso-motor centre in the medulla
through the cervical part of the spinal cord, pass out from it,
and procecd along the vertebral artery to-the third cervical
ganglion, thence to the first dorsal, and along the gangliated
eord and splanchnics to the liver. (See figure.) Division of
this nervous path causes the vessels to dilate, and produces
diabetes ; but it would appear that irritation of the cervical
ganglia, or at least of the first or the third, also causes diabetes,
which does not depend on paralysis, but on reflex inhibition of
the vascular nerves of the hepatic vessels.

Pathology of Exophthalmic Gottre.—All the symptoms seem
to point to an affection of the cervical sympathetic, and post-
mortem examination of a case by Peter showed that the lower
cervical ganglia, especially the right one, were thicker and
redder than normal; that the connective tissue was increased,
as well as nuclei and spindle-shaped cells, while there were
very few ganglion cells. It seems, therefore, that the third
cervical ganglion. may be looked on as the seat of the disease.
So long as we know so little of the pathology, it is impossible
to treat the disease scientifically ; but the treatment which
seems in practice to have given the best results is the use of
digitalis and veratria, and Meyer states that he has obtained
creat benefit from the application of galvanism to the neck. A
weak ascending current was passed through both sympathetics ;

VASO-MOTOR NERVES OF THE LIVER 425

Fia. 153,

Diagram showing the course of the vasomotor nerves of the liver, according to Cyon
and Aladoff. These nerves are indicated ly the dotted line which accompanies them
a, the vasomotor centre; 0, the trunk of the vagus; c, the vasomotor nerves of the liver
passing along the vertebral artery from the spinal cord to ithe third cervicai ganglion ;
d, the fibres connecting the third cervical and first dorsal ganglion. They pass on each side
of the subciavian artery, and form the annulus of Vieussens. Above e is the first dorsal
ganglion; f the gangliated cord of the sympathetic ; g, the spinal cord; h, the splanchni¢
merves; i, the semilunar ganglion, from which vasomotor fibres pass to the hepatic and
intestinal vessels; &, the lungs to which fibres of the vagus are seen to be distributed ; 1,
the liver ; m, the intestine; 2, the arch of the aorta.

Division of the vasomotor nerves of the liver by partial division of the spinal cord in the
neck or section of the fibres c or d causes diabetes, by allowing the hepatic vessels to dilate,
and the flow of blood through the liver to become more rapid. Division of the gangliated
cord f, or the splanchnics kh, would probably have a similar effect were it not that the vaso-
motor nerves of the intestine are contained in them as well as the nerves for the liver, and
therefore when they are divided the intestinal vessels dilate. The blood then goes to the
intestine, so that the circulation through the liver is not increased although its vessels are
dilated. Diabetes, therefore, does not result from section of for kh.

Irritation of the vagus 4, or of its branches, causes reflex dilatation of the hepatic vessels
and diabetes. A similar result sometimes follows irritation of the first and third cervical
ganglia.

Protrusion of the eyeballs was produced by Bernard, by irritating the branches con-
necting the first and second dorsal gang 11 with the spinal cord, The letter e lies between
these gangiia,

426 CASES OF EXOPHTHALMIC GOITRE. °

one pole was also laid on the submaxillary region, and the other
on the closed eye, or the thyroid gland. The treatment adopted
in the case of S. P. was of course modified on account of the
diabetes, and alkalies were administered, as experience has
shown these to be beneficial in this disease. The benefit prob-
ably depends on the action of the alkali on the ferment, by
which glycogen is converted into sugar in the body. The action
of the ferment is impeded by the alkali, the conversion of
glycogen into sugar takes place more slowly than usual, and
thus the quantity in the body is diminished.

ONE OF THE CAUSES OF DEATH: DURING
THE EXTRACTION OF TEETH UNDER
CHLOROFORM.

(Reprinted from The British Medical Journal, December 4, 1875.)

In a clinical lecture delivered by the late Professor Syme
several years ago, he made the somewhat remarkable statement
that, nothwithstanding his constant use of chloroform for many
years, he had never had a death from it occur in his practice.
The reasons he gave for this success were two. “ First,’ said
he, “we always use good chloroform ; and, second, we always
give plenty of it.” Now, others besides Professor Syme have
used good chloroform—have used, indeed, chloroform by the
same makers, and altogether undistinguishable from that
employed by him; and yet they have had to deplore the occur-
rence of deaths during its administration. This fact of itself is
sufficient to show that the second reason given by Professor
Syme for his success is of great importance; and that, in
administering chloroform, it is just as necessary to give plenty
of it as to use only the best quality. It is, indeed, very extra-
ordinary to see how timidity in the use of chloroform seems to
be associated with a more than ordinary fatality ; and how the
careless—one would say almost reckless—employment of it is
frequently unattended with any inconvenience. In Snow’s work
on Chloroform, p. 151, the following passage occurs : “In Guy’s
Hospital and St. Thomas’s, the medical officers had a strong
objection to narcotism by inhalation for the first two or three
years after the practice was introduced, and chloroform was
used much less generally in these institutions than in any other
of the hospitals of London; yet it was precisely in these two
hospitals. that two deaths from chloroform occurred before any
such accident had kappened in any other hospital in this
metropolis.” Dr. Snow seems inclined to attribute both of
these deaths to the administration of chlorvform; but a careful

498 ONE OF TIE CAUSES OF DEATIT UNDER CHLOROFORM,

consideration of them may lead us to another conclusion,
Before attempting to analyse these cases, however, I wish to
recall to the memory of some here an anecdote regarding the
introduction of chloroform into the Edinburgh Jnfirmary, which
Mr. Syme was accustomed to relate in his clinical course. One
of the surgeons of the infirmary, I believe the late Professor
Miiler, had agreed to Sir James Simpson’s request to perform,

for the first time, an operation under chloroform, Everything

had been prepared, and the tray containing the instruments and
bottle of chloroform was being conveyed into the operating
theatre, when the bearer stumbled and fell, and the whole con-
tents of the bottle were irretrievably lost, There was no time
to get more chloroform, and the operation was performed with-
out it. The patient died on the table. Had chloroform been
administered, the death would have been put down to the
anesthetic, and not to the operation ; and, in all probability, not
another drop would ever have been used.

This case shows us—and it is only one of many—that deaths
used to occur from shock during operations before the introduc-
tion of chloroform, but they were then put down to their true
cause; whereas, since its introduction, one hears little or
nothing of death from shock, and much of death from chloro-
form, Another circumstance which is well worthy of notice,
and which ought to be borne in mind, is the frequency with
which the remark occurs in the descriptions of these so-called
deaths from chloroform, that a fatal result was all the more
extraordinary and unexpected because the quantity of chloro-
form administered hal been exceedingly small. Mr. Syme

. . . . : . -
would have said that, instead of beine extraordinary, it was the

very thing to expect; and if, like him, the operators had given
plenty of chloroform, their patients would not have died,

And now let us look at the first two cases of death wnder
chloroform—I will not say from chloroform—in these two
London hospitals, where such a dislike to the anzesthetic was felt.

John Shorter, aged 48, a porter, known to Mr. Solly for some
time as a very active messenger, of intemperate habits, but
apparently in perfect health, was admitted into George’s
Ward, under Mr. Solly, on the 9th October, 1849, suffering from

CARDIAC STOPPAGE. 4°9

onychia of the left great toe, which had existed some time. I]t
was determined to remove the nail, the man having decided,
before entering the hospital, on taking chloroform. On
Wednesday, October 10th, at a quarter before 2 P.m., he began
to inhale the chloroform, with 1 drachm in the inhaler. It
had no visible effect for about two minutes; it then excited
him, and the instrument was removed from the mouth, and
about 10 drops more were added; he then almost immediately
became insensible; the chloroform was taken away, and the
nail removed. He continued insensible ; and, his face becom-
ing dark, the pulse small, quick, but regular, and respiration
laborious, his neckerchief was removed, and the chest exposed
to fresh air from a window near to the bed; cold water was
dashed in his face, the chest rubbed, and ammonia applied to
his nose. After struggling for about a minute he became still,
the skin cold, pulse scarcely perceptible, and soon ceased to be
felt at the wrist: respiration became slow at intervals, but con-
tinued a few seconds after the cessation of the pulse.

The subject of the second case was Alexander Scott, aged 54,
a police constable, who died in Guy’s Hospital in June, 1850,
whilst undergoing an operation for the removal of a portion of
the right hand. Mr. Cock, the operator, said that he was cer-
tain there was no disease about the patient. He described the
accident as follows :—The ordinary machine was used, and, as it
had not the effect, witness directed that a napkin should be
rolded into the shape of a cone, which was applied with chloro-
form. The removal of a portion of the bone occupied one
minute and a half; but, before it was completed, the blood,
-which was gushing out, suddenly stopped, when witness directed
Mr. Lacy to feel the pulse of the patient, and they found that
he had expired.

The sudden stoppage of the hemorrhage shows that, in this
case, as in others, the action of the heart was suddenly arrested.
The first attempt to cause insensibility failed in this as in some
other cases.

Let us take yet another case, the second one ever recorded of
death under chloroform. The patient, a healthy woman, 35
years of age, was taking chloroform in order to have several

430 ONE OF TIIE CAUSES OF DEATH UNDER CHLOROFORM.

teeth extracted. The following account of what occurred was
given by two female friends of hers who were present at the
operation :—“ The respiratory movements appeared to be free;
chest heaving. Whilst inhaling the face became pale. At the
expiration of about one minute the instruments were applied,
and four roots of teeth were extracted. The patient groaned,
and manifested what they regarded as evidences of pain while
the teeth were being extracted, although she did not speak or
exhibit any other sign of consciousness. . As the last root came
out, which was about two minutes from the beginning of the
inhalation, the patient’s head turned to one side, the arms
became slightly rigid, and the body drawn somewhat backwards,
with a tendency to slide out of the operating chair. At this
instant, Mrs. Pearson states, she placed her finger upon the
patient’s pulse, observed it was feeble, and immediately ceased
to beat. The face, which was previously pale, now became
livid, as did also the finger nails; and the lower jaw dropped,
and the tongue projected a little at one corner of the mouth, and
the arms were perfectly relaxed. The females regarded her as
being then quite dead.”

In two of these cases death occurred after the inhalation of
chloroform had been discontinued, and in the third the chloro-
form seemed to have no bad effects until the operation was
begun. In all of them the death followed the operation, and
must, I think, be attributed to the shock caused by it. But
what is shock ? and is there more than one kind of it? for the
symptoms were not the same in all these cases. In two of them
the heart seemed to stop suddenly, while in the third it failed
eradually, although it ceased before the movements of breath-
ing; and the death must therefore be attributed to arrest rather .
of the circulation than of the respiration. The circulation is kept
up in the body by the heart constantly pumping the blood out
of the veins into the arteries. Whenever the heart stops pump-
ing, or whenever it gets no blood to pump, the circulation will
stop. It does not matter how much blood is in the vena cava
or right auricle waiting to be sent into the arteries, if the heart
be not beating ; nor is the case a whit better when a wound in
the jugular has drained away all the blood, so that no efforts of

DILATATION OF VENOUS SYSTEM. 451

the heart, however numerous and however vigorous, can send a
drop of blood into the aorta.

It must be recollected that blood is only useful to the tissues
when it is in the arteries, just as water is only available for
household purposes while it is in the cistern or supply pipes.
Once the water gets into the sewer it is of no more use, unless
it can be filtered and again pumped back into the cistern ; and
once the blood has got into the veins, it is no more use unless
‘it can be purified by the lungs and pumped back into the aorta,
from which it may once again pass to nourish the tissues. The
only difference between blood still in the veins and blood which
has run out of them into a basin, is that, when in the basin, it
cannot get to the heart, and be pumped by it into the arteries;
while, so long as it is in the veins, it generally reaches the heart
readily. But although it generally does reach the heart easily,
it does not always do so. Sometimes it accumulates in the veins
of the abdomen, and never reaches the auricle; so that it might
just as well be in a basin for any use it is to the heart or body.
This was shown by Professor Goltz, of Strassburg, by a remark-
able experiment. After exposing the heart of a frog he noticed
that it beat regularly, and at each beat sent a quantity of blood
into the aorta, again becoming full of blood in the interval
between the pulsations. The frog’s heart is partially trans-
parent; so that it is easy to see by its colour when it is empty
and when it contains blood. He now struck the frog’s intestines
pretty hard, and found that the heart stopped. The irritation
produced by the blow had been conducted up to the medulla
oblongata ; and, being reflected down the vagus nerves to the
heart, had stopped it. After a little while, the heart seemed to
recover, and began to pulsate again. But there was a very
remarkable difference between its appearance now and _ its
appearance before the blow had been given. Instead of becom-
ing filled with blood during each diastole, and assuming a deep
red colour in consequence, it remained quite pale and einpty ;
and, although it contracted vigorously, the circulation stopped,
for the heart had no blood to propel. On looking at the vena
cava, Goltz found the cause of this phenomenon. The frog was
hanging with its legs downwards, and the vena cava was not

432 ONE OF THE CAUSES OF DEATH UNDER CIILOROFORM.

full up to the level of the heart. Usually the vena cava and
veins of the intestines are kept in a state of semicontraction or
tone by the vaso-motor nerves, but now they had become com-
pletely relaxed: so that the blood which usually would have
tilled them completely up to the heart was not sufficient, and so
they were only about half full. On Jaying the frog in a
horizontal position, the blood ran towards the heart. It was
thus evident that the blow on the intestines had done something
more than stop the heart. It had also stopped the usual action
of the vaso-motor centre; so that the veins, instead of remain-
ing in a state of tonic contraction, became widely dilated.
And, be it noticed, this dilatation of the veins in Goltz’s experi-
ments was more permanent than the steppage of the heart, and
continued after the cardiac pulsations had recommenced. But
all frogs are not alike; for sometimes a blow on the intestines
will stop the heart without having much effect on the veins;
and sometimes it will cause the veins to Cilate, and will not stop.
the heart, although very often, as I have already said, it will do
both. The same effects seem to follow blows on the abdomen
in man and in'the frog, but with this difference: in the frog,
the heart may stop for some time, and again go on without
much injury to the animal; in man, the stoppage of the heart
produces death in not many seconds. A good example of this
is to be found in Sir Astley Cooper’s Lectures on Surgery ;
where he relates that a healthy labourer belonging to the India
House was attempting to lift a heavy weight, when another
labourer came up and said, “Stand on one side; let an abler
man try.” At the same time, he gave the former a slight blow
on the region of the stomach, when the poor fellow immediately
dropped down and expired. On examination of his body, there
was not any mark of violence discovered. Here, no doubt, the
blow in the abdomen stopped the man’s heart, just as it does in
the frog; and death occurred before the organ had time to
recover from the shock. In another case, described by Pro-
fessor Fischer, a young man was struck in the abdomen by a
cearriage-pole ; and, after the accident, lay pale and motionless,
with a feeble pulse, empty arteries, deep sighing respiraticns,
and a livid tinge on his hands and lips. In this instance, the

“ ~
» a

TWO FORMS OF SHOCK—HEART AND VESSELS, 3

heart had either not been stopped at all, or had speedily
recovered itself; but the abdominal veins had been so dilated that
all the blood in the body could hardly fill them sufficiently to
leave a driblet over for the general circulation, although a little
still did trickle into the heart so long as the patient remained
in the recumbent posture.

We have, then, two forms of shock, according as the injury
produces its effect chiefly on the heart or chiefly on the vessels.
But it is not merely blows on the abdomen which have the
power of producing shock; irritation of other parts can do so
likewise ; and this seems to be peculiarly the case with regard
to bones. Thus Pirogoff records two cases in which death
occurred during operations before the introduction of chloro-
form. In both, the pain and loss of blood during the operation
was only a little greater than usual; yet in both, immediately
«after the bone had been sawn through, the face became pale, the
eyes staring, the pupils dilated, a peculiar rigidity of the body
eccurred, and death immediately took place.

The symptoms in these cases of Pirogoff’s are almost exactly
the same as those of Mr. Cock’s case I have already described ;
but Pirogoff’s deaths were put down to the operation, because no
chloroform had been given ; while the death in Cock’s case was
ascribed to the anesthetic, because some chloroform had been
administered ; although, on account of the operator’s unwilling-
ness to give it at all, the quantity. was probably very small.

In all three, it is evident that the heart stopped suddenly ;
and this in itself was sufficient to cause death, though it is
highly probable that dilatation of the abdominal vessels also
occurred.

In Mr. Solly’s case, the dilatation of the abdominal vessels
seems to have been the chief cause of death; for the pulse
became gradually, though rapidly, weaker and weaker, and then
stopped altogether, just as we would expect it to do if the hear
suddenly ceased to be supplied with blood.

In the third case I have described, probably the heart was
chiefly affected ; for, just as the fourth stump of a tooth was
removed, the pulse was felt to be exceedingly weak, and almost
immediately afterwards became imperceptible.

2 F

434° ONE OF THE CAUSES OF DEATH. UNDER CHLOROFORM.

Stoppage of the heart’s action, then, being of such importance
as a cause of death, we must now inquire how it is produced.
The heart is kept pulsating rhythmically by the motor ganglia
which it contains. within itself, and will continue to pulsate for
some time after its complete removal from the body. But
though it thus shows its power to contract independently of the
central nervous system, it is, nevertheless, influenced to a great
extent by the nerve-centres within the cranium. It would
never do to have the heart acting without reference to the
wants of the system, and pumping blood vigorously into the
arteries when the pressure within them was already too great,
or acting slowly and feebly when the limbs were engaged in
severe work, and wanted an abundant supply of blood to enable
them to perform it. There are, therefore, nerves, some accelerat-
ing and others retarding the heart, which pass to it from the
medulla oblongata, and, acting as the spur. and reins of a rider
do upon, his horse, regulate its beats in accordance with the
wants of the system. ‘The retarding fibres are contained in the
vagus nerve; and, when this nerve is irritated strongly, the
heart will either stop immediately in diastole, or will beat very
slowly and more feebly.. Nor is it only by direct irritation of
the vagus that this result can be attained. Just as irritation of
a sensory nerve sets motor nerves in action, and produces
various muscular movements by reflex action through the
spinal cord, so may irritation of a sensory nerve set the vagus
in action and produce stoppage of the heart, by acting reflexly
through the medulla oblongata. A good many sensory nerves
can do this; but there is one which possesses the power in an
especial degree. The roots of the fifth nerve are anatomically
closely connected with those of the vagus; reflex stoppage of
the heart is produced more readily by irritation of the fifth than
of any other norve. In many rabbits, the heart can be instan-
taneously stopped by iiritating the nasal branches of this nerve
by a pungent vapour, such as ammonia, held before the nose.
In every rabnit, or almost every rabbit, indeed, we can stop the
heart by a pungent vapour applied to the nose; but we do not
always do it in the reflex manner I have just described. The
animal always closes its nostrils to prevent the entrance of the

DANGERS OF IMPERFECT REFLEX ACTION. 435

vapour, and keeps them closed so long, that the carbonic acid
accumulating in the blood begins to act on the vagus and stop
the heart. But this only occurs after the vapour has been held
before the nose for some time: while the reflex stoppage which
I have just mentioned takes place at once, almost simultaneously
with the closure of the nostrils. This reflex stoppage has been
shown by Hering and Kratschmer to be due to the irritation
being conveyed along the nasal branches of the fifth nerve
to the medulla, whence it is reflected along the vagus to the
heart, and stops it.

Yet, notwithstanding the stoppage of the heart, the rabbit
does not die; nor is it, indeed, any the worse. Why is this ?
Usually, when the heart is: stupped, as, for example, when a
ligature is put round the aorta, the blood all runs out of the
arteries into the veins ; and then, as I have said, it is useless for
nutrition. But there is a nervous arrangement which prevents
this when the heart stops in consequence of an irritation
applied to the fifth nerve. This nerve not only contains
branches which are connected with the vagus and stop the
heart or retard it, but it also has branches which go to the
cerebral hemispheres, and there excite an action which passes
down the vaso-motor nerves, causing the auricles to contract,
and preventing the blood from running out of the arteries into
the veins, except very slowly indeed; so that, as soon as the
irritation stops, the circulation is ready to go on normally.
But it is only when the cerebral hemispheres are in good work-
ing order that this occurs. When they are removed, or when
their function is destroyed by chloroform, morphia, or chlvral,
irritation of a sensory nerve, such as the fifth, no longer has the
same effect; and it then always, according to Cyon, lessens the
pressure of blood in the arteries. As it is the pressure of blood
within the arteries which keeps up the flow within them, just
as it is the pressure of water within the pipes supplying a town
which keeps up the supply to the houses, we can readily see
that the diminished pressure which occurs on the irritation of a
sensory nerve, after the cerebral hemispheres have been rendered
useless by a small quantity of chloroform, is a most serious thing
for the animal. But here it is.a little chloroform which is a’

2F 2

436 ONE OF THE CAUSES OF DEATH UNDER CHLOROFORM.

Jangerous thing; and a full dose prevents any risk from this
reflex stoppage of the heart. For the small dose acts on the
cerebral hemispheres first, and destroys the reflex action, which
contracts the vessels, while it leaves the ganglia at the base of
the brain and the medulla unaffected, and thus allows the reflex
stoppage of the heart to go on as usual. A full dose, on the
other hand, affects not only the cerebral hemispheres, but the
ganglia and medulla, and prevents any reflex action whatever
on the heart. I have found that, when a full dose of chloro-
form has been given to. a rabbit, one may hold either strong
ammonia or glacial acetic acid before the nose, and not the
slightest slowness in the beats of the heart can be observed.
Sometimes, indeed, it has seemed to beat rather more quickly
than before.

Now let us try to apply these observations on the lower
animals, and, by them, try to explain the action of chloroform
on man, and the danger of employing it in the extraction of
teeth, as well as in other slight but painful operations. For it
is preciscly in these slight but painful operations—extraction
of teeth and evulsion of nails—that death most frequently
occurs; and it is just in them that little chloroform is given,
because the administrator thinks: “Oh, the operation won’t
last above a few seconds; and it is no use giving the patient
enough to keep him or her snoring for half an hour.” We
know perfectly well that many and many an one has teeth
drawn under chloroform without any bad result ; and we have
already seen that every rabbit has not the same liability to
reflex stoppage of the heart from irritation of its fifth nerve;
but every now and then we meet with a peculiarly sensitive
animal, and every now and again we meet with a case of death
from the extraction of a tooth under chloroform.

If the nervous system in man be at all like that of the rabbit,
the violent irritation of the fifth nerve caused by the extraction
of a tooth will tend to stop the heart. But it will also cause
contraction of the blood-vessels; and thus extraction of a tooth
in the waking state is rarely attended with any serious con-
sequences. But if the reflex action on the blood-vessels, which
usually occurs in the cerebral hemispheres, be prevented by a

COMPLETE AN.ESTHESIA—HORIZONTAL POSITION, 437

small dose of chloroform, just enough, as in the case I have
related, to abolish consciousness without preventing reflex
action in the ganglia at the base of the brain, and if the heart
of the individual be at the same time peculiarly sensitive to the
impression made on the fifth nerve, it may be stopped, and the ©
pressure of blood in the arteries may sink so low that it never
rises again. But if, on the other hand, chloroform be given, as
Professor Syme recommended, with a free hand, so as to produce
total abolition of reflex action, no irritation of the fifth nerve
by the extraction of any number of teeth will have any effect ;
the heart will pulsate as usual, and no danger is to be ADI:
hended from this cause.

I do not at all mean to say that the administration of
concentrated chloroform-vapour is free from danger—far from
it; but the limits of my paper will not allow me to enter into:
this subject. All I can attempt to do is to direct attention to-
the observation of Professor Syme, whose acuteness and.
accuracy few will question, and to try to impress it, by
showing the probable physiological reason why one ought
always to induce perfect anesthesia before beginning any
operation under chloroform. At the same time, I would
observe that, just as the circulation, which had ceased in the
frog in Goltz’s experiment so long as it hung vertically, went
on again when the animal was laid in a horizontal position so.
that the blood found its way to_the heart, so it may go on in
man; and, therefore, the safest position for operations is the-
recumbent one.

The two rules, then, for preventing death during the extraction:
of teeth under chloroform are: put the patient thoroughly over,
and lay him in a horizontal position,

ON IRRITANTS AND COUNTER-IRRITANTS,
WITH REMARKS ON THE USE OF BLIS-
TERS IN RHEUMATISM.

(Reprinted from St. Bartholomew's Hospital Reports, vol. xi, 1875.)

UnpDER the terms irritants and counter-irritants we include
those substances which first cause redness and then inflamma-
tion when applied to the surface of the body. When they are
used for their effect upon the part to which they are applied, as
¢.g.,a blister to a callous ulcer, they may be termed irritants ;
when used for their effect on a distant part, ¢g., a blister to the
chest in pneumonia, they may be termed counter-irritants.

But, before beginning to say a word about their action, it may
be advisable to try to clear the way by correcting a common
.error regarding congestion and its relation to inflammation.
Congestion generally means that there is more blood than usual
‘in some part or other of the body ; but the blood may be either
streaming rapidly through the vessels, or stagnant in them, so
‘that the condition in the two cases is utterly different. When
ithe sympathetic nerve is cut in the neck of a rabbit, the vessels
of its ear become dilated, the ear itself becomes rosy-red, and
“the warm blood coursing rapidly through it raises its temperature.
‘We then say that the ear is congested.* If we tie a ligature
round a finger, and leave it there for some time, the finger gets
swollen, cold, and blue, and we again say the finger is congested.
But the different colour of the parts is enough to show'us that
there is a great and important difference between the congestion
in the ear and that in the finger; and as the colour is due to
the blood shining through the vessels and tissues, we at once
ascribe the rosy colour of the ravbit’s ear to bright arterial

* In his lectures on Surgical Pathology, Sir James Paget wise y designates
what I have here called congestion, as determination of blood to.a part, and

limits the term congestion to the condititon which is present after stasis has
begun.

CONGESTION, ACTIVE AND PASSIVE. 439

blood filling the arteries and capillaries, and the dusky hue of
the finger-tip to dark venous blood filling the capillaries and
veins. But not only is there a difference in the vessels which
are distended in these two kinds of congestion, there is also a
difference in the current through them. In arterial congestion
the blood is streaming rapidly through the vessels, bringing a
constant supply of fresh oxygen and fresh nutriment to the
tissues, and removing the waste products as rapidly as they are -
formed, so that the part in which arterial congestion is present
is in the best possible conditions for health and growth, and
for repair if it should happen to be injured. This arterial
congestion is usually distinguished by the term active conges-
tion. In venous congestion there is no doubt more blood than
usual in the part, but it is of no service to it, for it is stagnant.
Instead of bringing fresh supplies of oxygen and nutriment, it
remains in the vessels until its oxygen is entirely consumed,
and its colour becomes almost black; the products of waste
accumulate in it, and interfere with the nutrition of the tissues,
as the ashes in a grate choke the fire. Nor is its injurious
action negative only, it is positive as well; for while it does no
good itself, it keeps the vessels filled, and prevents any new
blood from entering them. This is venous, or, as it is often
termed, passive congestion. Judging by the pictures I have
just drawn of the two sorts of congestion, one would say there
could be no doubt which was the better, and yet one would look
more alarmed at the news that some organ was in a state of
active congestion than if one were informed that the congestion
was passive. The reason of this is, that active congestion is
frequently regarded as almost synonymous with inflammation,
whereas the two are widely different. Congestion may, and
very frequently does, exist without inflammation, and inflam-
mation sometimes exists without congestion, although generally
accompanied by it. Nothing is easier than for any one to
convince himself of the fact that arterial congestion may exist
without inflammation. Let him put his hand into warm water
for a little while, and on taking it out he will find the whole
skin of a uniform rosy-red, showing that all the capillaries are
‘dilated and filled with bright blood; the veins will swell up,

440 ON IRRITANTS AND COUNTER-IRKITANTS.

become light-blue in. colour, and, when emptied by gentle
pressure, will fill rapidly, showing that they too are full of
bright blood, and that the circulation through them is rapid ;
the hand will be larger than before, and rings which previously
fitted will now be too small for the fingers; the skin will be
warmer than before, even when time has been allowed for the
warrnth due to the water to pass off; in fact, three of the signs
of inflammation, ruber, tumor, et calor will be present, but in-
stead of the dvlor there will be a feeling of great comfort,
whereby the hand signifies to its possessor that it is for the
time being in superabundant health. Perhaps the experiment
is even clearer if, instead: of putting his hand into hot water,
the observer will take a look either at his own or his neigh-
bour’s hands after a good dinner and several glasses of wine.
The same redness and swelling is noticeable, and the warmth
can also be observed, although no extraneous heat has been
applied to the surface, as it had in the other experiment. No-
body would think of calling the hands inflamed in either of these
two instances, for we all know that in a short time the red-
ness, &e., will pass off, leaving them in their ordinary condition.
Some may think, however, that if active congestion were to
continue for weeks and months, instead of for a few minutes or
hours, it would lead to inflammation in the part, but such is not
the case. What it does lead to is hypertrophy of the part, the
increased supply of nutrient material furnished by the full
current of blood leading to increased growth. This was well
shown in a rabbit exhibited by Dr. W. Stirling at the recent
meeting of the British Medical Association in Edinburgh.
Three months previously, Dr. Stirling had divided the sympa-
thetic in the neck of the animal, which was young and growing.
The ear at once became red and hot as usual, and instead of the
congestion subsiding more or less after some time, as it not un-
frequently does, it continued almost unaltered up to the time
of the Association’s meeting. The ears at the time when the
sympathetic was cut were of the same length, but in three
months the increased blood supply had caused the congested ear
to grow so much faster than the other, that at the time of the
meeting it was a quarter of an inch longer than its fellow on the

* INFLAMMATION WITHOUT CIRCULATION, 44}

opposite side. It is evident, then, that congestion is not in-
flammation, and does not cause it even when long continued.
That inflammation can take place without congestion, is shown
not only by the fact that it occurs in non-vascular tissues, such
as the cornea and cartilage, but even more strikinely by the
remarkable observation of my friend Dr. Ainslie Hollis, that
textural changes similar to those produced by inflammation in
hiyher animals, follow the application of irritants to anemones
which have no vascular system whatever.* The two processes
of congestion and inflammation are therefore quite ditferent, and
each can exist independently of the other. Nevertheless, con-
gestion accompanies inflammation in the great majority of cases,
and modifies its progress. While we carefully bear in mind
that the two processes are not identical, let us now try to see
what the connection is between them, and in doing this, let us
begin by inquiring how congestion is produced. From Dr. Stir-
ling’s experiment, it is evident that a copious supply of blood is
beneficial to the tissues, and that if all the vessels throughout
the body were dilated, and blood flowing freely through them,
the tissues in general would be much better off than they are.
But in order to have these dilated vessels sufficiently full, the
body would require twice as much blood as it has; to supply
the blood, the digestive organs would need to be larger, and the
heart must be more powerful in order to propel it; in short,
the individual would require to be re-made on a different plan.’
The arrangement, which has been found by experiment to exist
in animals, is much more economical. ‘The quantity of blood
in the vessels is not sufficient to fill them even half full if they
were all dilated at once,t but by means of the vaso-motor nerves
which have their centre in the medulla oblongata and spinal
cord, they are kept in a state of semi-contraction sufficient to
enable the blood to fill them. Whenever the vaso-motor nerves
are divided, the vessels they supply become dilated, so as to
offer little or no resistance to the flow of blood, and the current
through them consequently becomes rapid. Thus in the rabbit

* St. Bartholomew's Hospital Reports, 1874, p. 267. Journal of Anatomy
and Phusiology, vol. vi, p. 386; vii, p. 80; and viii, p. 124.
t+ Schiff, Zo Sperimendle, 1872, p. 360.

"449 ON IRRITANTS AND COUNTER-IRRITANTS.

the vaso-motor nerves for the ear pass from the medulla along
the cervical sympathetic to the arteries, as shown in Fig. 154,
When the cervical sympathetic is cut, the vaso-motor centre
can no longer exercise any influence on the arteries of the ear,
and they dilate as already descr:bed.

Fia. 164.—Diagram of the Vaso-motor Nerves of the Rabbit's Kar.

St te
SE Ge

a 7

SENSORY
NERVE

Vaso MOTOR CENTRE
JN MEDULLA

.
hui

Vaso moroR NERVES
FOR THE VESSELS
OF THE. EAR

Tit)

emt ee ewww nme men
mae 3

Vaso MOTOR NEAVES
~ FOR OTHER PARTS
OF THE BODY

hier) IMIDE) a 7
Wu. ¥
’

But there is another way of making them dilate, viz., by caus-
ing the vaso-motor centre to cease to exert its usual influence
over these vessels, instead of destroying its means of communi-
cation with them by cutting the vaso-motor nerves. This can —
be done by irritating a sensory nerve to the ear. The irritation
is conveyed up to the vaso-motor centre,and seems to arrest its
action over the vessels supplying the part.whence the sensation
has come, so that they dilate, and the ear gets red and: hot
This dilatation, in consequence of irritation applied to a sensory

ACTIVE (?) DILATATION OF VESSELS. 44°

nerve, is not peculiar to the vessels of the ear—it occurs in all
probability in every vessel of the body; and the dilatation
from irritation is not confined to the capillaries and small
arteries—it extends up to the larger branches, so that the artery
of the part is not only wider than usual, but it pulsates forcibly.
It is indeed so much greater than that produced by division of
the vaso-motor nerve, that some have supposed it to be due to
nerves causing the vessels to dilate actively, and not simply to
yield to the pressure of the blood inthem. But this hypothesis
is unnecessary, for Ludwig has found that irritation of a
sensory nerve has a double effect: (1) It causes the vessels of
the part to which it is distributed to dilate ; (2) it causes the
vessels in other parts of the body to contract, so that the general
blood-pressure is raised, and the blood driven into those vessels
which are relaxed. The part supplied by the irritated nerve
consequently gets its supply of blood doubly increased by the
dilatation of its own vessels, and the contraction of those in
other parts of the body. So constant is this contraction, that
Ludwig has employed the increased blood-pressure which it
‘causes as an indication that sensory impressions have been
conveyed to the nervous centres,* and its great importance in
regard to the action of counter-irritants will be hereafter ap-
parent. J ought to say, however, that the contraction really
seems to be universal, and to affect more or less the vessels of
the part whose nerves have been irritated, as well as those of
the rest of the body, but this contraction in them is more than
counterbalanced by «dilatation. Thus it is that the vessels of
this part not unfrequently contract before they dilate, and some-
times the dilatation is transient, and is succeeded by contrac-
tion. It may seem strange that the irritation conveyed by a
‘sensory nerve to the vaso-motor centre should arrest its action
over some vessels and increase it over others; but this idea
only occurs when we forget that what we call the vaso-motor
centre is really a collection of ganglionic cells connected with
nerves going to different parts of the body, just as a telegraph
station may contain numerous instruments, by which messages
may be sent to different parts of the country. The adaptation of
-* Ludwig and Dittmar, Zudwig’s Arbeiten, 1870, p. 4.

444 ON IRRITANTS AND COUNTER-IRRITANTS.

this arrangement to secure a full supply of blood whenever it is
wanted is obvious. Now, asI have already said, a copious bloed-
supply not only enables the tissues to grow rapidly, but to repair
themselves rapidly when injured, and a scanty blood-supply,
on the contrary, will cause repair to be slow, and will even
induce death and destruction of a part without any other lesion ;
as, for example, when the circulation is stopped by an embolus.
The effects of copious blood-supply in accelerating repair have
been beautifully shown by the experiments of Sinitzin.* When
the fifth nerve is divided within the skull, ulcers form on the
cornea, eyelids, and lips. If the superior-cervical ganelion is
torn out, so that the vaso-motor nerves of the vessels of the
face are destroyed, and the supply of blood to it increased after
these ulcers have formed, they heal up speedily; and if the
ganglion is torn out before the fifth nerve is cut, they do not
form at all. That the beneficial effect of evulsion of the
ganglion is due to the free supply of blood which it produces,
is shown by the fact that it has no action whatever if the carotid
of the same side is ligatured, so as to prevent the destruction of
the vaso-motor nerves from increasing the current. As we have
already seen, a still greater supply of blood is secured to a part
by irritating its sensory nerves than by dividing its vaso-motor
ones, and the utility of this in repairing injured parts is now
obvious. When a grain of sand falls into the eye, it irritates
the sensory nerves, and immediately the vessels of the conjunc-
tiva fill, as Sinitzin noticed them to do, after evulsion of the
sympathetic ganglion, and the free supply of blood is ready to
assist the repair of any damage caused by the sand to the
delicate structures of the eye, besides supplying materials to
the lachrymal gland for the purpose of washing away the
offending bocy. If the grain of sand is now, removed, the
vessels contract, and the tears being wiped off everything looks
as before. There has been congestion, but no inflammation.
But if the sand remains longer, inflammation occurs, sero-
fibrinous exudation takes place under the conjunctiva, or pus
may even be formed.

If we examine the process of inflammation more narrowly by

* Centralblatt d. med. Wissenschaften, 1871, p. 161.

‘
:
%
t-
3

RESULTS OF IRRITATION. 445

using the microscope instead of the unaided eye; we find that
irritation, such as a pinch applied to the web of a froe’s foot,
causes sometimes brief contraction, sueceeded by dilatation ; at
other times, immediate dilatation, first of the arteries, then of
the veins and lastly of the capillaries, at the site of irritation,
and at the same time, the velocity of the current through them
becomes greatly increased.* After a while the arteries contract
again, the contraction beginning at a distance from the irritated
spot, and progressing towards it. This contraction interferes
with the current of blood, and its velocity in the arteries
beyond becomes reduced to the normal. Next the capillaries,
contract, but the veins still remain dilated ; the current in them
becomes slow, and white blood-corpuscles stick to their sides ;
but after a little they also contract, and the normal circulation
becomes completely restored.

If a piece of caustic is applied to the web, similar changes are
produced : all the vessels in the neighbourhood, for some distance
around, dilate, and the blood streams through them with great
velocity. But here a remarkable condition makes its appear-
ance which was not present in the previous experiment.
Although the capillaries of the injured part remain dilated, and
the blood is streaming with unabated rapidity in the vessels all
around, it begins to get slower in them ; the red corpuscles seem
to find an impediment in their way, and accumulate in these
capillaries, like the vehicles in one of the crowded streets of the
City during a block. The current in the arteries and veins like-
wise becomes slow ; the so-called lymph-spaces, which, like side-
walixs, run along the interior of the arterial walls, and are usually
free from blood corpuscles, become invaded ; the corpusvles oscil-
Jate backwards and forwards, as if in a vain attempt to proceed,
and then, becoming stationary, seem to form an almost solid
mass. By-and-by the vessels in the neighbourhood contract
again, and the current in them becomes normal; but those
vessels which lead directly into the cauterised part—arteries as
well as veins—remain permanently dilated. The stasis in the
capillaries extends over a wider area; a few red corpuscles pass
through the walls of the capillaries, and colourless corpuscles

* Lister, Phil. Trans., 1858, p. 645. Cohnheim, Neue Untersuchungen.

446 ON IRRITANTS AND COUNTER-IRRITANTS.

Fig. 155.—Blood-vessels in normal condition. ~

Fic. 156.—Same Vessels after the application of an Irritant and commence-
ment of Inflammation.

emigrate in numbers from loth the capillaries and the veins
forming’ in great measure, if not altogether, the pus with which

DISTINCTION BETWEEN CONGESTION AND INFLAMMATION. 447

we are familiar as one of the products of inflammation. After
the pinch, then, we have had merely congestion; after the
caustic, inflammation. But in both we have had a similar dila-
tation in the calibre of the vessels, a similar increase in the
velocity of the circulation. Where, then, are we to draw the
line between congestion and inflammation? This question has
been well answered by Sir James Paget, who says that the line
appears to be crossed “when the circulation, which was rapid,
begins to grow slower without any diminution, but it, may be
with an increase, in the size of the vessels.” According to
Cohnheim, the changes which are observed in the diameter of the
vessels are mere accessories, and not integral parts of the
inflammatory process; and he also makes the slowing of the
circulation and stasis coincide with the commencement of
inflammation.* ;

There is no doubt about the fact, but it is difficult to see why
the blood corpuscles should stand still in a vessel where there
is no apparent obstruction, and. many explanations have been
advanced to account for the phenomenon. The one which finds
most general acceptation at present is that of Cohnheim, who
believes that it consists in some alteration in the tissues, which
begins in those forming the walls of the blood-vessels, or,
immediately adjacent to them. This opinion is supported by.
the observation of Ryneck,f that stasis may be noticed in
vessels where the blood has been washed out and replaced by
milk. The milk globules accumulate in the capillaries of the
irritated part in much the same way as the corpuscles usually
do. This would seem to show conclusively that it is the vessel,
and not the blood it contains, which obstructs circulation and
leads to stasis. Yet it is hard to see how the appearances
observed are to be explained thus, and they are exactly those
which we should expect from the blood suddenly becoming
thicker, and consequently flowing less easily. Both Henle and
Wharton Jones have adopted this view, the former supposing
that the blood became thicker, both by the plasma losing water
by exudation through the walls, and by having the proportion,

* Paget, Surgical Pathology, 1863, p. 227. Cohnheimn, Neue Untersuchungen.
+ Ryneck, Rollett’s Untersuchungen, 1870. p..103, -

448 ON IRRITANTS AND COUNTER-IRRITANTS.

of its albuminous constituents increased. The two brothers
Ernest Heinrich and Edward Weber ascribed it, without more
ado, to coagulation of the blood in the capillaries ; and it seems
to me that the view taken by those two wonderful men, although
long forgotten, is after all the right one.* It does not conflict
with that of Cohnheim, for the coagulation, if such be present,
no doubt owes its occurrence to changes in the vessels.
Briickef has found that, while blood remains fluid in living and
healthy vessels, it coagulates in them when they die, so that we
would naturally expect any injury which lessened their vitality
would tend to cause coagulation within them; and Wharton
Jones has actually noticed coagula form in the vessels after
pressure upon them. The absence of any fibrinous threads in
the interior of the vessels of inflamed parts does not in the
least disprove coagulation ; for, when experimenting with the
plasma from horses’ blood, I have seen the contents of a glass
tube, from 1 to 24} inches in diameter, in which there were three
layers, the upper one of pure liquor sanguinis, the middle or
liquor sanguinis plus white blood-corpuscles, and the third of
red corpuscles with liquor sanguinis, all apparently fluid. It
was only when I attempted to turn them out that I found
coagulation had occurred. Even when turned out, the soft
clots showed no sign of structure, until they had been squeezed
in the hand, and then fibrinous threads became perceptible. If
coagulation thus failed to become visible in such a large tube,
the absence of any easily recognised sign of it in a small capil-
lary is not astonishing. The chief difficulty in the way ot
accepting Weber’s theory is the occurrence of stasis, when
defibrinated blood or milk is made to circulate through the
vessels. But defibrinated blood, when made to circulate in this
way, takes up something while in the vessels, which re-imparts
to it the power to coagulate, so that it may form a clot after it
has issued from the veins. So far as I know, no similar experi-
ments have been made with milk, but it is possible that it too
acquires so much coagulating power as to cause stasis. In the
absence of the requisite data, it is impossible to look upon

* Virchow’s Archiv, 1857, p. 152.
+ Briicke, Virchow's Archiv, 1857, p. 183,

RELIEF OF PAIN. 449

Weber's explanation of stasis as anything more than an hypo-
thesis ; but, as I have already said, I am inclined to adopt. it,
and to consider that inflammation begins in vertebrates when
coagulation occurs in the capillaries, and arrests the flow of
blood through them.

But whether this view be taken or not, the facts are certain,
that stoppage of the circulation does occur in the irritated capil-
laries, and that the arteries leading to the part are dilated.
What the cause of the pain in inflammation is, we do not
exactly know ; but it seems very probable that it depends to a
great extent on the stretching of the vessels, and the nerves
surrounding them, at or near the site of stasis, by the blood
which is driven into them through the dilated arteries. For,
as every one knows, the pain of inflammation is of a throbbing
character ; it is increased at each time the vessel is distended
by a beat of the heart, and relieved by lessening the supply of

blood. Now, the supply of blood can be lessened in several
ways, and several means, apparently of an entirely opposite
nature, are used to relieve pain. Supposing that we take as an
example an inflammation of the tip of the finger, it is easy to
understand how it may be relieved by pressure on the radial
artery, or by raising the hand to the level of the shoulder, and
may be aggravated by allowing the arm to hang dependent by
the side. But how is it that the pain in the finger may be
relieved by dipping it in cold water, and also by the application
of a warm poultice? I believe the answer to this question to
be that the cold causes the arteries above the poiut of stasis
(Fig. 157) to contract—and thus lessens the force of the
current of blood which is being pumped upon that point. The
warm poultice, on the other hand, dilates those capillaries in
which circulation is still going on, and by thus offering another
channel to the blood, lessens the force of the current against the
point of stasis. It is well known, too, that the pain of a burn
can be greatly lessened by holding the burnt part before a fire.
But, as I can testify from personal experience, the pain is first
greatly increased before it is relieved. I placed a red-hot coal
on the back of my hand until the skin was corrugatea and
glazed. I then held it before a brisk fire for some time. At
2G

450 ON IRRITANTS AND COUNTER-IRRITANTS,

first the pain became so severe that I was tempted to withdraw
my hand ; but by-and-by the pain became easier, and’ almost
entirely disappeared shortly after I had finally taken my hand
away. ‘The explanation of this I fancy to be, that’ at first the
burn caused stasis in the capillaries of the part to which I

CAPILLARIES 7ZBESS

SOh\
PoInT OF _|WiAiZeS
STASIS

ARTERY Vein

appliel the coal, and that the irritation to the sensory nerves
caused the vessels to dilate, as in Loven’s experiment. The
blood being driven down on the obstructed vessels, produced
distension and pain, which was increased when the warmth of
the fire caused the larger arteries to dilate still further. But
after the warmth began to dilate the capillaries of the hand, the
blood passed through the newly enlarged channels, and its
impact on the obstructed vessels being thus removed, the pain
ceased.

Tn the days when blood-letting was much in vogue, it was
found to be a matter of every-day experience that the pain of
inflammation was removed for a time by opening a vein; and
although the pain again returned, the abstraction of a further
quantity again relieved it. The relief is explained by the
general diminution in the blood-pressure after phlebotomy
lessening the tension of the vessels of the inflamed part; while
the return of the pain is in all probability due to the fact that
after the abstraction of blood the vessels contract, so as to
accommodate themselves to their diminished contents, and thus
raise the pressure again. Unluckily, however, blood-letting
does something more than diminish the tension within the
vessels of the inflamed part in common with those of the rest
of the body; it drains away the vital fluid, and seriously
impairs the power of restoration. It is evident, therefore, that

SURFACE REGIONS AND VASCULAR AREAS. ‘451

if we can lessen the tension in the vessels of an inflamed part,
either by causing the arteries to contract or the capillaries to
dilate, we shall do more service to the body than if we weaken
the whole of it to relieve a part. This, I believe, we can do by
means of counter-irritants. I have already mentioned that the
application of an irritant causes contraction of the vessels of
other parts of the body, at the same time that it induces
dilatation in those of the injured part, but this action will not
afford us much help, if all the vessels are contracted alike, for
then the biood would pour with increased pressure into the
dilated vessels of the inflamed part, and the pain would be
worse than before. But clinical experience shows that irritation
to the surface of the body will relieve internal pain, and a
mustard poultice or blister to the side in pleurisy frequently,
indeed generally, gives more or less relief. And there are
several facts which tend to show that just as irritation applied
to different portions of the skin will induce definite reflex
movements distinct from each other,* so irritation applied to
different parts of the surface will induce contraction in different
sets of vessels, a definite correspondence existing between the
part irritated and the set of vessels which contract. Ludwig
-and Lovenf observed that when the sensory nerve of one ear
was irritated, dilatation of the vessels was sometimes observed
in the other ear also, although it was much less, and generally
was replaced by contraction sooner than on the side operated
upon; and Callenfelst noticed that pinching one ear caused
contraction in the vessels of the other. Plunging one hand into
cold water has been observed .to cause cooling of the opposite
hand, an effect which must be due to contraction of the vessels.
But the most important experiments on this point are those of
Ziilzer,} who painted cantharides collodion repeatedly over a
part of the back of a rabbit for 14 days. At the end of this:
time he found that the vessels underneath the skin were much
dilated and filled with blood, and the superficial muscles were

* Sanders-Ezn, Ludwig’s Arbeiten, 1867, p. 11.
+ Ludwig's Arbeiten, 1866, p. 11.
t Callenfels, Zeitsch. f. rat. Med., 1855 ; Bd. vii, p. 191.
§ Ziilzer, Deutsche Klinik, 1865.
2G 2

452 ON IRRITANTS AND COUNTER-IRRITANTS,

hyperemic, Those of the deeper layers, on the contrary, as well
as the thoracic wall, were much paler than on the uninjured
side, and even the lung itself was anemic. When a hair seton
was left in the knee of a rabbit for four weeks, suppuration was
induced immediately around it, but the muscles around the
joint, and the joint itself, were very anemic when compared
with the corresponding parts on the uninjured limb.

Supposing that the effects of blisters on man are similar to
those upon rabbits, we can understand the benefits derived from
their use in inflammation of internal crgans. If the pericardium,
pleura, or lung itself is inflamed, the application of a blister to
the chest will cause contraction of the arteries in them, and
lessen the pain, just as pressure on the radial or brachial would
do in inflammation of the finger. Their beneficial action in
pericarditis is well illustrated by two cases which, in the
absence of Dr. Church, I lately had under my care. J; Ea
male aged 25, was admitted into John Ward on September 13,
suffering from a first attack of rheumatism. Both wrists and
knees were swollen and painful. At 11 o'clock on the morning
of admission the heart sounds were normal. At 2 P.M. a distinct
pericardial friction was heard. A blister was applied over the
cardiac revion, blisters to both wrists, and poultices to the knees.
, Next day the friction had entirely gone, and the pain in the
wrists disappeared, although it still continued in the knees.
On the succeeding day a friction sound was again audible, but
the pain in the wrists never returned. A blister was again
applied to the cardiac region. Next day the friction had dis-
appeared, and did not return. No increased dulness in the
cardiac region could be detected. E. B., a female aged 16, was
admitted for scarlatina into Elizabeth Ward, on September 6.
On the 13th an acute attack of rheumatism came on, with
swelling and pain in the wrists, and distinct pericardial friction.
In this case also a blister was applied to the cardiac region
within four hours of the appearance of the friction. Next day
the friction had entirely disappeared, the pains in the wrists
were less, and on the succeeding day were entirely gone.

In both of these cases I believe that, had we been able to
examine the pericardium at the time the blister was applied, we

BLISTERS IN PERICARDITIS, ETC, a 453

should have found the membrane dry and injected, without any
deposit whatever on its surface, The irritation caused by the
application of the blister to the thoracic wall acted reflexly
through the vaso-motor centre in the medulla oblongata, and
induced contraction of the pericardial arteries, and a more or
less complete return to the normal condition. In the case of
E. B., it might be said that perhaps the friction would have
disappeared even had no blister been applied; but it is improb-
able that in the case of J. E. it would have reappeared on a
succeeding day, had its first disappearance been spontaneous,
and not the effect of the blister, The cessation of pain in the
joints I also attribute to contraction of the arteries in them,
induced by the blister, which had thus had an effect similar to
that of a hair seton in Ziilzer’s experiment. Several other cases
of acute rheumatism which I have had under my care this
autumn have convinced me of the efficacy of blisters to the
joints in young persons, especially those suffering from a first
attack, and in whom the vessels and tissues are probably
normal; but in elderly persons who have suffered from repeated
attacks, the benefit derived from blisters has not been great,

Having now considered the action of blisters as counter-
irritants, let us turn for an instant to their action as irritants,
One of the best means of treating a callous ulcer is to blister it.
Here the irritation of the blister dilates the vessels around the
ulcer, and by affording a free supply of blood, bringing fresh
oxygen and fresh nutriment, the ulcer is healed just like those
on the eye iu Sinitzin’s experiments.

The points which I have tried to show in this paper are—

1, That dilatation of blood-vessels, and a rapid circulation
through them, is advantageous for the tissues, and leads to
increased growth and more rapid repair. While this arterial or
active congestion is beneficial, venous or passive congestion is
injurious.

2. The application of an irritant induces dilatation of the
vessels, and a free current of blood through them. This will
help to repair any injury done to the tissues by the irritant, so
that the injury, to a certain extent, brings its own remedy,

o. Arterial congestion and inflammation are entirely different

454 ON IRRITANTS AND COUNTER-IRRITANTS.

from and independent of each other, although they generally
occur together.

4, Arterial congestion passes rane inflammation when stasis
begins to occur in the capillaries.

5. Stasis is not improbably due, as supposed by the brothers
Weber, to coagulation of blood in the capillaries, the coagulation
being induced by changes in the tissues composing the walls of
the vessels, or immediately surrounding them.

6. Pain in an inflamed part is probably due to distension of
vessels and pressure on nerves by the blood being pumped with
violence through the dilated arteries against the obstruction in
the capillaries.

7. Pain may be relieved by lessening tension in various ways:
by position—by cold—by warmth—by blood-letting—by counter-
irritants.

8. Cold probably relieves tension by contraction of the arteries
going to the inflamed part, warmth by dilating the capillaries of
the surrounding parts, and thus drawing away the blood from
the seat of inflammation.

9..At the same time that an irritant causes dilatation of the
vessels in the part to which it is applied, it causes contraction
of the vessels in other parts of the body.

10. It is probable that it does not cause contraction in all
parts alike, but that definite areas of skin correspond to definite
sets of internal vessels.

11. The relief of pain produced by a blister in pleurisy,
pneumonia, or rheumatic inflammation of a joint, is probably
due'to reflex contraction of the arteries in these parts. .

12. Blisters are useful in lessening congestion in pericarditis,
and in relieving the pain of inflamed joints in rheumatism.*

13. The benefit derived from their use in young persons,
especially those suffering from a first attack, is very great. In
elderly persons it is inconsiderable.

14. The beneficial action of a blister in callous ulcer is prob-
ably due to the increased supply cf blood to the part, induced
by its application.

* Introduced by Dr. Herbert Davies, Lond. Hosp. Rep.

talelln eel a! ie Ahad SIMD S65

!
,
q
:
,
j
fi

A SIMPLE METHOD OF DEMONSTRATING
THE EFFECT OF HEAT AND POISONS
UPON THE- HEART OF THE FROG.

(From the Journal of Anatomy and Physiology, vol. x, 1876.)

TuE fact that heat accelerates and cold retards the pulsations of
the heart, is one of such fundamental importance, both in regard
to a right understanding of the quick pulse, which is one of the
most prominent symptoms of fever, and to a correct knowledge
of the proper treatment to apply when the heart’s action is fail-
ing, that for the last year or two I have been accustomed to
demonstrate it as a lecture experiment. The apparatus I use is
exceedingly simple, but it answers its purpose well, and by its
means the pulsations of the frog’s heart can be readily shown to
several hundred persons at once. I exhibited it at the meeting
of the British Medical Association in London more than two
years ago, and a description of it appeared in the British Medical
Journal for August 23, 1873; but as I have reason to believe
that few physiologists have seen either the instrument or its
description, it may not be amiss to say a few words regarding it
here. It consists of a piece of tin plate or glass 3 or 4 inches
long and 2 or 3 wide, at one end of which an ordinary cork cut
square is fastened with sealing-wax in such a manner that it.
projects half an inch or more beyond the edge of the plate.
This serves as a support to a little wooden lever about 3 inches.
long, a quarter of an inch broad, and one-eighth of an inch thick.,
A pin is passed through a hole in the centre of this lever, and
runs into the cork so that the lever swings freely about upon it
as on a pivot. . The easiest way of making a hole of the proper
size, is simply to heat the pin red hot, and then to burn a hole
in the lever with it. To prevent the lever from sliding along
the pin, a minute piece of cardboard is put at each side of it,
and oiled to prevent friction. A long fine bonnet straw or

456 EFFECT OF HEAT AND POISONS ON THE HEART OF THE FROG,

section of one is then fastened by sealing-wax to one end of the
lever, and to the other end of the straw a round piece of white
paper cut to the size of a shilling or half-crown, according to
convenience, is also fixed by a drop of sealing-wax. The pin,
which acts as a pivot, should be just sufficiently beyond the
edge of the plate to allow the lever to move freely, and the lever
itself should lie flat upon the plate. Its weight too, increased
as it is by the straw and paper flag, would now be tco great for
the heart to lift, and so it must be counterpoised, This is
readily done by clasping a pair of bull-dog forceps on the other
end. By altering the position of the forceps the weight of the
lever can be regulated with great nicety. If the forceps are
drawn back as at c, Fig. 158, the flag is more than counter-
‘balanced, and does not rest on the heart at all, while the
position a brings the centre of gravity of the forceps in front of
the pivot, and increases the pressure of the lever on the heart,
The isolated frog’s heart is laid under the lever near the pivot

Fie, 158.—Instrument for showing the Action of Heat and Cold and of Poisons

on the Frog’s Heart.

33 e
65

and as it beats the lever oscillates upwards and downwards. If
the tin plate be now laid on some pounded ice the pulsations
will become slower and slower, and if the room be not too
warm the heart may stand completely still in diastole, On
removing the plate from the ice the pulsations of the heart
become quicker. Ifa spirit-lamp be now held at some distance
below it the heart beats quicker and quicker as the heat
increases, until at last it stands still in heat tetanus. On again
cooling it by the ice its pulsations recommence. At first they
are quick, but they gradually become slower and slower. On
again applying the spirit-lamp they become quicker, and by

anita Cini yy —_——

HEAT AND COLD—MUSCARIA AND NICOTIA. 457

raising the temperature sufficiently the heat tetanus is converted
into heat rigor. ‘Then no application of cold has the slightest
effect in restoring pulsation,

Not only the effects of heat and cold, but the effect of sepa-
rating the venous sinus or the auricles from the ventricle can
readily be shown with this apparatus, as well as the action of
various poisons, The best for the purpose of class demonstra-
tion is muscaria. A drop of saline solution containing a little
of the alkaloid being placed on the heart, it ceases to beat
entirely, Ifa drop of atropia solution be now added the beats
recommence, I have seen them do so on one occasion after
they had entirely ceased for four hours. When used for demon-
strating the action of poisons the wooden lever should be
covered with sealing-wax, so as to alluw every particle of the
poison to be washed off it, and thus prevent any portion from
being left behind and interfering with a future experiment. By
attaching a small point to the end of the straw in place of the
paper flag, tracings may be taken upon smoked paper fixed on a
revolving cylinder.

PHYSIOLOGICAL ACTION OF THE BARK OF
ERYTHROPHLEUM GUINENSE (CASCA,
CASSA, OR SASSY BARR).

In conjunction with WALTER PYE, M.R.C.S.
(From the Proceedings of the Royal Society, No. 172, 1876.)
(Abstract.) |

1. It diminishes oxidation, and thus prevents fresh vege-
table tissues from communicating a blue colour to tincture of
euaiac. ara

2. It does not hinder the development of the yeast-fungus
nor the germination of seeds.

Penicillium grows freely in a solution of it.

3. A watery solution of the alcoholic extract prevents the
development of Bacteria, but one of the watery extract does
not do so.

4. It does not destroy the life of Bacteria or Infusoria. The
motion of cilia is not arrested by it.

5. It arrests amceboid movement in leucocytes.

6. It has no action on fresh muscular fibre; but muscular
tissue, when kept in a solution of the alcoholic extract for some
days, undergoes extensive fatty metamorphosis, but does not
become putrid.

It does not alter the sensibility of muscle to electrical stimuli,
nor does it diminish its lifting power.

7. It has little, if any, poisonous action on the Inverte-
brata.

8. It has a comparatively slight action on fishes and frogs.
The symptoms produced by its administration are failure of
muscular power, preceded by irregular muscular movement.

9. On birds a small dose produces violent vomiting and
irregular muscular movements, with difficult respiration. These
symptoms are followed by loss of muscular power and death.

a ee eee

EY AS

PNR aoe

GENERAL ACTIONS. | 459

10. In cats and dogs the symptoms are restlessness, nausea
succeeded by violent vomiting, spasmodic jerks of the limbs
during locomotion, quickened respiration, staggering gait,
inability to stand, and death generally during a convulsion
of an emprosthotonic character, apparently connected with
an attempt to vomit. Consciousness seems to be preserved to
the last.

When injected subcutaneously, although it produces violent
vomiting, it never purges; division of the vagi before its
administration lessens or prevents the vomiting usually
observed, as well as the other symptoms of distress; and
in one instance a dose which would ordinarily have been
speedily fatal produced no apparent effect in an animal thus
operated on. |

11. When injected into the stomach of a cat it produces
violent vomiting and purging. Sometimes this is followed by
recovery, in other cases by loss of muscular power and death.

12. Injection of atropia does not prevent death; and although
in one case it prolonged life for two hours, in other instances it
seemed rather to accelerate a fatal issue.

13. It causes the heart in frogs to pulsate more slowly; the
ventricle becomes irregularly contracted, leaving pouches over
the surface, and finally is arrested in systole ; the auricles con-
tract for some time longer.

14. In cats the ventricle also becomes irregularly contracted
before finally stopping.

15. In frogs it causes no rise of the blood-pressure in the
aorta, but raises the oscillation of the mercurial column con-
nected with the vessel to three times its previous height. _

16. In cats and dogs moderate doses injected into the jugular
vein first raise the bluod-pressure without altering the rate of
cardiac pulsation or the extent of oscillation at each beat; they
then slow the heart by stimulating the roots of the vagus. The
tension rises, notwithstanding the slowness of the heart’s beats.
An additional dose paralyses the ends of the vagus in the heart,
aud quickens its pulsations; the pressure rises slightly. A
further dose again slows the heart by acting on its ganglionic
apparatus, and the beats sometimes fall as low as three per

460 ON THE PHYSIOLOGICAL ACTION OF CASCA BARK,

minute, three or four respirations occurring during each cardiac

diastole, Notwithstanding the very slow action of the heart,
the pressure may remain as high as 165 millimetres of mercury,
a fact which indicates that the arterioles are in a state of
extreme contraction. After the heart has ceased, the pressure
falls very slowly. Slight pulsations of the ventricle occasionally
occur when the thorax is opened.

17. Small doses do not seem to increase the excitability of
the peripheral ends of the vagi to electrical stimuli ; moderate
and large doses paralyse these nerves,

18, After injection of casca into the veins of an animal com-
pletely narcotised by chloroform, electrical irritation of the
central end of the divided vagus of one side, the other remain-
ing intact, is followed after a short interval by marked slowing
of the pulse, fall of blood-pressure and increased oscillation,

19. When injected into the veins of a cat after division

of the spinal cord opposite the second cervical vertebra, the
blood-pressure rises to a greater height than is attained under
other conditions.

20. When in the rabbit the sympathetic has been divided in
the neck on one side, subsequent injection of casca into the
jugular vein produces pallor of the recently congested ear of the
side cn which the division had been made.

21, When locally applied to the web of a frog’s foot tem-
porary slowing of the circulation was observed, but no alteration
in the diameter of the blood-vessels.

When injected beneath the skin of the back of a frog it pro-
duces no visible effect on the vessels of the web.

22. It does not appear to possess any special action on reflex
excitability.

23, In moderate doses it increases the secretion of urine at
the same time that it raises the blood pressure. Further doses
diminish the secretion, while they raise the pressure yet more;
and at the time when the pressure reaches its maximum the
secretion of urine is entirely arrested. When the pressure
begins to fall the secretion of urine again commences. The
urine collected after the recommencement of the secretion was
not. albuminous. |

‘
}

Be Fs ae

ACTION ON ORGANS. 461

24. When injected into a loop of intestine it does not
increase the secretion, nor does it produce any distinct con-
gestion.

25. When applied to the eye it has no-action on the
pupil, nor does it cause congestion of the conjunctiva or
lachrymation.

26. When administered to a pregnant cat it did not produce
abortion.

27. The temperature of the body is not affected by adminis-
tration of the drug.

ON THE PHYSIOLOGICAL ACTION OF
CASCA BARK.

In conjunction with WALTER PYE.
(Reprinted from St. Bartholomew’s Hospital Reports, 1876, vol. xii.)

THE practice of subjecting persons suspected of crime or
witcheraft to an ordeal by poison prevails very extensively
along the western coast of Africa. The poison employed is
not the same along the whole coast-line. In Calabar, which
lies about the middle, the natives employ the bean of the
Physostigma venenosum, or, as it is generally called, the Calabar
bean. To the north of Calabar, in Sierra Leone, and to the
south, in Angola, the favourite ordeal poison is not a fruit,
but a bark, which bears in different districts the names of
“doom,” “ gidu,” and “ sassy,” “ saucy,” “ cassa,” or “ casca.” This
bark is obtained from the Lrythrophleum Guinense, which, like
the Physostigna venenosum, belongs to the natural order Legu-
minose. The bark is of a brownish-red colour, is in pieces
about 8 inches long, 4 broad, and between + and $4 thick.
When treated with water it yields a brownish-red infusion.
There are two ways in which it is employed by the natives.
One is to make the suspected person fast for several hours, and
then to give him a few grains of rice and some infusion of the
bark. If he vomits all the grains of rice and is not purged, he
is said to be innocent; but if he is purged, he is pronounced
guilty. The other way is to bend both ends of several boughs
of trees into the ground so as to form a long archway, through
which the accused walks in a stooping position after a dose of
the infusion has been administered. If he is able to walk
through without stumbling, he is considered to be innocent;
but if he stumbles, he is said to be guilty and at once de-
spatched. The chief effects of the poison by which the inno-
cence or guilt of the accused are decided are thus vomiting,

3 6¢

Teer ee ee

GENERAL ACTION, 463

purging, and loss of muscular power or co-ordination. The
effects of the poison on man, as described by some missicnaries,
are vomiting, redness and glazing of the eyes, and loss of the
power of contracting the muscles throughout the body; so that
when the poison has fairly commenced its action on the system,
the sufferer is incapable of standing or walking, and the head
rolls heavily about the breast and shoulders. Its action on
animals was tried by Santos,* who says that the decoction pro-
duced alternate dilatation and contraction of the pupils,
appearance of delirium, violent retching, vomiting, symptoms of
tetanus, and finally death. Professor Liebreich has also in-
vestigated its physiological action, but we have not yet seena
full account of his experiments.

A small quantity of the bark having been brought from
Angola by Mr. Monteiro, who had obtained it with consider-
able difficulty, he kindly gave it to us, and we began a minute
investigation of its physiological action, so as to ascertain not
only the exact manner in which death is produced by the drug,
but the mode in which the various functions are affected by it,
and its possible uses in medicine.

General Action of Casca.

Beginning our experiments with the simplest forms of life,
and proceeding to the more complex, we found that a watery
extract of the bark did not interfere in the least with the ger-
mination of seeds; it did not hinder the growth of the yeast
fungus, and ordinary mould (Penicillium) grows freely in it.
It does not destroy full-grown bacteria nor infusoria; nor does
a watery solution of the aqueous extract prevent the develop-
ment of bacteria, but a watery solution of the alcoholic extract
does so, a fact which seems to indicate the presence in the
alcoholic extract of some principle which is absent from the
aqueous extract. It has little or no action on invertebrate
animals such as snails. On fishes and frogs its action, though
much less than on warm-blooded animals, is nevertheless quite
distinct, its administration being followed by irregular mus-

* American Journal of Pharmacy, April, 1849, p. 96.

464 ON THE PHYSIOLOGICAL ACTION OF CASCA BARK,

cular movements and failure of muscular power. Birds are
easily affected by it, a small dose producing violent vomiting
and irregular muscular movements with difficult respiration.
These symptoms are followed by loss of muscular power and
death.

In cats and dogs it causes restlessness and nausea succeeded
by violent and repeated vomiting. The respiration is very
much quickened. The first symptom of any affection of the
locomotor organs in cats is a peculiar jerk of the hind limbs,
as if something were sticking to the feet, and the animal were
trying to shake it off while walking; then the gait becomes
staggering, and the animal ceases to be able to stand. Death
generally occurs during a convulsion of an emprosthotonic
character, apparently connected with an attempt to vomit.
Consciousness seems to be preserved to the last.

The symptoms observed by us thus agree in most respects
with those described by Santos, but we saw no appearance of
delirium, nor any alternate contraction and dilatation of the
pupil, although we looked for it carefully.

Analysis of the Symptoms produced by Casca.

Vomiting. and Purging.—kIt has already been mentioned
that while vomiting in those subjected to the ordeal by casca
is regarded as a sign of innocence, purging is considered to be
a proof of guilt. It is stated that the priests who prepare the
infusion are able to produce either effect at will, the clear
infusion being given to those whom they wish to prove inno-
cent, while the dregs are administered to those who have
offended them, or who at any rate have not propitiated them.
In order to ascertain whether this was so or not we adminis-
tered an infusion without the dregs to one cat, and an infusion
with the dregs to another; but the result was contrary to
what we expected, the one which had got the dregs recovering,
while the other died. This might, however, be due to the fact
that the infusion with which we operated was prepared from
finely-pounded bark, which would readily yield up its active
principle to water, while the infusion is probably prepared by

~

VOMITING—MUSCULXR WEAKNESS. 465

the priests from coarsely-pounded bark, from which water
would extract the poison more slowly; and if ouly allowed to
vemain a short time in contact with the bark, the infusion
would be comparatively weak, while the dregs themselves
would yield up their active principle in the stomach after
being swallowed, and thus have a much more powerful action.
The purging is due to the local effect of the poison on the
intestines, for it only occurred when the poison was given by
the mouth, and was never present when the drug was admin-
istered by subcutaneous injection. Vomiting, on the contrary,
occurred as constantly when the casca was injected subcu-
taneously as when given by the mouth. The vomiting after
subcutaneous injection of the drug is prohably due to its being
carried with the blood to the stomach, and irritating the sensory
nerves of that organ in much the same way as when introduced
directly into it. The reason why we believe the vomiting to
be due to irritation of the nerves of the stomach rather than to
the action of the drug upon the vomiting centre in the medulla
oblongata, is that when the vagi nerves were divided in the
neck of one cat,a dose which would ordinarily have proved
fatal produced no vomiting, nor indeed any of the usual
symptoms. In other cases where vomiting occurred even after
division of the vagi, it was less than usual, and it might be due
to the irritation being conveyed from the stomach to the
medulla by branches of the solar plexus instead of by the vagi.
The purging is probably due to increased peristaltic action rather
than to increased secretion, fur infusion of casca introduced into
a loop of intestine produced no increased secretion, as a solution
of sulphate of magnesia would have done.

Muscular Weakness—Want of power to walk properly is the
second symptom regarded as a proof of guilt in those subjected
to the ordeal, those who stumble before they reach the end of
the archway of boughs being at once executed. In attempting
to ascertain the cause of this loss of power, we worked back-
wards thus: The motions of the limbs are due to the contraction
of muscles. The contraction of muscles is due to the stimuli
they receive from motor nerves. The stimuli which pass
gown motor nerves to muscles proceed from nerve-centres ir

2H

466 ON THE PITYSIOLOGICAL ACTION OF CASCA BARK.

the spinal cord or encephalon. Thus loss of muscular power
may be due to loss of power either in the muscles themselves —
in the motor nerves which supply them—or in the nerve-centres
in the spinal cord or encephalon.

Action on Muscles.—This was tested by laying one gastro-
cnemius of a frog ina solution of casca, and the other in an
indifferent liquid, such as a °75 per cent. solution of common
salt. After some time the excitability of the two muscles by
electrical stimuli was compared, and also their power to lift
weights. They were found to be equal. This showed that
casca was not a muscular poison, for had it been so, the muscle
immersed in a solution of it would have lost its excitability
before the other, and its power to lift a weight would have
been lessened.

Action on Motor Nerves.—In order to ascertain whether the
motor nerves were paralysed or not, the artery going to one
leg of a frog was ligatured and the poison injected under the
skin of the back. ‘The poison was thus carried to every part
of the frog except the ligatured leg. Immediately after death
the excitability of the motor nerves was tested by the appli-
cation of an induced electrical current from a Du Bois Rey-
mond’s coil. It was found that the motor nerves of the leg to
which the poison had been carried by the blood were not para-
lysed, and were quite as easily excited as those of the other
leg from which the poison had been excluded by ligature of the
artery. The poison, therefore, does not paralyse the motor
nerves.

Action on the Spinal Cord. ete, time after the injection
of casca under the skin of a frog the movements of the
animal become more sluggish, are imperfectly performed ;
and when the toes are pinched, the foot is either moved lazily
or not at all, instead of being promptly drawn up, as it
normally is.. The reflex activity of the cord is thus seen to
be impaired, but we must not hastily conclude that this impair-
ment is due to the direct action of the drug upon the nervous
structures; for imperfect circulation of blood through the brain
and spinal cord quickly deprives them of their power, and
although stoppage of the circulation does not abolish the

q
i.

SPINAL COKD—HEART. 467

functional power of the nerve-centres so quickly in the frog as
in warm-blooded animals, it nevertheless does so after a time.
In order to discover whether the casca destroyed the power of
the spinal cord by acting directly upon it or not, its action upon
the heart was investigated, and we found that a short time after
its administration it arrested the pulsations of that organ. It
seemed, therefore, quite possible that the loss of power in the
spinal cord was simply due to stoppage of the heart by the
poison, but of course this was only probability, as the casca
might act both on the cord and the heart. We decided this
point, however, by administering casca to one frog, and waiting
until the heart had stopped. The instant it had done so, we
arrested the circulation in a frog of a similar kind and size by a

ligature around the large vessels as they arose from the heart.

In these two frogs the circulation was equally arrested, but in
one of them the poison had been previously carried by the blood
to the spinal cord, and could still act upon it although the flow
of blood was stopped. If the casca had any paralysing action
upon the nervous structures of the cord itself, reflex action
ought to have ceased in the poisoned frog before doing so in the
ligatured frog, but this was not the case. In both frogs reflex
action ceased in almost exactly the same time. The abolition
of the function of the spinal cord is therefore due to stoppage
of the circulation caused by the casca, and not to the action
of the drug upon the cord itself. The staggering gait, inability
to stand, and paralysis which we have observed in dogs and
eats, we attribute, like the paralysis in frogs, to disturbance
of the circulation, and not to any special action on the nerve-
centres.

Action on Circulation. Action on the Heart.—The first action
of casca upon the heart of the frog is to cause it to beat more
slowly, then the ventricle becomes irregularly contracted, some
parts of it being firmly contracted and white, while here and
there other points are not contracted, and being filled with
blood, look like little red pouches studding the cardiac surface.
Finally, the ventricle stops altogether in a state of contraction,
while the auricles continue to pulsate for some time longer,
In cats also the ventricle sometimes becomes irregularly con-

2H 2

468 ON THE PHYSIOLOGICAL ACTION OF CASCA BARK:

tracted before finally stopping, the lower part of the ventricle
in one experiment having been contracted, while the upper half
was not, so that the lower half appeared to be partly pushed up °
into the. upper in such a way as to produce a deep transverse
wrinkle across the middle of the ventricle.

Action on the Vagus.—It will be seen from the description
thus given that the action of casca upon the heart of the frog
is almost exactly like that of digitalis, as described by Messrs.
Fagge and Stevenson.* Further experiments have shown us
that casca also resembles digitalis in its action upon the vagus.
A moderate dose of casca injected into the jugular vein first
slows the heart, a further dose greatly quickens it, and another
large dose again slows it. The first slowing is due to stimula-
tion of the vagus roots in the medulla oblongata, for when the
vagi are divided so as to cut the communication between the
medulla and the heart, the pulsations again become quick. The
quickening which a large dose of casca produces when the vagi
are uninjured is due to its paralysing the ends of these nerves
in the heart, and thus destroying the communication between
this organ and the medulla quite as effectually as the division
of their trunks by the knife. When the nerves, as they pass
down the neck, are irritated by an induced galvanic current in
their normal condition, they slow the pulsations of the heart, or
stop it altogether; but after the injection of casca has paralysed
their ends in the heart, no irritation of their trunks has any
power to slow its pulsations. The final slowing produced by a
large dose of casca must be due to the action of the drug upon
the ganglionic apparatus within the heart itself, as the vagus
ends are already paralysed. The extreme slowness of the heart
in this stage is sometimes very remarkable, as in one experiment
there were only three pulsations per minute, only one occurring
in the time occupied by three or four respirations.

Action on the Blood-vessels.—Casca has a most extraordinary
power of contracting the blood-vessels. This is indicated by
the pressure of blood within the vessels becoming high after its
injection, notwithstanding the slowness of the heart’s action;
but it is proved most unmistakably by the fact that during the

* Proceedinys of the Royal Socie’y, vol. xiv, p. 270.

i

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BLOOD VESSELS—PERIPHERAL ACTION. 469

long diastolic pauses the pressure does not sink as it ordinarily
does, but sometimes remains as high as 165 millimetres of
mercury. When the arterioles are in their normal condition as
regards dilatation, the blood flows readily out of the arteries
into the veins, and the pressure rapidly falls in the arterial
system during the cardiac diastole. When the arterioles are
much contracted, however, as after the administration of casca,
the flow of the blood out of the arterial into the venous system
is impeded, the arteries remain full, and the tension of the blood
within them high.

Digitalis also contracts the arterioles and causes the fall of
pressure during the cardiac diastole to be slow. The mode in
which casca and digitalis produce contraction of the blood--
vessels, however, seems to be different. Digitalis causes it by
stimulating the vaso-motor centre in the medulla oblongata,.
and this centre acts through the vaso-motor nerves upon the
vessels. These nerves pass down from the medulla, through
the cervical part of the spinal cord, along the splanchnics, Xc.,.
to the vessels. Consequently, when the communication between
the vaso-motor centre in the medulla oblongata and the vessels.
is destroyed by dividing the cervical and spinal cord, the:
vessels dilate, and no stimulation of the vaso-motor centre has.
any power to cause them to contract. The contraction usually
produced by digitalis, therefore, does not occur if the cord be
divided before its injection, and is removed if the cord be
divided after contraction has already taken place. This is not
the case with casea, however, for we found that after the
spinal cord had been completely divided in a cat opposite the
second cervical vertebra, the blood-pressure after the injection
of casca rose higher than in any other experiment. The casca
must therefore act either on the blood-vessels themselves, the
vaso-motor nerves, or some vaso-motor centre not contained in
the medulla.

A further proof that casca acts on peripheral ~2so-motor
canglia or nerves is afforded by an experiment in which the
sympathetic nerve was divided in the neck of a rabbit, so as
to sever the connection between the vaso-motor centre and
the vessels of the ear on one side. On the other the nerves

470) ON THE PHYSIOLOGICAL ACTION OF CASCA BARK.

were left intact. After injecting a dose of casca the vessels
in both ears became pale, and apparent'y there was no differ-
ence between them in the ear with the divided nerve and in
the other.

We are rather inclined to the supposition that it does act on
some such centre or centres—possibly ganglia—in or around
the vessels themselves, because the local application of casca to
a frog’s foot, or its injection under the skin of the back, causes
no contraction in the vessels of the web, as one would expect it
to do if it acted on the vessels themselves. The arterioles begin
to contract after a small dose of casca before any effect is
produced on the vagus, so that the blood-pressure begins to rise
before the pulse becomes slow. The contraction also seems to
last after the vagus is paralysed, and even after the heart has
ceased to beat, so. that when the aninal is dying the blood-
pressure falls very slowly.

The contraction of the vessels after the injection of casca is
‘mot confined to those which are under the dominion of the vaso-
motor centre in the medulla. It has been shown by Ludwig
-and Hafiz that while this centre can cause contraction of the
vessels going to the intestines, it has little or no power over
‘those supplying the muscles. Thus it happens that when this —
‘centre is irritated the blood-pressure does not remain bigh
-during the cardiac diastole, as one formerly supposed it would
do; for although the intestinal arterioles are firmly contracted,
and prevent any blood from flowing into the veins, the arteries
of the muscles remain uncontracted and the blood flows rapidly
through them. As the blood-pressure after the injection of
-easca remains so high during the cardiac diastole, the arterioles
in the muscles must be contracted as well as those in the
intestines. In its mode of action upon the blood-vessels casca
differs from digitalis, but agrees with ergot, which seems to
cause contraction by acting rather upon peripheral vaso-motor
nerves or ganglia, or on the muscular wall of the blood-vessels,
than on the vaso-motor centre.

Action on the Kidneys.—As the action of casca on the cireula-
tion so closely resembles that of digitalis, it seemed not
improbable that it might also have a diuretic action, and we

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ACTION ON TIIE KIDNEYS. 471

accordingly proceeded to try whether it had or not. The
manner in which we experimented was as follows. A dog was
aneesthetised with chloroform, the anesthesia being kept up
during the whole operation. A cannula was placed in one
ureter so that the urine dropped from the kidney as fast as it
was secreted, and the rapidity of secretion could be readily
ascertained. ‘The carotid artery was connected with a kymo-
evaphion and the blood-pressure measured. On then injecting
a dose of casca into the jugular vein, we found that the blood-
pressure rose and the urine began to be secreted more rapidly.
An additional dose raised the blood-pressure still higher, but
the secretion of wine began to get slower instead of quicker,
and when the blood-pressure had risen to its maximum the
secretion stopped altogether. After a while the blood-pressure
began to fall, and the secretion again commenced. The explana-
tion which we are inclined to give of these facts is that at
first the casca, by causing contraction of the vessels generally,
and raising the blood-pressure, increases the pressure in the
glomeruli of the kidney, and thus causes the watery con-
stituents of the blood to filter through them more quickly than
usual, It thus increases the flow of urine. It next causes the
vessels of the kidney to contract more and more, so that
notwithstanding the high blood-pressure in the arterial system
generally, there is little blood in the kidneys. The pressure of
blood in the glomeruli is consequently low, and the secretion of
urine scanty, and when the contraction of the renal. artery
becomes very great the secretion stops altogether. When the
arterial spasm again relaxes, the secretion recommences at the
same time that the blood-pressure falls. In this respect the
action of casca agrees completely with that of digitalis.* It
seems probable that casca will also, like digitalis, be found to
have a cumulative action, should it. be introduced into medicine;
for the effect of any drug depends on the amount of it cir-
culating in the blood, and this amount may be increased
either by increasing the introduction of new quantities or by
diminishing the excretion. It seems probable that the sudden

* Brunton and Power, “ On the Diuretic Action of Digitalis.” Proceedings
of the Ruyal Society, 1874, No. 158. Vide aniea, p. 410.

472 -ON THE PIIYSIOLOGICAL ACTION OF CASCA BARK.

appearance of dangerous symptoms during the administration of
digitalis is due to its stopping excretion by the kidney while
the drug is still taken by the mouth. The occurrence of
poisoning by digitalis would thus be completely analogous to
poisoning by curare in an experiment of Herrmann’s.* Curare
produces paralysis of motor nerves when quickly introduced
into the circulation by injection under the skin or into a vein,
but doves not usually prove poisonous when taken into the
stomach. The reason of this is that itis excreted by the kidneys
as quickly as it is absorbed from the stomach, so that there is
never enough of it in the blood at any one time to be injurious.
When Herrmann tied the renal vessels, however, so as to prevent
excretion, curare taken into the stomach proved as certainly
fatal as when injected into a vein. In digitalis-poisoning the
drug itself causes contraction of the renal vessels, producing the
same effect as the ligature applied to them by Herrmann in the
ease of curare, and the same would probably be the case witls
casca.

Action on Respiration.—The respiration is generally quickenec
by casca. This quickening appears to be due to a stimulating
action of the drug upon the pulmonary branches of the vagus,
as it was not observed when the vagi were divided before the
casca was administered,

Action on Temperature.—Casca does not appear to have any
action either in lowering or raising the temperature of a healthy
animal. We have not yet tried what effect it will have ir
fever.

Action on the Lye.-—When applied to the eye it has no action
on the pupil, nor does it cause congestiun of: the conjunctiva or
lachry mation.

Action on the Uterus.—Digitalis having been said to have a
powertul action upon the uterus, an action which has been found
by Dr. Dickinson to be useful in arresting menorrhagia by
causing contraction of the uterus, we administered casca to a
pregnant cat, but it did not produce abortion.

* Du-Bois Reymond’s und Reichert’s Archiv, 1867, p. 64

ee

CARDIAC TONIC—DIURETIC. 473

Probable Use of Casca in Medicine.

It is evident from the description we have given above of
the physiological action of casca, that it is quite different from
that of Calabar bean, the other ordeal poison employed on the
African coast, which has become such a useful remedy since its
physiological action was first ascertained by the admirable
researches of Dr. T. R. Fraser. Unlike physostigma, it has no
action on the pupil, aud no special action upon the spinal cord.
Its action is exerted chiefly upon the stomach, circulatory
apparatus and kidneys. Its action on the stomach seems to be —
rather a drawback than otherwise, as it would have been highly
advantageous to have had a drug which would act like digitalis.
upon the heart without producing the sickness which sometimes
obliges us to discontinue the use of the latter. As, like
digitalis, it strengthens the heart while slowing its pulsations,
it will be useful in mitral disease, and its diuretic action will
prove serviceable in dropsy arising from this cause. At the
same time its more powerful action on the vessels leads us to
hope that it will be useful in advanced cases of cardiac dropsy
when digitalis fails. This power of contracting the vessels also
indicates that it will prove a useful hemostatic, mcre powerful
than either digitalis or ergot, the virtues of which it seems to
combine. Mr. Monteiro having kindly promised to obtain for
us a large quantity of the bark, we trust we shail find that its
action in disease corresponds to the hopes we have tormed,

PRELIMINARY NOTES ON THE PHYSIO-
LOGICAL ACTION OF NITRO-
GLYCERINE.

In conjunction with E. §. TAIT.
(Reprinted from St. Bartholomew's Hospital Reports, 1876, vol. xii.)

From the olservations and experiments on the physiolo-
gical action and therapeutic employment of nitro-glycerine
made by numerous authorities, amongst whom may be men-
tioned Hering, Pelikan, Field, Thorowgood, Brady, Demme,
Albers, Onsum, Eulenburg, Werber and others, it is evident
that nitro-glycerine is a powerful poison, and exerts a marked
action on the nervous system when given even in exceedingly
minute doses. Although many facts regarding its action have
already been ascertained, it has not yet been made the subject
of an elaborate investigation, and it therefore seemed to us
advisable to ascertain its action more thoroughly than has yet
been done. Our research is still very imperfect, but cireum-
stances having obliged us to discontinue it for a few months,
we now give tlie results we have already obtained, and trust to
fill up the numerous deficiencies in them when we are again
able to resume work together. Whilst we confine ourselves in
our present paper to a statement of the results of our own
experiments, we purpose in a future one to enter into the
literature of the subject, and to compare the conclusions to
which our experiments have led us with those of previous
observers.

General Action on Frogs.—A number of experiments were
made by injecting a 10 per cent. solution of nitro-glycerine in
alcohol, in quantities varying from about one-tenth to four-
tenths of a cubic centimetre, under the skin of the back or
belly of a frog. The result was in all cases nearly the same.
Immediately after the injection the animals became very rest-
less, and the respirations became very rapid. In a minute or

GENERAL ACTION ON FROGS AND CATS. . 475

two the restlessness subsided and gave place to lethargy, the
frogs showing a great disinclination to move, and allowing
themselves to be gently pushed along the table without jump-
ing. The respiration still continued rapid. In about two
minutes more (generally three to five minutes after the injection
of the poison) the frogs gave a sudden spring, and fell into
tetanic convulsions. These lasted about half a minute, and then
became more or less relaxed; they soon returned, however, and
continued to do so at nearly regular intervals, when the frogs
were left alone, but they might also be brought on by touching
the animals. When the relaxation of the muscles was imper-
fect, so that the lees still remained extended during the inter-
vals, the convulsions were marked by twitchings of the toes.
In some instances the mouth seemed to be the part first
affected by the convulsion, as the jaws were seen to open and
shut, although it is possible that this was connected with respi-
ration rather than with the general convulsions; next the arms
were affected, and lastly the legs. The arms seemed also to be
more sensitive than the legs, as slight spasmodic twitches
could sometimes be produced by touching or pinching the arms,
when similar irritation of the legs had no effect. After con-
tinuing for some time the convulsions became gradually weaker,
and the animal died.

General Action on Cats.—The only warm-blooded animals on
which we have as yet experimented with nitro-glycerine are
cats, and although it is probable that a general similarity exists
between its action on these and on other mammalia, yet it is
not unlikely that there are minor differences which can only
be ascertained by farther experiments. On injecting 4 cubic
centimetres of a 10 per cent. solution into the peritoneal cavity
of a cat, the first symptom noticed two minutes after the injec-
tion was a stretching movement of the hind leg, as if the
animal were trying to shake something off the foot. In about
half an hour the cat cried as if in uneasiness or pain, and then
vomited. In about half an hour more the legs seemed to: fail
during walking, and the animal suddenly sank down and never
again rose. Vomiting again occurred once or twice, the respira-
tion becoming exceedingly rapid (120 per minute), and the

476 ON THE PHYSIOLOGICAL ACTION OF NITRO-GLYCERINE.

tongue and muscles of the lower jaw worked at each inspiration,
so that the tongue lolled back and forwards like that of a dog
which has been running.. This action we have never observed
in cats, either during health or after the administration of any
other poison. The nostrils also moved with the respirations,
and muscular twitching was observed over the body. The
cornea was now found to be insensible, and pinching called
forth no action in the limbs; but when the tail was pinched, a
deep inspiration took place. Slight spasms resembling hiccough
now occurred, and in five minutes more the animal died, two
hours and five minutes after the injection of the poison.

A large dose (10 cubic centimetres) injected in the same way
almost immediately caused the respiration to become rapid
(120 per minute) and the gait staggering. The animal also
cried, the tongue lolled out in the manner already described,
and the third eyelids were drawn half over the eyes in the
same manner as we have seen them in other cats after division
of the vagi. In five minutes the respirations had reached
160 per minute, and the animal lay quite quiet. In 15 minutes
voluntary action was quite paralysed, and reflex almost entirely
so. When either the fore or hind legs were drawn out, no
attempt was made to draw them up to the body, the limbs
seeming quite paralysed. On tickling the inside of the ear,
however, the ear was moved; and on touching the cornea, the
eyelids closed.

On applying a strong induced current 20 minutes after the
injection to various parts of the body and legs, muscular twitch-
ings were produced, but no reflex movements.

In five minutes more, respiration became slow and gasping
(6 per minute); the tongue ceased to loll, and in five minutes.
more the animal was dead, 30 minutes after the injection.

On post-mortem examination the heart was found still
pulsating, and the blood of a somewhat chocolate colour.

The principal effects produced by nitro-glycerine are thus.
seen to be— great acceleration cf the respiation, paralysis, loss
of reflex action, and apparently to a great degree of sensation,
and death from stoppage of the respiration. ‘The minor symp=
toms are muscular twitching and vomiting,

EEE

oe

ns

ON NERVOUS SYSTEM AND MUSCLES. 477

Action on the Nervous System.—In frogs nitro-glycerine pro-
duces, as we have already mentioned, languor, tetanus, and
finally paralysis. In cats there is paralysis without any tetanus,
although there may be movements of a convulsive nature—
such as vomiting, spasmodic respirations like hiccough, and
muscular twitches—when the poison is injected into the abdo-
minal cavity. In another experiment we found that after the
injection of 1 cubic centimetre of a 10 per cent. solution
directly into the jugular vein of a cat, tetanic convulsions
occurred.

In order to ascertain whether the tetanus in the frog is due
to the action of the nitro-glycerine on the spinal cord, or on the
nervous centres within the encephalon, the spinal cord was cut
across about the middle before the poison was given. The
upper part of the animal immediately became very restless,
and the arms were stretched out at right angles to the body
with the toes outspread. There was no alteration in the hinder
part of the body and legs. The nitro-glycerine, therefore, does
not cause tetanus by its direct action on the spinal cord, as other-
wise spasms would have been observed in the hind legs. This
result was confirmed by another experiment. A frog was
decapitated, and after the spinal cord had recovered from the
shock, and reflex movements were again observed in the limbs,
nitro-glycerine was injected under the skin. No spasm what-
ever was observed. Other experiments led us to believe that
the tetanus is not due to any action on the cerebral lobes, but
probably to the effect of the poison on the optic lobes; but we
are not yet in a position to decide this with certainty.

Action on Muscie-—In order to ascertain this, two gastro-
cnemii of a frog were immersed in two glasses, each containing
10 cubic centimetres of a °75 per cent. solution of common salt.
To the one glass about two drops of the solution of nitro-
glycerine were added. After three hours the muscle which had
been lying in the pure solution of salt contracted readily on the
application of an induced current, while the one which had been
lying in the salt solution with nitro-glycerine was in‘a state of
rigor mortis. Nitro-glycerine is therefore a muscle poison, and
in this particular its action agrees with that of nitrites, all of

478 ON THE PHYSIOLOGICAL ACTION OF NITRO-GLYCERINE.

which have been found to be muscle-poisons in an unpublished
research on which one of us (Brunton) in conjunction with Mr
Gresswell is at present engaged in this laboratory.

Action on Motor Nerves.—On ligaturing the vessels in one leg
of a frog so as to prevent the circulation of poisoned blood in
that limb, the nerve being left uninjured, we have found that
when paralysis had begun to appear, the spasms which could
be observed were slightly more. marked in the ligatured limb.
On testing the irritability of the motor nerves after death, they
were found to respond much more readily to an induced current
in the ligatured than in the non-ligatured leg; but as the
muscles of the non-ligatured leg responded but feebly to a
current directly applied to them, we are at present unable to
say whether the paralysis is entirely due to the action of the
poison on the muscles, or whether it affects the motor nerves as
well. We may possibly be able to decide this point by making
farther experiments, similar to those which we have already
performed, but in winter, when the muscles preserve their irrit-
ability longer than in summer, during which our experiments
were made. We also propose to try them with Rana esculenta
instead of Rana temporaria, the muscles of these two species of
frog having been shown by Schmiedeberg to be very differently
affected by caffein, a poison having an action similar in some
respects to that of nitro-glycerine.

Action on the Spinal Cord—tThe loss of reflex action both in
frogs and cats, in the advanced stages of poisoning, indicates
that the cord is paralysed ; and the persistence of reflex action
in parts supplied by cranial nerves, such as the eye and.ear,
after it has disappeared from other parts of the body, indi-
cates that the cord is paralysed before the ganglia at the base
of the brain. |

Astion on the Brain.—One of the most remarkable effects of
nitro-glycerine is the intense headache it produces, even in
infinitesimal doses. Almost all observers agree about the
fact of its producing headache, but they differ regarding the
nature of the headache. According to our experience, it is not
always of the same kind, being sometimes frontal, sometimes
occipital, sometimes affecting one side only, and at other times

ee a oe as

ON THE HEART, BLOOD-PRESSURE AND BLOOD. 479.

the whole head. In one of us (Brunton) it was several times
accompanied by vomiting. It has been said by some that con-
tinued use of nitro-glycerine makes the person more sensitive,
but in one of us (Tait) the contrary seemed to be the case, as
the headache was only suffered from during the first week of
the investigation. None of the poison was taken by the mouth,
and, as it is non-volatile, the amount taken in by the lungs must
have been infinitesimal. It is possible that, as some writers
have supposed, a little of it was absorbed by the skin, but the
quantity thus taken into the system must have been excessively
minute.

Action on the Heart.—When the excised heart of a frog is
put into 10 cubic centimetres of a “75 per cent. salt solution,
and two drops of a 10 per cent. solution of nitro-glycerine in
alcohol are added, the heart begins to beat more and more
slowly, and gradually ceases altogether. A similar quantity of
alcohol, added to the same amount of salt solution, had no
action on a heart immersed in it. In one instance, after the
addition of nitro-glycerine, we observed a slight quickening
before the beats became slow.

Two cubic centimetres of a 10 per cent. solution of nitro-
glycerine in alcohol injected into the jugular vein of a cat
stopped the cardiac pulsations entirely in 13 seconds. One
cubic centimetre in another experiment greatly quickened the
pulse. The power of the vagus over the heart appears to be
diminished, as irritation of its trunk had less effect upon the
heart after injection than before.

Action on the Blood-presswre.—Nitroglycerine diminishes the
blood-pressure considerably, but its power to do so is very much
less than that of nitrite of amyl.

Action on the Blood.—The blood of animals poisoned by
nitro-glycerine is of a chocolate colour, even in the arteries.
When blood is shaken up with nitro-glycerine solution, it
acquires a chocolate colour, though slowly. In this respect
nitro-glycerine agrees with nitrites, which also cause the blood
to assume that colour.

With the spectroscope at our disposal, however, we were
unable to discern any difference between the spectrum of blood

480 ON TILE PITYSIOLOGICAL ACTION OF NITRO-GLYCERINE.

from an animal poisoned with nitro-glycerine, or of normal
blood shaken up with it, and normal blood, either before or
after the addition of a reducing fluid. If our observation
were correct, this would constitute an important difference
between nitro-glycerine-biood and nitrite-blood as described
by Gamgee; but the strong similarity in colour between the
two kinds of blood makes us doubtful about the correctness of
our spectroscopic observation, and we hope to repeat it with a
better instrument as soon as opportunity allows.

Action on Oxidation.—Certain vegetable substances have the
power of oxidising tincture of guaiac, and causing it to become
blue. In order to ascertain whether nitro-glycerine had any
power to diminish or prevent this oxidising process, a potato
was pounded with water, and the liquid strained off and mixed
with tincture of guaiac and a small quantity of nitro-elycerine.
Instead of preventing oxidation, however, it rather seemed to
quicken it, the mixture assuming a blue colour more quickly
and more intensely than where no nitro-glycerine was added.
in this respect also its action resembles that of nitrites as
described by Binz and Pick.

From our experiments it would then appear that nitro-
elycerine agrees with nitrites in not lessening the oxidation of
guaiac by vegetable solutions, in causing the blood of animals
poisoned by it to become of a chocolate colour, in acting as a
muscular poison, and in diminishing blood-pressure. Its action
in this last respect is, however, much less than that of nitrite
of amyl. In a future paper we hope to give a more detailed
and complete account of the action of nitro-glycerine, and of
the resemblances and differences between its action and that of
nitrites, as well as a discussion of its possible use in medicine.

Note.—The severity of the headache which nitro-glycerine
induced in one of us (Brunton) was so great that it made us
delay in trying it on patients, and before we had done this it
was proposed by Dr. Murrell as a substitute for nitrite of amyl.
W. Marrell : “ Nitro-glycerine as a Remedy for Angina Pectoris,”
Lancet, 1879, i, 80, 118, 151, 220,

:

ON THE PHYSIOLOGICAL ACTION OF THE
BARK OF FRYTHROPHLEUM GUINENSE,
GENERALLY CALLED CASCA, CASSA, OR
SASSY BARK.

In conjunction with WALTER PYE.

(From Philosophical Transactions of the Royal Society, vol. clxvii, part 2.)
Received and read June 15th, 1876.

SEVERAL months ago we received from Mr. Monteiro a piece
of Casea bark, which he had obtained with great difficulty from
a native at Bembe during his residence in Angola. This bark
is used by the natives as an ordeal, persons suspected of theft,
witchcraft, or other crimes being made to drink an infusion of
it. If it causes vomiting only, the person is acquitted; but if
it causes purging, he is considered to be guilty, and is either
allowed to die of the poison or at once killed. Among some
tribes a practice prevails of making the accused, after drinking
the infusion, walk in a stooping posture under half a dozen low
arches made by bending switches and sticking both ends into
the ground. Should he fall down in passing under any of the
arches, he is at once considered guilty, and, without waiting for
a purgative effect to be produced, he is at once put to death.

All the natives agree in their description of the effect pro-
duced on a person poisoned by this bark. His limbs are first
affected, and he loses all power over them, falls to the ground,
and dies quickly, without much apparent suffering.

The same bark, or one haying precisely similar effects, is used
as an ordeal in Sierra Leone, under the name of “red-water
bark,’ and in Ashantee, under the name of “doom.” In both
these places the test of vomiting or purging only seems to be
employed, and not that of stumbling, as described by Mr. Mon-
teiro; but according to C. A. Santos, the missionaries describe
the bark as causing vomiting, glazing of the eyes, and loss of

21

482 ON THE PHYSIOLOGICAL ACTION OF CASCA BARK.

the power of contracting the muscles throughout the body; so
that, when the poison has fairly commenced its action, the
sufferer is incapable of standing or walking, and the head rolls
heavily about the breast’an‘1 shoulders.

Appearance of the Bark.—The pieces given to us by Mr. Mon-
teiro were from 8-12 inches long, about 4 inches broad, and
2 of an inch thick, dark brownish-red in colour, and deeply
grooved externally. Their appearance agreed exactly with the
description given by C. A. Santos, in the American Journal of
Pharmacy, April 1849, p. 96, of the bark which he terms Saucy
bark, or Gidu.

Chemical Reactions—When treated with alcohol it yields a
«lark brownish-red tincture, and boiling water gives an infusion
of a similar colour, which deposits a pale brownish-red precipi-
tate on cooling; but at the same time the supernatant fluid
‘remains turbid from suspended particles, which do not subside,
and which are not removed by filtration. It becomes clear
‘when heated, but the turbidity returns on cooling. The tinc-
‘ture, when evaporated, leaves a resinous-looking extract, and
when mixed with water gives a pale brownish-red precipitate.
The watery solution of either the alcoholic or aqueous extract
becomes much darker in colour after exposure to air.

An aqueous solution gives a brownish-black’ precipitate with
ferric perchloride, indicating the presence of some form of
tannin. It also gives a precipitate with tincture of galls or
tannie acid, mercuric chloride, stannic chloride, gold chloride,
silver nitrate, and lead acetate, either neutral or basic. If the
precipitate produced by neutral lead acetate be removed by
filtration, the addition of basic lead acetate to the filtrate causes
very little further turbidity. Platinum chloride causes little or
no precipitate.

These reactions closely agree with those given by Santos and
Procier.

Santos states that, by passing the dilute tincture through
animal charcoal, washing, drying, and boiling in absolute
alcohol, he obtained a crystalline substance which was poisonous ;
but Procter failed to obtain a poisonous substance, although he
got crystals which were non-poisonous.

ACTION OF A LARGE DOSE ON MAMMALS. 483

From the small quantity of bark at our disposal, we have not
attempted to isolate any active principle, as we feared our sup-
ply would not be more than sullicient for the investigation of
its physiological action.

Professor Liebreich, however, has lately succeeded in separat-
ing a crystalline substance, which is exceedingly poisonous.

General Action —lIlts action on the lower animals has been
investigated by Santos and Liebreich. The former found that a
decoction of the bark caused alternate dilatation and contrac-
tion of the pupils, appearance of delirium, violent retching,
vomiting, symptoms of tetanus, and, finally, death. The crys-
talline principle obtained from the bark by Liebreich caused
vomiting and sudden death, without previous loss of conscious-
ness. Death is attributed by him to paralysis of the heart.

In our own experiments on dogs and cats we have observed
vomiting, weakness, and death during a convulsion from the
effects of the drug, whether introduced into the stomach or in-
jected under the skin, into the peritoneal cavity, or into the
veins,

GENERAL ACTION ON MAMMALS.
ACTION ON CATS.

Experiment I.—February 23.
Effects of a very. Large Dose.

Four and a half ¢.c. of a saturated alcoholic solution of Casea*
were injected into the abdominal cavity of a half-grown kitten
weighing 746 grammes. At three minutes after the injection
it began to walk stiffly, and a peculiar jerk occurred in the hind
legs each time they were lifted. Respiration 60. At 5 minutes
after injection it seemed giddy, and rolled over on trying to
walk. Feces were passed. Lespirations 80, gasping. At ten

aninutes it was lying on its side with its mouth wide open;

respirations 120. At 10 minutes 30 seconds the respirations
were 160, gasping. At 11 minutes it made feeble and unsuc-

* This solution was prepared by ext acting the bark with alcohol and evapo-
rating to dryness. The solid extract thus obtained was dissolved in warm
alcohol in such quantity that on cooling a deposit occurred. The solution was
then filtered and the fi‘trate employed for experiments.

484 ON THE PHYSIOLOGICAL ACTION OF CASCA BARK.

cessful attempts to vomit; the respiration became intermittent ;
there was an oscillating movement of the eyeballs, and the pupils
were widely dilated. At 12 minutes the respiration became
slower, as well as irregular. At 16 minutes it was 60, irregular
and laboured. At 21 minutes the respiration appeared to be
entirely diaphragmatic. At 24 minutes there were strong, in-
effectual attempts at vomiting, followed by sudden stoppage of
respiration, and death in a condition of emprosthotonos. ‘The
pupils at that time were widely dilated.

On opening the thorax immediately after death, the ventricles
were found firmly contracted ; but they recommenced to pul-
sate, and continued to do so for a few minutes spontaneously.
They responded by a single contraction to irritation for 34 hours
after death. By this time the heart looked quite dry and glazed,
and rigor mortis was well marked in the muscles. The lungs
were pale,

Experiment IT.—February 22.
Lffects of a Moderate Dose.

Three e.c. of the same alcoholic solution were injected into
the abdominal cavity of a cat weighing 2238 grammes. At
25 minutes afterwards the animal vomited; and this was
repeated at 35 minutes and 41 minutes. At 41 minutes the cat
seemed weak; respirations laboured, 60 per minute ; pulse, 100,
regular. At 55 minutes respirations 80, shallow, irregular. At
75 minutes respiration deeper and more laboured. At 85 minutes
the gait was staggering, and the limbs were moved with a jerk
at the end of each step; respirations 40, more regular; pulse
100, regular. Four hours after injection the animal was sleepy ;
when roused it walked feebly ; there was no further vomiting.
Its condition remained unaltered as long as it was observed;
and it died between eight and twenty hours after the injection.

On post mortem examination rigor mortis was well marked.
The abdomen contained some yellow serum. The stomach con-
tained no solid food, but about 2 ounces of a greyish turbid
alkaline fluid.

EFFECT OF A MODERATE DOSE ON MAMMALS. 485

Experiment I1I.—April 28.

Seven c.c. of a similar solution to that used in Experiments I.
and II. were injected beneath the skin of a moderate-sized,
well-nourished cat. In 15 minutes the animal vomited for the
first time, and this vomiting was repeated four times within the
next hour and twenty minutes. During the rest of the day it
remained quiet, without further vomiting, and with no paralysis
or disturbance of muscular movements. It appeared to be quite
comfortable.

On the following day it remained sitting in one position, and
refused its food and milk. There was no vomiting, and no
urination or defecation. When disturbed, it would immediately
return to its former position in a mechanical manner.

On the following day it passed a very small quantity of
feeces ; it was not observed to urinate, and, as before, it neither
ate nor drank anything. It vomited once, very slightly.

From this time forwards, for a fortnight after the administra-
tion of the poison, the cat remained in this condition, neither
eating nor drinking, although tempted to do so with milk and
meat; and even when a live mouse was placed before it, it
merely pricked up its ears, and looked eagerly at it, but did not
touch it, nor did it pass urine or fzeces once for the last eleven
days.

It sat always in one position unless disturbed, and though it
got .steadily weaker, did not lose flesh in the way an animal
starved would have done. The temperature on May 2nd was
38° C.

Five days after the poison was given a subcutaneous abscess
formed over the right scapula and ribs. No other lesions were
ascertained during life. ‘The abscess did not form at the seat of
puncture.

It died, apparently from exhaustion, fourteen days after the
poison was administered.

Post-mortem Examination.

Rigor mortis well marked.
‘subcutaneous tissue contained a fair amount of fat.

486 ON THE PHYSIOLOGICAL ACTION OF CASCA BARK.

There was a large, sloughy, subcutaneous abscess in the
situation mentioned above, and another localized collection of
pus a little higher up in the skin of the neck. No other super-
ficial abscesses were found. .

The muscles were pale and rather dry. There was general
congestion throughout the body of the larger venous trunks, but
apparently not of the smaller ones.

Abdomen.—The omentum contained rather a large quantity
of fat.

The stomach was quite empty, pale, and contracted.

The small intestine contained a small quantity of bile-stained
mucus; it was otherwise empty.

The large intestine contained bile-stained mucus, and in its
lower half a considerable quantity of feces, also bile-staineu.
The mucous membrane appeared perfectly healthy.

The bladder contained only a few drops of high-coloured
urine, but had not contracted at all firmly. It had the appear-
ance of a bladder which has heen dried when inflated, and the
air then let out.

The kidneys were pale, although the renal vein was much
distended.

The vagina and uterus contained a large quantity of a greenish
smeary fluid, which, under the microscope, was seen to be muco-
pus. The mucous membrane had here and tliere patches of
injection on it (vide infra); near the orifice of the vagina the
secretion had quite the character of ordinary pus, but no abscess
existed there.

The diaphragm was pale, flabby, and very transparent (vide
infra).

Thorax.—The lungs were congested, but otherwise natural.

The heart was very pale and flabby ; all the cavities contained
moderate quantities of blood.

Microscopical Examination.

Kidneys: epithelium not degenerated.
Heart: muscle-tibres very granular; in many places hardly a
trace of transverse striation could be seen.

SS ee

SYMPTOMS PRODUCED. 487

Voluntary muscles (rectus abdominis) also granular (well
marked, but not quite so much as the heart).

Bladder: muscular coat not degenerated.

Intestines : muscular coat not degenerated.

Remarks on Experiments I—III.

Experiments I to III show the effects of the poison on cats
when administered in three decreasing doses.

It will be seen that, during life, the most prominent
symptoms of a rapidly poisonous dose were in their order of
constancy :—1, vomiting ; 2, respiratory difficulty ; 3, abnormal
muscular movements. .

After death the condition of the heart and great vessels and
of the lungs are most noteworthy.

Vomiting.—This was a constant symptom in all the cats we
experimented on, unless they were placed under special circum-
stances. The vomit consisted, first, of whatever food might be
contained in the stomach, and then of a white frothy mucus.
On no occasion did it ever have the appearance of intestinal
(feecal) vomiting.

In Experiment I no actual vomiting occurred. In this case
the stomach was found to be empty of food after death; and
the absence of the symptoms in this case was doubtless due to
the rapid paralysis caused by the very large dose administered.

Respiratory Dificulty—This is a constant symptom, except
when very small doses are administered.

On reference to Experiment I it will be seen that at one
time the respirations rose to 160 per minute. This, however,
was exceptional. From 40 to 60 respiratory movements per
minute is probably the average rate after administration of a
moderately poisonous dose.

Abnormal Muscular Movements—These are of two kinds;
thus, immediately after the administration of any dose, large or
small, there is very generally produced a peculiar twitching of
the muscles of the limbs, especially of the hind legs. This is
especially seen when the animal is walking.

When large, rapidly poisonous doses are administered

488 ON THE PHYSIOLOGICAL ACTION OF CASCA BARK.

symptoms of general muscular paralysis and loss of coordina-
tion are developed pari passw with the dyspnoea and frequency
of the vomiting. The animal rolls and staggers as it walks; its
head falls on the ground, and, finally, it falls over on its side
and is unable to stand. Death always occurs a very few
minutes after the development of these last phenomena.

Appearance of the Heart post mortem.—As a rule, post-
mortem examination of the heart shows a moderately firm con-
traction of the ventricles, with a somewhat distended condition
of the auricles. The ventricles, however, were never found to
be completely emptied of blood, and on one or two occasions
the heart was found to be moderately distended, the left
ventricle containing well arterialised blood.

On several occasions, but here also with one or two excep-
tions, a remarkable vitality of the auricles was noticed (Experi-
ment I).

The post-mortem appearances of the heart and their physio-
logical value will be noticed more particularly in the section
which treats especially of the action of that organ.

The lungs were, in all cases in which they were noticed,
‘round to be pale, except in Experiment III (see Experiment
XXXI).

One of the most noteworthy phenomena is the action of a
small dose upon a cat in causing an utter refusal to take either
food or drink, and that, notwithstanding this total abstinence
from nourishment, the animal should live such a long time,
should show considerable muscular power (being able to jump
from the floor upon a chair up to the day before its death), and
should have still retained so much of its subcutaneous and
omental fat. Another point to be noted is the occurrence of
subcutaneous abscesses, none of which were near the point
where the poison had been injected.

This long continuance of life and retention of strength seem
to us to indicate that the processes of tissue change had been
retarded by the poison; and the granular condition of the
striated muscles appears to indicate a diminution especially in
the processes of oxidation.

ACTION ON DOGS AND BIRDS. | 489

AcTION oN Doas.
Experiment 1V.—May 9.

The effect of the poison on dogs was investigated in the same
manner as it had already been on cats in Experiments I—III.
It will be seen that the results do not differ in any noteworthy
point from those previously obtained.

Six e.c. of the solution were injected beneath the skin of a
dog weighing 8 lbs. It vomited for the first time 20 minutes
afterwards, and this vomiting continued at gradually increasing
intervals of from 15 minutes to three quarters of an hour for
ihe next 4 hours. At the end of that time the animal was
very restless, and continued to be so while it was observed.’ On
the following day its gait became staggering ; and, finally, it lay
flat on its belly, and died about 30 hours after the drug was
administered.

. GENERAL ACTION ON Buinps.

Birds are affected very. readily by the poison, and the
symptoms produced in them are similar to those observed in
mammals. This will be seen by the results of the following
experiment.

Experiment V.

A full-grown pigeon had nearly 1 c.c. of the solution injected
beneath the wing. In 10 minutes a quivering motion of the
wings was noticed; in a quarter of an hour its feathers were
puffed out, its gait was staggering; 24 minutes after injection
it began to vomit. This was repeated 4 minutes afterwards
more violently, and several times subsequently. 40 minutes
after the injection it was unable to stand; and from that time
to its death, 1 hour and 35 ininutes after injection, it lay flat on
the table, occasionally attempting to vomit unsuccessfully. For

the last 40 minutes its respirations were hardly visible, but it

moved when roused. Violent expiratory movements came on
just before the respiration finally ceased.

490 ON THE PHYSIOLOGICAL ACTION OF CASCA BARK.

GENERAL ACTION ON FISHES AND FROGS.

In fishes and frogs there is but slight susceptibility to the
poison, and the effects produced by it are similar in the tio
classes. The most obvious general systems are muscular —
paralysis and cessation of respiration, preceded by spasmodic
movements. It will be seen later, however (Experiment X VIII),
that the particular action of the drug on the heart is well
shown in frogs.

Experiment VI.—February 21.

One-tlird of ac.e. of the solution was injected beneath the
skin of a medium-sized frog. In 2 minutes slight tonic
contraction of the limbs was observed; in 4 minutes it was
jumping rather actively, but fell over on its back; in 12
minutes the respiratory movements had become almost imper-
ceptible ; and from this time the reflex movements of the limbs
on irritation gradually got weaker and weaker, and finally
ceased 33 minutes after the injection. g

After death, the ventricle was found firmly contracted, the
auricles and venous trunks engorged.

Experiment VII.—February 21.

Experiment VI was repeated with double the dose. The
frog was slightly larger than the one first used; but reflex
action ceased within a few seconds of the same time after
injection. The general effects were almost the same as in

Experiment VI, save that 5 minutes before reflex move-
ments ceased there were four spasmodic inspirations.

Experiment VITI.—April 18.

The effect on fishes was tried. First, 55 c.c. of a 345 watery
solution of casca were added to 3 litres of water in which a
gold-fish weighing 3 ounces was swimming. At the end of.
3 hours no effect was produced on the fish. 1°3 ec. of the
alcoholic solution were then injected into the side of the fish, a
little in front of the tail. In 5 minutes it began to roll from
side to side; the respirations were catching. For the next 10

ACTION ON INVERTEBRATA AND INFUSORIA. 491

minutes it lay chiefly on its side, occasionally swimming about
actively.

At the end of 25 minutes from the time of injection it
appeared to have nearly recovered itself, and 1 c.c. more of the
alcoholic solution was injected. In 3 minutes from this time
it lay completely over on its side, having spasmodic twitchings
of its fins; in 5 minutes the respirations again became rapid
and gasping; in 10 minutes the reflex movements were very
weak, but respiration and reflex action did not entirely cease
before 30 minutes after the second injection.

GENERAL ACTION ON INVERTEBRATA.

The following experiments (Nos. [X and X) show that the
drug exerts very little, if any, poisunous action on the In-
vertebrata.

Experiment IX.

A leech was placed in a watery solution of casca nearly as
strong as could be made with cold water. At the end of
24 hours it seemed but little affected, but was found dead on
the following morning.

Experiment X.

Nearly 5c. of a concentrated alcoholic solution of casca
were injected beneath the back of a common snail. The animal
showed no signs of poisoning, and on the following morning
appeared to be uninjured.

ACTION ON INFU:ORIA.
Experiment XI.

In Experiment XI we investigated its action on Infusoria by
placing a drop of tank-water containing some infusorians under
the microscope, and adding a drop of a 51, solution of the
watery extract of casca. At the end of 2 hours no alteration
in the movements of the animalcules was observed; and it may
therefore be concluded that the drug exerted little or no action
on them.

The action of the drug on germination and oxidation pro-

A92 ON THE PHYSIOLOGICAL ACTION OF CASCA BARK.

cesses, and on different ferments and ferment organisms, was
investigated in Experiments XII—X-X.

On germination the casca infusion was found to exert no
effect.

Experiment XII.

A few mustard seeds were placed on flannel in two saucers,
and kept moist in a warm place, the one with an infusion of
casca, the other with water. The seeds began to germinate at
the same tiie in each, and no difference was observed in the
growth of the shoots for three days afterwards.

Effect on the Development of Bacteria.
Experiment XIIT.

This experiment, which was repeated on two other occasions,
shows that a weak solution of the alcoholic extract possesses
the power of hindering the formation of Bacteria, a property
not shown by the watery extract, as is shown in Experiment
XIV. This difference in the properties of. the two extracts
does not show itself in the general action of the drug on
animals; but the power of the alcoholic extract to prevent the
development of Bacteria, while it is without action on them
after their development, is interesting, as substantiating the
results of Buchholz’s experiments on this subject with other
drugs.*

Three pieces of fresh muscular tissue were placed in bottles
on March 22nd. The first contained a watery solution of the
alcoholic extract of easea, the second a z1, solution of sulphate
of quinia, and the third distilled water. On March the 29th
the bottles were opened; and while the bottle containing water
was very offensive, and the water was crowded with Lacteria,
neither the quinine nor casca solutions contained any Bacteria
at all.

The bottle containing the casca solution was again examined
on May 14th, and was found, as before, quite free from Bacteria,
Long before this a thick crust of Penicillium had formed on its
surface.

* Archiv f. erper. Pathologie u. Pharmakologie, vol. iv, p. 1.

ACTION ON BLOOD-PRESSURE AND CiLIARY MOTION. 493

Experiment XIV.

A piece of fresh cat’s liver was placed in a solution of casca
of the saine strength as that used in the preceding experiment ;
but the watery extract was used instead of the alcoholic. At
the end of two days the liquid was found to be crowded with
Bacteria.

This experiment was afterwards repeated with muscular and
other tissues with the same result.

Effect on the Life of Bacteria.

The effect of the drug on the life of Bacteria, when developed,
was tried in Experiment No. XV. For this purpose an infusicm
of hay was made, and found to contain many rod-shaped Bacteria.
To a drop of this infusion a drop of a solution 1 in 20 of both the
alcoholic and the watery extracts of casca was added at different
times, and the movements of the Bacterians carefully watched
under the microscope. They did not, however, seem in any way
affected by the addition.

For the sake of comparison a solution 1 in 100 of quinia sul-
phate was added to the hay-infusion. The Bacterian movements
were found to be instantly stopped.

| Effect on Red and White Llood-corpuscles.

In Experiment XVI the action on the red and colourless:
blood-corpuscles of the newt was investigated. The effects pro-
duced by the addition of dilute solution of casca to the blood
were cessation of amceboid movements and rounding of the
white corpuscles, with an irregular shrinking of the nucleus,
and general crenation of the red ones. These effects were pro-
bably due to the action of the tannic acid contained in the
extract.

Liffect on Ciliary Motion.

The drug appears to have no action on ciliary motion; for
when (Experiment XVII) two preparations of ciliated epithe-
lium were made, the one being placed in ‘75-per cent. salt
solution, and the other in a 54, solution of casca extract, it was.

‘ 494 ON TILE PHYSIOLOGICAL ACTION OF CASCA BARK.

found on microscopic examination that the movements of the
cilia ceased in about the same time in both specimens,

Effect on Processes of Oxidation.

It, however, does appear to exercise an inhibitory action on
oxidation processes generally. This point was investigated in
the following manner :—

Experiment X VIII.—April 20.

Four thin slices of potato were placed in two saucers, and
were just covered, the one with distilled water, the other with
a 3hy Watery solution of casca. When a drop or two of the
tincture of guaiacum were added, either to the liquid or to the
potato slices, the bluing produced was much fainter in the case
of the saucer containing the casca than in that containing dis-
tilled water. The results of the experiment on organized and
unorganized ferments were negative, neither the development of
the yeast-plant (Experiment XIX) nor the digestion of fibrin
by pepsin (Experiment XX) appearing to be in the least degree

hindered by the addition of the drug.

ACTION ON THE DIGESTIVE SYSTEM.

One of the most prominent symptoms of poisoning by casca
is the violent vomiting which it produces; and, as has already
been noticed, its occasional purgative action is used as a test
of innocence or guilt. The emetic or purgative action is sup-
posed by some to depend on the administration of a pure infu-
sion, or of one containing the drugs in suspension, and innocence
and guilt are thus supposed to be practically decided by the
priests, who have it in their power to administer either one or
other to the accused.

In order to test this, an infusion was given to one cat, B
(Experiment XXI), and an infusion containing a quantity of
powder to another. The latter, however, contrary to expecta-
tion, recovered, whereas the former died. The experiment,
however, was vitiated by the fact that the infusion was made
from the finely pulverized bark, the only kind we kad at our

ACTION ON STOMACH AND INTESTINES. 495

disposal at the time, and consequently contained a quantity of
it in suspension, which would not have been the case if the in-
fusion had been made from a coarsely pounded bark.

In order to ascertain whether the vomiting and purging were
due to the local action of the drug on the stomach and intes-
tines, or to its action on the nervous system after its absorption
into the blood, a comparison was made between the effects of
the poison when introduced into the stomach and when injected
under the skin. Our experiments show that whereas vomiting
was invariably produced by the casca, in whatever manner
introduced into the system, purging only occurred when the
poison was given by the mouth, and was never observed after
subcutaneous injection. The purgative action is therefore due
to the local action of the drug on the intestines.

The following is a brief account of two experiments we made
in investigating the action of the drug when injected into the
stomach.

Uxperiment XXI A.—May 10.

Ten c.c. of an infusion of the watery extract of the bark,
with the dregs which were deposited when the infusion cooled,
were injected into the stomach of a large cat. It appeared
quite well for 40 minutes and then vomited. Within the next
two hours and a half it vomited five times. A little more than
five hours after the exhibition of the drug it passed some solid
feces with great forcing, and from that time recovered.

Experiment XXI B.—May 10.

Ten and a half c.c. of a cold aqueous infusion of the pounded
bark, containing numerous fine particles in suspension, were
injected into the stomach of a small ill-nourished cat. Vomit-
ing came on 309 minutes afterwards, and free purging an hour.
and a half after the injection. During the rest of that day and
on the next it was very feeble, but showed no special symptoms,
and it died quietly on the morning of May 12.°

496 ON THE PHYSIOLOGICAL ACTION OF CASCA BARK.

COMPARATIVE ACTION OF THE ALCOHOLIC AND WATERY
EXTRACTS.

The action of the alcoholic and watery extracts of casca, when
administered subcutaneously to cats in large doses, is almost
identical; and their activity as poisons appears to be about
equal, the watery extract, if anything, being rather the more
powerful.

Experiment XXII.—April 28.

Two equal quantities of the alcoholic and watery extracts
were dissolved in equal volumes of alcohol and water re-
spectively. The quantities were 3 grammes of the extracts
and 4 c.c. of the fluids. These solutions were injected beneath
the skin of two cats of the same size. In the case of the aleo-
holic extract vomiting came on 15 minutes after injection, with
the other symptoms of poisoning by the drug (ae., respiratory
difficulty and ‘staggering gait). The vomiting was repeated
violently, and the animal died 1 hour and 15 minutes after in-
jection, death being preceded by general convulsions.

In the case of the watery extract vomiting did not come on
for 35 minutes, but death occurred, with symptoms similar to:
those of the former case, in 1 hour after the injection.

In order to ascertain whether the vomiting was due to the
action of the drug upon the sensory nerves in the stomach
itself, after it had been conveyed to that organ by the circula-
tion, or to its action upon the nervous centre in the medulla
oblongata regulating the movements of vomiting, the vagi were
cut, and the chief sensory nerves of the stomach thus divided,
before administering the poison. By this procedure the retch-
ing and vomiting were either completely prevented or very
greatly diminished, the dyspneea rendering it rather difficult to:
decide in some cases whether some convulsive movements were
due to it or were movements of retching. The vomiting is
therefore chiefly, and in all probability entirely, due to the
action of the drug on the sensory nerves of the stomach itself,
as the retching, if indeed really present, might be due to irrita-
tion conveyed to the medulla through the splanchnics after the
vagi had been divided.

SYMPTOMS AFTER VAGOTOMY. 497

Experiment XXIII.—March 6.

General Symptoms after Injection, both Vagt having been
previously divided.

A cat weighing 3 lbs. was chloroformed, and the vagi divided
in the neck. In 25 minutes after the operation it had recovered
from the effects of the anzsthetic. Its respirations were 18 per
minute. 3 c.c. of a concentrated alcoholic solution of alcoholic
extract of casca were injected subcutaneously. Five minutes
afterwards the cat had fallen over on its side. The respirations
were still reoular, 16 per minute. During the next hour, with
one temporary disturbance, the animal remained quiet, still
breathing quietly and slowly, with no symptoms of sickness and
no dyspnea. It remained on its side the whole time, except
when roused. It then staggered a few steps, and again lay
down. One hour after the first injection 2} cc. mvure were
injected. For the next quarter of an hour the animal con-
tinued to breathe easily, but appeared weaker. At the end of
that time there were some very slight convulsive movements.
and then respiration ceased. On beginning artificial respiration
one or two gasping inspirations occurred, and then entirely
ceased 1 hour and 15 minutes after the first injection. On post
mortem examination the heart’s cavities were found distended.
They did not contract on irritation or puncture. The lungs
were bright scarlet, and contained’a moderate amount of blood.
The liver and kidneys were congested ; the stomach was pale ;
the brain was normal.

Experiment XXIV.—April 28.

This experiment was in most points an exact repetition of
Experiment XXIII, but the results were even more striking.
A well-nourished cat was chloroformed, and both vagi were
divided in the neck. When it had recovered from the chloro-
form a solution of ‘3 gramme of the alcoholic extract in 4 ce.
of alcohol was injected subcutaneously. None of the ordinary
symptoms of poisoning by the drug were produced. There
was no dyspnea and no vomiting, except at one time, an
hour and 15 minutes after the injection, when the . animal

2K

498 ON THE PHYSIOLOGICAL ACTION OF CASCA BARK.

either coughed or vomited up a small quantity of frothy
mucus. When seen the next morning it was to all appear-
ance well, and was killed, to prevent suffering being caused
by the secondary effects of section of the vagi, which were
found to be completely divided.

Experiment XX V.—May 17.

This experiment was similar to Nos. XXIII and XXIV. As
before, no vomiting was produced by injection of the drug after
section of the vagi, but death occurred 1 hour and 10 minutes
after the injection, in consequence of dyspnoea occasioned by the
section of these nerves.

ACTION OF CASCA ON RESPIRATION.

Powdered casca, when inhaled, acts as a violent sternutatory.
All the men employed by us in grinding or pounding the bark
suffered severely from the violent and irresistible fits of sneezing
which attacked them; and in one instance these were accom-
panied by great faintness and tendency to syncope.

When injected into the circulation casca greatly accelerates
the respirations (Experiments I, II, XXXIV).

This acceleration appears to be due to stimulation of the pul-
monary branches of the vagus, and not to any action of the
drug upon the respiratory centre, as no acceleration is noticed
when the vagi are divided before the injection of the casca
(Experiments XXIII and XXIV).

ACTION ON THE INTESTINES.
Experiment XX VI.

In order to ascertain whether the intestinal secretion was
increased by casca, a cat was chloroformed, the abdomen opened,
and three loops of small intestine ligatured. Into the middle
loop 2 c.c. of a concentrated solution of the watery extract of casca
were injected, and 2 c.c. of water into the other two. The cat
vomited about an hour afterwards. At the end of about 5 hours,
the animal was killed and the body examined. The upper and

ACTION ON THE FROG’S HEART. 499

middle loops were both dry, and the mucous membrane was
normal in appearance, except slight congestion at the place of
ligature between the upper and middle loop. The lower loop
contained several ¢.c. of turbid greyish fluid.

The intestinal secretion is thus seen not to be increased by
the drug.

AcTION OF CASCA ON CIRCULATION.
Experiment XX VIT.
Preliminary Experiments on Frog’s Heart.

A watery solution of the alcoholic extract and a standard
salt solution were prepared; the hearts of two frogs of about
the same size were them removed, and placed for a minute or
two in “75 per cent. salt solution. When they had recovered
from the shock of removal, and were beating regularly, one was
placed in the casca solution, the other in the salt one. At the
commencement of the experiment the heart, A, placed in salt
solution, was beating at the rate of 6 per 10 seconds; the heart,
B, in casca, at the rate of 7°5. Both hearts became weaker and
their pulsations slower; at the end of 50 minutes the heart in
casca stopped entirely, that in salt solution pulsated feebly at
the rate of 3 per 10 seconds. In 15 seconds more it stopped.

In Experiment XXVIII we repeated the foregoing experi-
ment with a much stronger casca solution. The hearts at the
commencement of the experiment were beating at the rate of
4 per 10 seconds. At the end of 30 minutes the heart, B, in
easca, Which had previously got very slow and weak, stopped,
while the standard heart, A, was still beating strongly and
regularly at the rate of 4 per 10 seconds.

Experiment XXIX.—March 7.

The heart of a frog whose cerebrum had been destroyed was
exposed. Pulse 72 before injection.

h. Me

11 40. Injected 2 cc. alcoholic solution beneath skin of back.
11 50. Pulse 60; regular.

2K 2

500 ON THE PHYSIOLOGICAL ACTION OF CASCA BARK.

h. . m. “i ae

12. 2. Pulse 48

12 10. Pulse 60. Clonic eonvulaions,

12 15. Ventricle stopped in systole, firmly contracted in its
greater part, with a pouch-like dilatation of a small
portion. Auricles still contracting.

12 27. Ventricle firmly contracted. Still partial contraction
of auricles. Respiration and slight convulsive move-
ments continue.

12 50. Removed from frog-board. ‘ The ventricle is not so
firmly contracted. Still respiring and ‘occasionally
convulsed.

1 0pm. Ventricle relaxed. Slight movements of it, have
recommenced. 1'4 cc. alcohol solution aoa in-
jected.

1 7. Ventricle again firmly contracted. No respiration.
Still slight reflex movement. |

1 30. Died with heart in same condition.

Experiment XX X.—May 10.

The heart of a frog was exposed, and a little extract of casca
placed on it. Pulse 34 per minute.

It had no apparent action. |

A watery solution of casca was then poured into the thoi
The pulse became slower, = 24 per minute.

- The ventricle then expanded irregularly ; the diastole at the

base being later than that at the apex.

Then the distention became imperfect, the ventricle sco
wrinkled.

The heart then stopped in systole, having two pin-point
dilated pouches on it. :

These experiments show that a very weak solution of casca
applied to a frog’s heart, when removed from the body, slows
its pulsations, while, after the application of a stronger solution,
the pulsations become slow, then the systolic contraction ceases
to take place instantaneously over the whole surface of the
ventricle ; lastly, the heart stands still in systole.

When the heart of a frog i is exposed, but not removed frame

’

- ACTION ON BLOOD-PRESSURE IN THE FROG. 501

the body, and a solution of casca is injected beneath the skin,
the heart’s action is slowed, and is eventually stopped in sys-
tole; previous to its stopping, however, pouch-like dilatations
are formed; in this respect the action of casca is similar to
that of digitalis and other cardiac poisons.

Experiment XX XI.—April 27.

A cat was chloroformed ; a cannula placed in the left jugular
vein and one in the trachea. Artificial respiration was com-
menced, and the thorax was opened. The heart was beating
regularly, but it was difficult to count the pulsations. They
were counted by one person as 90, by another as 180.

Ten c.c. of a saturated watery solution of watery extract of
casca were injected-into the jugular vein. No apparent effect
was produced.

Seven ¢.c. more were injected in the course of a few minutes.
Within about a minute of the last injection the ventricle no
longer contracted as a whole, but became pouched, the upper
half seeming to overlap the under half so as to produce a trans-
verse fold.

A few seconds afterwards, the lungs, which had hitherto been
rosy, became white, and almost immediately the motions of all
cavities of the heart completely ceased. On irritation of the
ventricle no movement occurred.

Both vagi were divided, but without effect on the neart.

It was noticed that the rosy colour of the lungs returned,
although the heart did not again beat. No pulsations were
noticed in the pulmonary vessels. The heart was perfectly
firm, and seemed to be in systole; but on tying a ligature
round the base so as to include the large vessels, it contracted
to about one-third of its former size.

The action of casca on the mammalian heart is seen from this
experiment to be similar to its action on the heart of the frog.

Experiment XXXII.

Action on Blood-presswre in the Frog.

The cerebrum of a large frog was destroyed. A cannula was
then inserted into the left aorta, and was connected with a

502 ON THE PHYSIOLOGICAL ACTION OF CASCA BARK.

small kymograph, the pulse-wave and oscillation being recorded
on a revolving drum,

The appended curves give the oscillations of pressure in the
aorta, and show that under the influence of casca the blood-
pressure in the aorta rises to twice its normal height during
systole, although it falls to zero during diastole.

Normal pulse (10 mm.) ...+.0. ,

injection of 1 c.c. of a shy

Pulse three minutes after
solution of casca into flank.

Puise one minute after a
. gecond injection of 1 c.c.

Pulse three minutes later ......

Experiment XX XIII.—March 31.

Action on the heart and blood-pressure of a large dose of
casca. (For action on secretion of urine also, vide infra.)

A bitch, weight 264 lbs., was chloroformed.

A cannula was placed in the trachea.

. left femoral vein.
»9 = right ureter.
D » left carotid artery.

The operation was very long, and during it the intestines
became much congested.

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ON THE PHYSIOLOGICAL ACTION OF CASCA BARK

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MODE OF ACTION ON THE VAGUS. 505

The thorax was then opened, and the heart found beating ;
respiratory movements recommenced on opening the thorax.
The bladder was found greatly distended; there had been
micturition during the experiment, which was probably only
overflow.
Remarks.

We append a diagram (p. 518) showing the coincident varia-
tions of blood-pressure and secretion of urine, which will be
more fully commented on later. (Vide effect on urinary
secretion. )

So far as the phenomena of circulation are concerned, this
experiment shows that while a small dose of casca slows the
pulse, an additional one greatly quickens it. This action of
casca closely resembles the effect of digitalis, which first slows
the pulse by stimulating the vagus-roots, and then quickens it
by paralyzing the ends of the vagus in the heart. It therefore
seemed probable that the cardiac ends of the vagus would be
found to be paralyzed by large doses of casca.

It was possible that the primary slowing of the heart’s action
might be due to stimulation of the inhibitory apparatus in the
heart itself, and not to the action of the drug on the vagus-
roots. Two questions, therefore, were to be settled :—

1st. Is the primary slowing of the pulse due to stimulation
of the vagus-roots, or to stimulation of the inhibitory apparatus
in the heart ?

2nd. Is the secondary acceleration of the pulse due to
paralysis of the ends of the vagus in the heart ?

To answer these questions the following experiments were
performed (vide antea, p. 297) :—

Experiment XXXIV.—March 21.

Action on the Heart and Arterial Pressure of a small dose of
Casca.

A dog weighing 8 lb. was chloroformed, and kept under
chloroform during the experiment.

A. cannula was inserted into the right carotid and into the
right femorai vein.

506

ON THE PHYSIOLOGICAL ACTION OF CASCA BARK.

Blood-

pressure.

Pulse
in 10

seconds.

Oscilla-

tions.

eb
i)
ae

oust
e
oO

20
30

TO D OD
=
jo)

- 2» BE
S §
ed

Condition before injection

7 ¢.c. sig watery solution in-
jected into femoral vein

Rise of blood-pressure. Com-
menced pesiotenees of dia-
stole ..

Systole fairly sharp, Aiastole
very long :

Commencing fall of blood-
pressure

Great fall of blood-pressure |

and lengthening of diastole. .

Diastole extends over 15
seconds

Systole extends over 4 second;
does not vary with respira-
tion

Blood-pressure again lower.
Diastole further prolonged. .

Diastole 20 seconds

Systole 4 second. — Diastolic
curve slightly affected by
respiration

Blood-pressure recovering.
Diastole shorter

Diastole 5 seconds

Systole 4 second

Respirations affect diastolic
curve to extent of 3 mm.

Blood-pressure rising ..

Systole and diastole nearly
equal

Both affected by respiration to
extent of 4 mm.

| Blood-pressure nearly at the

height of commencement of
experiments. Systole sharp

Blood-pressure higher. JDia-
stole again prolonged

Diastole 4 seconds

Systole 4 second

Respirations affect curves to
extent of 10 mm.

There was again a fali of blood-
pressure with great pro-
longation of diastole similar
to that which occurred at
2.5 to 2.20, but less marked

Do., more marked - ae

Gradual fall of blood-pressure.
Cessation of heart’s action

mm.

110

125
130

155
140

65

45

50

100

130
140

115
80

183

16%
16

14

ool

23

mm.
10

10
10

10
40

25

30

25

35

35
60

50
30

Respira-
tions in
10 secs,

10

10

s%
25

WL tira ae

‘

|

Oe Nip GG LTR eS OV SRL ETE EM ONL SO

et lid ~ ol te

=a YF @ er

a |

STIMULATION AND PARALYSIS OF THE VAGUS. 507

Post mortem (immediately after death).—The heart contained
blood, and contracted on puncture. The auricles contracted for
3 minutes after death.

This experiment shows that the action of a small dose of
casca is to raise the blood-pressure and slow the heart at first.
Next, when the heart becomes very slow, the pressure falls, and
finally the heart ceases to beat, and death takes place.

The cardiac pulsations remained slow from the time of the
injection of the casca up till death; and although they at one
time rose from 1 pulsation in 30 seconds up to 5 pulsations in
10 seconds, they never came at all near to the normal, which in
this animal was 18} pulsations in 10 seconds.

The very slow pulse here indicates that the vagus is prob-
ably stimulated by the casca; and the continuance of the
blood-pressure at the height of 65 mm. during a cardiac
diastole, lasting for 30 seconds, shows unmistakably that the
arterioles are strongly contracted by the drug.

ACTION ON VAGUS,
Maximum Irritation.
Experiment XXX V.—March 4.

A cat, weight 41b., was chloroformed, and a cannula was
placed in the left carotid artery and in the left femoral vein.

: Pulse
Time. Blood- | Oscilla- in 10
pressure.) tions. PELE
m. s. mm. mm.
1 0 | Normal curve taken 1 minute after con-
nexion of cannula. Oscillation at top 9
of respiratory curve = 9, at bottom 2 80 { =; 23
215 | R. vagus ligatured and cut
218 | L. vagus do. do.
Condition after section of vagi .. ee ed! 2 40
440 | L. vagus irritated. Coil 5°* .. ev}. , GD 18 15
R. vagus irritated. do. ee ee 55 12 12

* The mark® here signifies distance in em. between primary and secondary
coils in Du Bois Reymond’s induction-apparatus.

508

ON THE PHYSIOLOGICAL ACTION OF CASCA BARK.

. Pulse
Time. reoware| dons, |
P ; * | seconds,
m. 8. mm. mm.
8 10 | Condition subsequent to irritation ..| 110 1 42
Jt was thus ascertained that irritation
of the strength of coil 5° was almost
sufficient to stop the heart’s action
when applied to the peripheral end of
either vagus previous to injection of
casca
8 10]| 33 c.c. of casca solution injected gradu-
9 12 ally into vein
10 O | Condition after injection ee «-| 120 2 40
11 O | A clot formed
12 0 | Condition after clot was removed e-{ 115 4 43
(Slight improvement of pulse)
12 35 | Peripheral end of L. vagus irritated.
Coil 5° .. 90 8 35
13 0 Peripheral end of R. vagus irritated.
Coil 5° .. ‘ ee a 95 8 35
Condition between irritations ee ee} 120 2 35
14 27 | Left vagus. Coil0°® .. oe ae 88 5 27
Right vagus. do. oe 110 0 0
Complete stoppage of heart's action
without fall of blood-pressure
15 20 | Experiment repeated with RK. vagus.
Coil 0° .. os ve ve 85 5 26
a a Fresh injection of 4 c.c.
18 3) | Condition after injection oe 115 2 40
19 5 | Right vagus. Coil 0°. Commencement
of irritation .. 100 3 30
Right vagus. Coil 0°. ‘Latter part of
irritation ee --| 118 2 36
19 30 | Left vagus. Coil 0°. Commencement
of irritation .. 104 4 30
Left vagus. Coil 0°. Latter ‘part of
irritation oe ee 120 2 35
20 O | Left vagus. Coil 0°. Commencement
of irritation .. 121 2 35
Left vagus. Coil 0°. Latter ‘part of
irritation . : -»| 150 2 35
20 30 | Condition after irritation oe «-| 120 2 46
< ag A third injection of 2 c.c. was given
24 25 | And the central ends of the vagi ex-
posed for irritation
24 30 | Condition before irritation oe 120 2 40
25 12 | Central end of left vagus irritated.
Coil O° .. 130 1? 30
(Blood-pressure increased ; pulse nearly
extinguished)
25 50 | Condition after irritation oe eo} 125 2 34
26 30 | Right vagus. Coil 0° .. ee «-| 130 1

(Effect as before)

34

EXCITABILITY OF THE VAGUS. 509

. Pulse
Time. Blood- Oscilla- in 10
pressure.| tions, dotanalie:
m. 8. mm, mm.
27 O | Condition after irritation 5% oot 326 2 36
28 16 | The sciatic nerve was exposed and irri-
tated with coil 5° at ee Pre ume b. 2 37
28 45 | Condition after irritation ee" cat 120 2 36

This experiment shows that when both vagi are divided the
injection of a small dose of casca no longer slows the heart;
and therefore the slowing usually observed after its administra-
tion is due to stimulation of the vagus-roots and not to stimu-
lation of the inhibitory apparatus in the heart itself.

It also shows that a large dose completely paralyses the ends
of the vagus in the heart, so that a strong interrupted current
applied to the trunk of the nerve produces no slowing of the
cardiac pulsations.

Action of a Small Dose on the Excitability of the Vagus.

As it has been stated that digitalis in small doses increases
the excitability of the ends of the vagus in the heart, so that a
slight irritation applied to the trunk of the nerve will cause
slowing or stoppage of the heart after the administration of the
drug, although previously it had no effect, it seemed advisable
to ascertain whether or not a similar action was possessed by
easca. The following experiment was therefore tried :—

Minimum Irritation of Vagus (peripheral end).
Experiment XXX VJ.—April 6.

A cat, weight 6 lbs., was chloroformed, and kept under chloro-
form the whole time of the experiment.

A cannula was inserted into the right carotid artery and
into the right femoral vein.

Both vagi were then cut, and the peripheral end of the right
vagus attached to Von Basch’s electrodes.

Operation lasted half an hour; the cat at first very feeble,
afterwards recovered. —

510 ON THE PHYSIOLOGICAL ACTION OF CASCA BARK.

Blood- | Oscilla- | Pulse in

Time pressure.| tions. | 10 sec.
m. 8. mm. mm
1 5) | Condition previous to seit both
vagi being cut . ee 120 1-2 40
2°20 Eight vagus irritated. Coil 30°. No 120 1-2 42
effect .. oe { 125 zi
8 20 | Right vagus irritated. Coil 25°. This
irritation was sufficient to slow the
heart and lower blood-pressure ee 100 5 20
5 0 | Condition previous to injection... «o| 155 2 44

As the cat was stronger, the normal
minimum irritability was again tried,
and coil 25° was again found to be
the weakest which produced any
effect

6 0O]/ 13 c¢.c. casca solution, as in Experiment

6 30 XXXIV, injected into femoral vein

7 © | Condition after injection.. ea 175 2 42
7 30 | Vagus irritated. Coil 30°. No effect..| 175 2 40
8 0 | Vagus irritated. Coil 25°. No effect..| 1890 2 42

From this experiment it appears that the excitability of the
peripheral terminations of the vagus-nerve is not increased by
casca. ;

Action on the Vagus-roots.

The slowness of the pulse which quickly follows the injection
of casca, and which we have already shown to be due to stimu-
lation of the vagus-roots, might be caused either (a) by stimu-
lation of the central end of the vagus by increased blood-
pressure in the nerve-centres, or (0) stimulation by the direct
action of the drug itself; (¢) it was also possible that without
actually irritating the vagus-roots the casca might increase
their sensibility to other stimuli, reflex or otherwise.

Effect on Minimum Excitability of the Vagus-roots.
Experiment XXX VII.—March 30.

A cat, weight 4 lbs., was chloroformed.
A cannula was inserted into the trachea.
left carotid.
ss e left saphena vein.
The right vagus nerve was cut, and its central end placed in
a Von Basch’s electrode.

3? 99

alate

The left vagus remained intact. A 54, solution of the watery

EXCITABILITY OF THE VAGUS ROOTS.

extract was used.

511

Respira-
tions in
10 see.

Blood-

pressure.

Oscilla-
tions.

Pulse
in
10 sec.

oo°o°o

15 0}
15 30

Condition before experiment ..

The normalexcitability of the
central end of the right
vagus was then tested ; it was
found that coil 10° produced
slight slowing of the pulse
and fall of blood-pressure,
while the respirations became
slower and deeper. This was
the slightest irritation which
produced any effect .. es

Condition after irritation ..
5 c.c. injected

Condition after injection

Rise of blood-pressure. No
alteration of pulse. Respira-
tions quickened and respira-
tory oscillations increased

Central end of right vagus irri-
tated. Coil15°.. ee

No effect

Central end of right vagus irri-
tated. Coil10° .

Same effect as before injection.

Second injection of 14 c.c.

Clot formed and removed

Condition before irritation ..

Irritation with coil 10° os

The thorax remained in a state
of permanent inspiration
during irritation, while the
effect on the heart and blood-
pressure was ail

Trritation with coil 6°.. 2%

No effect on heart. Respiration
as before

Condition immediately follow-
ing irritation.. oe oe

Slowing of pulse. Great fall
of blood-pressure. Great
oscillation. Systole and dia-
stole of same length, with no
pause between them

Irritation with coil 8°.. ee

As before there was no effect on
the blood-pressure or pulse,
and there was permanent in-

32

2¢

mm.
105

100
110

146

140

135

120
120

115

60

12)

28

38

30
34

34

34

38

43
40

49

12

49

‘

512 ON THE PHYSIOLOGICAL ACTION OF CASCA BARK.

Respira- “ Pulse
Tae ees a
10 sec. P ; f 10 see.

m. 8 mm. mm
spiration during the irrita-
tion
15 35 | Condition immediately after sa
irritation. See remarks on 4 <7 OO 15 { :
after effect of coil 6° i irreg,
16 O | Gradual cessation of after effect 2 100 ” 22
16 30 | After effect ceased .. 0} 120 2 85

17 O |Coil 8°. Irritation repeated
with same results

In this experiment, as well as in several others, the blood-
pressure rose without being accompanied by a slowing of the
pulse, and this indicates that the latter is not dependent on the
former.

The excitability of the vagus-roots to reflex stimuli does not
seem to be increased by casca, as a stimulus of the same
strength applied to the central end of one vagus had a similar
effect before and after the injection of the drug. We would
call attention, however, to the very extraordinary effect which
succeeded the application of a stronger stimulus, an effect which
seems all the more extraordinary from occurring after the
stimulus had ceased, and not during its application.

Irritation of the vagus-roots by the carbonic acid accumu-
lated in the blood during the tetanic inspiration, which lasted
during the irritation, at once suggests itself as a cause of the
slow pulse which followed the irritation; but the fact that the
pulse was not affected when the distance of the coil was 10 cm.,
although the thorax was tetanically expanded, seems to indicate
that the slowing which followed the stronger irritation from a
secondary coil at 8 or 6 cm. distance from the primary was due
to refiex action, which the first irritation had been too weak to
produce.

From Experiment XXXV it will be seen that after the
administration of a large dose of casca, irritation of the vagi,
instead of producing slowing or stoppage of the heart’s action,
increased the frequency of its pulsations. The acceleration

ACCELERATOR FIBRES—CARDIAC GANGLIA AND PULSE. 6513

was equally great after irritation of the left, as after irritation
of the right vagus. This shows that the accelerator-fibres in
the vagus are not paralysed by casca, and also that accelerator-
fibres, though usually, according to Boehm, contained only in
the right vagus, may occasionally be present in the left.

The effect of irritating the other accelerating nerves of the
heart contained in the rami cardiaci or in the sympathetic cord
was not examined.

ACTION ON CARDIAC GANGLIA, EFFECT ON PULSE, &C.
Experiment XXX VIII.—June 10.
A moderate-sized cat was chloroformed, and cannule were
placed in the carotid artery and jugular vein.

A solution of 3 cc. of saturated alcoholic tincture added to
50 ¢.c. of water was used for injection into the vein.

Time Blood- | Oscilla- | Pulse in
pressure.| tions. | 10 sec.
m. 8. mm. mm.
QO 65 | Condition before injection ee as 160 25 23
1 20 | Injected 1 ¢.c. casca solution
1 30 | Condition shortly after injection 180 50 14
Rise of blood-pressure, slowing of pulse
2 O | Later, quickening of pulse ee ee 165 7 26
3 0 | Same ‘effect, more marked oe ee 175 5 36
4 0 | Commencing slowing of pulse... ve 170 6 30
4 30 ; Ty oe 140 8 30
5 0 i bs es ee 150 14 24
5 5 | Further injection of 1 c.c. casca
5 40 | Secondary ee of ie with fail of
blood-pressure . ; ss os 115 25 16

From this experiment it is seen that after the primary
slowing due to stimulation of the vagus-roots and the quicken-
ing due to paralysis of the vagus ends in the heart, a second
slowing occurs.

This second slowing might be due either to stimulation of the
inhibitory apparatus in the heart or to weakening of the cardia
motor ganglia.

The latter seems improbable, from the fact that each systole
during this slow period instead of being weak is exceedingly

21

514 ON THE PHYSIOLOGICAL ACTION OF CASCA BARK.

strong, the pulsation in an artery being felt very powerfully
when the finger is laid upon it, and the rise of pressure during
it being very great, as shown by the oscillation of the mercurial
column of the manometer.

In order to ascertain more exactly whether the inhibitory
cardiac ganglia were stimulated or not the following experiment
was tried :—

Experiment XXXIX.

A dog was chloroformed, and 7 cc. of a concentrated watery
solution of casca were injected into the jugular vein.

The pulse at the time of injection was 37 in ten seconds.
-In ten seconds after the injection it sank to 20. After the
injection of 3 ¢.c. more the pulse rose to 37. After a further
injection of 26 c.c. more in divided doses it again sank to 16.

This number was, however, uncertain, as the tracing was a
very imperfect one.

The injection of 1 ¢.c. of liquor atropie, B.P., did not seem
to alter the number of the pulse, but the injection of $ a c.c.
more seemed to cause it again to become quick.

This seems to indicate that the slowing is due to an action of
the casca on the inhibitory ganglia. The imperfection of the
tracing renders the result somewhat uncertain; but want of
time prohibited us from repeating the experiment, although we
greatly desired to do so.

Experiments XL, XLI.—March 15.

The effects on the capillaries of the frog’s web were micro-
scopically observed in Experiment XL after an injection of
casca under the skin of the back, in Experiment XLI when
locally applied to the web.

The capillaries were observed with oc. 2 obj. 4 of Hartnack.
In the first case, 2¢., after the drug had been injected, the
results were purely negative. In the second, after application
of a drop of strong casca solution to the web, the results were
also indecisive. In the capillaries, and also in the larger trunks,
the current was at first slowed, and in some permanent stasis
occurred. When slowing only was producsd, the partial arrest

a ee

ne

ACTION ON ARTERIOLES AND VASO-MOTOR CENTRE. 515

was followed by reaction, which did not exceed the original
rapidity of the circulation. No dilatation or contraction of the
vessels was seen to accompany the original slowing.

Although the results of experiments on the frog’s web gave
no definite information regarding the contraction of the arterioles
under the influence of casca, yet no reasonable doubt can be
entertained that in mammals they do contract ; for this is the
only possible explanation of the exceedingly slow fall of the
blood-pressure during the intervals between the beats of the
heart when these have become slow, either from the action of the
drug or from irritation of the vagus-trunk. (Cf antea, p. 143.)

In order to ascertain whether this contraction was due to the
action of the drug upon the vasomotor centre in the medulla
oblongata or in the vessels themselves, the vasomotor centre in
the medulla was separated from its connection with the vessels
by division of the spinal cord in the neck previous to the injec-
tion of casca.

EFFECT ON BLOOD-PRESSURE AFTER DIVISION OF Corp.
Experiment XLIT.—May 17.

A large strong cat, weighing 74 lbs., was chloroformed. A
cannula was inserted into the left carotid, and another into the

jugular vein. The spinal cord was then divided opposite the

second cervical vertebra, and artificial respiration kept up.

Pulse '
E ‘| seconds.| “2028:
m. s. mm mm
0 O | Condition after section of cord and pre-
vious to injection of casca .. oi 80 25 5

. rt Injected 1 ¢.c. watery solution of casca
0 10 “ ‘“- Pe os se 89 25 5
0 20 = ‘ 2 - avh’ MESO 18 12
O 30 ‘ *. 140 13 20
0 40 F 150 13 25
0 50 - e ae os 150 18 12
a -0 ‘3 s% i wid +s gob 298 28 5
110 <4 in ee vs as --| 190 32 4
a 20 ee ee ee ee se ee 200 34 3

2uL 2

516 ON THE PHYSIOLOGICAL ACTION OF CASCA BARK.

Pulse .
Time. sto in 10 ee,
pressure, oconds,| tens:

m. 8. mm, mm.
1 30 ee ee ee ve ee «| 210 34, 3
1 4J ee oe ve ee ee ««| ' 220 41 4
2 0 ee ‘es + oa ve +-| .230 44 3
210 | Sudden alteration in character of pu'se,

which becomes slow. The curve flat-

topped, and both systole and diastole

showing numerous secondary oscilla-

tions. Blood-pressure falling av 7280 3y 40
2 20 ee ee ee ee ee . ee 180 5 30
2 40 ve dee) 32 es - --| 165 6 25
3 0 | Bleod-pressure rapidly falling .. --| 130 6 15
3 20 | Both pulse and oscillations are very

irregular Fs és os -.| 100 5 ?
3 40 ‘9 ee +3 oe ee «| 80
3 50 ee ee ee ee ee ee 25
4 0 ie wd af es bh oe 10

There was no more pulsation after this ;
but the blood-pressure took 1 minute
30 seconds to fall quite to zero
On opening the thorax the heart was

found moderately contracted; elec-

trical stimulation of the phrenic nerve

caused contraction of the diaphragm

The result of this experiment will be seen all the more clearly
by the following diagram, Fig.160, in which they have been
graphically represented.

The rise of pressure in this experiment was greater than in
any other in which the cord had not been divided. This seemed
to us so extraordinary that we thought at first that the cord had
not been properly divided ; but a careful dissection made imme-
diately after death showed us that the division was complete.
A year or two ago this result would have been regarded as a
proof that the drug acts on the vessels themselves; but recent,
researches having shown that much more importance must be
attributed to vasomotor centres in the cord and in the periphery
than was previously done, we cannot say whether the drug acts.
on these centres or on the walls of the vessels themselves. The
non-contraction of the vessels of the frog’s web would indicate
that the action of the drug is rather on nervous centres in the
cord or neighbourhood of the vessels than on the vascular walls.

' Millimetres of Mercury.

DIRECT ACTION ON ARTERIOLES. 517

1
Ee
|S!

—S-}

© 4
~~
1 >
as
| a> |
rs
»
BS
es
_
S-

Fic. 160.

In order to exclude all centres except those in the periphery
Experiment XLIII was performed.

Experiment XLIIL.

The sympathetic cord was divided on the right side of the
neck of a rabbit and the animal allowed to come out of the
chloroform aneesthesia. The ear of the right side was deeply
injected while the left ear was very moderately filled with
blood. A dose of casca was then administered. The vessels of
both ears became pale, those of the right ear equally so with
those of the other.

VESSELS AFFECTED BY THE Drua.

The vessels by which the blood-pressure in the body is chiefly
regulated are those of the intestines, those of the skin and

518 ON THE PHYSIOLOGICAL ACTION OF CASCA BARK.

muscles being very much less under the influence of the vaso-
motor centre in the medulla. As casca acts on the vessels
without this centre, however, it was natural to suppose that
other vessels than those of the intestines might be affected;
and this the curves show to be the case. During the stoppage
of the heart (Experiment XLII) for half a minute the pressure
fell only slightly. Now Ludwig and Hafiz found that when
contraction of the abdominal vessels was produced by irritation
of the vasomotor centre in the medulla oblongata, complete
stoppage of the heart was followed by a rapid fall in the blood-
pressure, the blood finding its way out of the arterial system
into the veins through the vessels of the muscles. The slow
fall after the administration of casca shows that the vessels of
the muscles must be contracted as well as those of the skin and
intestines.
ACTION ON SECRETION OF URINE.

A detailed account of our experiment on the action of the
drug on the urinary secretion, together with the accompanying
effects on the circulatory system, will be found in pp. 503 and
504. Underneath is a diagram showing the close dependence of
the rate of secretion of urine upon the blood-pressure (Fig. 161)

Experiment XXXIII.—March 31.

Urine in minims
per 10 minutes.

Blood-pressure in
millimetres of mercury.

Fie. 161.

~ rE oe

DIURESIS—PUPIL-——LACRYMAL GLAND. 519

Remarks.

Tke results of this experiment, as regards the vascular
phenomena of blood-pressure, pulse, &c., have been already
fully noticed.

The action of the drug on the secretion of urine is seen to be
very marked and characteristic, and the dependence of the
secretion on the blood-pressure is well shown in the accompany-
ing chart.

Thus the average rate of urine secreted before administration
of casca being 5 minims in 10 minutes, an increase of 50 mm. in
the blood-pressure caused by the drug brought the rate of
secretion of urine up to 25 minims. When the action of the
drug was further pushed there was first decrease and then total
suppression of urine, the blood-pressure at the time of suppres-
sion being 200 mm. of mercury.

Subsequently as the blood-pressure fell the secretion of urine
recommenced.

The physiological explanation of these successive phenomena
appears to be that the primary increase of blood-pressure pro-
duces arterial fluxion to the kidney; but that if the action of
the drug is pushed, the renal vessels become contracted so as to °
prevent the blood reaching the kidneys, notwithstanding the
high pressure in the arterial system. It is worth notice that
the urine collected after the secretion had recommenced did not
contain albumen.

In this respect the result of this experiment differs from those
obtained by Mr. Power and one of us in our experiments on the
action of digitalis ; it coincides, however, with those experi-
ments in its general results. (Cf antea, pp. 410 and 412.)

ACTION ON THE PUPIL AND LACRYMAL GLAND.

In order to see if the drug exerted any local action on either
of these organs, we (Experiment XLV) placed some drops of
strong watery solution of casca in the eye of a cat, but with
purely negative results.

520 ON THE PHYSIOLOGICAL ACTION OF CASCA BARK.

ACTION ON MUSCLE.
Effect on Structure of Muscular Tissue.

The effect on fresh muscular tissue of immersion in casca
solution was carefully watched with an oc. 3 obj. 7 of Hart-
nack’s microscope without any change in the structure being
discovered (Experiment XLVI). We then (Experiment XLVII,.
March 22nd) examined the “naked-eye” and microscopical
changes produced in muscular tissue by prolonged immersion
in a watery solution of the alcoholic extract, the effect of
which solution in preventing the development of Bacteria has
already been detailed (p. 493).

A. The solution in which the muscular tissue had been
placed presented, in addition to the absence of Bacteria, a few
noteworthy points ; it preserved its original slightly resinous
smell, and deposited a fine light-brown sediment, which, under
the microscope, appeared as a granular structureless detritus.

B. The muscular tissue to the naked eye appeared hardly
altered in consistence: the fibrous sheath was firm; there was
no smell. Under obj. 7 Hartnack the fibres were seen to be
_ very granular, in part only preserving their transverse striation ;
the general appearance closely resembled ordinary fatty degene-
ration. Some of the fibres were then soaked in ether for 24 hours ;
on examination after this the granulations had in great part
disappeared. Many of the fibres appeared to consist merely of
collapsed tubes of sarcolemma; where they were not collapsed
they showed plain transverse striz.

Six weeks later the muscle was again examined; it having
remained in the same casca solution all the while, it was now
reduced to the condition of a rather tough gelatinous pulp; the
sheath of the muscle retained its strength. Under the micro-
scope there was seen a mixture of granular and fibrous material,
with a large quantity of oil-globules and flat crystals, and when
treated with ether these were completely removed.

ON MUSUULAR POWER AND CONTRACTION. 521

Effect on the Lifting-power of Muscle.
Experiment XLVIII.

The lifting-power of a frog’s gastrocnemius which had been
placed in a 34, solution of casca was compared with that of a
similar preparation placed in salt solution, by attaching the one
muscle as quickly as possible after the other to an apparatus for
estimating their lifting-power connected with a revolving drum.
The irritations were made with electrodes connected with a
Leclanché’s battery.

The results of our first experiments appeared to show that
the drug possesses a stimulating action on the lifting-power of
muscle; but on repeating the experiment this result was not
confirmed—the conclusion we drew from the whole series of
experiments being that muscles which had been immersed in
easca and salt solution respectively possessed nearly the same
lifting -power.

Effect on Muscle-curves.
Experiments XLIX, L.

Two frogs were injected with casca, and when they seemed
dead, nerve-muscle preparations were made of the gastrocnemil.
In Experiment XLIX the preparation was attached to a Fick’s
pendulum myograph, and a tracing taken. In Experiment L the
nerve-muscle was made to trace on a revolving cylinder: the
curves obtained in these experiments are evidently normal.

In Experiment LI the action on the sensibility to electrical
stimuli of muscle and motor nerves was tried, also with com-
pletely negative results, by making two nerve-muscle prepara-
tions of a frog’s gastrocnemii, and immersing one in casca
solution, the other in salt solution. The sensibility of the two
preparations was then tested by various strengths of a Du Bois
Reymond’s coil connected with a Leclanché’s battery. The two
muscles responded quite similarly.

Remarks on the Action of Casca on Muscle.

1. When applied to fresh muscular fibre no change is observed
in its histological details.

ae ON THE PHYSIOLOGICAL ACTION OF CASCA BARK.

2. In addition to the absence of the development of Bacteria
which is noticed when muscular tissue is placed in a watery
solution of the alcoholic extract, and which has already been
remarked upon, the structural changes which the muscular
tissue undergoes appear to consist in a fatty metamorphosis,
which at first simulates very closely that of ordinary fatty
degeneration, while the later appearances resemble those of the
more complete fatty changes which go on after the death of
a tissue, large oil-globules and abundant crystals of the fatty
acids being everywhere found.

3. It does not diminish the lifting-power of muscle in a
nerve-muscle preparation, nor when the irritation is applied to
the muscle itself, and it probably does not increase it; for
although apparently positive results were attained on the first
occasion when the lifting-power was experimented on, these
results were not borne out by further experiments.

4, The muscle-curve given by a nerve-muscle preparation
taken from a frog poisoned by a large dose of casca appears to
be quite a normal one.

5. It also exerts no action on the sensibility of muscle to
electrical stimulation if this sensibility be tried quantitatively
by estimating the weakest interrupted current which will pro-
duce a contraction.

From all these results, then, it may be concluded that while
the drug produces a peculiar and characteristic change on
muscular tissue immersed in it for some days, it is not a muscle-
paralyzer.

ACTION ON Motor NERVES.

If casca had any paralyzing action on the ends of motor
nerves similar to that of curare, it would be found that after
immersion in a solution of the drug the muscle would respond
to electrical stimuli directly applied to it, but not to those
applied to the nerve. In Experiment LII, however, the nerve
also is seen to preserve its irritability, and therefore we may
conclude that casca has no action on motor nerves,

ACTION ON REFLEX EXCITABILITY. ; 523

ACTION ON SENSORY NERVEs.
Effect on Reflex Excitability.
Experiment LIT.—March 22.
The cerebrum of a living frog of medium size was destroyed.
The circulation through the left leg was cut off by ligaturing
the arterial trunks above the knee (vide fig. 162). The sciatic

nerve was left uninjured. } c.c. of the alcoholic extract was
then injected beneath the skin of the back.

fi

Fie. 162. The shading indicates the part to the body to which the poison was
carried by the blood. The unshaded part was protected by the ligature
from the action of the poison.

The reflex excitability was then tested at intervals of 5
minutes by irritating points above and below the ligature. No
difference in the sensibility could be detected.

As the frog was very little affected by the injection, another
2 c.c. was injected.

The frog became insensible to reflex irritation in 25 minutes ;

524 ON THE PHYSIOLOGICAL ACTION OF CASCA BARK.

during this time the irritability was tested every 5 minutes as
before: the rates of increase of the insensibility appeared to be
equal above and below the ligatures.

In this experiment the poison was applied to the terminations
of the sensory nerves above the ligature, but not to those below
it. Had it possessed any marked power of diminishing the
sensibility of these nerves, a stimulus applied above the ligature
would have had less effect than one applied below it; but this
was not the case. :

The poison therefore seems to have no action on sensory’

nerves, at any rate none of a paralyzing character.

Action on Reflex.
Experiment LIII.

In this experiment the action on reflex was tested by apply-
ing a very dilute solution of sulphuric acid to the leg of a frog
with its cerebrum destroyed and suspended by its head. Its
normal irritability was then tested. The tips of the toes only
were immersed in the acid. Contraction was immediate and
lasted 3 minutes (right leg). A } cc. alcoholic solution was
then injected; the animal immediately hung more flaccidly.
5 minutes afterwards, on immersing the tip of the toes of the
right leg, slight contraction occurred after 63 seconds. A
quarter of an hour later, on immersing half the leg, contraction
was immediate and lasted 5 seconds; in 10 minutes more a
similar immersion produced contraction after 10 seconds, and
5 minutes afterwards after 15 seconds. 50 minutes after the
injection of the drug the acid solution produced no reflex move-
ments, and only slight ones were excited by pinching. Reflex
ceased last in the eyelids 1 hour and 20 minutes after the casca
had been injected.

In Experiment LIII the reflex excitability disappeared very
much more quickly than it usually does.

This might be due to the action of the drug on the spinal cord
itself, or to the cessation of circulation caused by the action of
the drug on the heart.

In order to decide this the following experiment was made,

ANTAGONISM TO ATROPIA AND CHLORAL. 525

Experiment LIV.

The heart of a frog was exposed and cusca administered.
As soon as the heart had ceased to beat the heart of a second
frog was ligatured at the root of the aorta so as completely to
arrest the circulation. At first both frogs were able to jump
readily ; but gradually their movements became more sluggish,
and after a jump their legs trailed out behind them and were
only slowly drawn up to the body. They became less and less
sensitive to pinching, and insensibility and loss of motor power
occurred simultaneously in both.

The diminished power of movement and diminished reflex
action observed in the frog after the administration of casca is
therefore due to the arrest of the circulation caused by it, not
to any action of the drug upon the nervous system.

ANTAGONISM BETWEEN CASCA AND ATROPIA AND CHLORAL
HYDRATE.

The remarkable result of Experiment XXIV, in which a dose
of casca, usually fatal, produced no effect in an animal with
divided vagi, seemed to render it probable that such a drug as
atropia, which paralyzes the ends of the vagus in the heart,
might have an antagonistic action. On trying it, however, it
was found that the vomiting caused by the casca was even more
violent than usual; and therefore a combination of atropia with
chloral hydrate was employed, the chloral being given to lessen
the irritability of the vomiting centre in the medulla.

The results were not satisfactory, as will be seen from the
two following experiments.

Experiment LV.—May 1, 1876.
About 11.40. Injected 4 cc. of liquor atropize under skin of
flank of cat A.

12",. Injected 4 c.c. of a saturated alcoholic solution of alco-
holic extract of casca under skin of flank of cats A and B

526

ON THE PHYSIOLOGICAL ACTION OF CASCA BARK.

A. B.

h. m. ;

12 30 os oe os ee ee Sick and vomits. During the
intervals between the fits of
vomiting seems well,

12 40 | Crouching, trembling, and seems

about to be sick. Licks its lips.
Hind eyelid much drawn up.
12 52 | Very sick; vomiting. Seems| Vomiting. Disinclined to move. *
more uneasy than B, When disturbed and made to
; walk its hind legs give a shake
as if to shake off something
sticking to the feet every time
. they are drawn up.

1 O | Very sick. Very sick. Brings up fluid, which
appears to be digested meat.
Respirations 18 per minute.

115 | Gives loud squalling cries when | Seems weaker.

retching.

1 30 | Seems easier; not retching. Twitch or rather shake of hind
legs is very marked.

2 35 =| Walking about. Seems unable to move.

2 40 ee oe oe ee ee | Violent retching; crying. Con-
vulsive extension of legs and
emprosthotonos. Then two or
three sighing respirations; a
pause; one or two respirations
at intervals; then death.

4 0 | Has been vomiting at intervals.

Has a violent fit of sickness
and dies in the same way as B.

Post mortem.

Stomach contains a quantity of
fuod. Heart moderately con-
tracted. Ventricles continue
to make slight pulsations, au-
ricles not, Lungs somewhat
congested. No congestion of
interior of stomach.

Stomach empty, not congested.
Heart moderately contracted.
Lungs normal.

7
as i | * ry,
Pe Ges ea: Ly WE svidi HY eS eae Ph

—————

12 58. Muscular

—_—
>

ANTAGONISM TO ATROPIA AND CHLORAL. 527

Cat A.
Large.

. Injected 30 minims
liquor atropize sub-
cutaneously.

12 20. Injected 5 c.c. satu-

rated watery solu-
tion and suspension
of casca.

12 30. Vomited.
12 45. Vomiting has been

repeated 3 or 4
times. Is lying on
its side and cannot
stand. R.144. Ale
nesi working.

12 52. Eyelids much drawn

up. Respiration
irregular.

12 55. Gasps; seems to try

but to be unable to

vomit. |§Empros-

thotonic spasms.

twitch-
ings. Slow sigh-
ing respirations.
Death.

Cat A lived 38 minutes

after injection of casca.

Experiment LVI.

Cat B.
Medium,

12 45. Iniected 15 grs.
of chloral hy-
drate and 15
minimsof liquor
atropie with
5 c.c. of casca.

12 58. Mewing.

12 59. Vomited twice.
1 9. Vomited again.
1 14. Loud violent

retching but no
vomiting.

1 15. Involuntary ex-
trusion of feces
and urine.
Died.

Cat B lived 30 minutes.

Cat C.
Large and strong.

h. m.

12 40. Injected 5 c.c. of
the same casca
solution.

12 49. Very restless.

12 52. Vomited for first
time. After
this it vomited
frequently, but
remained rest-
‘less. TT. 371°.

1 30. Died rather sud-
denly, with vio-
lent gasping
and emprostho-
tonic spasm.

Cat C lived 50 minutes,

In this experiment the cat which had received the casca alone

lived longer than the others.

NOTE ON INDEPENDENT PULSATION OF
THE PULMONARY VEINS AND VENA
CAVA.

In conjunction with Sir J. /}AYRER, M.D., K.C.S.1.
(From the Proceedings of the Royal Society, No. 172, 1876.)

IN a former communication* we incidentally mentioned that in
a rabbit killed by the injection of cobra poison into the jugular

vein we had observed the pulmonary vein pulsating after all —

motion had ceased in the cavities of the heart. We have since
observed the same phenomenon three or four times under con-
ditions which show that this pulsation is not due to the action

of the cobra poison with which the animal in which we first

observed it had been killed. The following example will show
the changes in rhythm observed in these pulsations.

A cat was chloroformed, and the vagi exposed and irritated
by an interrupted current. Artificial respiration was kept up
by air containing chloroform vapour, and the thorax was then
opened, and a solution of atropia injected directly into the heart
by means of a Wood’s syringe. The vagi were again irritated,
but without any effect being produced on the heart, the inhibi-
tory apparatus in it being evidently paralysed by the atropia.
A solution of glycerine extract of physostigma was now injected
into the heart in a similar way. The vagi were now irritated
again, and the heart stood still, the effect of the atropia having
been counteracted by the physostigma. After the irritation
ceased the heart again commenced to pulsate.

Artificial respiration was now discontinued, but all the cavi-
ties of the heart continued to beat for a considerable time. The
ventricles then stopped, but the auricles continued to beat. It
was then noticed that the pulmonary veins in the right lung,

* Proceedings of the Royal Society, 1874, vol. xxii, p. 125.

SEQUENCE OF CONTRACTION IN THE HEART. 529
which was exposed to view, were pulsating. The veins, as well
as both auricles, pulsated at the rate of 119 per minute, but the
contractions of the veins were not synchronous with those of
the auricles. Both auricles next ceased to beat, but the pul-
monary veins in both lungs continued to pulsate. The ventricles
now began to beat again, while the auricles remained still. The
ventricles pulsated at the rate of 8 per minute, while the pul-
monary veins pulsated at the rate of 46 per minute; and no
motion was perceptible in any part of the auricles.

One hour and twenty minutes after the thorax had been
opened, and about an hour and ten minutes after artificial
respiration had been discontinued, the ventricle was still pul-
sating. Its rhythm was very irregular. After one beat a pause
of half a minute followed, and then 37 pulsations all together,
One hour and forty minutes after opening the thorax the inferior
vena cava was noticed to be pulsating close to its entrance into

-the auricle. A contraction spread like a wave from the vena
cava over the right auricle, and the appendix contracted after
the auricle itself. The superior vena cava also pulsated close to
the neart. The left auricle had ceased to pulsate a considerable
time previously, and the ventricles had also stopped. After the
auricles had pulsated for a while the ventricles again began.
At one hour and fifty minutes after opening the thorax the
inferior vena cava was still pulsating. In ten minutes more all
movement had nearly ceased, and the observation was discon-
tinued.

At one hour and fifty minutes after opening the thorax slight
contractions of the diaphragm were noticed.

The striking points in this experiment are the contractions of
the pulmonary veins and the vena cava independently of the
heart, the long time during which they retained their irrita-
bility, and the continuance of their pulsations after the other
parts of the heart had ceased. The pulsation of the pulmonary
veins and of the ventricles at the same time, while the auricles _
were motionless, is also deserving of attention.

In ancther experiment we found the pulmonary veins pulsat-
ing in a cat killed by a blow on the head. We have also seen
pulsation in animals killed in other ways; but the proportion of

2M

530 INDEPENDENT PULSATION OF PULMONARY VEINS, ETC,

cases in which we have seen it to those in which we have not
seen it is very small. On looking through several modern text-
books of physiology, we have failed to find any mention of the
rhythmical contractile power of the pulmonary veins and_vena
cava; but the earlier anatomisis were well acquainted with it,
and Haller* states that he has seen the pulmonary veins con-
tinue to pulsate for two hours, and that others had seen the
vena cava pulsate for three hours while all motion in the other
cavities of the heart had already ceased. Johannes Miillert
has also observed contractions of the vena cava and pulmonary
veins; and in young animals the contractions of the pulmonary
veins extend as far as they can be followed into the lungs.

The importance of contraction of the vena cava and pul-
monary veins in preventing reflux of blood into them during the
contraction of the auricle, under circumstances when any
hindrance is opposed to the free flow of its contents into the

ventricle, is self-evident. Indeed Hallerf says that it was sup-,

posed to exist by Senac, although he had not seen it. Especially
in cases of valvular disease of the heart is it likely to be of
great service; and we think it advisable to bring again before
the notice of physiologists and physicians this power of the
veins, which, although so long known, appears of late years to
have been overlooked.

* Elementa Physiologia, 1757, tom. i, »p. 410 and 399; and Mémoires sur la
Nature sensible et irritable des parties du corps animal, 1756, tom. iv, p. 4.

t+ Miiller’s Physio’ogy, translated by Baly, 2nd ed., vol. 1, p. 182.
t Op. cit., p. 410.

et

=, . o>... gill Ea

ON THE SCIENCE OF EASY CHAIRS.
(Reprinted from Nature, October 17, 1878.)

THERE is a reason for everything, if we can only find it out, but
it is sometimes very hard to discover the reasons of even the
very simplest things. Every one who has travelled much, and
even those who have merely looked through books of travels,
must have been struck by the variety of attitudes assumed by
the people of different countries. The Hindoo sits down on the
ground with his knees drawn up close to his body, so that his
chin will almost rest upon them; the Turk squats down cross-
legeed ; the European sits on a chair; while the American
often raises his legs to a level with his head. Nor are the pos-
tures assumed by the same people under varying circumstances
less diverse. Climate or season, for example, will cause con-
siderable alteration in the posture assumed, as was well shown
by Alma Tadema, in his pictures of the four seasons exhibited
in the Academy a year ago. In his representation of Summer
he painted a woman leaning backwards on a ledge, with one lee
loosely hanging down, while the other was drawn up so
that the foot was on a level with the body. In the picture
of Winter, on the other hand, we saw a figure with the legs
drawn up in front of the belly. The reason for these different
postures has been explained by Rosenthal. The temperature of
the body, as is well known, is kept up and regulated by the
circulation of the blood through it, and a great proportion of
the blood contained in the whole body circulates in the vessels
of the intestines. Now the intestines are unly separated from
the external air by the thin abdominal walls, and therefore any
change of temperature in the atmosphere will readily act upon
them unless they be guarded by some additional protection.
The Hindoos are well aware of this, and they habitually protect
the belly by means of a thick shawl or camarband, thus
guarding themselves against any sudden change of temperature.
This precaution is also frequently adopted by Europeans resi-
2M 2

532 ON THE SCIENCE OF EASY CHAIRS.

dent in hot climates, and is even retained by them after return-
ing to England. But the function of the camarband may,
to a certain extent, be fulfilled by change of posture alone.
When the legs are drawn up, as in the picture of Winter
already referred to, the thighs partially cover the abdomen, and
taking the place of additional clothing, aid the abdominal walls
in protecting the intestines and the blood they contain from the
cooling influence of the external air.

Thus it is that in cold weather, when the quantity of covering
in bed is insufficient, persons naturally draw up their lege
towards the abdomen, so as to retain as much heat as possible
before going to sleep. In hot weather, on the contrary, they
wish to expose the abdomen as much as possible to the cooling
influence of the atmosphere. The posture depicted by Alma
Tadema is the most efficient for this purpose. It no doubt
answers the purpose to lie down flat on one’s back, but in this
position the abdominal walls are more or less tight, whereas,
when one of the legs is drawn up as in the painting just alluded
to, the walls are relaxed, and the intestines not being subject to
any pressure, the blood in them will circulate more rapidly, and
the cooling process be carried on more effectually. In this
attitude also the thighs are completely separated, and loss of
heat allowed from their whole surface.

Varying conditions of fatigue also alter the postures which
people assume. When slightly tired one is content to sit down
in an ordinary chair in the position of the letter NY with the
middle limb horizontal. As we get more and more fatigued we
usually assume positions in which the limbs of the N) become
more and more oblique, the trunk leaning backwards and the
legs extending forwards. If we lie down in bed on our back
the legs will probably become straight, but if we rest upon our
side they will be more or less bent. The straightness of the
legs in the supine position is simply due to their weight, which
is then supported at every point by the bed, but when we lie on
our sides the genuflexion of the legs is most agreeable, because
not only are the muscles more perfectly relaxed, but, as the late
Professor Goodsir pointed out, the bones which form the knee-
joint are slightly removed one from another, and thus the joint

mis

EASIEST POSITION. 533

itself, as well as the muscles, passes into a state of rest. Some
of the bamboo easy chairs manufactured in India allow us to
obtain the advantages of both positions. These chairs are made
in the form of a somewhat irregular straggling YW, and in them
one can lie on one’s back with every part of the body thoroughly
supported, and the knees bent in the same way as they would
be if one lay upon one’s side.

Thus simple inaction, the relaxation of muscles, and the
laxity of joints, are some of the factors necessary for complete
rest, and an easy chair, to be perfect, must secure them all.

But it is possible for an easy chair to secure all these and yet
be imperfect. We have just said that usually, as the fatigue
becomes greater and greater, the tendency is to assume the
position of the N with the limbs at a more or less obtuse
angle, but when sitting in an ordinary chair we find relief from
raising the feet by means a foot-stool, although this tends to
make the angles of the N more acute instead of more obtuse..
Still more relief, however, do we obtain when the legs are raised
up on a level with the body by being placed upon another:
chair, or by being rested on the Indian bamboo seat already
described. If, in addition to this, the legs are gently sham-
pooed upwards, the sensation is perfectly delightful, and the:
feelings of fatigue are greatly lessened. To understand how
this can be, it is necessary for us to have some idea as to the
cause of fatigue. Any muscular exertion can be performed for
a considerable time by a man in average health, without the
least feeling of fatigue, but by and by the muscles become
weary, and do noi respond to the will of their owner so rapidly
as before; and if the exertion be too great, or be continued for
too long a time, they will ultimately entirely refuse to perform
their functions, The muscle, like a steam-engine, derives the
energy which it expends in mechanical work from the combus-
tion going on within it, and this combustion, in both cases,
would come to a standstill if its waste products or ashes were
not removed. It is these waste products of the muscle which,
accumulating within it, cause fatigue, and ultimately paralyse
it. This has been very neatly shown by Kronecker, who caused
a irog’s muscle, separated from the body, to contract until it

534 ON THE SCIENCE OF EASY CHAIRS.

entirely ceased to respond to a stimulus. He then washed out
the waste products from it by means of a little salt and water,
and found that its contractile power again returned, just as the
power of the steam-engine would be increased by raking the
ashes which were blocking up the furnace and putting out the
fire. These waste products are partly removed from the muscles
by the blood which flows through them, and are carried by
ithe veins into the general circulation. There they undergo
more complete combustion, and tend to keep up the tempera-
ture of the body. At the same time, however, according to
Preyer, they lessen the activity of the nervous system, pro-
‘ducing a tendency to sleep, and in this way he would, at least
‘to some extent, explain the agreeable drowsiness which comes
‘on after muscular exertion. It would seem, however, that the
‘circulation of the blood is insufficient to remove all the waste
products from the muscles, for we find that they are supplied
‘with a special apparatus for this purpose. Each muscle is
generally ensheathed in a thin membrane, or fascia, and besides
these we have thicker fasciz ensheathing whole limbs. These
fascize act as a pumping apparatus, by which the products of
“waste may be removed from the muscles which they invest.
‘They consist of two layers, with spaces between. When the
muscle is at rest these layers separate, and the spaces become
filled with fluid derived from the muscle, and when the muscle
‘contracts it presses the two layers of its investing sheath
‘together, and drives out the fluid contained between them.
‘This passes onwards into the lymphatics, where a series of
‘valves prevent its return, and allow it only to move onwards,
till at last it is emptied into the general circulation.

In strong and healthy people the veins and lymphatics
together are quite able to take up all the fluid which the
arteries have supplied to the muscles, and thus prevent any
accumulation from taking place either in them or in the cellular
tissue adjoining them, or at least prevent any such accumula-
tion as might become evident to the eye. In delicate, weakly
persons, or in those who suffer from certain diseases of the
vascular system, this is not the case; and after standing or
walking for a long time the legs become swollen, so that the

i

bf ’ - % ee VES Bo NORE
: ones

——

eS

CAUSES OF FATIGUE—USE OF ELEVATING LEGS. 535

boots feel tight, and sometimes even a distinct impression may
be remarked at that part of the ankle which was uncovered by

the boot. In such persons we can actually see the swelling

disappear after the feet have been kept rested for some time on
a level with the body, and it may be removed more quickly still
by gently and steadily rubbing the limbs in one direction from
below upwards. It is almost certain that what we thus see in
weakly persons occurs to a slighter extent in all, and that even
in the most healthy person after a long walk a slight accumula-
tion of fluid, laden with the products of muscular waste, occurs
both in the muscles themselves, and in the cellular tissue around
them, even although we cannot detect it by simple inspection.
So long as the limbs of such a person hang down, the force of
gravity retards the return both of blood through the veins and
of lymph through the fasciz and lymphatics, and thus hinders
the muscles from getting rid of those waste products which
eaused the fatigue. When the legs are raised, this hindrance
is at once removed, both blood and lymph return more readily
from the muscles, carrying with them those substances which
had been formed by the muscles of the limbs during the exer-
tions which they had undergone when carrying the body about.
So long as these substances remained where they had been
formed, they might cause in the muscles of the legs an undue
amount of fatigue, although when distributed over the body
generally, they may produce only a pleasing laneuor. When
the legs are long, the obstruction to the return of blood and
lymph is of course greater than when they are short, and this
return will take place more readily when the legs are raised
above the body than when they are only on a level with it.
This may be one of the reasons why some of our long-legged
American cousins are so fond cf raising their feet to a level
with their heads, or even higher, although it is very probable
that there are reasons still more powerful, which we may discuss
at a future time.

Tt has already been mentioned that the lymph is propelled
along the interstices of the fascie into the lymphatic vessels by
the intermittent pressure which the muscle exerts upon them
from within, and it seems natural to suppose that the flow

535 ON TIIE SCIENCE OF EASY CIIAIRS.

may also be aided by a pressure from without, in the form of
shampooing. Even when the hand is rubbed backwards and
forwards upon the leg it will relieve fatigue, but the relief is
greater when the leg is firmly grasped and the hand moved
gently upwards so as to drive onwards as much as possible any
fluid which may have accumulated in the limb, and the grasp
being then relaxed, the same process should be repeated.

But while the lymph is thus most readily removed by the
pumping action of intermittent pressure either of the hand
without or of the muscles alternately contracting and relaxing
within, it seems to us probable that this process may also be aided
by steady, constant pressure from without. No doubt it is im-
possible for such a steady pressure to take the place of the regular
pumping action produced. by the alternate contraction and
relaxation of the muscles when in action, yet it will have a some-
what similar action, though to a very much less extent. For at
cach beat of the heart, as Mosso shows, the entire limb is dis-
tended by the blood driven into the vessels, and during the pauses
between the beats it again becomes smaller. Each pulse, there-
fore, by distending the whole limb and each individual muscle,
will press out a little of the fluid contained in the fasciz in
the same way as the contractions of the muscles themselves,
and it seems to us probable that it is the aid which is afforded
to this process by the gentle pressure exerted on the outside of
the legs by a seat which supports them along their whole
extent, that renders such a seat so peculiarly restful and agree-
able. For an easy chair to be perfect, therefore, it ought not
only to provide for complete relaxation of the muscles, for
flexion and consequent laxity of the joints, but also for the easy
return of blood and lymph not merely by the posture of the
limbs themselves, but by equable support and pressure against
as great a surface of the limbs as possible.

Such are the theoretical demands, and it is interesting to
notice how they are all fulfilled by the afore-mentioned chair in.
the shape of a straggling W, which the languor consequent upon
a relaxing climate has taught the natives of India to make, and
which is known all over the sis a

|

solace 5 ais te

ON A SIMPLE INSTRUMENT FOR EXAMIN-
ING THE COMPETENCY OF THE TRI-
CUSPID AND MITRAL VALVES.

(Reprinted from St. Bartholomew’s IIospital Reports, vol. xiv, 1878.)

Ir has often seemed to me that the present method of examining
the tricuspid and mitral valves of the heart in a post-mortem
examination is not so satisfactory as that which we use for the
aortic and pulmonary valves. In examining the latter, we pour
water into the aorta and pulmonary artery, and actually see
whether the valves are competent or not ; but in the case of the
tricuspid and mitral valves we determined their competency
either by simple inspection, or at most by pouring a little water
into the ventricular cavities, and observing the appearance of the
valves as they float upwards upon it. It has occurred to me
that a simple instrument, such as has been used for experiments
on the cardiac sounds, might be useful for ascertaining the com-
petency of these valves under such con¢litions of pressure as
they are subjected to during life. Such an instrument may be
very readily made from the nozzle(A) of.an ordinary india-rubber
enema’syringe. This consists of «an ivory tube, about 24 inches
long, with a horizontal shield about half an inch from one end.
The longer end of the nozzle is pushed through the auriculo-
ventricular orifice, and onwards through the ventricle (B), until it
projects on the outside of the ventricular wall close to the apex.
It is then pulled through, and a thick india-rubber ring (C) is
pushed over it, so that the wall of the ventricle is compressed
between the ring outside and the ivory shield of the nozzle inside.
The nozzle is then connected by a piece of india-rubber tubing
either with a tap or with an enema syringe. If water be now made
to pass into the ventricle through the nozzle, the valves (D) float
upwards, and become firmly opposed. The aorta and pul-
monary artery are now firmly held with the finger and thum),
so as to prevent the water from flowing out at the ventricle

538 COMPETENCE OF VALVES.

through them, and the pressure inside the ventricle may be raised
to any necessary degree. If the heart be healthy, no water will
escape until the pressure becomes excessive, and then a small jet
may be seen to issue from between the valves. By connecting
the tube leading from the water supply to the heart with a
mercurial manometer, the pressure at which the valves become
incompetent may be at once ascertained. The ventricle may be

Fic. 163.*

N

‘}

VD
‘@)
AGE,
Y
iy
wo

a

then cut open, the nozzle removed, and the valves inspected in
the usual way. I do not claim the idea as an entirely new one.
The instrument has doubtless been used in various forms many
times before, but the form in which I employ it is exceedingly
cheap ; and the time required for its application is very short,
a couple of minutes sufficing to ascertain the competency of
both valves, and it does not in the least injure the heart if it
be wished to preserve it as a specimen afterwards. It may
therefore, I think, be more widely employed than any other
instrument of the sort, and may thus lead to the discovery of
very interesting results.

* This figure was not in the original paper.

;

ON PULSATION* IN THE JUGULAR AND
OTHER VEINS.

(From the Medical Press and Circular, July 2nd, 1879.)

PULSATION in the jugular veins is usually regarded as a sign of
tricuspid regurgitation, and therefore of grave import. When
I thus speak of pulsation in these veins, I of course exclude
the apparent pulsation produced by the motion communicated
to them by the pulsation of the carotids, and refer only to pul-
satile movements in the veins themselves. Several writers
have noticed that pulsations in the jugular veins may occur
without any cardiac lesion. Some have attributed these to con-
traction of the right auricle, while others have supposed them
to be caused by the aorta pressing the blood out of the intra-
thoracic veins into the jugulars during its distension by the
cardiac systole. Some observations which I have made upon
jugular pulsation have shown me that it is sometimes due to
the distension of the aorta acting in a somewhat different way
from that described by Friedrich. I cannot believe that the
phenomena I have observed have previously been unnoticed,
and I feel quite sure that they must have been already
described by older authors, although I have been unable to
find an account of them in more recent works. These
phenomena consist in apparent pulsation in the left jugular
alone, while it is absent from the right. In the first case of
this sort which I saw, the apparent pulsation was very marked
in the left jugular. On comparing it with the right, I noticed
that it also appeared to be much fuller ; and when I compressed
it just above the clavicle, in order to ascertain whether I could
thus stop the pulsation, it filled up very rapidly, and became
much distended. This showed that the peripheral vessels by
which it was supplied were much dilated, and that blood was
flowing very rapidly into it. On compressing the right jugular

* 'Lhis should rather be termed pseudo-pulsation.

540 ON PULSATION IN THE JUGULAR AND OTIIER VEINS.

in a similar manner, it also became very much distended. On
relaxing the pressure, it quickly emptied, and when I alternately
increased and diminished the pressure, the alternate filling and
emptying produced an appearance of pulsation. If it was
compressed with the finger simultaneously with each beat of
the pulse, an exact imitation of the pulsation observed in the
left jugular was produced. It therefore appeared to me that
the pulsation in the left jugular was simply due to alternate
compression and relaxation of the innominate vein by the aorta.
during its dilatation and contraction at each beat of the heart.
Since my attention has been attracted to this unilateral jugular
pulsation, I have observed several cases of it. These have all
been females, and all have been more or less anemic. The
following cases may serve as examples :—

Rosana K., wet. 22, cartridge maker, in following her occupa-
tion, stands in a close room. About twelve months ago she
began to get very pale. She had no fright, but during the
course of the last year she has had much worry. ‘The patient is
markedly chlorotic; menstruation is regular, but scanty; the
bowels are constipated; tongue clean; appetite rather poor.
There is an anemic murmur over the palmonary cartilage; the
cardiac sounds are otherwise healthy. There is apparent pul-
sation in the left jugular vein, none in the right. When either
jugular is compressed, it fills very rapidly. On compressing
the right jugular with the finger at each beat of the pulse,
apparent pulsation is produced in it. On first beginning to
auscultate, the pulsation in the left jugular was very distinct.
The heart’s action was somewhat excited. As the agitation
of the patient subsided, the pulsation in the left jugular
diminished, and finally disappeared. Jt did not return when
the patient walked across the room, but she could only be
induced to do so slowly.

Elizabeth G., set. 19, is also very pale. For nearly nine months.
she has had a slight cough, and has been losing flesh. Her appetite
is very poor; the bowels are regular; she has not menstruated
for the last three months. Percussion sounds are normal.
There is a slight click at the end of inspiration over the right.
infraclavicular region. The breath sounds are otherwise

x
LOCAL CONTRACTION OF VEINS. DAL

normal. - There is a systolic bruit over the pulmonary carti-
lage; the heart’s sounds are otherwise normal. Pulse, 150,
when the patient is standing. The left jugular vein pulsutes
visibly, but only during expiration. During inspiration the
vein empties completely. There is no pulsation in the right
jugular, and that in the left is stopped by pressure above the
clavicle. It may be imitated in the right jugular by pressure
with the finger. There is no distinct venous hum.

Margaret LB. came to the hospital complaining of weakness
and nervousness. While in attendance, she began to suffer
from vomiting, and, a week or ten days after the vomiting com-
menced, she spat a little blood. Her nose also bled frequently
about seven in theevening. There was no abnormal pulmonary,
or cardiac sound. On one occasion, a curious persistent con-
traction of the jugular vein was noticed at the place where her
eollar had pressed upon it.*

Tn the case of Rosana It., the pressure exerted by the aorta
on the left innominate vein was insufficient to produce the pul-
sation when the circulation was quiet, but it did so when it was
excited by emotion. In that of Elizabeth G., it was insufficient
to produce it when the thorax was dilated and the sternum
raised by inspiration, but did so when the thorax had collapsed
and the sternum had fallen during expiration. In all of them
the peripheral vessels were dilated, so that the vein filled very
rapidly during compression, and but for this no appearance of
pulsation would have been produced. These few observations
may serve to direct attention to a cause of jugular pulsation
which, so far as I can find, is not generally recognised.

There is another venous pulsation which is also omitted from
modern text-books, although it is to be found in the older
writers. This, however, is not a simulated, but a real, pulsa-
tion, occurring in the pulmonary veins, and in the vena cava.
Some time ago, Sir Joseph Fayrer and I foundf that occasionally
the pulmonary veins and the vena cava in rabbits might be
seen to pulsate rhythmically for a considerable time after the
auricles and ventricles had become perfectly still. In one

* Compare antea “ Local contraction of arteries,” p. 178.
t GC. p. 528.

542 ON PULSATION IN THE JUGULAR AND OTHER VEINS.

animal, all the cavities of the heart continued to beat for a
considerable time after the thorax had been opened. The
ventricles then stopped, but the auricles continued to pulsate,
as well as the pulmonary veins. The veins and auricles both
pulsated at the rate of 119 per minute, but the contractions
were not synchronous. The auricles then ceased to beat, but
pulsation continued in the pulmonary veins, and the ventricles
again commenced, although the auricles remained perfectly
quiet. The pulsation of the ventricles was at the rate of 8 per
minute; while in the pulmonary veins it was at the rate of
46 per minute. Both the superior and inferior vena cava in
the same animal were found to be pulsating an hour and forty
minutes after the thorax had been opened. From the inferior
cava contraction spread like a wave over the right’ auricle, the
ventricle being quiet. But after the auricle had contracted
two or three times, the ventricle again commenced to pulsate.
These rhythmical contractions of the pulmonary veins, and of
the vena cava, occur in animals killed in various ways. Sir
Joseph Fayrer and I observed them in animals killed by a blow
on the head, by the action of cobra poison, and by the com-
bined use of chloroform, atropia, and physostigma. They do
not oceur frequently, and the conditions under which they take
place are at present unknown, and we are unable to say
whether they occur in man at all. But it has been shown by
observations on decapitated criminals that the inferior vena
cava, as well as the hepatic, portal, and several of the sub-
pleural pulmonary veins, besides others, are strongly contractile.
It seems, therefore, not improbable that such contractions may
occasionally occur in the human subject. In one case, as I
have already said, Sir Joseph Fayrer and I noticed that the
contraction of the pulmonary veins was not synchronous with
that of the auricles. The ventricles, at this particular time,
were not pulsating, but, had they been doing so, their contrac-
tions must needs have been synchronous with those of the
pulmonary veins. Supposing that in a case of mitral regurgita-
tion a similar rhythmical contraction should occur in the
pulmonary veins, a most powerful obstacle would be opposed te
the backward flow of the blood, and the force of the current,

USES OF CONTRACTILITY IN VEINS. 543.

driven by the powerful left ventricle into the lungs, would be
broken, and the injurious effects it would otherwise produce be
greatly diminished. A similar action may be exerted by the
vena cava in cases of tricuspid regurgitation. :

We have already noticed the persistent contraction which
oceurred in the left jugular vein in Margaret B., at the point
where it had been compressed by the collar. This constriction
is an indication of one of the properties possessed by veins
which is little regarded in considering the mechanism of the
circulation—viz., that of contractility. This property they
possess to a very great extent, and it is especially remarked in
the smaller veins. In these, the walls sometimes approach
each other so closely as to completely obstruct the lumen,
and altogether prevent the flow of blood through the vein. In
them, too, rhythmical pulsations may frequently be noticed.
The importance of venous contractility im reference to the
maintenance of the circulation in health and in disease is very
creat. It is obvious that, if venous radicals contract, they may
oppose a resistance to the flow of blood in the capillaries, and
by thus increasing the pressure within them may cause more
fluid to exude from them into the tissues; while, on the other
hand, a rhythmical contraction may forward the onward pro-
eress of the blood in the normal condition, and may prevent
some of the injurious effects which are usually noticed in
tricuspid regurgitation. Everyone who has studied cases of
chronic bronchitis must have been struck with the variety of
forms in which the obstruction to the circulation manifests
itself in them. In one we find considerable cedema, but no
albuminuria; in another, great dyspnoea, with signs of pul-
monary cedema, although the legs may be very slightly, or not
at all, swollen. In the same case you may see the legs begin to
swell, and the pulmonary cedema and dyspnea at the same time
diminish. Such an occurrence I have observed in a patient
suffering from chronic bronchitis, and who was apparently at
death’s door from an acute exacerbation of the disease. This
patient was obliged to sit upright in bed, gasping for breath ;
the lips were purple, and all over the lungs there was loud
sibilus, and rhonchus, with occasionally coarse mucous rales

544 ON PULSATION IN THE JUGULAR AND OTHER VEINS.

and fine crepitation at the bases of both lungs posteriorly.
Notwithstanding the interference with the circulation, there
‘was but very slight cedema of the legs. After the administra-
tion of an emetic, followed by ipecacuanha and squill, the
patient was greatly relieved, but the cedema of the legs increased
temporarily. The increase did not, however, last long, and
the patient. from the moment of the administration of the
emetic, steadily recovered.

The action of drugs upon the veins has hitherto received very
little attention, and therefore we are unable at present to bring
together pharmacological experiment and clinical observation so
as to give us any efficient aid in treatment. But it is probable
that before very long we may have some definite knowledge of
the action of drugs on the veins, which may help us in many
cases where now we are sadly at a joss in the treatment of
those diseases in which venous engorgement piays a prominent
part,

SE

549

ON THE PATHOLOGY OF NIGHT-SWEATING
IN PHTHISIS, AND THE MODE OF ACTION
OF STRYCHNIA AND OTHER REMEDIES
IN IT.

(Reprinted from St. Bartholomew's Hospital Reports, vol. xv, p. 119.)

ArTER the night-sweats which occur in phthisis the patients are
very exhausted, and not unfrequently feel a certain soreness of
the limbs similar to that which occurs in healthy persons after
great exertion. The exhaustion produced by the sweating is
sometimes attributed to the actual loss of material from the
body in the perspiration, but this can hardly be the case, as the
amount of nutritive matter contained in the sweat is very small,
and we notice that the perspiration which occurs in healthy
persons after exertion does not cause any feeling of weakness,
It occurred to me, therefore, that instead of the sweating being
the cause of the exhaustion in phthisis, the exhaustion and the
sweat were both consequences of one common cause. In order
to discover what this cause may be, it may be well to proceed
to track, as it were, the process of sweating backwards, until we
find some condition that may account both for it and for the
weakness. Now, the production of sweat is due to the functional
activity of the secreting cells in the sweat glands, which remove
from the blood a quantity of water and salts, and pour it out
upon the surface of the skin. For the functional activity of
these cells two things are requisite: the one is a supply of blood
to them which will provide them with the fluid necessary to
form the sweat ; the second is the nervous stimulus imparted to
them by the secreting nerves, which excites them to functional
activity. Itis only recently that the importance of these nerves
as a factor in the secretion of sweat has been fully recognised,
although various circumstances seemed to point to the fact that
sweat was not dependent merely upon a full supply of blood
to the sweat glands. In the perspiration which follows active
2N

546 THE PATHOLOGY OF NIGHT-SWEATING IN PUTHISIS.

physical exercise, we no doubt find that the skin is suffused with
blood, and the sweat glands are therefore richly supplied with
it. But in fever we not unfrequently find that the skin is even
more suffused with blood, as is shown by its redness, so that the
glands may have an abundant supply, and yet, notwithstanding
this, the skin, instead of being covered with sweat, is perfectly
dry. This shows, then, that a free supply of blood alone is
insufficient to induce perspiration. On the other hand, we find
that perspiration may occur freely when the supply of blood is
exceedingly scanty. In persons stricken with sudden fear, or
in those at the point of death, we find that the skin is pallid or
livid, the surface cold, indicating that the supply of biood to it
is very scanty, and yet at this very moment it may be bedewed .
with heavy drops of perspiration. This fact shows that perspira-
tion may occur with a scanty supply of blood. The facts are
exactly analogous to what we find in the secretion of saliva
by the submaxillary gland. In this gland, irritation of the
chorda tympani nerve causes dilatation of the vessels of the
gland, a copious supply of blood to it and a free secretion of
saliva. Irritation of the sympathetic nerve also causes secre-
tion of saliva, but instead of the vessels being widely dilated and.
the circulation in the gland rapid and free, the vessels are con-
tracted and the circulation is very slow. We find, also, that.
there is a similarity between the secretion of saliva and’ the:
secretion of sweat, not only in the nervous conditions under which
they may occur, but in the way in which they are affected by
various drugs. The effect of atropine, for example, upon the.
submaxillary gland is to paralyse the ends of the secreting
nerves in the glandular structure, and the consequence of this:
is, that when the:chorda tympani is irritated after the adminis-
tration of a dose of atropia, the vessels of the gland dilate as:
usual, blood flows freely through it, but, the secreting nerves:
having been paralysed, the secreting cells take up nothing from:
the blood, and not a drop of saliva flows from the duct. . When,
on the contrary, calabar bean is administered, the: effect is.
strikingly different, for’ its action is not-to paralyse, but to.
stimulate the secreting nerves.: In consequence of this, the
secreting cells begin actively. to take fluid from the blood and to:

- EEE

ACTION OF ATROPINE AND PILOCARPINE. 547

pour it out through the duct of the gland in the form of saliva.
But this process does not last long, for the bean has a second
action. Its stimulating power is not confined to the secreting
nerves of the gland, but extends also to the vaso-motor nerves
which regulate the calibre of the blood-vessels which supply it.
These vaso-motor nerves, being stimulated by the drug, cause
the vessels to contract to such an extent as to cut off the supply
of blood from the glands almost entirely. The secreting cells
are thus deprived of the material from which the saliva ought
to be formed, and thus, notwithstanding the functional activity
which they are exerting under the stimulus of the secreting
nerves, the formation of saliva very shortly comes to an end.
In persons who are poisoned with belladonna it has been
observed that the vessels of the skin were much dilated, so that
the skin itself was covered with a scarlet flush, notwithstanding
which the surface was dry. This dryness was not confined to
the skin, but extended to the mouth, and it was caused both in
the mouth and on the skin by the paralysis of the secreting
nerves of the salivary and sweat glands produced by the drug.
Calabar bean, on the contrary, causes a certain amount of sali-
vation and cold sweats; and other drugs, such as pilocarpine,
which does not, like calabar bean, limit its own action upon the
secreting cells of the salivary glands by lessening their blood
supply, causes very profuse salivation as well as profuse sweat-
ing. Now the action of pilocarpine is exerted upon the termina-
tions of the secreting nerves in the salivary and sweat glands,
and does not seem to be dependent upon any action on the
nerve centres. But although pilocarpine may stimulate the
sweat glands by acting upon the ends of the secreting nerves
within them, it is probable that, in ordinary circumstances, the
secretion is regulated, not by the conditions of the terminal
filaments of the secretory nerves, but by the nerve centres
acting on the glands through those nerves. The nerve centres
for the secretion of sweat lie partly in the spinal cord and

partly in the medulla oblongata. In this respect they resemble

two other important nerve centres, viz., the centre for respira-

tion, or respiratory centre, and the vaso-motor centre—the

respiratory centre, by which the respiratory muscles are inner-
2N 2

=

548 THE PATHOLOGY OF NIGIIT-SWEATING IN PHTHISIS,

vated and the respiratory movements kept up, and the vaso-
motor centre, from which stimuli constantly proceeding to the
vessels keep them in a state of chronic contraction.

Both these centres were formerly supposed to be situated in
the medulla oblongata alone, because when the medulla was
separated from the cord by a transverse cut at the level of the
ecciput, respiration ceased, and the tonic contraction of the
vessels in the body at once ceased, and they became dilated.

It was first shown by Schiff, however, that if part of the
medulla were destroyed, so as to cause the respiratory move-
ments completely to cease, the death of the animal, which would
usuaily occur under such conditions, might be prevented by the
continuous use of artificial respiration for many hours. By
this process time was allowed for the remaining portion of the
medulla to learn, as it were, how to perform the function of
the part which had been destroyed, as well as its own, so that
after artificial respiration had gone on for several hours, the
animal began to make feeble attempts to breathe, and these
became stronger and stronger, until at last respiration was again
established. It was thus shown that when a part of the respira-
tory centre in the medulla was destroyed, the remainder might
become sufficiently powerful to perform the functions of the
whole; but the experiments of Prokop Rokitanski* have shown
that, instead of being limited to the medulla oblongata, as was
formerly supposed, the respiratory centre actually extends for
some distance down the spinal cord. When the medulla is
completely separated from the cord by a transverse cut of the
level of the occiput, respiratory movements usually cease, and
do not recommence. But if strychnia be injected into the
circulation immediately after the cord has been divided, the
respiratory movements again commence. It is evident that
these movements in this case do not depend upon the action of
the medulla at all, as they did in the experiments of Schiff, for
here the whole of the medulla has been cut off from any connec-
tion with the respiratory muscles, and the respiratory movements
must therefore depend upon stimuli proceeding to the respira-
tory muscles, not from the medulla oblongata, but from the

Vide antea, p. 328.

2 eee

SWEAT, RESPIRATORY AND VASO-MOTOR CENTRES. 549

spinal cord. It is clear, then, from these experiments, that the
respiratory centre is not confined to the medulla oblongata, but
extends to the spinal cord. Usually, however, the spinal part
of it is too weak to keep up the respiratory movements alone
without the aid of the medullary part, and can only do so when
it is stimulated to excessive action by means of strychnia. This
conclusion is also borne out by the fact that when strychnia is
given to an animal before the division of the cord at the occiput,
the respiratory movements do not entirely cease at the moment
of division, as they usually do. And what is true of the respira-
tory centre holds also for the vaso-motor centre. When the -
cord is divided at the occiput, the vessels being no longer under
the influence of the vaso-motor ceutre, usually dilate. But here
also, after the injection of the strychnia, the vaso-motor power
is restored, and the vessels again contract to a greater or less
extent. It is evident, then, that the vaso-motor centre, like
the respiratory, extends a certain distance down the cord, and
that it also, like the respiratory centre, is stimulated to increased
action by strychnia.

Closely associated with these two centres appear to be the
sweat centres. It was first observed by Goltz that irritation of
the sciatic nerve would produce sweating in a limb, and it was
shown by Kendall and Luchsinger that this sweat was indepen-
dent of any alteration in the vascular supply, for it occurred in
animals poisoned with curare, where all the vessels going to the
limb had been tied; and it even occurred inan amputated leg
for a quarter of an hour after its severance from the body. The
nerve centres by which the sweat nerves are usually excited were
localised by Luchsinger in the spinal cord, but Nawrocki, who
repeated his experiments, came to the conclusion that the sweat
centre was situated, not in the spinal cord, but in the medulla
oblongata, because he found that division of the spinal cord
high up arrested the secretion of sweat. The reason of this dis-
crepancy between the conclusions of Luchsinger and Nawrocki
probably is that the sweat centre, like the respiratory and vaso-
motor centres, is not confined either to the medulla or to the
cord, but extends through both. It is probable that, like the
respiratory and vaso-motor centres, a great portion of the sweat

550 #£THE PATHOLOGY OF NIGHT-SWEATING IN PHTHISIS.

centre is situated in the medulla, and in Nawrocki’s experiments,
when the influence of this part was destroyed by section of the
eord, the perspiration ceased, just as respiration and vascular
tone are also destroyed under ordinary circumstances. It is
probable, however, that in Luchsinger’s experiments the spinal
portion of the vaso-motor centres was sufficiently powerful to
excite perspiration, even after the separation from the medulla.
These centres were found by Luchsinger to be excited, and
perspiration produced by increased temperature of the blood, by
increased carbonic acid in the blood, and also by nicotine which
had been introduced into the circulation. Increased tempera-
ture, as we well know, causes sweating, usually accompanied
with dilatation of the vessels of the skin, as when we are
exposed to a hot sun or get warm from exertion. Tobacco,
on the other hand, causes sweating with diminished supply of
blood to the skin, the countenance becoming exceedingly pale
at the same time that a cold sweat breaks out, as most young
smokers find out by sad experience. The effect of increased
carbonic acid in the blood is visible in the cold sweats which
bedew the brows of dying persons. I have watched the pro-
cess, and have observed that it was just as the finger-nails, the
lobes of the ears, and the lips began to get livid that the sweat
drops began to appear on the forehead. It was a consideration
of this fact which led me to suspect that the sweats of phthisis
might be due to accumulation of carbonic acid in the blood
‘stimulating the sweat centres. Nor would it do this only, for
any imperfect aeration of the blood would lead to imperfect
oxidation of the products of tissue waste in the body, and their
consequent accumulation would produce the same soreness and
lassitude which come on from the accumulation through over-
production by excessive muscular exertion. But it may be
said, How is it that carbonic acid comes to accumulate in the
blood in this way? In a healthy person no such accumula-
tion takes place, because, although carbonic acid in the blood
acts as a stimulus to the sweat centres, the vaso-motor centres,
and the respiratory centres, yet the latter are more susceptible
than the two former, so that whenever a slight increase of the
amount of carbonic acid in the blood occurs, the respiratory

EE

es

ACTION OF VENOUS BLOOD ON SWEAT CENTRE. 551

centre is stimulated, the respiratory muscles are thrown into
increased action, and the blood being more aerated, the amount
of carbonic acid in it is once again reduced to the normal. But
supposing the respiratory centre is weakened in any way so as to
become less sensitive to the stimulus of carbonic acid in the
blood than the other two centres, this will no longer be the case,
and then we shall find cold perspirations occur. This is the
condition which I believe to be present in phthisis. The con-
stant stimulation of the respiratory centre by the irritation in
the lungs, and the violent respiratory efforts which occur in
coughing, so exhaust the irritability of this centre, especially
during sleep, that it no longer responds in the normal manner
to the stimulus of carbonic acid in the blood. The blood may
thus become more and more venous, until the carbonic acid in
it excites the sweat centres, and possibly also the vaso-motor
centres, before the respiratory centre begins to respond.

This, then, I believe to be the pathology of night-sweating in
phthisis. The respiratory centre becomes exhausted by the
reflex irritation from the lung, so that it no longer responds so
readily as it ought to the stimulus directly applied to it by car-
bonic acid in the blood circulating through the medulla and
through the spinal cord. In consequence of this the blood
becomes more or less venous, and to this venosity, and the
consequent imperfect tissue change, and not, as was formerly
supposed, to the actual loss of fluid or sweat in the sleep, are
the nervous and muscular exhaustion and prostration observed
in night-sweats to be attributed. If this pathology were
correct, it occurred to me that night-sweating might be pre-
vented by administering some remedy which would increase the
excitability of the respiratory centre. Now such a remedy exists
in strychnia, as has been shown by Rokitanski’s experiment.
If, then, a dose of strychnia or nux vomica were administered
at bedtime, the excitability of the respiratory centre ought to be
so much stimulated that any excess of carbonic acid would
excite it to increased action, and thus the accumulation of car-
bonic acid in the blood would be prevented, and the sweat, which
I have supposed to be the consequence of such accumulation,
would be arrested.

554 THE PATHOLOGY OF NIGHT-SWEATING IN PHTUHISIS.

was increased to twenty drops, and after this there was no
sweating. }

But it is evident that if strychnia increases: the excitability
of the respiratory centre to stimuli applied directly to it, such
as the carbonic acid present in the blood, it is likely also to in;
crease its susceptibility to reflex irritation, such as that’ caused
by tubercle in the lungs, and thus it might be that it would
tend to increase the cough in case of phthisis. This, indeed, it
appears, in some instances, to do. I have tried here to remedy
this by a combination of strychnia with opium, and this appears
partially to succeed. Where, however, strychnia does not appear
‘to suit, atropia may answer perfectly. Now, atropia, no doubt,
acts upon peripheral terminations of the secretory nerves in the
sweat glands, and thus it will altogether prevent sweating. But
this is not the whole action of atropia. It has been noticed by
Ringer that the beneficial action of atropia continues for a very
considerable time after its administration. Jt seems difficult to
believe that this is merely due to its action upon the sweat
nerves, for it is probable that the greater part of the atropia
has been excreted from the body before the beneficial action
which it produced has come to an end.

It seems not improbable, therefore, that the benefit derived
from the employment of this drug in the night-sweating of
phthisis is not due merely to its action upon the peripheral
‘terminations of the sweat nerves, for, as has been shown by Von
Bezold, it has a marked action in stimulating the respiratory
centre. At the same time it lessens the irritability of the sen-
sory nerves in the lung, and is thus likely to diminish the
exhaustion of the respiratory centre, which the reflex irritation
produced by the tubercle would otherwise occasion. It is to
) this stimulation of ‘the respiratory centre, as much as to the
-paralysing action on .the respiratory nerves, that I should be
inclined to attribute the benefit to be derived from atropia or
from hyoscyamus, which acts almost in the same way as atropia,
‘and is so frequently given, along with oxide of zine, in sweating
of this sort. In Dover’s powder we have a combination having
an action somewhat resembling that of atropia in certain
respects, though differing-from it very markedly in others. In

"
Py
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at

ACTION OF DOVER’S POWDER AND PICROTOXINE. D505

health, Dover’s powder is a powerful sudorific, but it frequently
arrests, in the most satisfactory manner, as Dr. Murrell has
shown, the night-sweating of phthisis.*

This seems at first sight extraordinary, and yet it is quite
natural if the view which I have advanced regarding the patho-
logy of night-sweating in phthisis be correct. For the opium,
by lessening the irritation from cough, will tend to prevent the
exhaustion of the respiratory centre. At the same time ipecacu-
anha is a powerful stimulant to this centre, and thus we have
in Dover’s powder two of the actions that we have already
observed in atropia, viz., a power of diminishing irritation from
the lungs, with a power of increasing the activity of the respira-
tory centre. Unlike atropia, it does not paralyse the peripheral
terminations of the secretory nerves in the sweat glands.
- Picrotoxine, also, has been found to be useful in night-sweating.
It also is a powerful stimulant to the respiratory centre
'(Biichheim, Arzneimittellehre, 3te Aufi.), and probably it is by
its stimulating action upon this centre that it arrests sweating.
But while it is probable that the night-sweats of phthisis chiefly
depend upon exhaustion of the respiratory centre, and are to be
arrested by stimulation of this centre, we must bear in mind
‘that this may not be the only cause of such sweats. They may
- cecur through stimulation of the sweating centres by increased
temperature as well as by increased amount cof carbonic acid
‘in the circulating blood. In such circumstances quinine will
probably be the best remedy, as Dr. Murrell has pointed out
(op. cit.).

One of the great difficulties which we have to contend with
in medicine is that of choosing the best drug in each particular
case. Much may no doubt be done by very long experience,
but it is hard, even for an old physician, and almost impossible
for a young one. The only way in which this difficulty can be
surmounted is by our obtaining an accurate knowledge of the
pathology of disease, and of the mode of action of the remedies
which we employ. In the night-sweats of phthisis atropia is pro-
bably the most powerful remedy which we possess, and we can
well see how it should be so, for it combines the power of

* Practitioner, vol. xxiii, p. 195, September, 1879.

554 THE PATHOLOGY OF NIGHT-SWEATING IN PHTHISIS.

was increased to twenty drops, and after this there was no
sweating.

But it is evident that if strychnia increases: the excitability
of the respiratory centre to stimuli applied directly to it, such
as the carbonic acid present in the blood, it is likely also to in;
crease its susceptibility to reflex irritation, such as that’ caused
by tubercle in the lungs, and thus it might be that it would
tend to increase the cough in case of phthisis. This, indeed, it
appears, in some instances, to do. I have tried here to remedy
this by a combination of strychnia with opium, and this appears
partially to succeed. Where, however, strychnia does not appear
‘to suit, atropia may answer perfectly. Now, atropia, no doubt,
acts upon peripheral terminations of the secretory nerves in the
sweat glands, and thus it will altogether prevent sweating. But
this is not the whole action of atropia. It has been noticed by
Ringer that the beneficial action of atropia continues for a very
considerable time after its administration. It seems difficult to
believe that this is merely due to its action upon the sweat
nerves, for it is probable that the greater part of the atropia
has been excreted from the body before the beneficial action
which it produced has come to an end.

It seems not improbable, therefore, that the benefit derived
from the employment of this drug in the night-sweating of
phthisis is not due merely to its action upon the peripheral
‘terminations of the sweat nerves, for, as has been shown by Von
Bezold, it has a marked action in stimulating the respiratory
centre. At the same time it lessens the irritability of the sen-
sory nerves in the lung, and is thus likely to diminish the
exhaustion of the respiratory centre, which the reflex irritation
produced by the tubercle would otherwise occasion. It is to
this stimulation. of ‘the respiratory centre, as much as to the
-paralysing action on .the respiratory nerves, that I should be
inclined to attribute the benefit to be derived from atropia or
from hyoscyamus, which acts almost in the same way as atropia,
‘and is so frequently given, along with oxide of zine, in sweating
of this sort. In Dover’s powder we have a combination having
an action somewhat resembling that of atropia in certain
respects, though differing. from it very markedly in others. In

ACTION OF DOVER’S POWDER AND PICROTOXINE. 30D

health, Dover’s powder is a powerful sudorific, but it frequently
arrests, in the most satisfactory manner, as Dr. Murrell has
shown, the night-sweating of phthisis.*

This seems at first sight extraordinary, and yet it is quite
natural if the view which I have advanced regarding the patho-
logy of night-sweating in phthisis be correct. For the opium,
by lessening the irritation from cough, will tend to prevent the
exhaustion of the respiratory centre. At the same time ipecacu-
anha is a powerful stimulant to this centre, and thus we have
in Dover’s powder two of the actions that we have already
observed in atropia, viz., a power of diminishing irritation from
the lungs, with a power of increasing the activity of the respira-
tory centre. Unlike atropia, it does not paralyse the peripheral
terminations of the secretory nerves in the sweat glands.
Picrotoxine, also, has been found to be useful in night-sweating.
It also is a powerful stimulant to the respiratory centre
' (Biichheim, Arzneimittellehre, 3te Aufl.), and probably it is by
its stimulating action upon this centre that it arrests sweating.
But while it is probable that the night-sweats of phthisis chiefly
depend upon exhaustion of the respiratory centre, and are to be
arrested by stimulation of this centre, we must bear in mind
‘that this may not be the only cause of such sweats. They may
- cecur through stimulation of the sweating centres by increased
temperature as well as by increased amount cf carbonic acid
‘in the circulating blood. In ‘such circumstances quinine will
probably be the best remedy, as Dr. Murrell has pointed out
(op. cit.).

One of the great difficulties which we have to contend with
in medicine is that of choosing the best drug in each particular
case. Much may no doubt be done by very long experience,
but it is hard, even for an old physician, and almost impossible
for a young one. The only way in which this difficulty can be
surmounted is by our obtaining an accurate knowledge of the
pathology of disease, and of the mode of action of the remedies
which we employ. In the night-sweats of phthisis atropia is pro-
bably the most powerful remedy which we possess, and we can
well see how it should be so, for it combines the power of

* Practitioner, vol. xxiii, p. 195, September, 1879.

506 THE FATIOLOGY OF NIGHT-SWEATING IN PHTHISIS.

lessening irritability of the sensory nerves in the lung, of
stimulating the respiratory centre, and of paralysing the ends
of the secreting nerves in the sweat glands. But it possesses
other actions which may render its employment inadvisable.
It may so influence the salivary glands as to arrest their secre-
tion, and cause very great discomfort to the patient by the
dryness of the mouth thus occasioned. In such cases we may
use Dover’s powder, but if this, again, should interfere with
digestion, we may resort to strychnia or nux vomica. The cases
in which strychnia seems to be specially indicated are those in
which the cough is not so violent as to be very distressing, and
where the general debility and weakness of the circulation and
digestion are prominent symptoms. It not unfrequently has
happened, probably owing in some measure to the difficulty of
obtaining correct statements from hospital patients, who are so
readily influenced by any bias of the physician, that a remedy
has had in the hands of its proposer a success which has not
been observed by those who have tried it subsequently. It may
he so with strychnia also as a remedy in niglt-sweating, but if
this should not be the case, and it proved in the experience of
others to have the same marked power of arresting the night-
sweats of phthisis which it has had in the trials I have made of
it, it will be interesting as being another remedy whose thera-
peutical use has been arrived at by a knowledge of its physio-
logical action, and of the pathology of disease liscovered by
experiments upou animals.

ON THE EXPLANATION OF STANNIUS’S
EXPERIMENT AND ON THE ACTION OF
STRYCHNIA ON THE HEART.

In conjunction with THEODORE CASH, M.D.
(Reprinted from St. Bartholomew's Hospital Reports, vol. xvi, 1880.)

THE remarkable experiment to which Stannius has given his
name consists in applying a ligature around the venous sinus of
the frog’s heart, just at the point where it joins the auricles. The
consequence of this is, that the auricles and ventricles at once
cease to beat, and remain in a state of quiescence, lasting for a
time varying from a few minutes to half an hour or more, while
the venous sinus still continues to pulsate uninterruptedly. A
similar result is produced when, instead of applying a ligature
round the sinus, the sinus itself is separated from the auricles
by an incision. If, however, instead of suddenly removing the
whole of the venous sinus from the remainder of the heart, it
is gradually removed, the instant stoppage of the auricle and
ventricle does not take place. If the ventricle be now separated
from the auricle, while the two are remaining in a state of com-
plete quiescence, the ventricle again commences to pulsate,
while the auricle remains perfectly still. Two explanations of
these phenomena have been given. The one is that the section
or ligature of the heart at the junction of the venous sinus and
the auricles excites the inhibitory apparatus in the auricles to
such an extent as to prevent both them and the ventricle from
moving. This explanation, however, seems to be disproved by
the fact that the same result is obtained after the heart has
been previously poisoned by atropia, which completely paralyses
its inhibitory apparatus, and it would therefore appear that the
still-stand of the heart in this experiment cannot be due to
excitement of the inhibitory apparatus. The second explana-
tion is, that the motor ganglia of the heart are unequally

558 ON THE ACTION OF STRYCHNIA ON THE HEART.

distributed in the ventricle and auricle, the greater number
being in the venous sinus and ventricle, and the fewest in the
auricle.

When the sinus, then, is separated from the remainder of the
heart, the motor power in the auricles and ventricle is insufficient’
to make them pulsate, although the ventricular ganglia are
sufficient, when separated from the auricle, to set the ventricle
in motion. This explanation is opposed to the fact that if the
venous sinus be gradually, instead of suddenly, separated from
the auricle, they will still continue to pulsate. Notwithstanding
this objection, however, it seems to us that this explanation,
although very probably it does not represent the whole truth, is’
to a considerable extent true, and the cessation of the auricular.
and ventricular movements, after the removal of the venous
sinus, is really due, in a great measure at least, to want of motor.
power. It occurred to us that if this were so, we ought to be.
able, by stimulation of the motor ganglia, to reinduce the cardiac
pulsations after they had ceased from ligature of the venous.
sinus. It is well known that if a single galvanic shock be
applied to the ventricle when in this state of diastolic quiescence,
the ventricle will contract once at each application of the stimu-
lus, but the single pulsation is not succeeded by a succession of
rhythmical beats. As warmth has a very powerful effect in
increasing the cardiac activity, it seemed probable that the
application of warmth to the heart, when in the condition of
still-stand thus described, might so far stimulate its motor
ganglia as to allow it to resume its rhythmical pulsations. We
therefore induced complete still-stand in the frog’s heart by
applying the ligature in the usual way. Ou then warming the
heart, either by directing upon it a current. of air heated by
passing it through a hot glass tube, or by bringing into its.
neighbourhood a heated copper wire, we found that the rhyth-
mical pulsations again commenced, and continued for two or.
three minutes after the time that warmth was applied.

The cessation of the movements of the heart, after the.
removal of the venous sinus, seemed to us analogous to the
cessation of respiratory movements and of vaso-motor tone after.
the influence of the medulla oblongata has been removed by

MODE OF ACTION OF STRYCHNINE. 5a)

division of the spinal cord at the occiput. It has been found by
Prokop Rokitansky that the movements do not cease completely
after division of the cord, when the animal has been previously
poisoned by strychnia, and that both vaso-motor reflex and respi-
ratory movements can be reinduced in such animals by strychnia
administered after the cord has been divided, ¢f, antea, p. 323.
It occurred to us that possibly a similar phenomenon might be
observed in the heart. We therefore administered strychnia to
a frog, and as soon as the spasm occurred, the animal was
killed and a ligature placed round the heart. No cessation of
movement, however, was observed. When a-frog was first
killed, however, and still-stand of the heart was induced by
application of a ligature, a solution of strychnia placed on the
outside of the heart did not reinduce rhythmical pulsations, but
when the solution was injected by a fine pipette into the inte-
rior of the ventricle, rhythmical pulsations again commenced.
This rhythm, however, was independent of that which the
venous sinus still continued to pursue. After maintaining this
for some minutes, it again stopped, and the auricle was seen to
contract after the ventricle. The aorta was now cut, and the
ventricle again contracted, but the auricles remained quiescent.
On stimulating the ventricle, it now went on beating regularly.
From these experiments it would appear that the still-stand
induced by ligature of the venous sinus has a deficiency of
motor power in the auricle and ventricle, and that when we
increase the excitability of the ganglia in these parts by warmth
or by strychnia, the pulsations recommence. The following
seems to us the best explanation of the phenomena observed.
The motor ganglia of the heart, we think, are in all probability
called into action by reflex stimulation. This reflex stimulation
may originate in impressions conveyed to them by afferent
nerves from the internal or external surface of the heart, or by
impressions conveyed to them by the afferent nerves from the
other cavities of the heart. We think, also, that although they
respond to the stimuli conveyed reflexly from the internal or
external surfaces of that part of the heart in which they are
contained—as shown, for example, in contraction of the ven-
tricle on stimulation by a needle or an electrical current—they

560 ON THE ACTION OF STRYCHNIA ON THE HEART.

are, nevertheless, most readily thrown into rhythmical action
by the impressions conveyed to them from the other cavities.
In a normal condition of the heart, the venous sinus is the first
cavity to contract; next comes the auricle, and next the ven-
tricle; and a stimulus of contraction probably proceeds from
one to the other along a channel furnished by the nervous
filaments which connect them. When the channel is suddenly
interrupted, as by ligature or division of the venous sinus, the
motor stimuli proceeding from the venous sinus to the auricie
and ventricle can no longer pass to them, and the reflex
impulses proceeding to their ganglia from the external and
internal surfaces of these cavities are insufficient to call them
into action. The auricles and ventricles, therefore, remain in @
state of quiescence for a longer or shorter period; this qui-
escence, however, is not completely permanent. After a while
the ganglia seem to become adapted to the new, conditions.
Their sensibility, too, increases, and the stimuli proceeding to
them from the surface of the heart are sufficient to call them
into action. When the venous sinus is gradually removed
from the auricles and ventricle, instead of being suddenly
detached, time is afforded for this adaptation to take place
before the removal has been completely effected, and thus the
rhythm is not disturbed, as it is when the division is suddenly
made or the ligature suddenly applied. In these respects the
cardiac nervous system is analogous to the vaso-motor and
respiratory systems. The ordinary channels through which
the vaso-motor and respiratory centres and spinal cord are
called into action are the fibres which proceed to them from
the medulla oblongata. If these channels are suddenly inter-
rupted by section of the spinal cord at the occiput, those parts
of the vaso-motor and respiratory centres contained in the
spinal cord cease to act. The same is the case when a large
portion, but not the whole, of the respiratory centre in the
medulla is destroyed, as by division of one-half of the medulla.
When a large portion of this respiratory centre is thus
destroyed, the animal at once ceases to breathe, and remains in
this condition for many hours. If left to itself, death would of
course take place; but if artificial respiration be maintained

USE OF STRYCIININE AS A CARDIAC STIMULANT, 561

for a long time, by and by faint respiratory movements occur,
which very soon cease if the animal be left to itself. But
Schiff has found that if artificial respiration be still kept up,
these movements become stronger and stronger, until at length
spontaneous respiration is sufficiently re-established to save
life.

In Rokitansky’s experiment, the ordinary channels for the
passage of stimulifrom the medulla oblongata to the respiratory
and vaso-motor centres in the cord were at once destroyed;
but the application of strychnia before or after the section had
so greatly increased the activity of the centres in the spinal
cord that they were able to take up their functions at once,
instead of after a lapse of time, as in Schiff’s experiment. It
seems to us, then, that the function performed by the venous
sinus in regard to the rhythmical movements of the froe’s heart
is to a certain extent analogous to the functions of the medulla
oblongata in regard to respiration and vascular tension, and
that the action of heat and of strychnia upon the systems is
very similar indeed. The very marked action as a cardiac
stimulant which strychnia is shown by the experiment to
possess, is one the practical importance of which it is hardly
necessary to point out. We would merely remark, that in
cases of general debility and lack of tone, especially when
occurring in consequence of overwork, there is, perhaps, no
tonic in the pharmacopceia to be~compared to strychnia; and
widely known though its utility may be, it is not nearly so
commonly employed as it deserves, especially at this season of
the year (July), when both medical men and their patients are
suffering from the consequences of prolonged overwork and
mental strain. Small doses of strychnia or nux vomica restore
both mental and physical power, and give a sense of well-being
in a manner in which, so far as our experience goes, nothing
else will.

ON THE ACTIONS AND USE OF CERTAIN
REMEDIES EMPLOYED IN BRONCHITIS
AND PHTHISIS.*

* Read before the Medical Society of London, December 19th, 1880.
(Reprinted from the Lancet, January 1st, 1881, p. 4.)

In both bronchitis and phthisis the first symptoms that attract
notice are cough and expectoration, and the first remedies that
claim our attention are the so-called sedatives and expectorants.
Cough consists in deep inspiration, closure of the glottis, and
violent expiratory effort, by which the glottis is forcibly opened
by the compressed air, which carries with it, in its exit, mucus
or other matters which may have lodged in the lungs’‘or respi-
ratory passages. The nervous centre for this act lies in the
medulla oblongata. It is bilateral, and situated on each side of
the central raphe. It is excited into action reflexly by irritation
of the respiratory branches of the vagus distributed to the
glosso-epiglottidean folds, to the whole interior of the larynx,
to the trachea, especially at its bifurcation, and to the bronchi,
and the substance of the lung itself, as well as the pleura when
it is inflamed. Irritation of the internal auditory meatus at
the point to which the auricular branch of the vagus is distri-
buted also causes coughing, and so also may irritation of the
liver and of the spleen. As coughing is a reflex act, excited by
irritation applied to a sensory nerve, and reacting through a
nerve centre upon the respiratory muscles, it is obvious that it
may be lessened, either by removing the source of irritation or
by diminishing the excitability of the nervous mechanism
through which it acts. Both methods are employed in medicine.
One of the commonest is that of lessening irritation by the use
of glutinous and saccharine substances. These have in them-
selves little or no action upon the nervous mechanism. They
do not pass down to the bronchi, or lung substance, so that they
can have no direct effect upon the mucous membrane there, nor

ACIION OF * LINCTUS.” 563
have they, so far as we know, any effect upon them after they
have been absorbed into the blood; and yet one of the com-
monest observations is that glutinous and saccharine substances
have a very great power to allay cough when applied to the
back of the throat, even in cases where we know that inflamma-
tion and consequent irritation exist in the respiratory passages
below the glottis, at a point which the mucilaginous substances
eannot reach. The probable explanation of this action of such
substances as marsh-mallow lozenges, jujubes, consisting of gum
and sugar and Spanish liquorice, is that the irritation which
occasions the cough exists at the root of the tongue and around
the fauces, as well as in the trachea, bronchi, or lungs, the com-
bined irritation rendering the cough worse than either the one
or the other alone would do; and, therefore, if we soothe the
tongue and fauces we relieve the cough, even though the irrita-
tion in the bronchial tubes or lung may remain as before. The
power of such substances as those mentioned to relieve cough
depends, no doubt, to a great extent either on their covering the
inflamed and irritable surface directly with a mucilaginous coat,
and thus protecting it from the action of the air or from irrita-
tion by other substances passing over it, or by exciting an
increased flow of saliva or mucus, which has a similar effect.
_ At the same time, we cannot deny the possibility of their having
- other actions, though with these we are at present unacquainted.
The use of the mucilaginous substances containing opium or
other sedatives, which we know under the name of “linctus,” is
a more complicated one. In them we have the soothing action
of the mucilaginous compound, combined with the local sedative
action of morphia, chloroform, or hydrocyanic acid upon the
inflamed or irritable mucous surfaces at the root of the tongue
and back of the throat, and this renders even their local action
more powerful than that of a mucilaginous substance alone.
Such drugs as opium, hydrocyanic acid, and chloroform have a
certain amount of local action upon the peripheral ends of
sensory nerves, and lessen their sensibility to impressions.
When they are applied to the ends of the nerves only for a very
short time, as they are when we swallow these drugs in a liquid
form, their local action is comparatively slight. It is much

202

564 REMEDIES IN BRONCHITIS AND PHTHISIS.

greater when they are taken in a mucilaginous vehicle, which,
adhering to the irritated mucous membrane over which it
passes, keeps the sedatives in contact with it for a longer time,
and thus allows them to exert a more powerful action. But the
sedatives which we give to relieve cough are not unfrequently
administered in the form of solution, and then, though their
local action must be comparatively slight, they still lessen a
troublesome cough. Their action here is a different one from
that which we have just discussed, but it is possessed by the
sedative whether given in the form of linctus or of solution.
In either way it is swallowed by the patient, absorbed from the
stomach and intestines into the circulation, and carried by the
blood to the medulla oblongata, and also to the inflamed mucous
membranes, in which the blood circulates freely, just as well as
in other parts of the body, although here its action is likely to
be very much less than if it were applied for a length of time
directly, as in the shape of the linctus; but, as we have
mentioned, the linctus can only be applied to the back of the
tongue and throat, and the source of irritation of the afferent
nerves may be in the bronchi or in the lung itself. Here, no
doubt, a linctus cannot penetrate, but we may to a certain
extcnt act locally upon the nerves by the use of spray and
inhalation. Some of these, such as the vapour of conium and
the vapour of hydrocyanic acid, are intended to lessen the
irritability of the sensory nerves in the respiratory passages, and
thus lessen cough. Others, such as the spray of ipe acuanha,
and inhalation of essential oils and terebinthinous substances,
have probably a different action, and do not lessen the irrita-
bility of the sensory nerves in the respiratory passages, but
alter the nutrition of the mucous membrane in such a way as
to diminish the irritation which the abnormal condition of the
membrane exerts upon the nerves. When the irritation is
situated in the larynx, as in cases of laryngeal phthisis, one of
the best means of relieving it is by applying the sedatives
locally, whether by means of a brush, or, what is perhaps still
better, by blowing it,in the form of a powder, directly upon
the irritated surface. A useful application in laryngeal phthisis
consists of a mixture of morphia and starch, in the proportion

SEDATIVES IN COUGH. 565

of about one-sixth of a grain of morphia to two grains of
starch. This mixture is introduced into a glass tube, of a
proper shape, and is blown down the throat at the instant that
the patient takes a deep inspiration... The powder is thus dis-
tributed over the interior of the larynx, and exerts its local
sedative influence upon the irritated surface, as well as a general
sedative effect upon the central nervous system after its absorp-
tion.

This brings us to the second mode in which sedatives relieve
cough. After their absorption into the blood, in whatever
manner they may have been applied, they are carried to the
medulla, and there lessen the excitability of the nerve centre
through which the reflex act of coughing is produced. In large
doses their sedative effect may be so great as to endanger life,
and the caution is given in every text-book, and by every
teacher, that respiratory. sedatives such as opium should be
carefully administered to persons suffering from bronchitis with
profuse expectoration, lest the irritability of the medulla should
be so far diminished that it will no longer respond even to a
powerful stimulus from the lungs, and the secretion may conse-
quently go on accumulating until when the patient awakes the
respiratory passages are so clogged with mucus that no effort
which he can make is sufficient to clear them, and he dies of
suffocation. By administering them in smaller quantities, how-
ever, the effect of respiratory sedatives may be graduated so as
to diminish cough without any risk of causing death, and their
effect would be exceedingly beneficial if they acted only upon
the respiratory centre. Unluckily, however, this is not the case,
and the most powerful of all—viz., opium—not only influences
the respiration, but the digestion. It diminishes the cough,
but sometimes, also, it diminishes the appetite, and may inter-
fere with the proper action of the bowels. When this is the
case, we are obliged carefully to steer between two dangers:
(1) the injurious effects of the cough itself, and (2) the injurious
effect of disturbed digestion. If we leave the cough alone, it
exhausts the patient, for the muscular exertion involved in a
violent fit of coughing is very considerable indeed, and the
muscular effort exerted by a patient with a bad cough during

566 REMEDIES IN BRONCHITIS AND PHTHISIS.

the twenty-four hours is really more than equivalent to that of
many a man in a day’s work. Nor is this all. Anyone who
watches the face of a patient during a violent fit of coughing
will see the skin become flushed, and. then dusky ; the veins in
the forehead and in the jugulars swell up, and become so tense
that they seem as if about to burst; so that there is both
venous engorgement and interference with the respiration.
But what we see in the face takes place elsewhere. The same
tension which we see in the jugulars is also present in the right
side of the heart, in the vena cava, and in the portal system ;
for the portal vein has no valves, and the increased tension is
transmitted backwards to the veins of the stomach, spleen, and
intestines. By-and-by this all begins to tell upon the heart
and upon the digestive system as well as, to some extent, upon
the kidneys. The stomach becomes congested, and we have loss
of appetite, nausea, and vomiting. The patient, too, is kept
awake, and we have nervous exhaustion, or loss of sleep, added
to the weariness caused by the muscular exertion, and to the
depression occasioned by digestive disturbance. These are what
we have to fear: on the one hand, continuous coughing ; on the
other, we must avoid the digestive disturbance produced by our
sedatives ; and the duty of the physician is, so far as possible,
to relieve the cough without disturbing the digestion. Numerous
combinations have been devised, and are found to be, empiri-
cally, of very great service. If we take one of them and
attempt to analyse it, we shall find that its components are
such as to diminish the excitability of the respiratory centre,
and at the same time to lessen the injurious effect of the
sedatives upon the stomach. Such a one is the following
mixture :—Solution of hydrochloride of morphia and dilute
hydrocyanic acid, of each eighteen minims; spirit of chloroform
and dilute nitric acid, of each one fiuid drachm; glycerine,
three fluid drachms ; infusion of cascarilla or infusion of quassia,
two fluid ounces; a sixth part to be taken three or four times a
day.

In this mixture, which in its essence was much used by the
late Dr. Warburton Begbie of Edinburgh, to relieve the cough
in phthisis, we find the sedatives morphia, hydrocyanic acid,

CAUSES OF COUGII. 567

and chloroform to lessen the excitability of the respiratory
centre ; we find glycerine, which will tend to retain the seda-
tives for a longer time in contact with the back of the throat,
and will also act to some extent as a nutrient. We have com-
bined with these nitric acid and infusion of cascarilla or of
quassia, which have so-called tonic (?) action upon the stomach.
In what this effect precisely consists we cannot at present say,
but we may imagine that it will in some way partially counter-
act the effects of the congestion which the cough produces, and
at the same time we know that they have the power of exciting
appetite, and they will thus in a great measure counterbalance
the injurious effects of the morphia upon digestion. Nor is this
all. The nitric acid, as I shall shortly have to mention, has a
very definite effect indeed upon the secretion in the lungs
themselves ; and this brings us to the consideration of another
part of our subject—viz., the effect of drugs upon the secretion
and nutrition of the lungs, by which they tend to restore the
healthy condition of the bronchial and pulmonary tissues, and
thus diminish coughing.

First of all, then, we must consider those drugs which lessen
congestion. If a person, hastily eating or drinking, gets a
erumb of bread or a drop of fluid down the larynx, or into the
wrong throat, as it is termed, he suddenly begins to cough
violently, and the cough continues until the source of irritation
has been removed. If the irritation has been violent he may
give a few coughs after the crumb has been coughed up, although
the primary source of irritation—namely, the crumb—has dis-
appeared; but the congestion which it occasions still remains
for a short time, and acts as an irritant. If a person suffering
from disease of the mitral valve makes any sudden exertion he
is very likely to bring on a cough, which, however, quickly
subsides after a short rest. The cough here is not due to
inflammation of the mucous membrane, but simply to conges-
tion, and when the congestion disappears the irritation goes
with it. In cases where we have inflammation of the respira-
tory vessels actually present, as in persons suffering from
bronchitis, the congested condition of the membrane is a source
of considerable irritation, and we frequently notice that such

568 REMEDIES IN BRONCIIITIS AND PIITIIISIS.

persons, on going out into the cold air, may cease to cough, but
again begin to cough violently when they return from the cold
air into the warm room. The reason of this is that the cold air
has acted upon the congested vessels of the respiratory passages
in a somewhat similar way to what it does upon the vessels of
the face ; it causes them to contract, and the congestion being
thus diminished the cough is lessened. When the patient goes
into the warm room the face, which may have been pale while
he was exposed to cold, flushes up with the heat, the vessels of
the respiratory passages also become engorged, and the increased
congestion causes irritation, bringing on the cough. In other
cases, again, we notice that, just as the face becomes pale when
exposed to cold, it shortly afterwards becomes flushed, although
the application to cold continues. A person suffering from
bronchitis, on going into a cold room, will begin to cough
violently, the cold here increasing instead of Saar
congestion.

The pulmonary capillaries have great contractile power. Ten
years ago I made some experiments, which I have not yet
published, on the subject (ef antea, p. 334). I found that
on the application of cold to the lung of a frog, when
placed under the microscope, the capillaries would contract
to two-thirds of their former diameter. We have, however,
very few observations on the action of drugs upon the
pulmonary circulation, the difficulties in the operative pro-
cedure being very considerable. I have observed that mus-
carin appears to have a power of contracting the pulmonary
vessels, and that this effect is abolished by atropia. I am
unaware, at present, of any other observations on the action of
drugs upon the pulmonary circulation. Circumstances have
prevented me from studying the recent researches on this
subject in the way I should have wished while drawing up this
paper. From its power of contracting the vessels in other
parts of the bedy, we should expect that digitalis would have a
similar action upon the lungs; and we find, in looking over
Beasley’s “ Book of Pibsivipkiona: ” that digitalis has been used
in pulmonary affections—as, for example, in the following
draught, employed by Sir A. Crichton in acute phthisis : lemon-

PULMONARY CAPILLARIES—EXPECTORANTS. 569

juice, half an ounce; carbonate of potash, to saturation; decoc-
tion of sarsaparilla, ten drachins; tincture of digitalis, ten to
thirty minims ; acacia mucilage, ten drachms: to be taken every
sixth hour. In such a prescription as this we have the tincture
of digitalis, which will, in all probability, by contracting the
vessels, diminish the pulmonary congestion and lessen cough.
It is combined with carbonate of potash, and the effect of potash
upon the lungs is very marked indeed. For my knowledge of
its action I am indebted to Dr. Andrew Clarke. Its action is
perhaps best noticed in a patient suffering from consolidation
and softening of a limited portion of one lung. When sucha
patient is in ordinary health, one may observe, on stethoscopic
examination, crepitant rales, limited to one spot. When he
catches cold, one may hear, in addition to those, dry rales
extending for some distance around the irritated spot, and the
cough at the same time becomes more frequent and troublesome,
while there is very little, if any, expectoration. If potash be
now given alone, or, still better, in combination with a vegetable
acid, the dry rales subside, and are replaced by moist ones,
which in the course of a day or two, as the potash is continued,
alter in character, giving one the impression of their being
caused by less viscid fluid. At the same time the expectoration
becomes more copious, and the cough less frequent and less
troublesome. Now is the time to alter the treatment, and for
the potash to substitute nitric acid. If this be given too soon
the cough, which had begun to get easier, will again become
drier and harder, but if it be administered at the proper moment
the cough becomes still less troublesome, the expectoration
diminishes, and the moist rales disappear from the neighbour-
hood of the consolidated part of the lung, although they may
still remain, as before, in that part itself. Potash, then, has a
very marked effect in rendering the pulmonary secretion more
tluid and abundant, while nitric acid has an opposite effect. As
in many cases we wish to diminish the secretion rather than
increase it, it 1s nitric acid rather than alkalies which we
employ for long periods in the treatment of phthisis, as we have
already seen in the modified formula of Dr. Begbie’s phthisis
mixture.

570 REMEDIES IN BRONCHITIS AND PHTHISIS.

One of the most powerful expectorants is simply a little
warm food in the stomach, and in cases of chronic bronchitis,
in which the patients complain of viclent coughing imme-
diately after rising, one of the best expectorants is a glass of
warm milk, either with or without a little rum, and a biscuit or
a piece of bread about a quarter of an hour before they get up.
A little warm beef tea will have a similar effect. After taking
this for a short time they generally tell you that the sputum
comes away much more easily than before, and they are not so
much exhausted by it. But perhaps the remedy, par excellence,
not only in cases of phthisis, but in chronic bronchitis, is cod-
liver oil. Persons suffering from long-standing chronie bron-
chitis will often come to a hospital to beg for cod-liver oil,
saying that it eases their cough far more than any cough
mixture. Other oils or fats have not this power to the same
extent as cod-liver oil. We cannot say positively what the
reason of this may be, but I think there is no doubt about the
fact. My own belief is that cod-liver oil is more easily assimi-
lated than other oils, and not only so, but more easily trans-
formed into tissues themselves. Whether it owes this property
to its admixture with biliary substances, or to its chemical
composition, we cannot say. In his book on “ Fat and Blood,
and how to make them,” Dr. Weir Mitchell quotes a remark
made by an old nurse, that “some fats are fast, and some fats
are fleeting, but cod-liver oil fat is soon wasted.” By this she
meant that there were differences in the kinds of fat accumu-
lated under the subcutaneous tissues of men, just as there are
differences in subcutaneous fats which accumulate in horses.
The horse fed on grass soon gets thin by hard work, while fat
laid on when the horse is feeding on hay and corn is much more
permanent. Persons fattened on cod-liver oil soon lose the
fatness again, and this, I think, points to the power of ready
transformation which the oil possesses. Supposing that it does
possess this power, we can readily see how very advantageous it
will be. In chronic bronchitis, and in catarrh and pneumonia,
we have a rapid cell-growth, but want of development. The
cells lining the respiratory cavities are produced in great

numbers, but they do not grow as they ought to do. They

- s ’
aes ee ae

tee, eae

VOMITING IN COUGH. 571

remain, more or less, lymphoid cells, instead of developing into
proper epithelium. They so rapidly form, and are thrown off
so quickly, that they have not time to get proper nutriment,
and if they are to grow properly we must supply them, not
with an ordinary kind of nutriment, but with one which is
much more rapidly absorbed, and is capable of much more
rapid transformation in the cell itself than the usual one. This
power is, I believe, possessed by cod-liver oil, and to its quality
of nourishing the rapidly-formed cells in the lungs in cases of
bronchitis and catarrhal pneumonia I believe its great curative
power is owing.

The next subject we will consider is the action of some drugs
in the vomiting associated with cough. The action of vomiting,
like that of coughing, is reflex; the nervous centre for it is also
in the medulla oblongata, closely associated with the respiratory
centre, and it is excited by various afferent nerves, the chief of
them being the branches of the vagus distributed to the
stomach. When congestion of the stomach is present, these
become irritated, and we get loss of appetite, nausea, and
vomiting. Like coughing, vomiting may be prevented by the
removal of the irritant. For examplé, where the irritant is
indigestible food, the vomiting ceases after the ejection of the
offending substances. When the irritation depends on inflam-
mation of the walls of the stomach, it may be soothed by
sedatives having a local action upon the nerves, such as ice and
hydrocyanic acid, or by drugs having the power of lessening
the irritability of the nerve centre of the medulla, such as
opium. In the chronic vomiting of phthisis, all these drugs
may be employed, but there is one other which has been useful
in this affection, and which probably has no effect either upon
the nerve centre or the nerve ends. This is aluin. Its mode of
action probably is that by its astringent power it contracts the
vessels of the stomach, and thus lessens the congestion and
consequent irritation produced by the continued coughing in
the manner already described.

NOTE REGARDING THE EFFECT OF ELEC-
TRICAL STIMULATION OF THE FROGS
HEART, ETC.

THis research was the outcome of the observations made by

tomanes in 1876 and 1877 upon Meduse. He found in these
animals that the rhythmical movements of the bell are kept up
by a ring of ganglia round its margin. When a strip of con-
tractile tissue containing the ganglia is cut away from the bell
for a certain distance but left attached at one end, stimuli can
pass along the strip in two ways, either as contraction in the
contractile tissue of the strip or along the nerves. The nervous

Fie. 164.

conduction may either pass along in front of the contraction
when this is present, or may pass along without any contraction
at all occurring in the strip, and only become manifest by
movements in the tentacles which fringe the strip and are more
sensitive than the strip itself.

It was in order to find cut, whether the cardiac contraction

4
ca

TWO-FOLD CONDUCTION OF STIMULI. 573

which begins in the venous sinus or auricle passes along to the
ventricle through the contractile tissue of the heart, or through
its nerves, or through both, that the following experiments were
undertaken.

But the research was not so easy as that upon Medusz, for
the bell of the medusa shows by its contraction, or the tentacles
on a strip by their motion when the stimulus has reached
them, whilst in the heart there is a refractory period during
which the application of a stimulus produces no contraction.

This rendered the research a very long and tedious one,
requiring an immense number of experiments, so that although
the results of a number of them were communicated to the
Royal Society in 1881, the full research was not published till
1883.

After the publication of our first notice, an admirable paper
by Gaskell appeared on the transmission of stimuli in the frog’s
heart, but his method of working was different from ours, as he
employed compression of the contractile tissue as a means of
reculating the passage of stimuli along it.

The results of our experiments appear to show that stimuli
in the heart may pass from one part to another along nervous
channels as well as along contractile tissue.

In regard to this, I may note especially that stimulation of
the auricle causes contraction both of the auricle and ventricle,
but the ventricular contraction follows the auricular one in a
way that seems to indicate that the stimulus has been propa-
gated through the muscular substance. On the other hand,
stimulation of the venous sinus sometimes produces a simul-
taneous contraction of the auricle and ventricle, which appears
to indicate that the stimulus has been conveyed along nervous
channels to the auricle and ventricle, and not along the
muscular substance from the sinus to the auricle and then to
the ventricle.

ON THE EFFECT OF ELECTRICAL STIMULA-
TION OF THE FROGS HEART, AND ITS
MODIFICATION BY COLD, HEAT, AND
THE ACTION OF DRUGS.

In conjunction with THEODORE CASH, M.D.

(Reprinted from the Proceedings of the Royal Society, vol. zxxii, No. 214, 1881.)
Received May 16,1881. Read June 16, 1831.

From the results of the recorded experiments conducted on the
frog’s heart in its normal position and still exercising its circu-
latory function, we have found-—

I. That electrical stimulation by a single induced shock has
either an obvious effect on the contraction and rhythm of the
organ, or no such effect is apparent.

II. That the effect is modified by— .
(a.) The Time of the Cardiac Cycle in which Stimulation Falis.
—Thus Marey has already shown that a so-called refractory
period is demonstrable under certain conditions.* Well-marked
variations in latency when the stimulation is potent to induce a

systolic contraction are to be recognised. aches

(b.) Zhe Strength of the Stimulation Applied—Refractory
periods possible under minimal stimulation can no longer be
demonstrated under maximal, whilst a disturbance of the rela-
tionship of auricular and ventricular contractions may be
induced.

(c.) The Area of the Heart to which Stimulation is Applied —
A refractory period demonstrable under stimulation of the ven-
tricle may cease to occur when the sinus venosus is the seat of
irritation.

* The conditions of this refractory period, or ‘‘ period of diminished excit-

ability,” have been very fully investigated by Dr. Burdon Sanderson and Mr.
Page. Proc. Roy. Soc., vol. xxx, p. 373.

MODIFIED ACTION OF STIMULI. 575

(d.) The Action of Heat, Cold, and Drugs——Thus cold pro-
longs the systole, the refractory period, and the latency of an
induced contraction; whilst strychnia, leaving the curve of
systole unaltered, lengthens the refractory period to a marked
degree.

ON THE EFFECT OF ELECTRICAL STIMU-
LATION OF THE FROG’S HEART, AND ITS
MODIFICATION BY HEAT, COLD, AND THE
ACTION OF DRUGS.

In conjunction with THEODORE CASH, M.D.

(Reprinted from the Proceedings of the Royal Society, vol. xxxv, p. 455,
No. 227, 1883.)

Received May 16, 1881, read June 16, 1881. Revised June 13, 1883.

In the following research we have examined the effect of elec-
trical stimuli applied to the different cavities of a frog’s heart,
and the modifications of their effect by heat, cold, and the
action of strychnia. The effect of electrical stimuli upon the
ventricle, and the alterations occasioned in it by the applica-
tion of heat, have already been studied by Professor Marey.
The time relations of excitation in the frog’s heart have also
been very exactly determined by Dr. Burdon Sanderson and
Mr. Page. But it seemed desirable to extend the scope of the
research, and instead of confining ourselves like previous ob-
servers to the effect of stimulation applied to the ventricle
alone, to observe also the effect of stimulation of the ventricle,
auricle, and venous sinus, both on the ventricular and the auri-
cular contractions. This we did with the hope that from such
series of observations we might be able to arrive at some con-
clusions regarding the transmission of stimuli from one part of
the heart to the other in the ordinary course of the circulation.
Professor Marey found that when an electrical stimulus was
applied to the ventricle of a pulsating frog’s heart the effect
differed according to the condition of contraction or relaxation
in which the ventricle was at the time the stimulus was applied.
During the first part of the contraction of the ventricle, from
the commencement of the contraction until nearly its maximum,
stimulation had no apparent effect at all, and this period Marey
terms the “refractory period.” Following this phase is a second

SENSITIVE PHASE AND REFRACTORY PERIOD. 577

one, to which we have given in the following paper the term of
the “sensitive phase,” lasting from the maximum of systole to
its end. The refractory period varies in duration according to
the intensity of the stimulus, and the conditions under which
the heart is operated upon. The feebler the stimulus, the
longer is the refractory period. When the stimulus is very
slight the refractory period may persist during the whole ven-
tricular systole; as the stimulus is increased, the refractory
period becomes shorter, and finally, when it is very strong, disap-
pears altogether.

Heat applied to the heart shortens the refractory period or
abolishes it altogether. Cold has an opposite effect, and
lengthens the refractory period. The contractions caused by
artificial stimulation do not much alter the cardiac rhythm, for
the accelerated beat is followed by a longer pause than usual
which compensates for the diminished interval between the two
first beats. Sometimes no ventricular contraction is induced,
and then instead of acceleration there is apparent inhibition, the
application of the stimulus being followed simply by a longer
diastolic pause than usual.

Marey’s observations were confined entirely to the movements
of the ventricle, but we have extended ours to the movement of
the auricle as well. Weemployed two levers: one resting upon
the ventricle, and the other upon the auricle, which recorded
movements upon a revolving cylinder covered with smoked paper,

It is unnecessary to enter here into a fuller description of the
apparatus, which is given elsewhere.*

By the method employed we are able to study the effects of
maximal and minimal stimulation applied to the ventricle,
auricle, and venous sinus upon the movements both of auricle
and ventricle,

By minimal stimulation we understand the smallest shock
that produces any visible effect that in any way modifies
the course of contraction or the rhythm of the organ; and by
maximal stimulation we mean the electrical irritation of such a
strength that its intensification produces no visible increase in
its effect.

* Cash, Journal of Physiology, vol. iv, No. 2.
2P

578 ELECTRICAL STIMULATION OF THE FROG’S HEART.

The apparatus for stimulation consisted of a bicromate battery
with two zinc (3$ inches by 2 inches) and three carbon plates,
the size of these being 8 inches by 2 inches. This was con-
nected with a coil,and a key was interposed by which the
primary circuit could be made and broken at pleasure. The
moments of opening and closing the circuit were registered upon
the same revolving cylinder as that upon which the cardiac
pulsations were noted, by means of an electro-magnet, the
marker of which was placed immediately under the pens of the
cardiac levers. In all the tracings the upper curved line shows
the ventricular contractions, the lower curved line the auricular
contractions, and the broken straight line the moment of excita-
tion. The descent of the line indicates the opening, the ascent
the closing of the current.

In the secondary circuit were placed the electrodes for stimu-
lating the various parts of the frog’s heart, and this circuit also
could be broken or changed at pleasure by means of an inter-
posed double key.

The heart was stimulated by a single induction shock. In
minimal stimulation only the breaking shock was effective, in
maximal stimulation both making and breaking shocks. The
apparatus, which is described in a separate note, admitted of the
venous sinus, auricle, or ventricle being stimulated at will |

When recording the effects of stimulation of the venous sinus
we speak only of changes in rhythm of auricle and ventricle.

We shall examine serzatim the results of irritation of each of
these. The temperature of the room in which the experiments
were conducted was 67° to 70°F. The frog employed was, on
all occasions, the Rana temporaria.

Stimulation of the Ventricle—Minimal,

On stimulating the ventricle with a single induction shock of
minimal potency we find—-

(1) That between the commencement of the ventricular
systole up to or nearly up to its maximum there is a refractory
period (Fig. 165, a and 0) during which stimulation applied to the
ventricle has no effect whatever on that beat of the heart, or
the one succeeding it, nor is the auricle in anywise affected.

’ NORMAL HEART-STIMULATION OF VENTRICLE. 579

(2) That after the refractory period has elapsed stimulation
causes a reduplication of the beat (ig. 165, c).

Fria. 165.

Stimulation of Ventricle (minimal).

a and 4, stimulation in different phases of refractory period.
c, stimulation after refractory period has passed, showing different
forms of reduplication.

(3) The latency of this reduplicated beat becomes distinctly
shorter as the systole passes into the diastole. Thus supposing
the value of a single cardiac systole to be 1”3, stimulation fall-
ing just at the maximum of a beat will cause a reduplicated
beat with a latency of 0°33. When the stimulation occurs half
way down the curve of relaxation, the latency is 0°18 or 0°2, and
when applied at the instant before the abscisse would have
been reached the latency is only 0°13.

(4) Where acceleration or reduplication occurs, the snb-
sequent diastolic pause is prolonged, so that the time occupied
by the two beats, the interval between them longer or shorter,
and the subsequent pause, is nearly equal to the time which
would be occupied by two normal beats with their associated
diastolic pauses (Fig. 165, c).

2P2

580 ELECTRICAL STIMULATION OF THE FROG’S HEART.

(5) The ventricular reduplication is often associated with a
reduplication of the auricular beat, but in no case has the latter
its commencement before the former. It is usually, in fact,
distinctly later (Fig. 166, a).

It is to be noted that, minimal stimulation applied to the
ventricle during its refractory period produces no effect on the
auricle.

Fra. 166.

Stimulation of Ventricle (minimal). Tracing shows long pause after reduplica-
tion. The two opening stimulations occur after maximum of systole has
passed.

Fig. 167.—Time- Writer, marking seconds. Applicable to all tracings in the
paper, except those in the Appendices.

We may divide each ventricular cycle into three parts, the
first reaching from the commencement of systole nearly up to
its maximum, the second from nearly the maximum of the
systole to its end, and the third embracing the whole diastolic
period from the end of one systole to the beginning of another
(vide diagram A) except when the stimulation falls immediately

Fie. 168.—Diagram A shows the division of the ventricular cycle into three
parts.—1. Refractory period. 2. Sensitive period. 3. Accelerative period.

NORMAL HEART-STIMULATION OF VENTRICLE. 581

after the end of the refractory period. In all these points our
results agree with those already obtained by Marey.*

Stimulation applied to the ventricle during the first period
has no effect whatever either in accelerating the occurrence of
the second beat, or altering the length of the subsequent
pauses. This constitutes the refractory period.

Stimulation applied during the second period causes redupli-
cation of the systole, the next systole succeeding with a con-
stantly diminishing latency up to the end of the period. When
the stimulation is applied in this period, the two systoles being
more or less united, there is no distinct pause between them,
but the diastolic pause succeeding the second occupies very
nearly the interval of time corresponding to two normal dia-
stolic pauses. In this second period the heart is more sensitive
to the action of minimal stimuli than in the first period. In
the third period, that of acceleration, stimulus applied to the
ventricle hastens the advent of the succeeding systole, and the
latent period is very short, being nearly equal throughout its
whole extent to the latency at the end of the second period. The
sensibility of the heart to stimuli is scarcely so great in this
period as in the second.

The length of the diastolic pause succeeding the accelerated
systole is longer than normal, the increase in length being nearly
equal to the amount of acceleration.

Stimulation of the Ventricle—Maximal.

When stimuli of maximal potency are applied to the
ventricle between the maximum auricular systole and the com-
mencement of ventricular systole, the ventricular systole im-
mediately following the stimulus is rarely slightly higher than
normal, and the diastolic pause succeeding it is excessively
long—so long, indeed, as to be nearly, if not quite, equal to the
time which would, as a rule, be occupied by two diastoles, so
that the time occupied by the systole and diastole after stimu-
lation applied at this period of the heart’s cycle, is equal to the
time usually occupied by one systole and two diastolic pauses,

* Op. cit., p. 72.

582 ELECTRICAL STIMULATION OF THE FROG’S HEART.

In most cases this systole was apparently no higher than
normal, and consequently we cannot with plausibility regard it
as a case of superposition of two systoles.

In some cases the time within which this pause may be pro-
duced is strictly limited to the point indicated; in others, how-
ever, it may extend some little distance towards the maximum
of systole, though it never reaches this. In other words, it
may encroach upon the refractory period which we have men-
tioned when speaking of minimal stimuli, although it never
extends through the whole of it.

This phase may occasionally, though rarely, be absent. Its
place is then taken by reduplication, or very rarely by insensi-
bility to stimulation, as in the refractory period.

Reduplication with maximal stimuli occurs during all times
of the cycle, except at the very commencement of the systole.

A very considerable latency is to be observed in cases where
stimulation falls early in the systole. The latency, when this
is the position of the shock, is usually 0°5' or even more, and
occasionally where stimulation is coincident with the earliest
possible attempt at systole, nearly the whole beat may lapse
before reduplication.

The latency is greatest when the stimulus is applied at the
commencement of the ventricular systole (with the exception
of its very beginning), and it gradually decreases towards the
end of systole, at which time it is ata minimum. During the
diastole the latency seems to remain constantly the same as at
the end of systole. The later in the phase of ventricular
activity the reduplicated systole commences the more perfect
is it.

In all the points already mentioned our results agree with

those of Marey.
Stimulation of the ventricle falling before or at the maximum
of ventricular systole, z.¢., during the refractory period of a

minimal stimulation, frequently causes a reduplication of the.

auricular systole which holds the same relation to the induced
ventricular beat that the auricular contraction normally holds
to the ventricular. _

Stimulation falling after the maximum of ventricular systole

2 mr ee © a” = -hCUCU ee UC

Te

EFFECT UPON AURICLE. 583

may cause an induced auricular contraction, but this is nearly
synchronous with, or even subsequent to, the induced ventri-
cular contraction (Fig. 170, a and 0, and Fig. 169, c).

Fie. 169.

Stimulation of Ventricle (maximal).
a, normal tracing ; 0, effect of maximal stimulation. In 8 inhibition is seen.

Fie. 170.

Stimulation of Ventricle (maximal).

Sometimes reduplication of the ventricular beat may occur
without reduplication of the auricular (Fig. 169, c).

6

‘584 ELECTRICAL STIMULATION OF THE FROG’S HEART.

These results may be possibly due, in part at least, to direct
stimulation of the auricle itself by the strong current used to
stimulate the ventricle.

Stimulation of the Auricle—Minimal.

When minimal stimuli are applied to the auricle, there is
occasionally a refractory period, extending from the beginning
to the maximum of auricular systole. When the stimulus is
applied at the maximum of auricular systole, or just after it, it
sometimes produces an omission, or, as we may term it, an
apparent inhibition of the next auricular and ventricular
systoles (Fig. 171, 6). Stimulation falling after this point and
occasionally on it, wili cause a reduplication of auricular and
ventricular contractions to occur which may have a latency of
as much as 1°25 seconds.

Fre. 171.

Stimulation of Auricle (minimal).

No secondary contraction can usually be produced in the
ventricle till an induced auricular contraction has occurred; and
as the auricular latency is considerable, the ventricular latency
is also very long. Thus, should the stimulus producing con-
traction fall at the commencement of ventricular systole, the
auricle may have a latency of one second and the ventricle of 1°4
seconds,

The sensibility of the auricle to minimal stimulation may
generally be divided into three phases :—

NORMAL HEART-STIMULATION OF AURICLE, 585

Istly. Stimulation may fall at such a stage of auricular
activity that it does not cause an instantaneous response, but
allows the auricle to pass through its diastole before it causes
reduplication.

2ndly. It falls at such a time that the auricle responds in-
stantaneously.

3rdly. About or shortly after the period of auricular maxi-
mum stimulation may cause inhibition of the auricular and the
ventricular sequential beat.

Stimulation at any period during the diastole of the auricle
until the abscissa is reached, causes areduplication. The latency
of this reduplicated beat is shorter the further the diastoie is
advanced. It is followed by an induced ventricular beat in
ordinary rhythm.

Stimulation during complete auricular diastole ana before
systole commences causes a contraction with very short latency,
succeeded by an induced ventricular contraction. But it is to
be noted that occasionally stimulation at this period causes a
normal auricular contraction with an appreciable latency, and
followed by a ventricular contraction.

Stimulation of the Auricle—Maximal.

Maximal stimulation of the auricle almost always produces
some effect both on the ventricular and auricular beat; this
effect is usually one of stimulation, but it may be of apparent
inhibition.

Fia. 172.

Stimulation-of Auricle (maximal).

———

586 ELECTRICAL STIMULATION OF THE FROGS HEART.

Maximal stimulation usually induces a ventricular beat when-
ever it is applied (Fig. 172, a), excepting when it falls just after
the summit of the auricular contraction.

Stimulation at this point may cause no auricular contraction,
but on the contrary may induce omission of the subsequent
auricular and ventricular beat (Fig. 172, b 2).

When an auricular beat has been induced by stimulation, it
is followed in the ordinary way by a beat of the ventricle,
excepting when the stimulus is applied to the anricle just at the
commencement of the ventricular systole. In this case an
auricular beat may be induced, which instead of being followed
by a corresponding ventricular one, is followed, on the contrary,
by an omission of the ventricular beat (Fig. 172, a1).

At this point the latent period may be looked upon as indefi-
nitely long, as stimulation produces no contraction at all.

The more closely after this point stimulation is applied the
longer is the ventricular latency.

Stiumulation of Venous Sinus—Minimal.

The venous sinus appears to be more sensitive to stimulation
than either auricle or ventricle, so that stimuli applied to it
produce an effect, although they are much slighter than the
minimal stimuli of either auricle or ventricle.

Fre. 173.

Stimulation of Venous Sinus (minimal). In neither a nor } is the closing
shock effective.

NORMAL HEART-STIMULATION OF VENOUS SINUS. 587

Stimulation of the venous sinus by a minimal shock is usually
potent to produce some effect or other at every stage of ven-
tricwar activity (Fig. 173, bd).

Stimulation at the instant of commencement of ventricular
systole usually causes omission of the following sequential beat
of both auricle and ventricle.

This period may occasionally be slightly prolonged into
systole.

Stimulation of the sinus at all other periods of ventricular
activity causes a reduplication of the systole. This induced
ventricular systole is preceded by an induced auricular systole,
and therefore has the prolonged latency before referred to.

Stimulation falling at the commencement of ventricular
systole may cause auricular reduplication with ventricular
omission (Fig. 171, @).

In consequence of the long latency, we find all ventricular
curves separated by a distinct interval from (their) reduplica-
tions.

Stimulation of Venous Sinus—Maximal.

The period during which stimulation causes ,ventricular
omission is well marked, and in some cases extends into the

Fria. 174.

Stimulation of Venous Sinus (maximal). a, normal rhythm; 8 and e¢,
“ stimulations all effective.

588 ELECTRICAL STIMULATION OF THE FROGS HEART.

ventricular systole as it advances towards its maximum, though
the effect is never produced at the maximum.

This omission of the ventricular beat is most usually associated
with a reduplication of the auricular beat, the second auricular
contraction occurring within that ventricular systole at the
commencement of which the shock was communicated
(Fig. 174, 0). |

Reduplication occurs in all phases except at the period when
stimulation causes omission. The latent period of this redupli-
cation is usually short, as in the case of a ventricle stimulated
directly, inasmuch as the induced auricular contraction does not
precede the induced ventricular, except when stimulation falls
before the maximum of ventricular systole, in which case there
is usually a regular sequence of auricular and ventricular con-
traction (Fig. 174, c).

Usually after the maximum of ventricular systole stimula-
tion causes a reduplicated beat with short latency, inside of
which curve falls that of the induced auricular contraction ;
however, genuine sequential reduplication of auricle and ven-
tricle with long latency is not uncommon. Not unfrequently,
after repeated stimulation of the sinus, the heart assumes a new
rhythm, which may be twice as rapid as it was originally, and
though omission of the alternate beat may still be produced by
stimulation at the time already indicated, the organ returns
again to its accelerated pace. In time, if stimulation be with-
held, the rhythm returns again to the normal. The auricle
shares in the ventricular excitement (Fig. 175).

Fie. 175.

PXININIRP ANS.

Aue Ray eet nin, 3

Rhythm which has been changed by repeated stimulation of Sinus returning
to normal,

COLD HEART-STIMULATION OF VENTRICLE. 589

THE EFFECT OF COLD ON THE FrRrOG’S HEART.

In these experiments the animal was placed upon a wire
gauze grating, and covered with a small bell-jar. Underneath
the grating and around the bell-jar was placed ice, so as to
surround the frog, which was kept in this position for an hour
or longer. When its movements had become slow and torpid it
was killed, without loss of blood, and placed on the cardiograph,
already described, the temperature in the vicinity being kept
low by means of blocks of ice placed-on the metal bars sup-
porting the animal. The apparatus was employed in the same
manner as in our observations on the effect of electrical stimuli
on the normal heart, and the same order was observed in record-
ing the results.

Effects of Electrical Stimulation of the Ventricle—Minimal
Stimult.

The contraction of the chilled frog’s heart, as is well known,
lasts for longer time than in the ordinary condition. When
minimal stimuli are applied to the ventricle (Fig. 176) it is
found that there is a distinct refractory period, extending from
the beginning of systole up to the last third of the summit of
the curve in the accompanying tracing, and persisting past the
maximum of systole.

Fia. 176,

Stimulation of the Ventricle (minimal). Opening stimulation only effective

It is, therefore, always longer than in the normal heart.
After the refractory period has passed, stimulation causes
reduplication of the ventricular beat. The later on in the
diastole that the stimulus falls the shorter is the latency.

590 ELECTRICAL STIMULATION OF THE FROG’S HEART.

Ventricular Stimulation—Maximal.

Stimulation sometimes causes omission when applied at the
very commencement of systole. All stimulation thereafter
applied causes a reduplication of the ventricular systole, with a
latency that becomes shorter the later the stimulation is
applied. If auricular reduplication occurs it is always sequen-
tial to ventricular (Fig. 177, a). Stimulation at the maximum °
of systole may cause a blending with the reduplicated beat
closely resembling one prolonged systole (ig. 177, 6). The
induced beat is most perfect when stimulation falls, just as the
abscissa is reached. Stimulation before the maximum of
systole has longer latency than stimulation at the maximum.

Fie. 177.

Stimulation of the Ventricle (maximal).

Auricular Stimulation—Mininal.

A refractory period is obviously present, but it is not of so
great length as in the case of ventricular stimulation. It may
be said to extend usually through the maximum of auricular
systole (Fig. 178), and even up to near the maximum of ventri-
cular systole ; occasionally it exists only just at its commence-
ment.

As regards the reduplication, we find that as in the case of
the normal heart, along latency prevails, because an induced

COLD HEART-STIMULATION OF AURICLE AND SINUS. 591

auricular systole must occur before the ventricle contracts
again. But if the stimulation fall just at the time when the

’ Fie. 178.

Stimulation of Auricle (minimal),

abscissa is reached, or rather before this point, a ventricular
contraction may exceptionally be produced with a short latency,
and the auricular induced contraction succeeds it.

Auricular Stimulation—Maximal.

The same features are to be observed as in the last section,
except that there is no refractory period (Fig. 179).

Stimulation in all phases of the ventricular cycle usually
causes a reduplicated auricular and ventricular beat. Should
the stimulation fall before the ventricular maximum is attained,
the auricular reduplication precedes the ventricular in the
ordinary way, but should the stimulation fall after the ventri-
cular maximum, the auricular reduplication is exceptionally

synchronous with, or subsequent to, the ventricular; usually
- however, the induced ventricular beat precedes in ordinary
rhythm the induced ventricular.

Stimulation of the Venous Sinus—Minimal.

A refractory period may be present on minimal stimulation,
nearly up to the maximum of ventricular systole. Thereafter
reduplication results. A strictly minimal stimulation may origin-
ate a reduplication at any period of the beat having a long
latency, that is to say, the ventricular reduplication is preceded
by the auricular induced contraction (Fig. 180). Thus stimula-
tion applied just before the ventricular relaxation is completed,
instead of having an instantaneous ventricular and auricular

ELECTRICAL STIMULATION OF THE FROG’S HEART.

592

stimulation of auricle or ventricle, has

response resulting from

The further

a long latency, wherein the auricle reduplicates.

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HEATED HEART-STIMULATION OF VENTRICLE. 593

on in the systole the stimulation is applied, the shorter is the
latent period, and the more perfect the reduplicated contraction.

Stimulation of the Venous Sinus—Maximal.

Omission may be caused by stimulation applied at the com-
mencement of systole, or reduplication may occur in all’ phases
(Fig. 181).

- Reduplication has the longest latency at the commencement
of systole, and there is true auricular precedence up to or
beyond the maximum in this phase. In the decline of systole,
after the maximum is passed, and the abscissa has been nearly
reached, there is occasionally reduplication with short latency,
the auricular and ventricular contraction being synchronous.

ACTION OF HEAT ON THE HEART.

In this series of experiments the pithed frog in which the
brain and spinal cord had been destroyed, was laid upon a
metal plate, the temperature of which was gradually raised by
means of a flame beneath it.

Ventricular Stimulation—Minimal.

The refractory phase is generally wanting in the ventricular
systole, but it may be present in exceptional cases, not unfre-
quently in the same tracing in which stimulation most generally
produces reduplication (Fig. 182).

It may be noted that irregularity of response to stimulation
is one of the characteristics of the heated condition. Stimula-
tion usually causes reduplication. Should stimulation fall at
the commencement of ventricular systole, no effect is produced
till the whole cycle of the systole has been passed through, when
reduplication by a very perfect systole occurs. Latencies
diminish in proportion as the stimulation occurs later in the
systole of the heart. Reduplication occurring in response to
stimulation falling at the maximum is often demonstrated by a
beat originating when the relaxation after systole is completed,
and therefore distinct from the original beat: this is due to the
fact that the curve of the heated heart is much shorter in

2Q

594 ELECTRICAL STIMULATION OF THE FROG’S HEART.

duration, and therefore the reduplication falls outside the systole
during which stimulation occurs, the latency being actually
shorter, however, than in the unheated heart.

Ventricular Stimulation—Maximal Stimuli.

When stimuli of maximal intensity are applied to the ven-
tricle of the heated heart, we notice (Fig. 183) :—

(1) That there is no refractory period; (2) Stimuli at the
commencement of the ventricular systole may cause omission
of the succeeding beat; (3) Reduplication occurs at all phases,
and has the same characteristics as in minimal stimulation ;
(4) Latencies follow the same rule as in minimal stimulation; —
(5) The reduplicated beat is most perfect when stimulation
falls—

I. At the very commencement of systole.
II. At its termination.

The value of any beat and its reduplication, with the time
intervening and of the succeeding pause, was about equal to
two normal cardiac cycles. Occasionally a double reduplication,
or a series of contractions, resulted from a single stimulation.

Auricular Stimulation—Minimal Stimuli.

There is apparently no refractory period. All stimuli cause
reduplication, and in all cases induced auricular systole pre-
cedes an induced ventricular systole. This occurs even in
advanced auricular diastole, when occasionally in the normal
heart a simultaneous auricular and ventricular systole results.

Auricular Stimulation— Maximal Stimuli. —

There is no refractory period. Stimulation just after the
auricular maximum has been passed frequently causes an
apparent omission of the following beat.

Stimulation before the maximum of the ventricular systole
causes an induced ventricular beat preceded by an auricular
contraction.

After the maximum, stimulation usually has the same effect,

HEATED HEART-STIMULATION OF VENOUS SINUS. 595

but occasionally causes an instantaneous reduplication of both
auricular and ventricular beats.

A reduplicated ventricular beat is of the character already
described. 7

Stimulation of the Venous Sinus—Minimal Stimuls.

The venous sinus in its general absence of a refractory phase
shows a resemblance to the ventricle, but it may manifest the
same exception in exhibiting it.

When this occasional refractory period is present it may exist
during active systole, and up to its maximum. It is excep-
tionally present in cases which as a rule show no refractory
period.

Stimulation falling before the maximum of systole (Fig. 184,
a ventricular tracing alone given) causes a reduplication which

Fria. 184.

Stimulation of Venous Sinus (minimal).

is preceded by an auricular contraction, whilst stimulation fall-
ing immediately after maximum of systole causes reduplication,
which may be preceded by an auricular pulsation, or may
occasion an induced systole, auricle and ventricle contracting at
the same time.

The most perfect reduplicated beat occurs when stimulation
falls at the end of systole.

Venous Sinus—Mazimal Stimulation.

Occasionally a stimulation of maximum strength falling at
the commencement of the ventricular systole causes an appa-
rent omission of the following pulsation ; but this result is not
so frequent as in the case of the normal heart. Usually a dis-
tinct reduplication occurs at whatever time in the cycle stimu-
lation falls (Fig. 185).

2Q2

596 ELECTRICAL STIMULATION OF THE FROG’S HEART.

The reduplication is at all times, except in the last stage of
systole, preceded by an auricular contraction.

Fia. 185,

Stimulation of Venous Sinus (maximal).

The auricular induced contraction appears to follow stimula-
tion more rapidly than in the case of the normal heart. There-
fore the induced ventricular contraction (Fig. 185, ventricular
tracing alone given) which follows the auricular has a shorter
latency than is normally the case. The heating process having
been carried so far that a rapid cardiac rhythm with imperfect
systole has resulted, it is often found that there is an indifference
to stimulation in the so-called refractory period, or even in all
phases of the cardiac cycle alternating with the usual sen-
sibility.

ON THE EFFECT OF STRYCHNIA UPON THE FROG’s HEART.

The apparatus used in this series of experiments was identi-
cal with that employed in the investigation of stimuli applied
to the frog’s heart. The frog was killed by the brain being
destroyed, and a small dose of strychnia was then introduced
into the dorsal lymph sac. As soon as the effect of the drug
upon the spinal cord was evidenced by distinct spasm, the
heart was rapidly exposed, placed on the cardiograph, and
stimulation applied. The same order will be observed as in the
description of the experiments on the normal heart.

Stimulation of the Ventricle—Minimal.

On applying a minimal stimulus to the strychnia heart (Fig.
186) we were struck, in the first instance, by the extreme length
of the refractory period. Stimulation has usually no effect, not
only when applied before the maximum of the systole as in the

STRYCHNIA-STIMULATION OF VENTRICLE. 597

normal heart, but also in the maximum, and often far into
relaxation. After the phase has passed the stage of reduplica-

Fie. 186.

Stimulation of Ventricle (submaximal),

tion ensues. Reduplication is very complete; its latency
becomes diminished as diastole advances. The reduplicated
ventricular beat is succeeded by an auricular pulsation. After
the customary pause, the heart resumes its wonted rhythm. It
is rarely that stimulation falling at the commencement of
ventricular systole causes inhibition. If the auricle is un-
stimulated and its rhythm is unaltered, there is short latency
for the ventricular reduplication. If the auricle is stimulated
and contracts before the ventricle, there is long latency, but the
latter is rarely seen when a refractory phase is present.

Ventricular Stimulation—Maximal Stimulz.

In this case no refractory period exists. An inhibitory period
exists occasionally, but with this exception, all stimulations pro-
duce reduplication (Fig. 187). Should stimulation fall at the

Fra. 187.

Stimulation of Ventricle (maximal).

commencement of systole, the latency is long, nearly equal to
the length of the beat ; and the reduplication is very complete.
Stimulation at the maximum of systole has a latency of about

598 ELECTRICAL STIMULATION OF THE FROGS HEART.

two-fifths of a second, and thereafter during the subsidence of
the ventricle, the period of latency rapidly diminishes. The
most perfect beat of reduplication is produced by stimulation
at the commencement of systole, or after relaxation of the

ventricle.

Stimulation of the Auricle—Minimal.

It is but rarely that we see a refractory period whilst apply-
ing minimal stimuli to the auricle. Usually, stimulation at all
times causes a reduplicated beat, the auricular reduplication
preceding that of the ventricle in the usual rhythm. On
stimulation, an auricular systole is produced, and not until this
movement has reached the usual point does the ventricle com-
mence its systole (Fig. 188).

Fie. 188.

Stimulation of Auricle (minimal).

Maximal,

Stimulation of the Auricle

There is no refractory period. Occasionally the stimulus
falling at the very commencement of the ventricular systole
will cause inhibition or coincidence of the following beat, or it
may cause a reduplication with a latency of about one second
(Fig 189).

Fie. 189,

Stimulation of Auricle (maximal).

STRYCHNIA-STIMULATION OF VENOUS SINUS. 599

The latencies are invariably long when the auricle is so
stimulated that its induced beat is a normal one and precedes
the induced ventricular systole in its normal rhythm.

Stimulation of the Venous Sinus—Minimal Stimuli.

With minimal stimulation of the venous sinus there is no
refractory period except occasionally for an instant at the maxi-
mum auricular systole. Reduplication occurs at all phases of
the ventricular systole. Length of latency depends upon
whether the stimulation induces an auricular contraction or
not. If the auricular systole follows the stimulus, then the
ventricular latency must be long (Fig. 190).

Fie. 190.

Stimulation of Venous Sinus (minimal).

It is longer if stimulation falls at the commencement of
ventricular systole, because at that phase, until the auricle has
contracted, no ventricular reduplication occurs. Occasionally,
though rarely, and that after the maximum of ventricular con-
traction, auricular reduplication follows, or is synchronous with
the ventricular systole, and then latency is invariably short.
Reduplication with prolonged latency, probably from auricular
reduplication, is well seen in the appended tracing (Fig. 191).

Fre. 191

Stimulation of Venous Sinus (minimal).

600 ELECTRICAL STIMULATION OF THE FROG’S HEART.

The stimulation at the end of relaxation in one case causes
reduplication of the auricle, coinciding with that of the
ventricle.

The tracing illustrates the rule that when the sinus is stimu-
lated no refractory period is observed as regards the ventricular
reduplication.

Venous Sinus—Maximal Stimulation.

There is no insensitive period as far as regards the ventricle.
During all phases of the systole stimulation causes a reduplica-
tion of the ventricular beat (Fig. 192). Inhibition of the ventyri-
cular systole has not been found in many of the hearts
examined, though it occasionally occurs.

Fie. 192.

Stimulation of Venous Sinus (maximal).

Should the exciting shock fall at such a time as to cause an
instantaneous auricular systole, we find this systole is nearly
synchronous with that of the ventricle, and that the latter has
a short latency, but should the shock fall so that the auricle
responds by a genuine contraction, the ventricular reduplication
follows with a long latency.

Inhibition of the ventricular with reduplication of the auri-
cular beat may result occasionally from stimulation of the
venous sinus.

Appendi« A. CooLeD HEART.

The construction of a simple piece of apparatus has enabled
us to obtain curves much more striking than those which
appeared in the foregoing paper, as they represent a far greater
variation of temperature.

COOLED HEART-STIMULATION OF AURICLE. 601

Instead of the gutta-percha support for the heart already
described, a hollow copper pan of similar shape was employed.
It was provided with influx and efflux tubes, and insulated
below by a plate of ivory in which ran also the electrodes
destined for the stimulation of the sinus. This was connected
with the usual support passing over the body. Upon minimal
stimulation of the ventricle itself the succession of auricular and
ventricular contraction is illustrated in the charts A 1—4 (Fig.
193) here inserted. It is seen that the action of cold modifies
considerably the relation between the ventricular contraction and
the succeeding auricular beat. In A, we find a reduplicated
ventricular beat succeeded by a normal auricular contraction.

In A, cooled through about 2°5 C., the ventricle responds to
the same stimulation. and the way does not pass upward to the
auricle; and in A,, in which the contraction and relaxation of
the heart had become very slow from a further reduction of 2°,
we find the auricular rhythm is regular in spite of ventricular
reduplication. There is in A, and A, an indication of aortic
expansion ; it is to be noticed that after the reduplication in A,
this is omitted.

Auricular Stimulation.

Many additional experiments upon cooled hearts have tended
to show that it is very rarely that stimulation of considerable
strength calls forth a ventricular beat, preceding or coexistent
with the auricular. Usually at all phases of stimulation which
causea reduplication of the auricular beat, the ventricularsucceeds
in normal relationship (B 1 and 2 Fig. 194), There is an excep-
tion to this, however, which is frequently demonstrated ; this is
that whilst the auricular beat is reduplicated the ventricular is
not, but is succeeded by a long diastolic pause (B,), after which
the auricle takes up its oldrhythm. Still more rarely stimulation
just before commencement of ventricular systole causes omission
of both succeeding auricular and ventricular beats (B,).

The latency of reduplication varies considerably in minimal
stimulation of the auricle, but this variation is not so much
owing to loss of time in the auricular as in the ventricular

ELECTRICAL STIMULATION OF THE FROGS HEART.

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COOLED HEART-STIMULATION OF AURICLE.

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604 ELECTRICAL STIMULATION OF THE FROG’S HEART.

reduplication. Thus in C, (Fig. 195) stimulation at the end of
auricular relaxation, ventricular latency is 1’’2,in C, stimulation
halfway to ventricular maximum latency is 1’’,and in C,, when
stimulation, is at ventricular maximum, the latency is for the

ventricle only 6”.

Fie. 195.

C, to C3. Levers asin A. Auricular Stimulation (minimal) of Cooled Heart.

On the other hand, more powerful stimulation of the auricle
causes reduplications of the ventricle, which are at all times of

Fie. 196.

D, to D,. Leversasin A. Auricular Stimulation (maximal) of Cooled Heart.

COOLED HEART-STIMULATION OF VENOUS SINUS. 605

equal or of very slightly differing values. Thus in a heart much
cooled (D 1 and 2 Fig. 196) we have towards the commence-
ment of ventricular systole and towards the end of relaxation
a latency for the induced ventricular beat of 1/2.

Venous Sinus.

In the heart which has been moderately or slightly cooled,
4—6* C., the occurrence of ventricular reduplication without a
precedent auricular reduplication is very rare, even when strong
stimulation is employed. The refractory period occasionally
observed may disappear after a few stimulations have been
given, or it may persist. Furthermore, on coolinga heart which
has at a certain temperature, E, (Fig. 197), shown a refractory
period, we may find this converted into a period during which
stimulation causes an omission of the following beat, E,,.

Fia. 197.

HK, to Ej. Levers as in A, but no auricular tracing given. Stimulation of
Venous Sinus. E,, before cooling; Ez, after cooling.

The duration of the diastolic pause is markedly influenced by
temperature, whereas it appears to be but slightly aifected by
variation in the instant of stimulation by which it is produced.

606 ELECTRICAL STIMULATION OF THE FROG’S HEART.

In (Fig. 198) G, water of melted ice had passed through the
support for two minutes.

rer

G, water had passed 5’.

G, 39 33 1 0’.
G, ” ” 2 0’,

G, to G;, gradual cooling of Heart.

Fig. 198.

Levers asin E. Stimulation of Venous Sinus.

COOLED HEART-STIMULATION OF VENOUS SINUS, 607

G, Duration of contraction 1/4 Length of pause from

stimulation ... 4/2.
G, ” * eee 1”9 29 ”» 5°""6
G, ” ra eee 2"2 ” ” 60
G, ke x oD OIA - F. 6/2

G, was obtained from a heart cooled for a considerable time,
and shows a remarkable prolongation of the systole and diastolic
pause.

G, Duration of current 4”4 Length of pause from
stimulation ... 10”

It will be seen in all these cases that there is a certain
relationship between the length of the contraction and of the
pause.

The reduplication of the ventricular beat varies in regard to the
time of stimulation under minimal stimulation. Thus in H (Fig.
199) when stimulation falls near the commencement of systole,
auricular reduplication occurs in 18 and ventricular reduplica-
tion in 3’"2. But in the same heart a stimulation during a
period of relaxation yielded an instantaneous auricular re-
sponse, the ventricular reduplication occurring 1/°3 after
stimulation.

In the case of maximal stimulation, the usual result is an
instantaneous auricular systole succeeded by a ventricular.
The latter, therefore, has a latency equal to the auricular beat:
this is seen in I,, I, (Fig. 200), in both of which the latency is
about 0°7”; but in I, we have, on the other hand, no auricular
reduplication for 1”-1. In both this instance and H, stimulation
occurred at the commencement of ventricular systole

ELECTRICAL STIMULATION OF THE FROG’S HEART.

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Fre. 200.

I, tol; Levers asin A. Stimulation of Venous Sinus (maximal).

Fie. 201.

a

Time tracing. Electro-magnet recording seconds. Applicable to all tracings
in Appendix A.

Appendix B. HEATED HEART.

In some cases, heating a frog’s heart through 4°°5 C. may fail
to obliterate entirely the period of resistance to stimulation.
Heat, however, in the same experiment may be shown to shorten
the refractory period much, and to limit it to the very com-
mencement of ventricular systole (in stimulation applied to the
ventricle). The series of tracings given were taken from a large
specimen of Rana esculenta, which had been kept at a low

2k

(610 ELECTRICAL STIMULATION OF THE FROG’S HEART.

temperature for a considerable time before the experiment. The
tracing obtained at room temperature (K, Fig. 202) is therefore
that of a cold heart, and the refractory period extends up to the
commencement of relaxation after systole. After hot water
had been run through the support for 5’, and the temperature
raised about 2° C., we find diastole increased and systole much
shortened; at the same time there is a refractory period as
extensive as in the cold heart, that is to say, extending to the
commencement of relaxation K,,.

Fie, 202.

eee ed

Stimulation of Ventricle (maximal stimulation).

K,. Heart at room temperature, frog long kept in cold room.

K,. Temperature raised 2° C,

K;. Taken 10’ later than K,, during which time temperature was raised 1° ©
K,. Temperature raised again 1° C.

K;. Temperature raised 1° C., making about 5° C. altogether above Kj.

HEATED HEART-STIMULATION OF VENTRICLE. 611

Fig. 203.

|

Drum of more rapid rotation used in tracings given in Appendix B. The
electro-magnet marks seconds.

In K, after heat had been applied 10’, and the temperature
raised another degree, stimulation at an earlier phase produces
reduplication. Heated ‘still further, K,, there is reduplication
at systolic maximum, and at K, everywhere except at the very
commencement of systole. After heating through about 5° we
still have a refractory period, whilst the curve has been reduced
from 1/4 to 0-4’... In many cases, however, the same amount
of heat may obliterate the refractory period completely. The
heart which yielded these curves passed into rigor without
showing the abolition. In the heated heart, of which the ven-
tricle is stimulated, we may find that the auricle does not in
any way participate in the ventricular excitement, but con-
tinues tu beat in its usual rhythm. Thus when the heated
heart yields a series of contractions in answer to a single stimu-
lation—a result not; unfrequently obtained—the auricle does
not reduplicate, but may give its systole in due place, whilst
-the ventricular contractions are still occurring. Not only is
this indifference to ventricular action observed on the part of
the aur cle, but the counterpart may be occasionally seen in the
ventricle, failing to fullow the normal systole of the auricle L
(Fig. 204). This is in part due to the fact that the auricle has
only shared imperfectly in the heating.

Fia. 204.

Stimulation of Ventricle (maximal). Heart heated about 7°C. Time as in K,

2 RZ

612 ELECTRICAL STIMULATION OF THE FROGS HEART.

There is thus a disturbance of both muscle-wave and nervous
impulse, produced by the heating to which the auricles and
ventricle have been exposed. This failure on the part of the
ventricle occurs only after there has been a reduplication of its
beat, and does not often occur, so far as we have seen, when
stimulation, applied to the auricle itself (M Fig. 205), originates

Fie. 205.

Stimulation of Auricle (maximal). Heart heated about 6° C.

a systole there, for then the ventricle follows in due course;
we should therefore regard the exhaustion of the ventricle after
its unusual activity as the cause of its quiescence after the
normal auricular beat. Should stimulation be applied to the
auricle during ventricular diastole, a reduplicated auricular
beat succeeded by a ventricular at once occurs. In all phases
this natural sequence is maintained, though sometimes at the
end of its systole the auricular reduplication may be 0:5’,
Whilst a long pause follows this reduplication, it is very rarely
that a stimulation of the auricle produces omission of the
succeeding auricular and ventricular reduplication.

In stimulating the venous sinus, however, omission of the
following ventricular beat is frequently produced when the
shock falls at the commencement of ventricular systole (N,
Fig. 206), but we may find that there is an impulse propagated
to the auricle, for this may reduplicate whilst the ventricle
remains quiescent (N,).

A little later, and up to the maximum of systole, the auricular
reduplication is succeeded by a ventricular (N,), and after the
maximum, and during the diastole of the ventricle, the induced
auricular beat may occur synchronously with the ventricular, or
it may precede it in regular course.

Both of the charts N, and N, (Fig. 206) are taken from a

HEATED HEART-STIMULATION OF VENOUS SINUS. 613

heart warmed through about 5° C., and N, gives a tracing of the
same, in which stimulation does not occur.

Fria. 206.

Stimulation of Venous Sinus (maximal).

In the stronger tendency to cause omission of a ventricular
beat, as well as in the frequent occurrence of an auricular
contraction coincident with or succeeding the ventricular, when
stimulation fails after ventricular maximum or in diastole, we
see a marked contrast in the reaction of the venous sinus and
the auricle to stimulation.

From the charts O,, O,, 0, (Fig. 207) we see that the latency
of the auricular beat varies. Thus stimulation occurring just at
the end of auricular relaxation (O,) causes an instantaneous
reduplication, whilst during diastole proper it has a reduplication,
with a latency of 0-2”. In the former case auricular induced
systole precedes the ventricular, in the latter they occur at the
same moment (Q,, O,).

Contrast this result with the stimulation of the auricle itseh,

614 ELECTRICAL STIMULATION ‘OF THE FROG’S HEART.

in which reduplication occurs at once on stimulation, and ven-
tricular reduplication succeeds or occurs occasionally (stimulation ;
at the end of auricular relaxation) in 0°5’’, followed by ventricle.

Fre. 207.

Ne Se TN ION See:

ea ee ae oe

—
a No Fo NS Se

Stimulation of Venous Sinus (maximal).

Appendix C. ACTION OF STRYCHNIA ON THE FRoG’s HEART.

In order to test the correctness of the conclusion that
strychnia lengthens the refractory period, we placed frogs in
which the medulla and cord only existed on the cardiograph.
The effects of stimulation were then observed, and subsequently
a small dose of strychnia was injected into the dorsal lymph
sac; as soon as the resulting spasm was well developed, stimu-
lation was again applied, the strength of stimulation and the
position of the electrodes remaining constant.

Thus in Fig. 208 P,, a frog’s heart, in which active circulation
was present, showed arefractory period through about one-half of
the maximal maintenance of systole. In 3’, after the injection,
of a small dose of strychnia into the dorsal lymph sac, distinct;
spasm was present, and in 5’ Fig. P, was taken, which showed:
that the refractory. period. had become prolonged, until relaxa--
tion of the ventricle had commenced.

It may happen that stronger stimulation before the maximum,
of systole is. reached, causes an auricular beat, which precedes

STRYCHNIA-STIMULATION OF AURICLE. 615

in normal rhythm the induced ventricular contraction. This is
observed when the electrodes are placed near the base of the

Fie. 208.

Stimulation of Ventricle.
1. Before injection of strychnia. 2. After injection of strychnia.

Fra. 209.

Time-marker, recording seconds. All tracings in Appendix C taken at this
speed, except 8 and T.

ventricle, or when stimulation is passed through the same
portion of the heart from the float to an electrode placed
beneath the heart upon the supporting shelf. After the maxi-
mum of systole, however, the auricular contraction succeeds the
induced ventricular. Both these facts are demonstrated in
Fig. 210 Q, in which this occasional increased auricular
excitability is shown.

Auricular Stimulation.

Occasionally maximal stimulation applied to the auricle pro-
duces at all times an auricular contraction succeeded by a
ventricular; more usually, however, this relationship exists
only up to the maximum of systole (ventricular), and thereafter
the induced auricular beat succeeds the ventricular.

616 ELECTRICAL STIMULATION OF THE FROG’S HEART.

Should stimulation cause an instantaneous auricular systole,
then the ventricular reduplication has a latency of nearly equal
value at all times at which it may occur, but should there be,
as in Fig. 211 R,, a considerable auricular latency (about 1”)
then the ventricular latency is liable to great variations.

1, 2, 3, varying times of stimulation.

Stimulation of Ventricle (maxima)).

Stimulation of Auricle (maximal).

STRYCHNIA-STIMULATION OF AURICLE AND SINUS. 617

At the maximum cf auricular systole, Fig. 211 R,, we have an
immediate auricular response, and a ventricular latency of 0°4”;
and in Fig. 211 (R,) there is an almost instantaneous ventricular
systole, with an auricular latency of about 15”, The diastolic
pause is the longer the later stimulation falls. In Fig, 211 Ry
it is 0°9’’; in Fig. 211 R, it is 1’°9; in Fig. 211 R, it is 2’"3.

Stimulation falling just after maximum of auricular systvle,
and at the commencement of ventricular systole, may cause in
addition to the results enumerated, omission of the succeeding
auricular and ventricular contractions, or reduplication of the
auricular, but omission of the succeeding ventricular (Fig. 212 8).

Fig. 212.

Stimulation of Auricle (maximal). Levers as in Fig. Q.

Thus the induced auricular contraction in this instance,
instead of passing a motor impulse downwards to the ventricle,
appears not only to check the reduplication, but greatly to
prolong the diastole.

It is easily recognised from the auricular tracing that the
induced contraction is one of the unfilled cavities (Fig. 212 S),
but though little or no blood passes into the ventricle, a positive
effect upon the latter is still produced.

Venous Sinus.

As regards the relationship of the auricular reduplication to
the time of stimulation, we find the latency of the auricle occa-
sionally varying in length, but usually it has very nearly equal
values, except when the shock, falling during ventricular re-
laxation, calls forth a simultaneous auricular and ventricular

618

Fie. 218.

ELECTRICAL STIMULATION OF THE FROG’S HEART.

Stimulation of Venous Sinus (maximal).

contraction, and in this case latency
is reduced. It is to be noted that
this induced auricular contraction
does not cause another induced ven-
tricular systole: its further effects
seem to be lost or dissipated.

At two points in chart T (Fig.
213), ventricular systole being ad-
vanced half-way and 0°6of the way to
its maximum, the auricular latency’
is equal, and when at the end of ven-
tricular relaxation the auricle con-
tracts at the same time as the
ventricle, the latency is still about
the same. The time lost, therefore,
in this case is in ventricular redupli-
cation: either the impulse from the
auricle is transmitted at different
speeds at different times, or it meets
at different times with variation in
the excitability of the ventricle.
The later in the systole the stimu-
lation falls the less is the resistance
to the transmission of the impulse
or the greater the excitability of the
ventricle. a

The whole subject of the rhyth-—
mical contraction of the frog’s heart
and its stimulation and inhibition
is a very complex and difficult one.
The points upon which our present
research seems to us to throw some
light are the nature and mode of
transmission of the stimuli which
one cavity transmits to another in
the ordinary process of rhythmical ”
contraction. Marey’s researches have
shown that in the ventricle itself

PROPAGATION OF STIMULI IN THE HEART. 639

there is a time when stimulation applied to it has no apparent
action ; this time is, however, in many cases of very short dura-
tion and limited to the commencement of ventricular systole. At
the commencement of ventricular systole stimulation without
provoking contraction causes often a positive effect, namely, a
greatly prolonged diastolic pause, which we have been inclined
to regard as due to omission of a ventricular contraction.

It seemed of interest to ascertain whether a similar condition
occurred in the other cavities of the frog’s heart. We find that
in the auricular stimulation about or shortly after the period of
maximum contraction of the auricle may cause inhibition of
the next auricular beat. :

We have not yet succeeded in registering the contractions of
the venous sinus with sufficient accuracy to enable us positively
to determine the occurrence of a similar refractory period in the
venous sinus itself, but the results we have obtained lead us to
hope that we shall soon be able to do so. |

Another interesting consideration is, whether the stimulus
which each cavity of the heart transmits to the succeeding one,
consists in the propagation of an actual muscular wave, or in
the propagation of an impulse along the nerves. The observa-
tions of Gaskell have given very great importance to the
muscular wave occurring in each cavity of the heart of cold-
blooded animals as a stimulus to the contraction of the next
succeeding cavity. Our observations appear to us to show that’
while this is an important factor, it is not the only one in the
transmission of stimuli. We have observed that stimulation of
the auricle rarely or never causes contraction of the ventricle
unless the auricle also contracts. - When stimulation of the
auricle causes both itself and the ventricle to contract, the
auricular contraction precedes the ventricular one in such a
way that we might be justified in regarding the ventricular
contraction as due to the propagation of the contractile wave
from the auricle to the ventricle. It would also appear
that a contractile wave may be propagated backwards, for on»
stimulation of the ventricle we have observed the contraction
of the ventricle produced by stimulation has been succeeded by
an auricular contraction such as might be supposed to be due

620 ELECTRICAL STIMULATION OF THE FROG’S HEART.

to propagation of the contractile wave back from the ventricle
to the auricle. While these observations appear to show that
the propagation of the contractile wave from one cavity of the
heart to another is of importance in keeping up the rhythmical
sequence, we consider that stimuli are also propagated from
one chamber of the heart to another through nervous chan-
nels:—thus we find that irritation of the venous sinus will
sometimes produce simultaneous contractions of the auricle and
ventricle instead of the ventricular beat succeeding the auricu-
lar in the usual way, This. we think is hardly consistent with
the hypothesis that a stimulus consists of the propagation of a
muscular wave only from the auricle to the ventricle.

As additional evidence we may notice the occurrence of an
auricular beat followed by absence or inhibition of a ventricu-
lar beat as the result of stimulation of the auricle, or venous
sinus. Moreover, we have noticed in the heated heart the
occurrence of groups of regular beats in the ventricle in con-
sequence of a single stimulation applied to it, while the auricle
has continued to beat with its ordinary unaltered rhythm un-
disturbed by the ventricular excitement.

It is not however our purpose to do more in this paper than
state the results we have hitherto obtained, and we shall there-
fore reserve for a future communication the consideration of
this and some other questions of importance closely allied
to it. |
Another question is the nature of the inhibitory influence
exerted by one cavity of the heart upon another. Marey had
shown that stimulation of the ventricle during a great part of
the refractory period exercises an inhibitory instead of a motor
action upon the ventricle itself. It might be supposed then
that a stimulus of either kind, whether proceeding from the
auricle in the form of a contractile wave, or a nervous impulse,
might produce inhibition of the ventricle, provided the stimulus
reached it during that part of the refractory period in which
stimulation usually causes inhibition. From our observations
it seems that the inhibition of the ventricle which may follow
stimulation of the auricle is not due to the muscular wave
propagated from the auricle and striking the ventricle during the

INHIBITION-BACKWARD PROPAGATION OF STIMULI. 621

refractory period. In Fig. 172, p. 585, we notice that the
auricular contraction succeeded by ventricular inhibition occurs
after the refractory period of the ventricle has passed ; we must,
therefore, look upon the inhibition as due to the propagation of
a nervous impulse from one cavity to another. In the auricle
we find that stimulation may produce inhibition of the auricu-
lar and ventricular beats, or of the ventricular beats alone.
We may, therefore, suppose that the stimulus applied to the
auricle acts upon two different nervous mechanisms; seeing
that it is enabled to inhibit the ventricular beats without affect-
ing the auricular ones, we are unable to say precisely what the
effect of a single stimulus applied to the venous sinus is upon
the sinus itself, but here we note that the same result will
follow stimulation of the sinus, as of the auricle, viz., inhibition
of the ventricular without inhibition of the auricular beat, or
inhibition of both together.

As has been already pointed out by Professor Marey, the
refractory period is increased when the heart is artificially
cooled. We have also found that there is a prolongation of the
time during which stimulation causes an inhibition or omission
of the following systole.

It is very seldom that stimulation of the auricles or of the
venous sinus causes a ventricular contraction without auricular
systole preceding it in the ordinary rhythm. In this respect
the action of the heart offers a contrast to the normal. Though
the muscular wave started in the auricle is usually succeeded
by a ventricular contraction, it may occasionally be succeeded
by a ventricular inhibition, or auricular stimulation may be
followed by inhibition of both auricle and ventricle.

The propagation of the wave in an upward direction, viz.,
from ventricle to auricle, is not so regular as in the normal
heart, the time elapsing, when it does occur between the ven-
tricular and auricular systole, bearing a relationship to the
degree of cold produced. Whilst the ventricle is reduplicating
in response to direct stimulation, the auricle may maintain its
regular rhythm. Stimulation of the venous sinus almost in-
variably gives an auricular contraction at all times preceding
the ventricular. It has been already shown that in the case of

622 ELECTRICAL STIMULATION OF THE FROG’S HEART.

the normal heart stimulation in advanced diastole frequently
causes a spontaneous auricular and ventricular contraction, or a
ventricular beat preceding the auricular. |

In the heated heart we have noticed, in addition to the ex-
cessive diminution or abolition of the refractory period in the
_ventricle already observed by Marey, that usually the refractory
period in the auricle entirely disappears. A single stimulation
of the ventricle sometimes gives rise to a series of contractions
with incomplete relaxation intervening. After this has occurred,
or after a simple reduplication has been caused, it often happens
that the auricular beat occurritig in normal sequence is not
followed by ventricular, which seems to show a temporary state
of exhaustion of the ventricle. In the heated heart the dura-
tion of a systole is so short that two beats immediately succeed-
ing one another may be perfectly distinct, while, in the normal
heart, the second one would have fallen within the time of the
systole of the first, so that it could only have appeared, if it
were possible at all, as an increase either of the height or length
of the first systole. Inhibition occurs in the heated heart as
well as in the normal, which is most frequently observed upon
stimulation of the venous sinus, and it is frequently at this time
associated with a reduplicated auricular contraction. The effect
of strychnia is to prolong the refractory period of the ventricle.
Stimulation of the ventricle is frequently succeeded by con-
traction of the auricle. There is an increased tendency for
stimulation of the ventricle to induce a beat of the auricle
preceding the ventricular systole. There is less tendency for
the stimulation of the venous sinus or auricle to induce a beat
of the ventricle succeeded by one of the auricle; and, indeed,
this only occurs when the stimulus falls just at the end of the
ventricular systole, z.e., when the ventricle itself is most sensi-
tive. These facts seem. to indicate that the nervous channels
are more active in transmitting stimuli, both downwards from
the venous sinus to the auricle and ventricle, and from the
ventricle back to the auricle.

In its effect upon the refractory period, andin the tendency it
produces to maintain the regular rhythm, the action of strychnia
agrees with that of cold, as shown in the present series of

a ee

ACTION OF STRYCHNIA. 623

experiments; but, as we have already shown in a former paper,*
its effect in causing the ventricle when arrested by a ligature
applied around the junction of the venous sinus with the auricles
to recommenee pulsation resembles that of heat.

_ There are many other points on which we think that a fuller
consideration of our experiments will throw light, but to take
them up at present would involve too lengthy a discussion of
doubtful points in the physiology of the frog’s heart, and so
we must reserve them for a future time.

% St. Bartholomew's Hosp. Reports, vol. xvi, p, 229,

624

THE VALVULAR ACTION OF THE LARYNX.
In conjunction with THEODORE CASH, M.D.

(Reprinted from the Journal of Anatomy and Physiology, vol. xvii, 1882-1883.)

CLosuRE of the glottis plays a most important part in all expul-
sive acts, such as coughing, sneezing, vomiting, or defecation
or in those muscular actions where it is necessary to have the
thorax fixed, in order to enable the muscles attached to it to act
with greater advantage or greater precision. On looking at the
human larynx, it not unfrequently happens that the mere act
of introducing the mirror into the fauces excites movements of
retching. The appearance which the larynx then presents, is
that of a somewhat circular or slightly elliptical opening com-
pletely filled by three bulging segments, strongly reminding one
of the appearance of the aortic valves, as seen from below in an
injected aorta. On consulting several text-books on physiology
we find that the mode of closure of the glottis is treated in a
very cursory way. In the wonderfully complete physiology of
Haller we can find no definite information, nor is there any in
Todd’s Cyclopedia of Anatomy and Physiology. In Miiller’s
Physiology, translated by Dr. Baly, 2nd edition,* we find the
statement that in holding the breath the air tubes are cut off
from the mouth and nostrils by approximating the posterior
palatine arches, and pressing the root of the tongue against the
palate. In Carpenter’s Physiology, 9th edition, and in Foster's
Physiology, 3rd edition, we have also failed to find a definite
account of the mechanism of the closure of the glottis. In
Czermak’s, Treatise on the Laryngoscope,t he states that during
closure of the glottis he has observed that—

“(1) The arytenoid cartilages intimately meet at their in-
ternal surfaces and processes, and they bring the edges of the
vocal cords in contact; (2) the superior vocal cords approach

* Vol. i, p. 360.
+ New Sydenham Society publications, vol. xi, 1861.

SUPERIOR AND INFERIOR VOCAL CORDS. 625

the inferior vocal cords, so as to obliterate the ventricles of
Morgagni, at the same time they «lso meet in the median line;
(3) the epiglottis being lowered, and its cushion becoming more
prominent still, it presses against the closed glottis; the contact
takes place from before backwards. These three-fold occur-
rences in the hermetic closure of the larynx explain the resist-
ance which the glottis successfully opposes to the pressure of
the air, without a development of much force during the effort.”

Czermak also gives an accurate picture of the appearance of
the glottis when completely closed during effort, though a still
better one is given by Griitzner in Hermann’s andb. ch der Phys.
(Band 1, Theil 2, page 59). In Griitzner’s picture (Fig. 214)

——_

Fie. 214.,—Glottis closed by the approximation of the false vocal cords (/f. s.)
after Griitzner.

the rounded and bulging nature of the protuberances formed by
the false vocal cords is very evident, and suggestive of inflation
from below. Griitzner, however, only remarks that the false
vocal cords, or ventricular bands, are often approximated, and
the cushion of the epiglottis depressed upon them, whereby a
very firm closure is produced. In an inaugural thesis presented
to the Edinburgh University by Dr. Wyllie in 1865, the author
discussed the mode of closure of the glottis very fully, and
illustrated it by very numerous experiments. These showed
very clearly, indeed, what an important part is played in the
closure of the glottis during expiration by the false vocal cords,
and that, indeed, it is chiefly if not entire y through them that
the closure is usually accomplished. These experiments were
published in the Edinburgh Medical Journal, September, 1866,
but as they are not referred to in many standard text-books,* it

* We must except Turner’ 2ntroduction to Human Anatomy, in which these
experiments are referred to.

28

626 THE VALVULAR ACTION OF THE LARYNX.

would appear that they have not received the attention they
deserve. Wyllie points out that Czermak was probably de-
ceived in regard to the second factor in the closure of the
glottis.

Czermak thought that the superior vocal cords approach the
inferior, so as to obliterate the ventricles of Morgagni, at the
same time that they also meet in the median line,

As Wyllie points out, and as reference to the accompanying
Fig. 215 will show, it is impossible to say anything with certainty
regarding the condition of the entrance to the ventricles of

SAL QQw a ete ee meernnece

Fic. 215.— Anterior half of a transverse vertical section through the larynx
near its middle. (From Allen Thomson in Quain’s Anatomy.) 1, Upper
division of the laryngeal cavity; 2, central portion ; 3, lower division con-
tinued into 4, part of the trachea; e, the free part of the epiglottis ; e’, its
cushion; 4, the divided great cornua of the hyoid bone; At, thyro-hyoid
membrane ; ¢, cut surface of the divided thyroid cartilage ; c, that of the
ericoid cartilage ; 7, first ring of the trachea; fa, thyro-arytenoid muscle ;
vl, thyro-arytenoid ligament in the true vocal cord covered by mucous
membrane at the rima glottidis; s, the ventricle, above this the superior
or false cords; s’ the sacculus or pouch opened on the right side,

EXPERIMENTS OF WYLLIE. 627

Morgagni when the glottis is closed, inasmuch as these are
simply oblong orifices in the lateral walls of the larynx, and
the false vocal cords completely hide them from view when
they are approximated. Wyllie points out that an anatomical
misconception prevails regarding the nature of the vocal cords,
many considering them as the free edges of membranes which
are flattened above and below. They are, however, really
wedge-shaped projections from the sides of the larynx, the apex
of the wedge being directed downwards and attached to the
laryngeal wall, its upper flat surface forming the floor of the
ventricle of Morgagni, and its projecting edge forming the true
vocal cord.

Their shape is as badly adapted as we can possibly imagine
for retaining air in the thorax, though very well adapted for
preventing air from entering it. Wyllie’s experiments showed
that by no adjustment could the true vocal cords completely
prevent the exit of air, but that when they were simply
approximated, not even being pressed together, they completely
prevented its entrance. With the false vocal cords the case
was just the reverse; they present no obstacle whatever to the
entrance of air, but when they are approximated they com-
pletely obstruct its exit from the lungs, and the air getting
behind them into the ventricles of Morgagni, inflates them, and
thus the greater the pressure behind them is, the more perfect is
their apposition.

Our own investigations completely confirm those of Dr. Wyllie.
He extends his experiments to the production of voice, we have
restricted ourselves to the simple mechanism of the closure of
the larynx during effort; but instead of confining our observa-
tions to the human larynx, we have made comparative observa-
tions on the larynges of some animals.

Before entering into those in detail, it may be advisable to
say a few words regarding the comparative anatomy of the
larynx.

A good anatomical classification of laryngeal variations is the
following, proposed by Milne-Edwards* :—

* Milne-Edwards, Legons sur la Physiologie et Vanatomre comparée de
Vhomme et des Animaua,
282

628 THE VALVULAR ACTION OF THE LARYNX.

I. The aglottic type, in which the laryngeal cavity is not
separated into two spaces by well-marked vocal cords.

IJ. The simple glottic type, in which there are well-marked
vocal cords, but in which no false cords nor ventricles are
present. :

III. The composite type, in which the upper or anterior
portion of the larynx is furnished with a second pair of cords—
commonly termed false or superior cords—and which are sepa-
rated from the true cords by a distinct ventricle.

IV. The cavernous type, in which the cavity of the larynx is
in communication with a sinus possessing accessory pouches, of
which the mouths are situated in the ventricles of the larynx,
or in other parts of this organ.

In following this classification, the animals whose larynges
determine their serial position will be mentioned indiscrimi-
nately, and peculiarities of the glottis briefly expressed, whilst
reference to the author who is responsible for the statement
will be made in a footnote.

Class I.—In the pisciform mammals, where the larynx has not
the function of a vocal instrument, but only that of insuring
continuity of respiratory work during deglutition, and main-
taining free communication between the trachea and nasal cavi-
ties. This form of organisation is found in the Cetaceans.

The Dugong has no ventricle.

In the Dolphin* the glottis opens into the posterior nares,
and has a pyramidal form. It is patent only at its summit,
and leaves at either side a passage for food. The pyramidal
elevation is formed by the arytenoids and the epiglottis. Prob-
ably in these, and in the Cetaceans generally, there is no voice,
as no true means for its production are present.

Marsupialia.—In the Kangaroof there is no false cord, no
ventricle, and only the faintest indication of true cords. The
arytenoids are capable of considerable elevation, and permit the
passage of air through a large gap between their inner surfaces,

The Kangaroo has a cavernous sinus.

It is probable that the Kangaroo is mute.

The foetal Hippopotamus has no cords but a simple longi-

* Cuvier, p. 797. + Milne-Edwards, p. 442.

COMPARATIVE ANATOMY OF THE LARYNX. 629

tudinal elevation, formed by the anterior extremity of the
arytenoid*,

Class II is a very large one, and embraces mammals from
very widely differing orders.

The Hedgehog belongs also to this class.

In the Elephantt the arytenoids do not touch by their inner
surfaces, and the true cords are placed obliquely. The false
cords are indicated in position by a faint projection of the
mucous membrane, and the ventricles are only formed by an
excavation of the upper surfaces of the true cords. At the
anterior commissure there is a transverse fold.

In the Ruminants§ the arytenoids have, besides their articular
facette, a superior angle which is curved forwards, and an in-
ferior to which the vocal cords are attached.

The inferior margin of these cords is obtuse and continuous
with the rest of the internal lining membrane, the superior
margin is more or less free and trenchant—it is much more so
in the Deer than in the Gazelles, and it is very indistinct in
the case of the Cow and Sheep. The internal fauces of the
arytenoids touch, and air could only pass between the anterior
margins and the epiglottis. This passage is more or less narrow
according to the species. There is no superior ligament and
no ventricle properly so called, neither does any cuneiform
cartilage exist.

Sometimes, as in the Antilope gutturosa,]| the thyroid is
bulged outwards in the neighbourhood of the attachments of
the vocal cords.

In Hares and Rabbits (Lepus timidus et cuniculus) there is an
intermediary form, as the false cords are wanting, but the
ventricle exists. In the Lepus timidus, however, Wolff denies
the existence of a ventricle.

In the Rein-Deer** there is a large subepiglottal sac,but this
is not found in the Deer.

The Sloth (Bradypus tridactylus) has a peculiar form of vocal

* Cuvier, p. 791. + Milne-Edwards, p. 442.
I Op. cit., p. 442. § Cuvier, p. 795.
|| Cuvier, p. 795. {] Wolff, Dissertatio Anatomica, p. 19.

** Milne-Edwards, p. 442.

630 THE VALVULAR ACTION OF THE LARYNX.

cord. The true cord recurves at its free margin in such a
manner that with its fellow it could exert a valvular action
which would seem to be sufficient to prevent the exit of air,
and in the expiratory movement it vibrates with the impulse
of the passing air. Cuvier* has shown that there is neither
ventricle nor false cord to be found in the glottis of the
Bradypus.

Class JJJ—Man and the greater part of Ungulate mammals
are to be referred to this class, though others have the caver-
nous glottis which is embraced in the fourth and final division.

Here the vocal cords are not only well developed and possess
a free border more or less fine, while each is capable of
advancing to meet its fellow of the opposite side in the median
line, but there exists above the true cords a second pair of
analogous folds, less adapted to phonation, and between these
projections one recognises a fossa, bilocular but not communi-
cating with a sac or cavern. This structure is found in the
Carnivora for the greater part, but this group has many varia-
tions amongst its members. In the Dogt (Canis domesticus) the
larynx is very large. The true cords are well developed and-
broad. They are capable of being bulged to a considerable
extent when air distends the ventricles, which are very deep,
and ascend a considerable distance along the inner surface of
the thyroid. The false cords are neither strong nor prominent.
Wolfft testifies to the strength of the cords of this animal, and
mentions that the ventricle is deeper at its extremities than in
its middle part. Canis lupus.§§—The ventricles of Morgagni
are large and deep. In the different species of the Genus Felis
the false cords are very prominent and well detached from the
walls of the larynx. They are attached directly to the aryte-
noids, and at their point of juncture, under the epiglottis, they
form a small vault-like attachment. In the Lion|| the true
cords are neither so free nor their borders so trenchant as in
the Dog; they are, in fact, thick, and but slightly prominent.
The superior part of the larynx is dilated. There is no

* Tbid., p. 790. + Milne-Edwards, p. 445,
t Wolff, Dissertatio Anatomica, p. 10. § Op. cit., p. 10.
|| Milne-Edwards, p. 445.

COMPARATIVE ANATOMY OF THE LARYNX. 631

ventricle according to Wolff* In the Cat (Felis catus) the
larynx is small, and guarded by a long upper and pointed epi-
glottis. Anteriorly, the false cords are widely separated; they
are in structure very fine, instead of being thick as in the Lion;
the true cords touch at their anterior extremities. There are
no cartilages of Santorini.f

In the Tiger the arytenoids are much raised.

In the Hyenat (Hyena striata) the superior ligaments are
scarcely visible, and there is but a faintly-inmarked ventricle.

Plantigrada.—In the Bear§ both pairs of cords are so arranged
as to raise themselves nearly to the same level by their free
edges, and to direct towards the epiglottis the slit which forms
the entrance to the ventricles.

Cuvier|| says:—The posterior ligaments or true cords, which
are thick but very distinct, and which are attached to the
arytenoids, rise between the two anterior ligaments, which are
attached to the cuneiforms in such a manner that the four liga-
ments are upon the same level, and that the ventricles of the
glottis are simply two deep slits, open no longer towards the
-laryngeal cavity but facing the epiglottis. They bend inwards
very little between the epiglottis and the thyroid. The liga-
ments—or rather the external anterior—are little separated
from the epiglottis.

Wolff also adopts the terms external and internal for the
ligaments of the larynx as being topographically correct. He
mentions that, whilst the external are inserted into the cunei-
form cartilages, the internal are attached to the arytenoids. All
four are inserted into the root ef the epiglottis. (His examina-
tion was made upon a specimen of Ursus arctos).

The ventricle of the Ursus meles he found large and very deep.
The Hrinaceus Europeus** has only small superior cords,
though the ventricles are deep and sacculated.

* Dissertatio Anatomica, p. 9.

+ Wolff, Dissertatio Anatomica, p. 8.
ft Op. cit., p. 9.

§ Milne-Edwards, p. 446.

|| Anat. Comp., Tom. viii, p. 787.

{| Dissertatio Anatomica, p. 12.

** Op. cit., p. 15.

632 THE VALVULAR ACTION OF THE LARYNX.

The Coati* has a somewhat similar arrangement to the Bear,
but the Badgerf has ligaments of the usual position, the anterior
with a sharp margin, the posterior, however, being obtuse. The
ventricle is open and leads into a sac. The sound which this
animal emits is probably produced by the friction or impaction
which the air suffers against the posterior border of the anterior
cords and its division into these diverticula.

The Civett has a glottis like that of the Cat.

It results from the structure of the larynx in the genus of
the cat tribe, that it is chiefly the anterior ligaments which
must perform the functions of vocal cords. Their union towards
the epiglottis forming a little vault against which the air must
strike with force, favours this view.§

Movements of the false cords only become apparent in great
expiration and inspiration. In phonation they do not advance
in the manner of a platform above the true cords, but they
depress and apply themselves on the basal portion of these so
as almost entirely to efface the entry of the ventricle of the
larynx, and to limit the vibrations of the true cords to a certain
length.|| As the voice rises, these membranous folds cover pro-
gressively from without inwards the vocal cords.{

Pinnigrada.—The Seal** has an obtuse vocal cord which is
but slightly free. The anterior ligament blends with the base
of the epiglottis. The ventricle is superficial.

The Marmot has a very sharp margin of the anterior liga-
ment, more so, in fact, than that of the posterior.fT

Class IV may be regarded as containing animals which would
belong to the third class, had they not some “ cavernous”
character superadded, and also animals of a less perfect type.

The Llama has false and true cords, a ventricle, and a
common larynx, and therefore with the Camel (Camelus bactri-
anus) forms an exception to the usual Ruminant type. (The
latter animal has a trachea 3 feet in length, but very narrow;
its larynx is small and its voice proportionately weak.){{t

* Cuvier, p. 788. + Ibid.

t Lid. § Ibid., p. 787.

|| Milne-Edwards, p. 512. ¥ Tdid., p. 525.
** Thid., p. 788. tt Cuvier, p. 789.

It Dissertatio Anatomica, p. 23.

COMPARATIVE ANATOMY OF THE LARYNX. 633

In Solipedes* the vocal cords are narrow and situated deeply.
There are no false cords, and no ventricle properly speaking,
but a hole pierced in the lateral wall above the true cords con-
ducts into a large oblong sinus, hidden between the wall and
the thyroid, and covered, to a great extent, by the thyro-aryte-
noid muscles, which should be able to compress it.

This opening is large in the Horse,f but the cavity is not
very deep. Theref is also in this animal a triangular membrane
situated in the angle of the thyroid. This easily vibrates as it
rests upon the moving cords beneath it. The commencement
of the “hinny” is due to repeated shocks of expired air upon
this membrane.

In the Ass§ two sacs are situated above the attachment of
the cords. A tendinous membrane is also present. There is a
great deepening of the thyroid.

Cuvier || considers the larynx of the Mule more allied to that
of the mare, and speaks of Herrissant’s observations as inaccu-
rate, and as regards the triangular membrane of the horse’s and
ass’s larynx, exaggerated.

The Rhinoceros! has well-marked vocal cords and deep
ventricles, before each of which is a nearly vertical opening,
and it is at the bottom of this excavation that the anterior liga-
ments are attached.

In the Pig** the true cords are free and sharp. The superior
ligament is large and its margin rounded. The ventricle is
shallow, and from this opens an oblong sinus which rises up
between the mucous membrane and the thyroid, and is the size
of the end of the little finger...... (It is to be observed
that in many animals of this class, @¢., quick runners,}f the two
cartilages are arranged in such a manner as not to coaptate
completely, and so allow a space to remain free between them

* Cuvier, p. 793.
+ Ibid., p. 793.
I Herrissant, Récherches sur les Organs de la Voix, p. 282.
§ Op. cit., p. 285.
|| Cuvier, p. 793.
{ Op. cit., p. 791.
** Op. cit., p. 791.
tt Miine-Edwards, p. 455,

634 THE VALVULAR ACTION OF THE LARYNX,

when they are touching by their summits. It results from this,
that by the approximation of the true cords the glottis is not
closed, and that there remains always a passage for the air
behind the membranous part. Mr. Mandl thinks that this is
peculiar to the species which run rapidly.)

In the Howling Ape* (Mycetes) the hyoid is enormously de-
veloped in the form of a bell to lodge the air sacs peculiar to
this animal. There are also air sacs in the pharynx.

In Simia sabeat at the root of the epiglottis, and above the
ligaments, there is a transverse opening which leads to a mem-
branous sac situated between the thyroid cartilage and the
hyoid bone. In the walls of the sac the fibres are partly tendi-
nous and partly muscular.

In Simia parniscot there is a sac between the cricoid and
trachea. The trachea has continuous rings in some Simians.

If the view that the function of the false cords or ven-
tricular bands is to close the glottis during effort, and thus to
fix the thorax, we should expect them to be very strongly
developed in those animals whose habits render such fixation
likely to be serviceable; on the other hand, we should expect
them to be absent in those animals where fixation of the thorax
would be of little or no service; and this seems to be actually
the case. |

In animals whose motions are chiefly those of running, we
find the ventricular bands absent, or slightly developed. But
in animals where the anterior extremities are used for striking,
hugging, or climbing, the vocal cords are strongly developed.
We might at first expect also, that in cases where the anterior
extremities were employed for the purpose of prehension, we
would also find the ventricular bands developed. But this is
not always the case.

When engaged in any very delicate work where the least
oscillation of the hand might be injurious, we often hold our
breath, but for ordinary prehensile actions we do not close the
glottis, unless considerable effort is required at the same time.
In marsupials such as the kangaroo, the anterior extremities

* Op. cit., p. 448. et ae ¢ Tbid., p.1.
olff, p. 1.

RELATION OF LARYNX TO MOVEMENTS. 635

are used for holding food and conveying it to the mouth. We
might therefore expect that the false vocal cords would be
strongly developed. But the fore limbs are small and weak,
and very slight muscular effort is employed in the movements
just mentioned. The fact that in these animals the ventricular
bands are absent, is, therefore, very much what might have been
expected. In the solipedes they are also absent. In the pig
they are rounded; and there is a shallow ventricle in the
hedgehog. They are present, but small, in the llama, and in
the camel they are fairly well marked. In the dog the true
cords are well developed and broad; the ventricular bands are
not strong or prominent, but the ventricle of Morgagni is deep.
In the wolf the ventricle is also deep and large. In the lion
and tiger the ventricular bands are prominent and well detached
from the walls of the larynx, In the cat they are not large;
and they are very fine instead of being thick as in the lion. In
the three-toed sloth they are well developed. In the bear, in
which the closure of the glottis would require to be specially
strong, from its habit of climbing trees and destroying its
enemies by hugging, the arrangement of the ventricular bands
is very remarkable ; the vocal cords are capable of being raised
until they and the ventricular bands are nearly at the same
level, and the opening between them is directed towards the
epiglottis from which the false cords are but little separated.
During the closure of the glottis the cushion cf the epiglottis
will, therefore, to a considerable extent, be directed against the
opening of the ventricles, and the glottis will, we should think,
be closed with very great firmness.

We have, however, not seen any specimen of the larynx of
the bear, and these considerations are drawn only from the
description which we have read.

In the howling monkey the ventricular bands are well
developed.

Our own experiments were made upon the fresh larynx of
the sheep, of the dog, of the cat, of the ape, and of man.

The experiments were made by fixing a T-cannula in the
trachea below the larynx. The lower arm was connected with
a bellows, and the side branch with a water or mercurial

636 THE VALVULAR ACTION OF THE LARYNX.

manometer ; the arytenoid cartilages and the vocal cords were
then approximated, as well as the ventricular bands when these
were present. The strength of current which these structures
could resist in various positions, and during inspiration and
expiration, was estimated by the height at which the water or
mercury stood in the manometer. A curved needle was passed
through the bases of the arytenoids which were then coaptated
by means of a figure-of-eight ligature. In some experiments in
which the larynx possessed cords of such dimensions as to
admit of it, needles were passed through the thyroid cartilage,
one on either side of the middle line, and just external to the
anterior attachment of the false cords, and the points were
pushed backwards inside the edge of the false cord towards the
arytenoid cartilage. In this way, approximation of the cords
could be easily produced by movement (separation) of the eye
end of the needle. In smaller larynges, however, approxi-
mation was assisted by seizing the coaptated edges of the cords
with a pair of fine pointed curved forceps. Lateral pressure
was exercised by means of a weighted scale pan which was
connected with a movable concave surface of wood placed
externally over the line of attachment of the cord to the wall
of the larynx.

This was aided or substituted by manual pressure, and
manipulation was also resorted to in pushing the base of the
tongue with the epiglottis backwards over the larynx.

In the sheep the ventricular bands are absent. The follow-
ing figures represent the result of these experiments :—

RESISTANCE,
’ ti ws >,
In millimetres In inches
of mercury. of water.
Experiment 1 ....sesecece 4 2
3° Dido puccned 6 5 2°5
9° >, Rp eae SPP UE Se 8 4°25
Average about 5°5 3

On blowing upwards through the glottis, the true vocal cords
being closed (no false cords).
On sucking air downwards through the glottis, the resistance

~

*
ee ee ee eee © ee ae

OT —

vo —

EXPERIMENTS ON THE LARYNX. 637

rese to heights varying from 54 to 140 mm. of mercury, or from
about 28 to 724 inches of water.

In the cat the resistance to the exit of air from the larynx
presented by the true vocal cords alone is very small, generally
about 6 mm. of mercury. ?

When their approximation is aided by a lateral pressure
of 100 grammes, a resistance of 16 mm. of mercury may be
reached.

The ventricular bands in the cat are thin and easily coap-
tated, but they are not calculated to resist much pressure unless
they are supported: such support is afforded by the epiglottis,
if it is slightly pressed backwards, and the gentle lateral pressure
is made so as to coaptate the cords.

If firm pressure is applied in this way the resistance pre-
sented to the exit of air by the ventricular bands is very con-
siderable, and they may not yield even under pressure of from
24 to 40 mm. of mercury. To reach the latter figure, however,
considerable support from the base of the epiglottis and from
the lateral aspects of the larynx is required. When the true
cords are approximated, as well as the ventricular bands in the
cat, the epiglottis being at the same time slightly depressed and
gentle lateral pressure exerted, they easily resist a pressure of
30 mm. of mercury, or more.

The resistance to the ingress of air afforded by the true cords
alone, in the cat is very considerable ; when a lateral pressure
of 20 grammes is exerted so as to bring them together they
easily resist a suction power of 50 or 60 mm. of mercury, and
when the lateral pressure is increased they will resist consider-
ably greater suction than this.

The ventricular bands when ordinarily approximated will not
resist more than 2 or 3 mm. of mercury.

In such experiments as these there is not a little difficulty in
approximating the vocal cords so as to imitate their closure
during life. The lateral pressure exerted, the position of the
epiglottis in regard to the cords, the freshness of the larynx.
and many other circumstances modify the results obtained to a
very considerable extent. By way of example we may mention
that in eight measurements of the resistance offered by the

638 THE VALVULAR ACTION OF THE LARYNX.

approximation of true and false cords in the cat, at the same

time, variations from 30 to 60 mm. were registered. The
former figure is, however, the more exact, though, if there be a
slight increase of lateral pressure, and the epiglottis be pushed
gently backwards over the glottis, a pressure of 40 and 60 mm,
may be obtained.

The following figures in mm. of mercury may be taken as
representative of the results :—

BLowIne. Suction.
Aoe and True False us and True False
False alone. alone, False. alone, alone.
80-50 4-10 24-40 60-120 60-120 2-10

It appears from these figures that closure of the superior
cords did not increase the powerful resistance afforded by the
inferior to the ingress of air as represented by suction. A
quick, powerful suction (7.¢., inspiration) movement closes the
true cords, but this does not affect the false cords in the same
manner, nor does the negative pressure in the trachea extend
to them. The larynx again tends to pass downwards, and the
“telescoping” due on the one hand to the elevation of the
larynx, and on the other to the pressing backwards of the root
of the tongue and of the epiglottis with its supporting pad,
which occurs in efforts to vomit, is here entirely absent.

We could, however, imagine that the ventricle becoming dis-
tended in expiration after narrowing of the larynx by muscular
action and approximation of the false cords, the inferior might
themselves be closed by the pressure from above, and that thus
a slight measure of support might be afforded.

The false cords in the dog are inconspicuous and weak in
comparison with the broad well-developed true cords,

They offer almost no resistance to the ingress of air: 4 mm.
of mercury being the utmost, and this amount is only reached
when sticky mucus on the bands adds to the resistance.

The true cords, either alone or with the false cords, resist the
ingress of air with a force of 80 to 180 mm. of mercury.

The true cords alone offer a resistance of only about 9 mm. to

the exit of air.

CLOSURE OF GLOTTIS BY VENTRICULAR BANDS. 639

The ventricular bands alone offer 18°5 mm., and this may be
increased to 60 mm. if the glosso-epiglottidean sulcus be
thoroughly distended ; and the true and false together, 21 mm.

The relatively high pressure of the true and false cords
together was accompanied by a bulging upwards of the glosso-
epiglottidean sulcus. It is possible that the inflation of the
ventricle tends also to push the true cords together, and that
thus they aid, to a slight extent, in closing the glottis during
expiration. |

The larynges examined were those of small dogs.

In the ape, when the ventricular bands alone are approxi-
mated, inflation of the ventricles is well marked at the bases of
the bands. It is distinctly seen in this animal that powerful
expulsion of air, and especially sudden expulsion, tends to close
the ventricular bands, and this strongly confirms the views
already expressed in regard to the function of these structures,

A sudden inspiratory effort when both true and false cords,
or when the true cords alone, are approximated, is seen to cause
the lateral fosse to sink considerably downwards, and the
resistance to the ingress of air which they afford is very great :
being equal to 75 mm. of mercury and more.

When the ventricular bands alone are approximated, their
power of resistance is very small, unless they are firmly coap-
tated, when they present considerable resistance to the ingress
of air. But it is very improbable that in the living larynx
they can be pressed together in this way; and their functions,
therefore, are evidently very different from that of the true
cords, in which the simple occurrence of a rapid inspiratory
movement, when the true cords are approximated, effectually
closes the glottis.

Ovp Wortp APE (Small Specimen).

PRESSURE. Suction.
rae closed True False Trae closed True False
and False. closed, closed. and False. closed, closed.
30 mm. 2-5 m. 24 m. 70-140 70-140 2-4,

Only two specimens of the human larynx were examined.

640 THE VALVULAR ACTION OF THE LARYNX.

The ventricular bands alone afforded a resistance of 30:0 mm.
when gentle lateral pressure was employed. Whilst blowing
air from below, a slight telescoping, by pressing the base of the
tongue and the epiglottis backwards, being permitted, a bulging
upwards of the hyoid fossa and the root of the ventricle under-
neath the attachment of the ventricular bands could be dis-
tinctly seen. When firm lateral pressure was associated with
this movement a much higher pressure was resisted. The
ventricular bands alone, when not forcibly held together, pre-
sented no resistance whatever to inspiration—in fact, they
separated even when the true cords were in contact, and resist
ing a powerful suction.

The true cords alone resist the ingress of air quite as much
as when the ventricular bands also are approximated. The
resistance is very great, and sometimes reaches 140 mm. of
mercury, and even more—in fact, suction of greater power than
we could employ failed to separate them, but rather tended to
increase their resistance.

Closure of the glottis is so important a factor in the act of
vomiting, that we must now consider how far the development
of the false vocal cords in different classes of animals is asso-
ciated with the easy and perfect performance of the act.

We find that in Ruminants generally true vomiting is either
difficult or impossible. The same is the case with the Solipedes
and the Rodentia, while in the cat and dog it is performed most
effectually. There is no doubt, in the act of vomiting, another
factor than that of simple increase in intra-thoracic, or, more
accurately, intra-tracheal pressure, for however greatly this
pressure be increased, as in coughing, defecation, or parturition,
vomiting does not occur unless the cardiac extremity of the
cesophagus be dilated. One explanation of the difficulty with
which vomiting occurs in horses, for example, is that the
cesophagus passes a considerable way below the pillars of the
diaphragm, and that thus the fibres which radiate from it on to
the stomach tend to exert rather a longitudinal than a lateral
action, and to pull the cesophagus down, or the stomach up,
rather than to dilate the orifice. This explanation may, to a
cousiderable extent, be correct, but we think that the other

ee

Aletta a a

EFFECT OF VOMITING. 641

factor, viz., the want of true vocal cords, and the consequent
difficulty of greatly increasing the intra-thoracic pressure, is
also a factor which ought not to be entirely disregarded. We
have made some experiments on the intra-thoracic pressure in
vomiting ; these were performed by narcotizing an animal with
ether, passing the arms of a T-shaped cannula upwards and

Fie. 216.—Cuart A.—Retching movements of cat, showing sustained intra.
tracheal pressure of 12°5 mm. mercury.

Fig. 217.—Cuart B.—Vomiting movements of same, showing resistance to
intra-tracheal pressure yielding at x to 31 mm. mercury,

downwards into the trachea, the cross-limb of which was con-
nected with a manometer. Sulphate of zinc was then injected
into the stomach, and the action of the anesthetic was
diminished to the same point as in surgical operations where
vomiting occurs before the return of consciousness. The results
will be seen from the portions of the curves which were obtained
and which we here append.

The middle curve was merely of retching.

The secondary waves arise from mercurial oscillation.

By the same kind of experiment it was proved that vomiting
was still possible when the projecting arm of the T-cannula was
unconnected with the manometer, and left open, but in this

case vomiting occurred with much greater difficulty than when

2 T
\

642 THE VALVULAR ACTION OF THE LARYNX.

the resistance of the mercurial column was brought to bear in
closing the trachea, and thus permitting the cords to resist the
pressure favourable to this action.

CONCLUSIONS.

Our experiments completely confirm those of Dr. Wyllie.
The ingress of air into the glottis is prevented by approxima-
tion of the true vocal cords, but these have very little power to
prevent its egress. The false cords or ventricular bands, on the
contrary, have very little power to prevent the ingress of air
into the lungs; but when the edges are brought together they
act as valves and offer great resistance to the egress of air: they
are, therefore, to be regarded as the chief factors in the closure
of the glottis during exertion...

Although our data are insufficient to enable us to speak with
certainty, so far as they go, they appear to show that, in such
animals as do not require to have the thorax fixed, ventricular
bands are rudimentary or absent: that in those animals where
fixation of the thorax is advantageous for giving greater
precision or force to the movements of the anterior limbs in
striking, climbing, or hugging, the ventricular bands are well
developed. This condition is seen in the cat, lion, sloth, bear,
ape,andman. =,

Though the power of any species of animal to vomit is not
entirely dependent on the presence of the false cords, yet, when
present, their action in closing the glottis is an important factor
in the act of vomiting.

See, for description of larynges referred to, the following
authors, from the works of some of whom we have translated
largely :-—

Milne-Edwards, Legons sur la Physiologie et 1 Anatomie Comparée
del Homme et des Animaux, xii, pp. 422 et seq.

Cuvier, Anatomie Comparee, viii, pp. 772 et seq.

Wolff, Dissertatio Anatomica de Organo Vocis Mammalium.

Herrisant, Récherches sur les Organs de la Voix.

Cyclopedia of Anat. and Phys., vol. iv, pt. ii., “ Voice.”

Turner, “ Balenoptera Sibbaldii,” Trans. Roy. Soc. Ed., xxvi.

Watson & Young, “Anatomy of Northern Beluga,” Trans. Roy.
Soc. Hd., vol. xxix.

te ee See

APPENDIX,

EXPERIMENTAL INVESTIGATION OF THE
ACTION OF MEDICINES.

V.—RESPIRATION.
- (Reprinted from the British Medical Journal, January 2, 1875.)

[This Lecture ought to have followed on at the end of Lecture IV on p. 322,

but it was accidentally omitted and the omission was not discovered until

-the whole of this book had been printed off, and it was consequently
impossible to insert the Lecture in its proper place. ]

Respiration in Unicellular Organisms ; in the Cells composing higher Organisms.
—Distinction between Respiration in an Amoeba and a Fixed Cell.—In-
ternal Respiration.—External Respiration.—Internal Respiration may be
diminished or arrested by Diminution or Arrest of the Circulation generally
or locally.—Pathology of Fatty Degeneration, by lessening or destroying the
power of Hemoglobin to act as an Oxygen-carrier. (a) Action of Carbonic
Oxide; (4) Action of Nitrites ; Action of Phosphorus.—Examination of the
effect of Drugs on Hemoglobin.—Colour.—Spectrum—Reducing Agents.
—Absorption of Oxygen.—Action of Carbonic Oxide.—Ozonising Power of
Blood.—Formation of Acid in Blood.—External Respiration.—Respiratory
Movements.—Respiratory Nervous Centre; Excitants to this Centre.—
Venosity of Blood.—Dyspnea.—-Apnea: two opposite meanings of this
term.—Effect of temperature on this Centre.—Effect of Drugs: Tartar
Emetic, Chloral, Opium.

THERE is a great deal of truth in the oft-repeated comparison
between an animal body and a steam-engine. In both, the
motion which is their characteristic function is kept up by
combustion, and for combustion there is necessary a free
supply of fuel and a free supply of oxygen. Simple organisms,
such as the ameba, which consists of a single cell or minute
mass of protoplasm only, derive their oxygen, as well as their
nutriment, from the fluid in which they swim, and the
individual cells which compose the tissues of the higher
animals are nourished in much the same way. As Bernard
strikingly puts it, “we do not live in air” any more than a
number of amcebz swimming about in a glass of water live
272

644 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

in air. The cells of which our bodies are composed live, like
the amcebe, in a fluid—the intercellular fluid or lymph in
which they are bathed; and our skin may be compared to the
glass in which the amcebe and the water in which they swim
are contained. There is, however, a very great difference
between the amceba and the cells composing the bodies of the
higher animals, for it can swim about freely, whereas they
are for the most part fixed. The ameeba can thus obtain fresh
supplies of nutriment and oxygen by moving through the
water in which it lives, while in higher organisms the fluid
moves over the cells. This fluid, or lymph, is the liquor
sanguinis, which passes out of the capillaries and supplies
all the tissues with nutriment and oxygen, at the same time
that it removes from the system carbonic acid and the pro-
ducts of tissue-waste.

The interchange of oxygen and carbonic acid between the
tissues and the blood is termed internal respiration.

But this interchange would soon remove all the oxygen —

from the blood and load it with carbonic acid, unless it had
some means of absorbing oxygen and giving off carbonic acid
to the atmosphere. This is effected in the lungs, and the
interchange of gases between the blood and external air is
termed external respiration.

The blood, therefore, acts as an oxygen-carrier between the
lungs and the tissues. A certain amount of the oxygen taken
up by the blood is simply dissolved in it; but the amount
of this is not sufficient to supply the wants of the tissues, and
the greater part of the oxygen which they require is carried
to them by means of the hemoglobin, or colouring matter of
the blood. This substance forms a loose compound with
oxygen in the lungs, and gives it off to the tissues when it
reaches the capillaries, and on again passing through the
lungs it takes up a fresh supply. The carbonic acid which is
formed in the tissues by their oxidation is taken up by the
blood in the capillaries and given off in the lungs; but it
seems to be carried from the tissues to the lungs, not by the
heemoglobin, but by some one or other of the salts in the blood.
Both internal and external respiration are essential for the

ee ee ee a

APPENDIX—RESPIRATION IN CELLS. 645

maintenance of life, and it may be destroyed by putting a stop
to either one or other of them.

1. Internal respiration may be completely stopped by pre-
venting supplies of fresh blood from reaching the tissues.
The stoppage may be general or local. General stoppage of
internal respiration is produced by arresting the circulation in
the whole body, by stopping the action of the heart, or
obstructir g the flow of blood through the large vascular trunks
which are connected with it. Internal respiration may be
arrested locally in any part of the body by compressing or
tying either its arteries or veins. Thus, if the arteries going
to the head be tied, so that no fresh blood can reach it, or the
veins coming from it be ligatured, so that the deoxygenated
blood cannot leave it, the blood which is present in the
capillaries of the brain loses all its oxygen and becomes
charged with carbonic acid. The nervous centres are thus
effectually suffocated, although the lungs may be working
vigorously, and the blood in the rest of the body may be
richly arterialised. That the loss of function which follows
stoppage of circulation in a part is due to the want of the
oxygen carried to it by the blood, rather than to the want of
nutriment, is well shown by the experiment of Kronecker,
who found that contractility could be restored to the excised
gastrocnemius muscle of a frog, after exhaustion by repeated
contractions, by passing through its vessels a solution of per-
manganate of potash, which supplied oxygen to the interior of
the muscle, but conveyed to it no nutrient matter.

When the circulation is diminished but not completely
arrested, as, for example, by weakening the heart, or by
contracting without obliterating the lumen of the blood-vessels,
or when the oxidising power of the blood is impaired, internal
respiration will be diminished, but not stopped.

The tissues, or at any rate the albuminous tissues, in all
probability do not undergo combustion directly, ie, the
albumen does not combine at once with oxygen. It is first split
up by the action of a ferment into (1) nitrogenous substances,
which, after being oxidised, form urea, and (2) non-nitrogenous
substances, such as fat, and probably also glycogen. When

—

646 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

internal respiration is imperfect, the nitrogenous substances
may not be oxidised, and appear in the urine instead of being
converted into urea. The non-nitrogenous substances may
also continue unoxidised, and, instead of being converted into
carbonic acid, remain in the tissues as fat, giving rise to fatty
infiltration or fatty degeneration. This is seen in the heart
when the size of the coronary arteries is diminished by
atheroma. The supply of blood being insufficient to keep up
perfect combustion in the muscular fibres, the non-nitrogenous
products of decomposition accumulate and cause the heart to
become fatty.

When there is little hemoglobin in the blood, as in anemia,
internal respiration is diminished, and there may frequently
be noticed a tendency to the deposit of fat in anemic girls.
The peasantry in some parts of Germany are acquainted with
this fact, and bleed their cows so as to induce an artificial
anzemia whenever they wish to fatten them.

2. Internal respiration may be arrested by the action of
substances which deprive hemoglobin of its power to take up
and give off oxygen easily, and thus render it useless as an
oxygen-carrier. a. Certain gases—for example, carbonic oxide
and nitric oxide—do this by driving out the oxygen from its
combination with hemoglobin, and forming compounds with
it themselves. These compounds resemble those with oxygen,
but are more stable, and are not decomposed during the

passage of the blood through the capillaries, nor by the action _

of reducing agents added to the blood, as oxyhzmoglobin is.
b. The oxygen-carrying power of hemoglobin has been shown
by Dr. Arthur Gamgee to be also destroyed by nitrites, but
in a different way. Instead of driving out the oxygen from
its combination with hemoglobin, the nitrites combine with
the oxyhemoglobin, and as it were lock up the oxygen in it,
so that the oxygen no longer separates from the hemoglobin
when the compound is placed in a vacuum, nor can it be
driven out by the action of carbonic oxide. At the same time,
the blood which has been acted on by nitrites is deprived of
its power of absorbing any more oxygen. But, although the
nitrites lock up the oxygen in oxyhemoglobin so firmly that

' q
4
:

APPENDIX—RESPIRATORY CHANGES IN BLOOD. 647

it cannot be driven out by carbonic oxide, they do not prevent
its removal by reducing agents. These first break up the
nitrite compound, and then deoxidise the hemoglobin ; and
when this is next exposed to air, it takes up oxygen in the
normal way. On this account, the action of nitrites in
impeding or arresting internal respiration is only transitory ;
for, when the blood on which they have acted once becomes
deoxidised during its passage through the capillaries, it is
restored to its normal condition. The action of carbonic
oxide, on the contrary, is permanent, the blood with which
it has combined remaining unaltered during its circulation
either through the body or the lungs; and, if the greatest part
of the hemoglobin have been acted upon, life can only be
saved by the transfusion of fresh blood into the vessels,
although, in slighter cases, a fatal issue may be averted by the
dilig nt use of artificial respiration. Internal respiration is
also diminished by phosphorus; and the fatty degeneration
produced by this substance has been shown by Voit and
Bauer to be partly due to this action. It is not due to this
alone, however, for the phosphorus has a double action: 1. It
causes the albuminous tissues to split up more rapidly;
2. It lessens the combustion of the products of decomposition.
The increased rapidity of albuminous decomposition causes
more urea to appear in the urine; and, if the nitrogenous
compounds be not sufficiently oxidised, leucin and tyrosine
may appear instead of urea. Fat is also formed from albumen
more rapidly, as well as more slowly oxidised, than in the
normal condition.

In order to ascertain whether the hemoglobin of the blood
has been altered by the action of a drug: 1. If it be poisonous,
examine the blood from the arteries and veins of an animal
which has been poisoned by it, and note whether its colour
is normal in both sets of vessels or not. 2. Dilute a portion
of this blood with water, examine it with the spectroscope, and
see what. spectrum it presents. Shake it with air, and observe
if the bands of oxyhzemoglobin alone are present, and if they
are of their normal intensity and in their normal place. Take
another portion of the diluted blood and add to it a deoxidis-

-

648 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

ing solution, such as sulphide of ammonium or Stokes’s fiuid,*
and see if the spectrum of reduced hemoglobin appears.
3. Take two portions of normal blood, or of a solution of
hemoglobin, and add to one of them the drug to be tested,
or pass it through, if it be a gas. Note, as before, whether
any change is produced in the colour or spectrum, or in its
behaviour to oxygen or reducing agents. 4. Take two equal
portions of diluted blood or solution of hemoglobin in small
test-tubes, shake them with air till they are thoroughly
oxygenated, and add to one of them the drug to be tested.
Then add to each an equal quantity of deoxidising solution.
Let the test-tubes be full, and cork them so as to exclude the
solutions from contact with air. Note the length of time
which elapses before the spectrum of oxyhemoglobin dis-
appears and is replaced by that of reduced hemoglobin in each,
5. Take two equal portions of normal blood, and act on one
of them with the drug. Bring them into contact with equal
portions of oxygen or air, and let them remain so for some
time. Then ascertain how much oxygen has been absorbed
and how much carbonic acid has been evolved by each, by
seeing whether any alteration has taken place in the volume
of the gas, and by analysing it in order to determine its com-
position. 6. Act on a portion of normal blood with the drug;
arterialise it completely, and then determine the amount of
each gas which it contains by extracting them by means of
warmth and a vacuum, and analysing the mixture thus
obtained. 7. Oxygenate a portion of blood thoroughly, act on
it by the drug, and then ascertain whether the oxygen can be
driven out by carbonic oxide. To describe the methods of
gas-analysis would occupy more space than can be devoted
to it here; and I must, therefore, refer to Bunsen’s or Frank-
land’s text-books on the subject, or to Sanderson’s Handbook
for the Physiological Laboratory ; for an excellent example of
the mode of ascertaining the action of a drug on the blood,
to Dr. Gamgee’s paper on the Action of Nitrites in the

* Stokes’s fluid consists of a solution of protosulphate of iron, to which is

added a sufficient quantity of tartaric acid to prevent precipitation, and then as
much ammonia as will render it decidedly alkaline.

q

APPENDIX—ACTION OF DRUGS ON OXIDATION. 649

Philosophical Transactions of the Royal Society for 1858,
pp. 589-625; and to Dr. Harley’s paper on the Action of
Alkaloids, etc., in the Zransactions for 1864, p. 687.

The object of adding the drug to the blood before arterial-
ising, as in 6, and after arterialising, as in 7, is to discover
whether it prevents the blood from taking up oxygen in the
former experiment, or of giving it off in the latter. Normal
blood has the power to produce ozone, or to withdraw it from
substances which contain it, and transfer it to others which
are easily oxidised. Arterial respiration may be modified, and
the process of oxidation diminished, by the action of certain
substances which deprive blood of this power. The usual test
for ozone is fresh tincture of guaiac (1 part guaiac to 6 of
alcohol), which is oxidised by it with extreme rapidity. It
shows the progress of the oxidising process with great dis-
tinctness by the blue colour which it assumes. A few drops
of tincture of guaiac are put upon a piece of porous paper,
allowed to become almost quite dry, and a drop of blood or
solution of hemoglobin is then placed on it. In a few minutes,
the drop becomes surrounded by a blue ring from the forma-
tion of ozone and the oxidation of the guaiac in its neighbour-
hood. The formation of ozone is independent of the oxygen
contained in the hemoglobin ; and carbonic-oxide-hemoglobin
will produce it as well as oxyhzmoglobin, provided air be
present. When the hemoglobin itself contains oxygen in the
form of oxyhzemoglobin, the presence of air is not necessary
to the reaction. The oxidation of guaiac by means of blood
alone is, however, not nearly so easily observed as when
another substance containing ozone is added to it, such as
peroxide of hydrogen or oil of turpentine which has been kept
for some time. The hemoglobin takes the ozone from these
substances, and yields it up again to the guaiac.

The method adopted by Binz, in order to test the influence
of drugs on this ozonising power of hemoglobin, is to take a
mixture of tincture of guaiac with a few drops of ozonised oil
of turpentine, and divide it into two parts. A few drops of
a solution of the drug to be tested is added to one of them,
and a few drops of solution of hemoglobin then dropped into

~

650 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

both. If the drug increase the oxidising power of the
hemoglobin, the solution containing it will become blue more
quickly than the other, but more slowly if the oxidising power
be diminished.

Another process more simple than that of analysing the
gases of the blood has been used by him and his scholars
Zuntz and Schultz, in their observations on the effect of drugs
on oxidation in the blood. This process is based on the fact,
noticed by Zuntz, that, immediately after blood has been
drawn from the body, an acid begins to form in it, so that its
normal alkalinity goes on decreasing. The formation of acid
is most abundant during the first few minutes after the blood
has been drawn, and before coagulation has taken place, so
that Zuntz considers it a vital phenomenon ; but it continues,
though in a less degree, till putrefaction commences. They
take the rapidity with which acid is formed as an index of
the rapidity with which oxidation takes place in the blood;
and, when they find that.the addition of a drug to the blood
has diminished the formation of acid in it, they consider that
the drug has diminished oxidation in the same proportion.
The following method is the one which they employ :—Three
equal portions of the same blood, of fifty cubic centimetres each,
_are measured out. The alkalinity of the first portion is then.
determined at once. To a second portion, the drug to be
tested is added. The solution of the drug must be neutral; or,
if it be acid, the amount of its acidity must be determined
and allowed for in the final calculations. To the third portion,
nothing is added. The second and third portions are then.
kept for one or two hours at a temperature of about 40° C.
They are then allowed to cool, and the alkalinity of both
portions is determined. If acid have been formed in either
of these portions during this time, the alkalinity will of course.
be less than that of the first portion, and the amount of acid
formed is estimated by the diminution which the alkalinity
has undergone. The alkalinity is ascertained by noting what
quantity of a standard solution of phosphoric acid must be
added to the blood before it begins to give a red colour to.
blue litmus paper. But, if phosphoric acid were used alone,

APPENDIX—-EXTERNAL RESPIRATION. 651

the red colouring matter of the blood would be apt to stain
the litmus paper, and it would be almost impossible to say
when the reddening was due to it, and when to free acid. In
order to prevent this, a quantity of chloride of sodium is
added to the acid. The salt prevents the corpuscles from
being dissolved, and the hemoglobin from disturbing the
reaction. The acid and salt are gradually added to the blood,
and the reaction tested from time to time by putting a drop
of the blood on a piece of fine satin paper coloured with litmus.
The paper should be first moistened with a tolerably strong
salt solution, the drop of blood allowed to remain on it for
a few seconds, and then wiped off with blotting paper. The
point of saturation is held by Schulte, who has also employed
this process, to be reached whenever the blue litmus paper
becomes distinctly reddened, even though the red colour
should disappear again immediately. This transient reddening
is due to carbonic acid; and Schulte prefers it to the first
permanent reddening, because it can be more easily observed.
This does not give the absolute amount of alkalinity ; but all
that is wanted is the comparative alkalinity of the three
portions, and this is got accurately enough if they be all
treated in the same manner as regards temperature, shaking,
etc. In this way, Zuntz, Scharrenbreich, and Schulte, find
that quinine lessens oxidation in the blood, and Binz finds that
it does the same in a solution of hemoglobin.

External respiration, or the interchange of gases between
the blood and the atmosphere, takes place whenever they come
into sufficiently close relation with one another, as they do in
the capillaries of the skin, intestinal canal, or lungs. In the
frog, respiration is carried on by the skin to such an extent,
that it can live for a considerable time after the lungs have
been excised; but in mammalia respiration is carried on
almost entirely by these organs, and any interference with
their function quickly puts an end to the life of the animal.
In order that the blood which circulates through the body
may get rid of its carbonic acid and take up oxygen sufficient
for the wants of the tissues, fresh portions of it must con-
stantly be brought into contact with the air, and therefore

652 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

it must constantly circulate through the pulmonary capillaries.
But the air in the lungs would soon become saturated with
carbonic acid and deprived of its oxygen by the blood which
comes into contact with it, and all farther diffusion would be
arrested, unless it also were constantly renewed. This is
effected by the respiratory movements. These consist in the
alternate enlargement and diminution of the thoracic cavity,
after the fashion of a pair of bellows, by the motion of its
walls and of the diaphragm. These movements are kept up
in a rhythmical manner by a nervous centre, situated in the
medulla oblongata and upper part of the spinal cord, which
sends off periodic motor impulses to the diaphragm and
inspiratory muscles. When the breathing is quiet, expiration
is usually a passive act performed by the elasticity of the
lungs and ribs, and by the weight of the thoracic walls. But
when it becomes excited, active expiratory muscles are brought
into action, and they receive their motor impulses from the
respiratory centre alternately with those of inspiration. It
is probable, though not certain, that the respiratory centre
is not a mere reflex apparatus, which simply transmits im-
pressions which it receives from sensory nerves to motor ones ;
for its activity continues, although its connections with
sensory nerves be almost entirely destroyed. The periodic
impulses which it imparts to the motor nerves of the respira-
tory muscles are not due to its being periodically excited by
impressions from afferent nerves, but to its being constantly
excited by the venosity of the blood circulating in it ; while
some resistance within itself prevents the excitation from
being constantly transmitted to motor nerves, and only allows
it to be so at periodical intervals.

The venosity of the blood consists in the absence of oxygen
and the presence of carbonic acid, and it is not certain whether
or not both of these act as excitants to the respiratory centre;
but it seems not improbable that the presence of carbonic

acid is the excitant, while the amount of oxygen simply alters

the excitability of the centre. According to this view, when
there is much oxygen in the blood, the excitability of the
centre will be slight, and little affected by any irritant applied

APPENDIX—APN@A AND DYSPNCA. 653

to it, whether this be carbonic acid or anything else. When
the amount of oxygen in the blood is small, the centre will be
very excitable and easily affected by any irritant. In venous
blood, there is both little oxygen and much carbonic acid, so
the centre is both rendered more sensitive, and is more
strongly excited by the acid. The more venous the blood, the
greater is the excitation of the respiratory centre, and the
more active the respiratory movements. When other
interfering circumstances are excluded, it would appear that
greater excitement of the respiratory centre causes the respira-
tions to become quicker, and, at the same time, deeper. This
excited respiration is termed dyspnea, and it occurs when the
blood becomes venous in the respiratory centre. As the
venosity increases, the ordinary muscles of respiration are no
longer employed alone, but the expiratory and accessory
muscles are called into play; and, lastly, all the muscles of
the body are affected by clonic convulsive movements, called
asphyxial convulsions.

When the blood which circulates in the respiratory centre
is not at all venous but is perfectly arterialised, as it is when
artificial respiration is vigorously performed, the centre is both
rendered less sensitive, and the irritant, viz., the carbonic acid,
is at the same time diminished or removed, the centre is not
excited at all, and respiratory movements cease.

This condition, in which no desire for respiration is felt, and
respiratory movements cease, is termed “apncea” by German
writers, and it must be carefully distinguished from the
“apnea” of English authors, which is simply extremely great
dyspnoea; so great, that the blood is hardly aérated at all.

The activity of the respiratory movements and the amount
of air respired in a given time, depend on the degree of
excitement of the respiratory centre. As we have just seen,
this excitement depends on two factors: 1. The excitability
of the centre; and 2. The amount of irritation applied to it.
In general, the venosity of the blood determines both factors,
and it is not the venosity of the blood in the general circula-
tion which does this, but only of that blood which courses
through the vessels of the medulla. This was shown by

654 EXPERIMENTAL INVESTIGATION OF THE ACTION OF MEDICINES.

Hering,* who passed a stream of arterialised blood through the
vessels of the head while venous blood was circulating in
those of the body. The respiratory movements then ceased
exactly in the same way as if the whole blood in the body had
been perfectly oxygenated. When he reversed these condi-
tions, and passed arterialised blood through the body and
venous blood through the head, asphyxial convulsions took
place. This shows that the degree of activity of the respira-
tory centre in the medulla oblongata depends on the greater
or less venosity of the blood circulating through it, and not on
an irritating action exerted by venous blood on the ends of
afferent nerves in the lungs, or other viscera.

The excitability of the respiratory centre may be greatly
modified: 1. By the temperature of blood in it; 2. By the
action of drugs upon it. When the blood becomes warmer,
the excitability of the respiratory centre is greatly increased ;
the movements of respiration become much more vigorous,
and it is no longer possible, by the most active artificial
respiration, to produce a state of apnoea. Certain drugs, as
tartar emetic, or apomorphia, when injected into the veins
also prevent the production of apnoea, but whether they do so
by increasing the excitability of the centre, or by acting as
irritants to it, is uncertain.

Other drugs, such as chloral, greatly diminish the excit-
ability of the respiratory centre, so that the respirations

* The request of a correspondent for a reference to Hering’s experiments has,
fortunately, directed my attention to a mistake of some importance in this lecture.
I stated that Hering found that respiratory movements ceased when arterialised
blood was passed through the head and venous blood through the body; while,
on the contrary, asphyxial convulsions took place when venous blood was passed
through the head and arterial blood through the body. I ought to have said that
movements occurred in the blood-vessels such as woul! have taken place had the
same sort of blood which circulated through the brain been passing also through

the body. The experiments, however, were made on curarised animals, so that — _

respiratory movements were impossible. Hering had previously ascertained that
the arterial movements were synchronous with the respiratory movements, and
might, indeed, be regarded as caused by impulses proceeding from the respiratory
centre. They might thus serve as indications of the condition of the centre,
where respiratory movements had been paralysed by curara. This paper is to
be found in the Wiener Acad. Sitzungsber., Math.-naturw. Classe, vol. 1x,
abth. 2, pp. 829—856.

APPENDIX—APNGA AND DYSPNCGA. 655

become fewer, notwithstanding the increase of carbonic acid in
the blood to which their diminution gives rise, and if the dose
be large they may stop altogether. Apnoea may also be
produced by means of artificial respiration with great ease
after their administration, and it may last so long, that one
is sometimes inclined to think that the animal is not going to
breathe again at all.

rN

637

INDEX.

AnpomeEN, the, in relation to Posture and
Bodily Temperature, 532.

Abdominal Vesse!s, Dilatation of, due to
Shoek, 432.

—Viscera and Genita!s, Shock induced by
Injuries to, external or internal,
394-401, 407.

Accelerating ganglia in the Heart, 314.

—Nerves of the Heart,

—Investigations on, of von Bezold, 11.

—Stimulation of, a cause of Palpita-
tion, 421.

Acid. formation of, in Blood, 652-3.

Aconitia, action of, on the Inhibitory
ganglia of the Heart, 314.

Action of

—Carbenic Oxide and Nitric Oxide on
Internal Respiration, 646.

—Digitalis on Blood Pressure in the
Arteries, tables, 103 e¢ seq.

—on the Blood Vessels, (with A. B. Meyer,
M.D.), 141.

— Experiments on

—Kymographion employed

144, 1467.
Results and conclusions, 145-6,
—Diuretic, (with Henry Power,
F.R.C.S.), 412,

—Joint, of Drugs, On the Apparent Pro-
duction of a New Effect by,
within the Animal Organ-
ism, 390.

~—Medicines, Experimental Investigation of,
220 and Appendix.

-Nitrite of Amyl, on the Circulation, On
the, [and on Active Dilatation
and Contraction of Arterioles
independently of Nerve-
Centres |, 174.

—Nitrites on Hemoglobin, 646-7.

—Physiological of the Bark of Erythro-
phleum Guinense (Casca, Cassa,
or Sassy Bark), with W. Pye,
M.R.C.8.), 458, 481.

—of Condurango, 340.

—of Nitro-Glycerine, Preliminary Notes
on, (with KE. S. Tait), 474.

—Phosphorus on Internal Respiration and
Fatty Degeneration, 647.

in, 141,

M.B.,

Action of

—Strychnia on the Heart, On the Ixplana-
tion of Stannius’s Experiment,
and on, (with Theodore Cash,
M.D.), 557.

—the Mode of, and of Other Remedies,
On the Pathology of Night-
Sweating in Phthisis and, 545.

—Vagus, see Vagus.

Actions and Use of Certain Remedies
Employed in Bronchitis and
Phthisis, 562.

Active, or Arterial Congestion, 439, 453.

~when it becomes Inflammation, 447, 454.

Administration of Drugs in Investigations
on Animals, 249.

Africa, West, use of Calabar Bean in, and
Casca Bark, 462-3, 481.

Air, (see also cold Air), ingress and egress
of, how controlled in the
Glottis, 642.

Albuminuria and Anuria induced by
Digitalis, 413.

Albumoses, formation of, 26.

Alkalies in Diabetes, action of, 426.

Alkaloids, alteration of their Physiological
Action by union with other
specified bodies, (Crum Brown
and Fraser), 390.

Alum, probable action of, in relief of
Vomiting, 571.

American posture of Legs, 531, probable
reason for, 535.

Ammonia, see also Smelling Salts.

—elfect of, on a Rabbit.

—(a) w hen nasally inhaled, 327, 407,
436.

—(b) when Bre aad inhaled, (Kno!l),

327.

—(c) when injected, (Funke), 327.

Ameeba, the, Respiration in, 645.

Amputation, Death from Shock induced
by, 398.

Amyloxyds, Salpetrig-sauren, Ueber die
Wirkung des, auf den Blut-
strom, 154, for detailed sub-
heads see under Salpetrig-
Sauren Amyloxyds.

Amyl, see Nitrite of Amyl.

2U

658

Anezmic Persons, Cause of Palpitation of
the Heart in, 422.

Anesthesia, induction and maintenance
of, in Animals, 337-9.

—temporary, producible by compressing
the Carotids, (Waller), 403.

Anatomical Classification of Laryngeal
variations proposed by Milne-
Edwards, 627 et seq.

Anemones, effects similar to those of In-
flammation produced in, by
irritation, (Hollis), 441.

Aneurism, effect of Nitrite of Amyl in
cases of, 139.

Angina Pectoris,

-—causes of, 16, 17, a) enner, and oi: 19,
(Brunton), 370.

-defined by Walshe, 137, 191.

-—two classes of, ib.

--effect of, on the Pulse and Arterial
tension, 189-40.

—Pathology of, 191-2.

-—as defined by Walshe, 191.

-—as divided by Friedrich and others, 7d.

-—views of Eichwald on, 191.

-Pulmonary and Systemic Capillaries in,
Effect on, of Nitrite of Amy]l,
ill., 370-3.

—Pulse-tracings in, 195.

—Symptoms during, (Nothnagel), 192.

-Treatment of, rationale of various
methods of, 20 ef seq.

— Bleeding, 138, 140, 185 et seg., 191.

—Nitrite of Amy], 187, 185,
used, 175.

—salpetrig-saures Amyloxyd weshalb
gebraucht, 155.

—-Stimulants, 187, 191.

Animal Blood, Transfusion of, into Man,
objections disposed of, 385-7.

—Heat, manner in which kept up, (Lud-
wig and others), 11 e¢ seq.

-Organism, the, On the Apparent Pro-
duction of a New Effect by
the Joint Action of Drugs
within, 390.

Animals, see also under names.

-action on, of Casca Bark, (Santos), 463,
(Brunton and Pye), 463-4,
(Santos, and Liebreich), 483
et seq.

~Artificial Circulation through Isojated
Organs of, (Ludwig and
Mosso), 335.

-Comparison of the effect of Drugs on dif-
ferent, in different doses, 291.

-Experimental Investigations on the
Action of Drugs on, 241.

-Steps of an Investigation, and animals
chiefly employed, 249.

why

INDEX.

An‘mals, Steps of an Investigation, &e. -

—Adninistration of Drugs, 219.

——Minimum Fatal Dose, 251.

Various Channels of, 7d.

—-Observation of Effects, 250.

cf Excretion, 251.

—-Results, Interpretation of, 250.

—Mode of Securing Subject, 338-9, and

Instruments required, 252, 253,
how to make the latter, 255-6.

Narcotizing Subjects, 256.

—- Action of Narcotics, 253.

—-Procedure During,

—Introduction of Cannule, 269, and
injection of fluid, 260.

—Nerve Division and Simulation, 261.

—Respiration, Artificial,

—-in the Frog, 263.

—-of Gases or Vapours, 264.

apparatus for introducing,

all., 265.

—-in Mammals, 262.

Cannule for, tll., 1b., 268.

-induction and maintenance of Anss-
thesia in, 337-9.

-ki'led in various ways, Rhythmical con-
tractions in, of Pulmonary
Veins and Vena Cava, 542.

—Physiological Action of Digitalis on, 39.

-Vocal cords in, false tone, 627-35,
development of the false, in
relation to vomiting, 6410-?.

Anthrax poison, destroyed by Thyroid
juice, (Wooldridge), 27

Antilope gutturosa, Larynx and Thyroid
in, 629.

Antirrhinice Acid, in Digitalis, 36.

Anti-tuxins, treatment of Disease by,

264,

26.

Aorta, the, effect of Compression of, in
experiments with Nitrite of
Amy! on Rabbits, 183 dizgs. :

-Kinfliiss der Verschliessung der, figs.
164 et seq. a

—Ligature of, and Artificial Respiration,
318, zl., 319. a

Apes, see also Howling Ape and Simia. —

—Larynx of,

—Experiments on, 635, 639.

—Ventricular bands in, 639, 642. 49

Apex-beat, the, as registered by Marey
and Chauveau, 9.

Apnea, defined, 653.

—Drugs preventive of, 654,

~in the physiological sense, 382-3. a

— by Artificial Respiration,

54,

Apomorphia, prevention of Apnoa by — 3
injection of, 654, 4
Apoplexy, Artificial Respiration i in, 379.

INDEX. 659

Apparent Production of a New Effect by
the Joint Action of Drugs
within the Animal Organism,
390.

Arteria radialis, Wirkung des salpetrig-
sauren Amyloxyds auf deren
Pulseurve, (Gamgee), 154.

Arterial Congestion, 439, 453.

—in relation to Inflammation, 439-40,
453-4, 457.

—Elasticity, Importance of, 272-3.

-Ossilication, (Brodie, Jenner, Parry),
18, 19 et seq.

Arterial Pressure, see also Arterial Tension,

—automatic recording of variations in,
initiated by Ludwig, 8.

—in a Dog,

—Action on, of Casca Bark, 502, small
Dose, 503-7, table 406.

—fir-t investigated by Hales, 4, 279.

—Pulse rate and, in experiments with

Digitalis, 145-6.

Arterial Tension, (or Blood-Pressure,
gv), 273.

—influence on, of Respiration, 45-6.

—in Man and Animals, as affected by
Nitrite of Amyl, 138-40.

—Physiological Action of Digitalis on, 54,
see also 45.

—spasmodic, in Angina Pectoris, relieved

_ by Nitrite of Amyl, 193.

—two factors of, 45.

Arterien, Selbststandige Bewegungen der-
selben, 159-60.

Arterienwiinde, Bewegungen derselben
wenn beriihrt, nach Durch-
schneidung der Nerven, 160.

Arterioles,

—Action on, of

—Casca, 458-90, 515, 517.

—Condurang, 357.

—Smelling Salts, 407.

-Active Dilatation and Contraction of, in-
dependently of Nerve-Centres,
On the Action of Nitrite of
Amyl on the Circulation and
on, 174.

-in Cholera collapse, 345.

—Contractility, independent, in Muscular
fibres of, and the results, 12.

—Contraction of, caused by

—Casca, 468-90.

—)igitalin, 141, 143, 145-6,

—Divitalis, 469.

—Evgot, 470.

-R-laxition of, a cause of Palpitation,
421,422.

Artery (ies), see Coronary and Pulmonary
do., also Arverien and Arte-

~ rioles.

Astery (ies)—confd.

—Blood-pressure in, first measured by
Hales, 4.

—Experiments on the Influence of Digi-
talis on, (tables and diags.),
103.

-and Capillaries,

—Arteriul Blood Filling, one cause of
Co» gestion, 439-40.

-discovery of action on, of Vaso-dilator
nerves, 11.

-Effect on, of touch, after division of
nerves, 178 et seq.

-in Muscles, Dilatation of, 405 et seq.

-rizidity of, causes and consequences
of, 18-19.

Artificial Circulation: Investigation of
Blood Pressure, 266.

—Blood, Artificial Circulation of, 266.

—irculation of Warm and Cold, 267.

—Mode of Conducting Artificial Circula-
tion, 7b.

— Application of the method to Pharma-
cological Investigation, 268.

—different kinds of, in, 336.

-Blood Pressure, or Arteria] Circula-
tion, 273.

—Oscillations in, caused by the Heart and
Respiration, 273.

—-Cnuses of, 273, tabular view of, 278.

Action of Counter-irritants, 277.

— Influence of Nerves, 274-6.

——xperimental Examination of, 279.

Forms of Manometer, 279.

—-Kymogruphion, the,

Fick’s, 284, 7d.

Ludwig’s, 280-3, zl. 281.

Mode of using, 285.

Reduction of tracings made by, 286.

Mode of Recording Experiments,

288.

Graphie do., 289.

-in Frogs, 319.

-in Mammals, 318, 77/. 319.

—Plan of, due to Ludwig 8.

—power of, to maintain Life in separated
or severed parts of the Body,
374-6 et seqg., and the Con-
verse, 376.

-through Isolated Organs, (Ludwig and
Mosso), 335.

Artificial Respiration in a Frog, 263-4,

Artificial Respiration in Mammals,

-after division of medulia, (Schiff), 560-1.

—On the use of, and of Transfusion as a
Means of Preserving Life,
374, 383-7,

—Apneea induced by, 654.

—pparatus for, iJ/., 262 et seg.

—Processes induced by, 377-8.

2U 2

660

Arterial Respiration in Mammals (cont.).
—Some Practical Applications of, alone, in
—Apoplexy, 379.
—Asphyxia (Drowning, Charcoal Poison-
ing, Strangling, etc.), 378,
382-4.
—Poisoning (Hydrocyanic Acid, Snake.
bite, Woorara, etc.), 379-85.
Arytenoid cartilages, function of, in Closure
of the Glottis, 624
Asphyxia, (see a’so Drowning), Artificial
Respiration in, 382.
Ass, Larynx of, 633.
Asthma, Spasmodic, suggested use of
Nitrite of Amy] in, 140.
Atropine,
—action of,
—in demonstration of the Effect of Poisons
on the Frog’s Heart, 457.
—on the Inhibitory Apparatus of the
Heart, 528, 557.
—on Night Sweats of Phthisis, 554,
555-6.
—in Poisoning by Cusca Bark, 459.
—on Pulmonary Capillaries, when con-
tracted by Muscarin, 588.
—on the Pulse, 294.
—effects of
—different doses of, on different Ani-
mals, 291.
—the same, on the Blood in Artificial
Circulafion in Isolated Organs,
336.
—given before Muscarin, 313.
—given before Veratria, 315.
-and Chlorate Hydrate, antagonism be-
tween, and Casca, 525-7.
-and Phyostigma, antagonism between,
bearing of, on Therapeutics,
313.
Auricle (s), (see also Inhibitory Influence)
in the Frog’s Heart
—Effect on, of
—Electrical Stimulation,
— (a) in normal condition, 573.
Maximal, 577, 585-6.
Minimal, 577, 584-5.
—~(6) under the influence of Cold, 575,
577, 589, 600-5.
Maximal, 591.
Minimal, 590.
——(c) under the influence of Heat, 575,
577, 594, 609, 622-3.
Maximal, 594.
Minimal, 7d.
——(d) under the influence of Strychnia,
575, 596, 614, 622-3 e¢ seg.
Maximal, 598, 615-7.
Minimal, 598.
-pulsation in, rhythm of, 528-30, 541-2.

INDEX.

Auricle (s)—cont.

—Stimulation of

—Auricular and Ventricular contraction,
induced by, sequence of, 573.

Auscultation of the Heart, introduced by
Laennec, 5.

Author’s Pulse, see Pulse.

—Urine, see Observations on Urine.

BaActTERIA,
—Action on, of
—Casca Bark, 458, 463, 492-3, 522.
—Drugs, 244.
Badger, Larynx in, 632.
Bark, the, of Erythrophleum Quinense,
(Casca, Cassa, or Sassy Bark),
Physiological Action of, (with
Walter Pye, M.x.c s.), 458, 481.
Disease, see Exophthalmic
Goitre.
Bear, Ursus arctos and Ursus meles,
—Larynx in, 631.
—Ventricular bands in, 635, 642.
Legbie, Dr. Warburton, cough mixture
used by, constituents of, and
their action, 566-7, 569.
Belladonna,
~Action of, on the
—Respiratory Centre,
—benefits from, in Night Sweat of
Phthisis, case illustrating, 553.
—Skin and mouth, how caused, 547. :
Bennett, Prof., his case of Angina Pectoris
treated with Nitrite of Amy},
185-6, et seq.
Bernard, cited on the Physiological Action
of Woorara Poison, 380-1.
Bezold, — von, investigations of, on the
Accelerating Nerves of the
Heart, 11.
Birds, as affected by Casca, 453, 464, in
various doses, 489.
Blake, James, Quantitative experiments —
of, on the Effects of Drugs, 7.
Bleeding, (see also Phlebotomy and Vene- —
section), for relief of Angina
Pectoris, 138, i40, 185 ef
seq., 191. vi
~in Cases of Charcoal Poisoning, 384.
~in relief of Pain, 450-1.
Blisters in Rheumatism, the Use of, On
3 Irritants and Counter-I[rri-
tants, with Remarks on, 438,
—application of,
—to Callous Ulcers, 488, 453, 454.
—to Chest, in Pneumonia, 438, 454. 7
—to Side, in Pleurisy, relief given by, —
deductions from, 451, 454.
—in Pericarditis, action of, 452-3, 454.

Basedow’'s

INDEX.

Blisters in Rheumatism, application of
in Kheumatic affections of the Joints,
452-3, 454.
Blood, see also Artificial Circulation, Cir-
culation, ede.
~Action on, of Nitro-glycerine, 479.
—Admixture of, through circulation, from
various parts of the body,
Harvey on, 22-3, some specu-
lations 28-6, use of digestive
ferments, 25.
~Carbonic Acid in excess in, the cause of
Cold Sweats at Death, and
Night Sweats in Phthisis,
550, 555.
~changes in, Chemical, produced by
Gastric glands, 23.
—in circulation through isolated organs,
investigations on, (Ludwig and
others), 11.
~in Cholera, alterations in, 364-7, & note,
364,
~Constituents of, two most important,
—-Chloride of Sodium, 23.
—— Water, zd.
—Probable action of, 23 e¢ seq.
-different kinds of, in Artificial Circula-
tion, in Isolated Organs, 336.
—mode of supplying Head and Body
with, 298.
—formation in, of Acid, 652-3.
—Increased Temperature of, a cause of
Sweat, (Lachsinger) 550, 555.
~—Increased Venosity of, as po-sible cause
of Quickened Breathing, 329.
—Causes of
—-Prevention of Air from reaching
Blood, 330.
of Blood from reaching Air, 7d.
——-how this last may be effected, by
Contraction of the Pulmonary
Capillaries, 331, Action of
Muscarin in, il/., 332.
Embolism of the Pulmonary
Artery, 330, Action (sup-
posed) of Condurango in,
330-1.
Stoppage of the Heart, 330, Action
of Quinine in, 7d.
—in the Intestines, how chilled and how
protected from Chill, 531.
—Nicotine in, a cause of cold Sweat, 550.
—normal quantity of, in the vessels, 441.
—Ozonizing Power of, 649.
~Physiological Action of Digitalis on, 43.
—on Circulation, 41, 44.
—Arterial ‘lension, 54 and see 45.
~—-Capillaries, 55.
—-Pulse, 41, 46.
~Re-piratory change in, 646 e¢ seq.

661

Blood (cont.)

~Transfusion of, in conjunction with
Artificial Respiration, 383-7.

—in Charcoal Poisoning, 384, 386.

—-Snake Bite, 385-6.

—-Strychnine and other Poisoning, 386.

—objections to, disposed of, 386-7.

—Venous,

—Action of, on Sweat Centre, 551.

—Venosity of, what it consists in, 652.

Blood corpuscles,

—Nuclei of, Chemical Composition of, 147.

—Red, coagulation of, in Capillaries, in
Jvflammation, 447-9.

—Red and white, (Newts), Action on, of
Casca Bark, 493.

-White, Action of Drugs on, 247.

Llood-letting, see Phlebotomy and Vene-
section.

Blood Pressure, see also Arterial Pressure,
Arterial Tension, and Blut-
druck.

-Action on, of Nitro-glycerine, less than
that of Nitrite of Amyl, 479.

-in Animals,

—Cat and Rabbit,

—-Action on, after division of Spinal

Cord, of Casca drug, 515-7.

Vessels affected by the Drug, 517-8.

—Frog,

—Action on, of Casca, 501.

—in the Arteries,

—Automatic recording of,
Ludwig, 8.

—Experiments on the Influence of Digi-
talis on, 103.

—first measured by Hales, 4.

Blood-pressure,

—Diminished, produced by Nitrite of
Amy], 175.

—Probably due to dilation, 182-4,

—Kxperimental Examination of

—Forms of Manometer, 279.

—-Kymographion, the,

——Fick’s, 284, <//.

——Ludwig’s, 280-3, i/. 281.

Mode of using, 285.

—-Reduction of tracings made by, 286.

—Mode of Recording Experiments, 288.

Graphic do., 289.

—Oscillations in, due to Heart and Respi-
ration, 273.

—Causes of, 15, 273, tabular view of, 278.

—-Action on, of Counter-irritants, 277.

—lInfluence of Nerves on, 274-6.

—Raising, Mode of, 273.

—Registering by Marey and Chauveau, 9,
(Stricker's instrument for),
293-4.

—Graphic Method, Ludwiy’s, 9.

duc to

662

Blood pressure, Registering by (cont.)
—Sphymograph, 321.
-in relation to Syncope, 5, 404 e¢ seq.
Blood Pressure,
-what it depends on, 316.
—changes in, caused by Action of
Drugs, 316-7.
—mode of determining whether due to
Alterations in Heart, or Ves-
sels, 317.
—Heart,
— Division of Heart Nerves, 317.
—Elimination of Heart Action, 7d.
—Irritation of Vagus, 318.
—Ligature of Aorta, 7d.
—-Subsequent use of Artificial Circula-
tion, 318.
in Frogs, 319.
— in Mammals, 318-9,
Vessels observed in, 319-20.
—Influence of Action of Surrounding
Parts,
in Frogs, 319.
in Mammals, 318-9, vessels observed
in, 319-20.
—Influence of Action of Pulmonary
Capillaries, and of Sur:ound-
ing Parts on Vessels, 321,
—Respiration and Museu'ar Effort,
— Elimination of, 320.
—-Vaso-motor Centre,
—FElimination of, 320.
Use of the Sphygmograph, 321.
Blood-supply,
—copious,
—effects of, on the tissues, 441, 444.
—in accelerating repair, experiments
illustrating, (Sinitzin), 444.
—scanty,
—effects of, in retarding repair and
causing death, 444.
-in relation to sweat, 546.
Blood-vessels, see also Blutgefiisse.
—Action on,
—of Casca, 468.
—of Digitalis, (with A.B.Meyer,M.D.),141.
—Contractility of, 11.
—Cutaneous, contraction of causing in-
creased heat production, !4.
—dilatation of, caus:d by Nitrite of
Amyl, 180-4.
-in Muscles, 12, dilatable capacity of,
and results, (Ludwig and
Hafiz), 13-14.
—normal condition of, 441, i/., 446.
—state of, after application of Irritant and
commencement of Inflamma-
tion, ill., 446.
—on division of Vaso-motor nerves, 7d.,
441, 444.

INDEX.

Blood-vessels (cont.)

-observed in Examination of Effect of
Drugs on the Heart, 319.

Blutdruck.

-Erniedrigung derselben, von dem sal-
petrig-sauren Amyloxyd her-
beigefiihrt, 155.

—-Unabhingig von einer Schwichung der
Herzkrifte, 164, 168.

-Wahrscheinlich von der Gefiisser-

weiterung verursacht, 1/ 8-9.

der Digitalis auf demsel-

ben, 410.

Blutgefiisse,

-alleinige wirkung des Salpetrigsauren
Amyloxyds auf die, 169.

Blutstrom, den, Ueber die Wirkung des

Salpetrigsauren Amyloxyds

auf, 154,
temperature of,

tained, 531.

Bones, Injuries to, and Amputation of,
Shock induced by, 398.

Bowditch, Dr. H. P., Apparatus of, for
Experiments on Frogs’
Hearts, 304, i//. 305.

Bowels, distention of, suffering caused
by. 16.

-the Physiological Action of Digitalis
on, 59

Brain, see also Cerebrum, and Medulla.

—Action on, of Nitro-glycerine, 478.

—Headache induced by, 478-80.

—Cardiac centre in, (Ludwig), 11.

—Centre in, controlling Voluntary move-
ments, (Ferrier), 14.

—not necessary to Life, (Fontana), 374.
Brain-activity, relation hetween, and cold
feet, explained, 12,
Brain-functions, dependent on constant
Blood supply, 403.

Brandy in Shock, 408.

Breathlessness, due to faulty contractility
of the Heait, 16, 17.

Brodie, Sir Benjamin, experiments of,
on Artificial Breathing in
Woorara Poisoning, 381.

Bronchi, in relation to Cough, 562.

Bronchitis, Carbonate of Ammonia
in, 327.

—-Chronie, obstruction to the Cireulation
as seen in, 543-4.

Bronchitis and Phthisis, On the’ Actions
and Use of Certain Remedies
employed in. 562.

-cell-growth in, in relation to the use of
Cod-liver oil, 570-1.

—congested Mucous Membrane in, a cause
of Cough, 567.

—remedies for, 562.

-Wirkung

Body, how main-

INDEX,

Bronchitis and P).thisis (cont.)

-remedies for (cont.)

—Cod-liver oil the best, 570-1.

-Symptoms in

—Oough and Expectoration, 562.

Brown, Crum, and Fraser, researches of,
on the modification of the
action of certain Alkaloids by
union with specified bodies, 390,

Brown-Séquard,

—experiments of

—demonstrating Respiratory Centre in
the Spinal Cord, 323.

—in restoring Life to a severed (Dog’s)
Head, 375.

—use of testicular extract by, 25.

Bruce, Alice, death of, from Syncope due
to Torture, 393.

Brucine Poisoning, Artificial Breathing
in, (Uspensky), 383.

Brunton’s

—Pulse, Sphymographic Tracings of, 129
el seq.

-Stop-cock, and its uses, i2/., 265.

-Theory of the Mode of Action of
Digitalis, 72.

Burns,

—Pain of, relieved by Fire-heat, 449.

—probable reason for relief, 450 7.

—Shock induced by, 398, 400.

Ca¥FFEinE Poisoning, Artificial Breathing
in, (Uspensky), 383.

Calabar bean, (Phyostigma Venenosum),
in ordeal by Poison, West
Africa, 462.

-effect of, on the Salivary Nerves, 546-7.

—physiological action of, discriminated from
that of Casca Bark, 473.

Caleuli, agony caused by distention pro-
duced by, 16.

Camarband, reason of its usefulness, 531.

Camel, (Camelus bactrianus), Larynx of,
632, 635.

Cannule, T-tubes and Pens, il/., 255-6,
making of, 255-6.

-Introduction and Uses of, 259, 262.

Cantharides, Diuretic action of, applied
externally, 6.

Capillaries,

—Coagulation of the Blood in, the snp-
posed cause of Stasis, (Weber
brothers), 448-9, 454.

—contractile power of, 316.

—Physiological Action of Digitalis on, 55.

—resistance of, to the circulation, first
investigated by Young, 4.

—Venous Blood tilling, oue cause of Con-
gestion, 439,

663

Cap l'aries (cont.)

-Pulmonary,

—action of, on Drugs injected, 321.

—in Angina Pectoris, as acted on by
Nitrite of Amyl, 7/., 370-3.

—in Cholera Collapse, 365-8.

—-Treatment indicated for, 368.

Nitrile of Amy] in, il., 369-73.

—Contractile power of, 568.

—Contraction of, effect of, on Respira-
tion, 331.

—Action of Muscarine

all,, 332.

Action on, of Drugs, how

observed, i/., 333.

—Systemic, Action on, of Nitrite of Amyl,
369 et seq.

Carbonate of Ammonia, use of, in Bron-
chitis, 327.

Carbonic Acid,

—Action of, on the Vagus, 300.

~in blood, action of, 652-4.

-Increased quantity of, in the Blood,
cause of Cold Sweats at Death,
and of Night
Phthisis, 550, 555.

—how accumulated, 550-1.

—in relation to Internal Respiration, 644.

Carbonic Acid Gas,

-Action of, on Artificial Circulation in
Isolated Organs, 337.

-Poisoning by, Artificial Respiraticn
in, 382

Carbonic Oxide, action of, on Internal
Respiration, 646.

-action of, on Hemoglobin, 646,

Carbonic Oxide Poisoning (from Charcoal
fumes), Artificial Respiration
in, 383, conjoined with Trans-
fusion, 384.

Cardiac centre, position of, 11.

—contraction, research on transmission of
Stimuli producing, 572-3.

—Cycle, as described by Senac, 5.

—Refractory period in, 573, 574 & note,
578 et seq., 619 et seq., moment
of, 576, duration of, 577.

—effect on of Co'd and Heat, 577.

—sensitive phase in, 576-7.

—Dropsy, anticipated use of Casca in, 473.

—rationale uf treatment of, 20.

-Ganglia, (Cat, Dog, Frog),

—Action on, of Casca, 513-5.

—Co-ordinating Apparatus of, in relation
to Quickened Heart action, 315.

—Paralysis of, 303.

—-part of the Ganglionic Apparatus
affected, 309, 315.

—Stimulation of, effect of, on

Pulse, 294,

in causing,

—Frogs’,

Sweats in

the

664

Cardiuc (cont.)
—Lesion in organie Angina, 191.
—how deduced in Bennett’s case, 192-3.
~Murwurs, investigation of, by various
observers, 4, 5.
the, as affected by Drugs,
274 et seq.
-Nutrition, impaired, Syncope and Heart
Stoppage due to (Brodie), 19.
~Pain, (see also Angina Pectoris), due to
faulty contractility of the
Heart, 16, 17.
-Rhythm, as affected by Artificial stimula-
tion, 577.
-Sounds, see Heart, Sounds of.
Cardiograph, Marey’s, and its uses, 208.
Carotiden, Klopfen derselben, von dem
salpetrig-sauren Amyloxyd her-
be.gefiihrt, 154.
Carotids, the, throbbing of, produced by
Nitrite of Amyl, 154, 174.
Carnivora, Larynx in, 630.
Casca, Cassa, or Sassy Bark, Lrythro-
phleum Guinense, Physiological
Action of, (with W. Pye,
M.R.C.S.), 458, 481.
—Action of,
—aAlcoholic and Watery Solutions of,
compared, 462, 482, 492, 496.
—-Experiment XXIL., 496 e¢ seq.
—-on Animals, Bacteria, &c.,
symptoms produced by, 483.
—on Bacteria, 559.
Experiments XITI-XIV., 492-3
—-Life of,
Experiment XV., 493.
—-on Birds, 458.
Experiment V., 439.
—-on Cats, 459-61, see also 501.
Experiments J-IITI., 483-5.
-in Doses, Large and Moderate,
483-4.
Remarks on Experiments I-III.
Abhormal Muscular Movements,
487.
———Appearance of the Heart and
Lungs, post-mortem, 4S8.
———Respiratory difficulty, 487.
Vomiting, 487.
——-in Injections, 485.
Post-Mortem and Microscopical
Examinations, 485-7.
—-Ciliary Motion, 458.
Experiment X VII., 493.
—-on Dogs, 459, see also 505-7.
Experiment IV., 489.
—-Fishes and Frogs, 548-60.
Experiments VI-VII., 490-91.
—~Infusoria, 458.
Experiments XI-XII., 491-2.

—Nerves,

INDEX.

Casca, &c., Action of, on (cont.)

—Invertebrata, 458.

——Experiments IX-X., 491.

—-Blood, red and white Corpuscles of,

(Newts),

Experiment X VI., 493.

—Action of, on

— Blood Pressure, in the Frog, 459.

—-Experiment XXX1T. 501 diag., 502.

—Do., in a Bitch,

— Experiment o.5.004 502, diag. show-
ing coincident variations of the
above, and secretion of urine,
508, remarks, 505, 519, tables,
503-4.

—Blood Pressure after division of Spinal
Cord,

—Experiments XLII-XLIIL., (Cat, and
Rabbit), 515-17, table, 515,
diag. 517.

—Blood Vessels, (Frog), 460, 468.

—Cardiac Ganglia, effect on Pulse, &e.

—-Experiments XXXVIII-XLI., (Cat,
Dog, Frog), 513-15, table, 513.

—Circulation, 460, 467.

—Digestive system, 494,

—-Experiments XXI.,
XXII, 495.

—Eye, 472.

—-Pupil and Lacrymal Gland, (Cat’s),519.

—Germination, 458, 492.

—Heart, (Frog’s), 459, 467, and see 525.

—~—Experiments XX VII-X X XJ.,499-501.

—TIntestines, (Cat’s), 461, 465, 495.

—-Experiment XX YVI., 498-9...

—Kidneys, 460, 470.

—Mammals, 483 ef seq.

—Man, in Angola ordeals, 481-2.

—Motor nerves, see under Nerves.

—Muscles, 458, 466.

on Lifting power thereof,

——-Experiment XLVIIL., 524.

on Muscle Curves,

——-Experiments X LIX-L , 521.

on Structure of Muscular Tissue,

Experiments XLVI-VIL., 52u.

—-remarks on the above, 521-2.

—Negative, 458 (2, 3, 6, 7, 15, 17, 21, 22, 24-7),
463, 483. 4

—Positive, 458 (1, 4, 5, 8-16, 17-21, 23), 463, ©
433.

XXIa, and

—Nerves, see also Vagus, infra,

_—-Motor do., Experiment LII., 466, 522,

diag. 523.
—Peripheral vaso-motor
nerves, 469-70. a
—-Sensory do., Experiment LII., 523-5,
diag., 523.
Reflex Action in Frog, Experiments
LIII-IV., 524-5.

ganglia or 4

INDEX.

Casca, &c., Action of, on (cont.)
—Orxidation, 455.

—-—Kxperiments X VITI-XX., 494.
—Pupil and Lachrymal Gland, 451.
—~KExperiment XLV., 519.
—Respiration, 459, 472, 498.
—Spinal cord, 460, 466.

—Stomach, 459, 463, 464-5, 495.
—Temperature, 472.

—Urine, secretion of, 460, 505, tables, 508.
—Experiment XXXIII., diag.
remarks, 519.

— Uterus, 472.
—Vagus, 466, 468.
—Maximum irritation,
Experiment XXXV., (Cat,
table 307-8.
—-Minimum do.,
——LExperiment XXXVI., (Cat), 509-10,
table 519.
—Vagus-roots,
—-Minimum excitability of,
Experiment X XX VIT., (Cat), 510-13,
table 511-12.
—Action of, after
—Injection, 459, 460, both vagi being
previously divided.
—-Experiments XXIi]-XXV., (on Cats),
497-8.
—do., into the Intestines,
—FExperiment XXVLI., (un a Cat), 498-9.
—Antagonism between, and Atropia and
- Chloral Hydrate, Experiment
(Cats) LV, 525, tables, 526-7.
—Appearance, 462, 482.
—Chemical reactions of, 482.
—Doses of,
—Ditferent effects of, on
—Cats and Dogs, 483-9.
—the Pulse, 505.
—-the Vagus, 507-10.
—Small, effect of, on
—-Heart and Arterial Pressure (Dog),
505, 507, table, 506.
—Infusion yielded by, 462.
—modes of employment of, 462, and results
on man and on animals, 462-3.
—Investigations of its Action,
—in producing Death, 459, 460, 463-4,
483.
—-in animals, 464.
—in affecting the various
463 et seq.
—in its possible Medicinal uses, 463, 473.
-—Symptoms of, in animals,

597-9,

Functions,

— Muscular weakness, 459, 462-3, 464,

465.

—-Vomiting and Purging, 458-9, 462,

463, 464.
—Vessels affected by, 517.

518,

665

Cascarilla, action of, on the Stomach, 567.

Case of Poisoning by Digitalis— Re-
covery, 99.

Cash, Theodore, M.D., (joint-author), see
Frog’s Heart, Larynx,
Stannius’s Experiment, and
Valvular Action of the Larynx.

Castration, Shock induced by, 398.

Catheter or bougie, Shock induced by the
passage of, 398.

Cats,

—Action on, of

—Casca Bark, 459, 464, in various doses,
483-8, 496-9, 501.

—Nitro-glycerine,

—-Special, on various
"477 ef seq.

—Hering’s experiment on, in’ supplying
different kinis of Blood to
Head and Body, 298.

—Larynx in, 631.

—experiments on, 635, 636-8.

—-Ventricular bands in, 635, 637.

-Pulmonary pulsation in, after Chloro-
‘forming, 528-9,

—Retching in, i//., 641.

-~Vomiting in, 640 all., 641.

Caustic causing Inflammation when ap-
plied to the web of a Frog’ 8
foot, 445.

Cell(s), see also Unicelluiar Crsaniaia!

-of Higher Organisms,

—Respiration in, 644.

-of Human body, fluid in which they
live, 7d.

—-Life and death of, 227.

Cell-growth, in Bronchitis and Phthisis,
in relation to the use of Cod-
Liver Oil, 570-1.

Cerebral Centre for Voluntary Move-

ments, (Ferrier), 14.

action on, of Opium, &ce.,

299-300.

Cervical Ganglion, the Third, association
of, with Diabetes and with
Exophthalmic Goitre, 416,
422-4,

Cervical Sympathetic, the, es affected in
exophthalinic goitre, 424,

Cetaceans, Larvnx of, 628.

Chairs, Easy, On the Science of, 531.

Change of Colour, see Emotion and

&e.,

organs,

Ccrebrum,

| Charcoal Poisoning, see Carbonic Oxide do.

Chauveau, see Marey and Chauveau.

Chemical Composition, On the, of the
Nuclei of Blood Corpuscles,
147.

-Constitution of Drugs, in velation to
Physiological Action, 240,

666

Chemical History of Digitalis,
—Constituents of -
—-Antirrhinic Acid, 36.
—Digitalic Acid, 76., 37.
—-Digitalide, 35.
—-Digitalin, 7d.
—Digitaline, 34, 36-9.
—-Digitaloic Acid, 36.
—-Digitalose, 35.
—-Digitalosmin, 36.
—Pectin, 36.
—Sugar, 7d.
—-Tannie Acid, 7d.
Chest, the, Blister applied to, in Pneu-
monia, acting as a Counter-
irritant, 428.
Chloral,
~Action of, on the
—Cerebrum, 299-300.
—Respiratory muscles, 300.
—Death from, Effects of Warmth in Pre-
venting, 197.
-Effects of, as regards
—Muscular co-ordination, 197,
—Pulse, 7d.
—Respiration, 197.
—Respiratory Nervous Centre, 654,
—Sleep or coma, 197.
'—Temperature reduction, 193.
—Experiments in relation to, tables,
198-204, and deductions there-
from, 198-9.
-in experiments on Rabbits’ Hearts and
Temperature, 213 e¢ seq.
Chloral Hydrate, effect of, on the Blood,
in Artificial Cireulati ion in
Isolated Organs, 336-7.
-and Atropia, antagonism between, and
Casca, 525-7.
Chloroform, in Linctus, and Solution,
-Action of, on
—Cough, 563-4.
—Dogs, 257, 337.
—Respiratory centre, 566-7.
—when Bronchially inhaled, 332.
~One of the Causes of Death during the
Extraction of Teeth under,
427, see also 338.
—Importance of giving full doses of,
427-8, 435-6, 437.
—of position of patient under, 432-8,
437.

—successful use of, reasons given for, by
Prof. Lyme, 427.

Choking, as a cause of Cough, 567.

Cholera, the Collapse of, On the Employ-
ment of Nitrite of Amyl in,
[with Experiments upon the
Pulmonary Circulation], 359.

—Symptoms in, 361.

INDEX,

.-Capillary resistance to, first investiga

Cholera, Symptoms in (cozt.)

—arrested Pulmonary circulation, 365.

—condition of the Blood, 364, 3805,
note, 367.

—-~Arterioles in, 365.

——Pulmonary Capillaries in, 365-8.

—Paralysis of Intestinal Nerves, One
able), 363.

—Rice- Water Stools, 361.

—-composition of, 362.

—-—posrible cause of, 563.

-—Thirst, 361, 364, and Dryness of Tissues
after death, probable cause
of, 364,

~suggested use of Nitrite of Amy]
in, 140.

-Treatment indicated by Symptoms, 368.

—necessarily empirical, 369.

—Nitrite of Amy] in,

—-Action of, on the Pulmonary Capil-
laries, 359-61.

—Oxygen in, 359-61, 369, 372.

Chorda Tympani Nerve,

-effect of irritation of, on Saliva, 546.

~do. after administration of Atropine, id.

Circulation, see Arterial, Arteries, ¢c.,
also Capillaries and Artificial,
and Pulmonary Circulation.

—Action on, of

—Casca Bark, 458, 460, 467, 493-4, 499
et seq., diag. 502 table, 506.

—Do. on the same, and on the Urinary
Secretion, tables, 502-4, diag.,
579, remarks 519.

—Counter-irritants, 277.

—Digitalis, 41, 44.

—-as affecting

Arterial Tension, 54 cf. 45.

Capillaries, 55.

Pulse, 46.

—Drugs, (Leech), 27.
—-Quantitative Pa
(Blake), 7

—Nitrite of Amyl, 174.

on,

by Young, 4.
-effe.t of modifications of, on Internal —
Respiration, 644-5 et seq.
-extended knowledge of, work of cdi
in connect’on with, 8, 9.
-function of, in relaticn to Muscular a
Waste Products, 534. sy
-in the Living Body, 272. F
-obstructions to, as seen in Chronic a
Bronchitis, 543-4,
—Pathology of, 277-8.
—Schema of, ill., 270,
—sequence of, how maintained, 430.
-speed variation. in, in various ‘parts simul- |
taneously, Harvey cn, 9, 10,

INDEX.

Circulation (cont.)

-through muscles, on what dependent, |.

(Ludwig and Sadler), 14, 21.

-of Warm and Cold Blood, 267.

Circulation and Respiration, Effects on, of
Condurango, 350-7.

Civet, Larynx in, 632.

Clark, Sir Andrew,

27-8.
as affecting the Action of
Drugs, 235.

-or season, as affecting Posture, 531.

Closure of the Glottis, see Glottis,
Closure of.

Coagulation of Blood in the Capillaries,
as the cause of Stasis, (Weber
Brothers), 448-9, 454.

Coati, Larynx in, 632.

Coats, see Ludwig and Coats,

Cobra di Capello, Poison of,

-death of Rabbit from, subsequent Pul-
monary pulsation not due
to, 528.

—Physiological Action of, 381, 385, 386.

Cod-liver Oil, in Bronchitis and Phthisis,
immense value and probable
action of, 570-71.

Cold, see also Heat and Cold.

-action of, in relief of Inflammation pain,
449, 454.

—Heat, and the Action of Drugs, Modifi-
cation by, of the Effect of
Electrical Stimulation of the
Frog’s Heart, (with Theodore
Cash), 574, 576.

— Action of, on the Frog’s Heart,

—Effect on the Cooled Heart of

Electrical Stimulation, 575, 577, 589,

591, 600-5.

Auricular,

Maximal, 591.

Minimal, 550.

——-Ventricular,

—— -—Maximal, 590.

———Minimal, 589, and on the

Venous Sinus,

Maximal, 593.

Minimal, 591.

Cold air, inhalation of, and Cough,
568.

Cold feet, relation of, to Brain Activity
explained, 12.

Collapse, (see also S!.ock), certain causes
of, 399-400.

-the, of Cholera. On the Employment in,
of Nitrite of Amy], [with Ex-
periments upon the Pulmonary
Circulation ] 359.

Colocynth, purgative action of, applied
externally, 6.

death of, 1, 2,

Climate,

667

Comparison of the Fffect of Drues on
Different Animals in D.fferent
Doses, 291.

Competency, the, of the Tricu-pid and
Mitral Valves, On a Simple
Instrument for Examin-
ing, 537.

Composition, see Chemical Composition.

Conditions of Health and Diszase, 223.,

Condurango, Physiological Action of, 340.

—Extract of,

—Characters of, 340.

—General Action of, on Frogs, 7d.

—on Mammals, 342.

Post-Mortem Examination after Ex-

periments on, 313.

—Results of Experiments on, 344, 358.

—FE flects of on,

——-Circulation and P-espiration, 450-7.

on Arterioles, 257.

Reflex Action, 345.

Conclusions regarding, 270,

—suppos¢ d action of, in inducing Embolism
of the Pulmonary Artery, error
note’, 330-1.

Congestion, definition of,

—two possible conditions of the Blood
in, 438.

—-Arterial, or active, congestion, 488-9.

—Venous, or passive do., 439.

—due to Cough, 567-4.

—Drugs lessening, 567-71.

-how produced, 441.

-in relation to Inflammation, 438, 439,
441, Paget on, 447, and see 454.

—protracted, Hypertrophy caused by, 440.

Conia, action of, on the Vagus, 314.

Conium, Vapour of, Action of, on
Cough, 554.

Constitution and Jdic syncrasy, as affecting
the action of Drugs, 236.

Contractility of Blood-vessels, indepen-
dent, and inherent, 11.

-Veins showing, 542. ,

—uses of, 543.

Contraction, see also Cardiac do.

-of Arterivles cuused by Digitalin, 141.

—proof of, 113,145 6.

-of Blood-vessels, universal, caused by
Irritation of a Sensory Nerve,
(Ludwig), 443.

-of the Pulmonary Capillaries, effeet of,
on Respiration, 331.

—action cf Muscarin in causing, ill., 332.

—sequence of, in the Heart, 529-30,

-of Veins, local, 541.

Cooled Heart, see Electrical Stimulation of
the Frog’s Heart, subhead (b).

Cooper, Sir Astley, cited on Death from
Shock, 393-4, 432.

668

Co-ord nating Apparatus of the Cardiac
Ganglia, in relation to Quick-
ened Heart Action, 315.

Coroniry Arteries, ossification of, and
Angina Pectoris, 19.

Corpora cavernosa, dilation of, (Eck-
hardt), 15.

Corpuscles, see Blood Corpuscles.

Cough, causes of, 567 et seq.

—definition of, 562.

—effort exerted during, 565-6.

—congestion of the jugulars and o'her
veins caused hy, 566, 567-9.

—other bad results of, 566.

-~methods of lessening, 562, drugs useful
for, 567-71.

—(a) removing source of irritation, 562.
—-by Linctus, Solution, Spray, Vapour
and Powder, 563-5.

—(b) lessening excitability of the nervous

mechanism involved, 562.
—-by respiratory sedatives, 568, ‘risk indi-
cated, 565.
—nervous centre for, 562.
—Vomiting associated with
—Drugs affecting, 571.
Cough mixtures, objects aimed at in, an
instance of, 566-7.
Counter-Irritants, On Irritants and, with
Kemarks on the Use of Blisters
in Rheumatism, 438.

—action of, on the Circulation, 277.

—definition of, 438.

Cow and Sheep, Larynx in. 629.

Cricliton, Sir A., use of Digitalis by, in
Phthisis, 568-9.

Cumulative Action of Drugs, 233.

Curare, see also Woorara.

~action of, on the Respiratory Muscles,
300.

—poisoning by, (Herrmann), 472.
Curare, Wirkung desselben, bei Amyl-
versuchen an Kaninchen, 156,
158.

Blood-vessels and glands,
effects on Bodily Heat of the
Contraction of, 14.

Cutaneous

—Nerves

—-as affecting the Respiratory Centre

—-(a) normally, 324-6.

—~(b) when affected by inhalations, 227.

—effect of Stimulation of, on the Pulse, 15.

Cyon, Experiments by, on the influence of
Warmth on the externalised
Heart of the Frog, 205 et seq.

{'zermak, cited on Closure of the Glottis,
624-5.

INDEX.

Darwin's theory of Pangenesis, 384.
Jaturia, action of, on the Inhibitory

ganglia of the Heart, 314.
Death

—from Casca Poisoning, due to Paralysis
of the Heart, (Liebreich), 483,

-from Chloral, Effect of Warmth in
Preventing, 197.

—Cold Sweat at moment of, how caused,
550.

—during the Extraction of Teeth under
Chloroform, One of the Causes
of, 427.

—Insufficiency of dose, 428, et seq.

—-explanation, 435-7.

—vshock, 428, e¢ seq.

“from Shock, (Animals), while under
Chloroform, 338.

—(Human beings), Astley Cooper's in-
stance cited, 393-4, 432, cof.
428.

—caused by Mental Emotion, 399.

-from Syncope, due to Torture, case of
Alice Bruce, 393.

—sequence of, 377.

Decapitated Criminals, Contractility of
the Veins shown by Observa-
tion on, 542.

Deer and Gazelles, Larynx in, differences
in, 629.

Delphinia, action of, on the Inhibitory
Ganglia of the Heart, 314.

Depressor nerve, the, function of, 16.

Determination of Blvod to a part, (Paget),
438 note.

Determination of the Exact Structures
through which Drugs affect
the Heart and Vessels, 290. |

Diabetes, association of, with the third —
Cervical ganglion, 416, 419,
424, tll. 423. ;

—raw meat as remedy in, first used, 25.

—use of Alkalies in, 426.

Diagnosis, not the sole aim of the —
Physician, 6. o.

mode of —

Diaphoretics and Purgatives,
action of, 24-5.

Diastolic sound, the, haw pr.duced, 6.

Digestion,

—Action on, of,

—Digitalis, 57.

—Dover’s Powder, 55+.

—Opium, 565.

Digestion, Chemistry of, 23-

-some processes occurring during, ag —
affecting the Blood, 23-5. a

Digestive Ferments, use of, in stimulating —
Stomach and Intestines, 25.

—System, Action on, of Casca Bark,
494-5, =

IN DEX.

Digitalacrin, 36.

Digitaletin, 37.

Digitalic acid, analysis of, 36.

Digitalide, 35.

Digitalin, 35, action of, on the small
blood-vessels, 141.

Digitaline, 34, 56-9.

Digitalis, On, with Some Observations on
Urine. (Gold Medal Thesis,
1866), 29.

—action of,

—on Arterial Tension, 34, 52, 54.

—-—-Experiments on, 103 e¢ seq.

—on the Arterioles, 141, 143, 145-6, 409,
469, 470.

—Pulse rate, as affected by, 145, 146.

—in Bennett’s case of Angina Pectoris,
185, 191.

—on the Blood, 43.

—on the Blood-Vessels, (with A. B. Meyer,
M.D.), 141.

—on the Capillaries, 55.

—on the Circulation, 44 ef seq.

—on the Digestion, 37.

—Diuretic, discovery of, 1770., 32, (with
Henry Power, M.B.), 412.

—Diuretische Wirkung der, (mit H. Power,
M.B.), 410.

—-derselben, wovon bedingt, 410-11.

——Versuche dariiber an Hunde ange-

stellt, 410.

Resultate, 410.

deren einstweilige Erklarung, 411.

—on the Eyes, 67-8.

—on the Frog’s Heart, similarity of, to that
of Casca, 468.

—on the Human Heart, 49-53, 473.

—in Horses, on Urine, and Circulation,
experiments on, 42-3.

—on the Kidneys, similarity of, to that of
Casca, 471.

—on the Nasal Mucus, 60.

—on the Nervous System, 66-7.

—on the Vaso-motor nerves, probable,
412-3.

—in Phthisis, as used by Sir A. Crich-
ton, 568-9.

—Physiological, on Plants and Animals,
experiments, 39.

—on the Pulse, 32, 46-9, 145, processes
of, 505.

—-Tables of Pulse, Urine, &¢., while
taking, 82 et seq.

—on Respiration, 57.

—on Sweat, 59-60.

—on Temperature, 65.

—on Tissue-metamorphosis, 34.

—on Urine, 60, and see tables, 82 et seq.,
and pp. 42-3.

—on the Uterus, &c., 68.

669

Digitalis, Action of (cont.)

—on the Vagus, similarity of, to that of
Casca, 468.

—-on the Ventricle, 315.

-Analysis of, by Ifomolle and Que-
venne, 34-6.

-Applications of, internal and external, by
various authorities, 31-4.

—Chemical History of, 34.

—Mode of Action of, various observers on,
€8 et seq.

—Poisoning by, 472.

—Case of, Recovery, 99.

—Poisonous Action of, sequence of, 41.

—Physiology of, 49.

—Therapeutic Action of, 74 et seq.

—tHistory of its use in Medicine, 31, 3%
et seq.

—-Various uses of:

in Ague, as Antispasmodie, 33.

in Cardiac Dropsy, 34.

in Continued Fever, 33.

in Delirium Tremens, 33 -4.

as Emetic or Cathartic, 31-2, 58.

in Epilepsy, 33.

in Exophthalmic Goitre, 42 t.

in General Pareses of the Insane, 53.

in Hemoptysis, 32.

in Hemicrania, 33.

in Menorrhagia, 34.

in Neuralgia, 33.

as an Oxytoxic, 34.

in Pneumonia, inaction of, 211.

in Shock, 409.

in Strong Doses, 33.

in Typhoid, 33.

Digitalissic acid, (valeric acid), oS.

Digitaloic Acid, 36.

Digitaloin, 36.

Digitalose, 35.

Digitalosmin, 36.

Digitasolin, 36.

Dilatation,

-of Arterioles in relation to Syncope, 404
et seq.

-of Blood Vessels caused by

—Division of Vaso-motor Nerves, 441, 414.

—hrritation of asensory Nerve, (Ludwig),

—Nitrite of Amyl in the, 180-4.

-of Venous System, due to Shock, 431-2.

Dilatation and Contraction, Active, of
Arterioles independently of
Nerve-Centres, On the Action
of Nitrite of Amyl on the
Circulation and on, 174.

Diphtheria, treatment of, by Anti-
toxin, 26,

Disease and Health, Conditions of, 225.

—different effects of Drugs in, 239.

670

Diseases in which Digitalis haz been, and
is, employed, 31-4, 74-7.

Distention of Hollow Muscular Ov-gans,
p+in induced by, 16.

Diuretic Action of Divgitalis, On the, (with
Heury Power, M.B., F.RGS. ),
412; the same in German,
410.

—use of Casca bark anticipated, 478.

Dogs, see also Hunde,

-Action on, of

—Atropia, in different Doses, 291.

—Casca, 459, 464, in various doses, 489.

—Chloroform, 256, 337.

—Circu'ation of, as affected by Nitrate of

Amyl, 176.
a Severed, Life restored to,
(Brown-Séquurt), 375.

—Heart and Blood Pressure of

—Action on, of

—-Casca Burk, 502, do. in small doses,
505 7, table, 506.

—Kidney and Liver of, Isolated, Artificial
Cureulation through, (Ludwig
and Mosso), 335.

—Larynx in, 630.

—experiments on, 685, 638-9.

—Ventricular bands in, 635, 639.

—Vomi'ing in, 640,

Dolphin, Larynx i in, 428.

Doom, see Redwater Bak.

Doses, see Comparison of the Effects of
Drugs, see also Drugs.

-and the Action of Drugs, 231.
—different, of Casca, effect of, on the
Froz’s Heart, 463.

—Homeopathic, 235.

—Large and small, 7d.

Dover’s Powder, action of, (anti-sudorific),
in Night Sweat in Phthisis,
(Murrell), 555, 556.

Dropsy, see Cardiae do.

Drowning, Se gid Respiration in, 378,

—ITead,

—Deaths Pate Roueis future of Strychnia
in, as a restorative, 323.

Drugs, see Cold, Heat, and the Action of.

—Action of, on

—Animals, metho1 of experimental! in-
vestigation, 241 e¢ seq.

—Pacteria and Vibriones, 244.

—Cell Life, 229.

—Cumulative, 233.

—Direct and Indirect, 230.

— Local and Remote, 7, 231.

—Fermentation, 245.

—Fungi, 7d.

— Hemoglobin.

—Infilammation, 248.

—Infusoria, 242,

INDEX.

Drugs, Action cf, on
—Inhibitory «ippiratus of the neal
(various), 314,
—Leucocytes, 247.
—Nerves affectin,s the circulation, 274-76,
—-~alfecting the Respiratory Centre,
(a) inhaled, 327.
(d) injected, ib.
—' xidation, 247, 647-51.
—Protoplasm, 242.
—Putrefaction, 246.
—Respiration, see Respiration, and under —
names of Drugs.
—Respiratory Nervous Centre, 654.
—Veins, need of further knowledge on,
544, as affecting, Contractile —
Power of the Pulmonary 7
Capillaries, 5 i8-9, *
—Vomiting associated with Cough, 571.
—Chemical Constitution and Physiologie 4
Action, 240. a
—Constitution and Idiosyncrasy, 236.
— Disease, 239.
—lloses, 231.
—-ttomeopathic, 235. %
—~Large and Small, 7d. “a
—Habit, Climate, Fasting, and Form of
Administration, 235.
-aim of experiments on the effects of |
localisation of action, 241.
—beneficial in combating Night-Sweati
of Phthisis, ‘BSL et SEQ, ce
culty of
555-6.
—Determination of the Exact Struchunan
through which they affect the —
Heart and Vessels, 290.
—-Effects of, on Different Animals in —
Different Doses, Comparison —
of, 291.
— Quantitative experiments on (Blake), 7.
—-Externual poe of, Harvey’s ‘knowled ge
of, 6. ee
—Injection of, into the Blood, first ried a
by Sir Christopher Wren, 6, 7 3
-Joint Action of, within the Anir al
Organism, On the Apparent
Production of a New Effect —
by, 390. ..
—Method of data iemee to Animals
under Experiment, 249. _
Dublin, Cholera Epidemic in, of 1866,
use of Nitrite of Amyl in, and
Oxygen, and results, 359-61.
Dugong, Larynx of, 628. or
Dybkowsky’s theory of the Mode of
Action of Digitalis, (and
others), 71. c
Dyspnea, 653, defined, 382.

‘a

choosing among

INDEX.

EAR-FLUSHING in Rabbits, see under
Rabbits.

Easy Chairs, On the Science of, 531.

-—climate or season as affecting Posture,
531-2.

-essentials in perfect, 536.

—fatigue as affecting Posture, 532, 535,
536, rationale of, 533-4,

-shampooing in relief of Fatigue, as
adjunct to, 533, 536.

-sitting or squatting postures in different
countries, 531.

-W shape, the most reposeful, 533,
536

Effect, A New, Apparent Production of,
the Joint Action of Drugs by,
within the Anim.l Organism,
399.

-of Drugs, on Cell Life, 229.

-of Electiical Stimulation of the Frog’s
Heart, and its Modification

by Cold, Heat, and _ the
Action of Drugs, (with
Theodore Cash, M.D.), 574,
576,

—Note regarding, 572.
-of Heat and Poisons upon the Heart

of the Frog, A Simple
Method of Demonstrating,
455.

-of Warmth in Preventing Death from
Chloral, 197.

Eichwald, on the Pathology of Angina
Pectoris, 191.

Eiweiss, bei Digitalis experimenten im
Harn gefunden, 411.

Electric shocks and constant currents,
effect of, on the Blood, in
Artificial Circulation in Iso-
lated Organs, 336-7.

Electrical Stimulation of the Frog’s
Heart, &c., Note regarding
the effect of, 572.

-On the Effect of, and its Modifica-
tion by Cold, Heat, and the
Action of Drugs, (with
Theodore Cash, M.D.), 574,
576.

—Area to which applied, 574.

—Conditions under which applied,

—-(7) in normal condition,

Auricular, 573, 576.

Maximal, 577, 585-6.

-———-Minimal, 577, 584-5.

——-Ventricular, 573, 576.

~--—~Maximal, 577, 581-4.

—-——Minimal, 577, 578-81, and of the

——Venous Sinus, 573, 576.

Maximal, 577, 587-8.

Minimal, 577, 586-7.

671

Electrical Stimulation,&c.,On the Effect of,

—Conditions under which applied (cont.)

—-(6) under the influence of Cold, 575,
577, 589, 600-5.

— Auricular,

Maximal, 591.

Minimal, 590.

Ventricular,

—-Maximal, 590.

Minimal, 589, and of the

Venous Sinus,

—-~ Maximal, 593.

—Minimal, 591.

—-(c) under the influence of Heat, 575,

577, 594, 609, 622-3.

Auricuiar,

——~Maximal, 594.

——-~Minimal, ib.

Ventricular.

—-Maximal, 594.

—-Minimal, 593, and of the

Venous Sinus,

Maximal, 595.

Minimal, 7d.

——(d) under the influence of Strychnia,

575, 596, 614 et. seq., 622-3.

Auricular,

——-~Maximal, 598, 615.

—-Minimal, 598.

Ventricular,

——-~Maximal, 597.

—-Minimal, 596-7, and of the

Venous Sinus,

Maximal, 600.

Minimal, 599.

—Strength with which applied, 574.

—Time of cardiac cycle at which applied,
ib.

—Transmission of, 573, 619-20.

—Two-fold conduction of, 572.

Electricity, effect of,

—after injection of Casea, 4£0.

-on the Vagus roots, 301.

Electrodes for Nerve Stimulation in
Experiments on Animals, 261.

Elephants, Larynx in, 629.

Embolism of the Pulmonary Artery, effect
of, on Respiration, 330.

-error regarding the Action of Condu-
rango in producing, 380-1.

Emotion, effect of, on the Heart, Harvey
on, 9.

-and Change of Colour, Harvey’s obser-
vations on, 9-10, endorsed by
Milton, 10.

—mechanism of, 10,

Empirical Treatment,
221.

Energy, Evolution of, the distinguishing
mark of Life, 224,

Necessity for,

672

Epilepsy and Exophthalmic Goitre, 415.

—use of Digitalis in, 33.

-use of Nitrite of Amvl in, 140.

Erzot, Contraction of Blood-vessels caused

by, 470, 473.

Girtner's, in Treatment of

Heart Disease, 22.

Frinaceus Europeus, Larynx in, 631.

Erréthen des Kaninchenohres, nach
Einathmung. des _ salpetrig-
sauren Amyloxyds, 159.

Lrythrophleum Guinense, ‘On the Physio-
lozical Action of the Bark of,
(Cusca, Cassa, or Sassy Bark)
(with Walter Pye, M.R.C.8.),
458, 481.,

Ergostat,

Ether, as an Anesthetic for Dogs, (Schiff),’

338, see ill. 254.

Excitants to the Respiratory Nervous
Centre, 653.

Exertion, effects of different forms of, on
the Muscles, 18.

Exhaustion, consequent on Night-sweats
in Phthisis, probable common
cause of both, 545.

Exophthalmic Goitre, Cases of, 414.

—Spasmodic in character, (M.M.) 415.

—Typical in character, (S.P.) 416 et seq.

—Pathology of, 424.

—Symptoms of,

—the chief, 414.

—the collateral, 421, 424, and 416-20.

~Treatment of, by—

—Drugs, (Iron unsuited to, and why)
(Trousseau), 422.

—-Digitalis, 424,

—-~Veratria, ib.

—Galvanism, 421-6.

Expectorants, in Bronchitis and Phthisis,

Experimental Investigation of the Action
of Medicines, 220, and see
Appendix.

-I. Standard of Health, 220.

—Cells, Life and Health of, 227.

—Conditions of Health and Disease, 225.

—Drugs, Action of, on Cel! Life, 229.

Cumulative, 233.

Direct and Indirect, 230.

Local and Remote, 231.

——Effect on, of.

—Chemical Constitution and Physio-

logical Action, 240.

Constitution and Idiosyncrasy, 236.

-——Disease, 239.

Doses, 231.

Homeopathic, 235.

Large and small, 7d.

—Habit, Climate, Fasting and form of
Administration, 235.

INDEX,

Experimental Investigation, &c. (cont.) —
-II. Action of Drugs on Protoplanatel sf
General Directions for Ex-
perimental Investigation, 2
Caution, 242.
—on Bacteria.and Vibriones, 244.
—-~Fermentation, and Fungi, 245,
—-Inflammation, 248.
—Infusoria, 242.
—Leucocytes, 247.
— Oxidation, 7d.
—-Protoplasm, 242.
—-Putrefaction, 246.
—-Steps of an Investigation on Animals, —
249 ef seq.
—Administration of Drugs, 249,
—-—Various Channels of, 251.
—-Minimum Fatal Dose, 1b.
——-Observation of Effects, 250.
of Excretion, 251. 7
——-Results of, and their Interpreta-
tion, 250. =
Mode of Securing the Subject and In-
struments required, 252, 253,
how to make the latter, 255,
Narcotisiag Subjects, 256, (cf. oe
and ill., 254). :
Action of the Narcotics used, 258.
Procedure during,
Introduction of Cannule, 259, and —
Injection of fluid, 260.
Nerve Division and Stimulotion, 261. —
—~Respiration, Artificial, in the Frog, 263. 3
——of Gases and Vapours, apparatus for
introducing, 264, </l., 265. “al
in Mammals, 262.
Cannule for, iil., 7b. =
-IIl. Artificial Circulation, Investigation — a
of Blood Pressure. See Arti-—
ficial Circulation and Blood
Pressure, see also Appendix oe :
this Lecture, p. 335.
-IV. Determination of the Exact Struce
tures through which Drage
affect the Heart and —
290.
—Blood Pressure,
-—Changes in, caused by action of =
mode of determining whether dia he
{o Alterations in Heart or
Vessels, 317. :
—Determining exact Cause of Symp
toms, 292, s
—-Raising Blood Pressure, Mode of, 293. e
—-Registering the Heart Beats, 293,
(294, -
—Heart’s Action.
—-How Quickened by Drugs, 294-7. )
—How Retarded by ‘Drugs, 297 et seq.

INDEX.

Experimental Investigation, ke (cont.)

-IV. Determination, &c. (cont.)

—Nervous System in the Heart, (diag.),

311.

—-Accelerating ganglia, 314.

——Stimulation of, by Drugs, 314.

—-Cardiac Ganglia,

Co-ordinating Apparatus of, in
quickened Heart beats, 315.

——Stimulation of, in the same, 294.

—-Inhibitory Ganglia, 310.

Action of Drugs on, 311, 314.

—-—Motor Ganglia, 314, 315.

-V. Respiration (Appendix),
Hemoglobin.

—Apnea and Dyspnea, defined, €53,
production and prevention of
the former, 654.

—in Cells

composing the Higher Organisms,

643,
in Unicellular Organisms, 7d.
distinction between, in free and
fixed Cells, 644.

—External, in Man,

—-Function of the Lungs in, 644.

how exercised, 651.

-—-in the Frog,

Function of the skin in, €51.

—Internal,

—-defined, 644.

—effect on, of

action of substances depriving Hemo-

see also

globin of its oxygenating
power, 646.
modifications of the Circulation,
644-6.
—-effects of the above on the Tissues,
645-7.

—Respiratory Centre,

—-Excitability of, how induced, 653.

how it may be modified,

————(1) by the Temperature of the Blood
in it, 654,

(2) by the
Drugs, i.

— Excitants to, 652-3.

dependent on

——-Excitability of the centre, 653.

~extent of irritation applied to it, 7d.

due chiefly to Venosity of the Blood

in the Medulla, 652-3.

—VI. Respiration.

—Acceleration of, by Drugs, causes to
which it may be due, and how
tested,

— Excitement of the Voluntary Nervous
Centres, 329.

—Increased Temperatures, 329.

action on it of

673

Experimental Investigation, &c. (con.)

—-VI. Respiration, &c. (cont.)

—Venosity of the Blood, 329.

Causes of,

Prevention of Air from reaching

Blood, 330.
———-of Blood from reaching Air, <b.
-How this last may be efiected by
Contraction of the Pulmonary
Capillaries, 331.
Action of Muscarin in causing,
i/l., 332.

———— by Embolism of the Pulmonary
Artery, 330.

Action (supposed) of Con-
durango in causing, 7d.

———— by Stoppage of the Heart, 330.

Action of Quinine in induc-
ing, ibd.

Experimental Physiology, the two chief
modera exponents of, 8.

Experiments on the Influence of Digitalis
on the Pressure of Biood in
the Arteries, tables and ill.,
103.

—upon the Pulmonary Circulation, On the
Employment of Nitriteof Amy]
in the Collapse of Cholera,
with, 359.

External Respiration, 644, 651.

Extraction of Teeth under Chloroform,
One of the Causes of Death
during, 427.

Eye(s), see also Hiweiss, and Pupil.

-Action on, of Casca, 461, 472.

~as aifected by a grain of Sand, if soon
removed, and if allowed to
lodge, 444.

-the, Physiological Action of Digitalis

on, 67.
Eyeballs, Protrusion of, in Exophthalmic
Goitre, 414 et seq.
—probable causes of, 423-4, id/., 425.
Eyelids, impaired motion of, in a case of
Exophthalmic Goitre, 417, 421.
~causes of, (Von Grafc), 424.

FACE-FLUSHING, produced by Nitrite of
Amyl, 138, 154, 179, 174,
176, 860, cf. 186.

Fainting, (see Syncope), Pathology of, 403.

False Vocai Cords, in relation to Closure
of the Glottis, 625-7; 640, 642.

-development of, in different Animals, in
relation to Vomiting, 640-2,

-in Larynges of the Cat tribe, 632.

—Moven ents of, when apparent, 632.

—in Phonation, id.

2X

674

Fascia of the Muscles, funciion of, in

relation to Waste products,

584, 535.

affecting

Drugs, 235.

Fatigue as affecting Posture, 532, 535-6.

—Cause of, explained, 533.

Fatty Degeneration, Hemoglobin in rela-
tion to, 646.

Fayrer, Sir J., M.D., K.C.8.1., (joint
author), see Pulmonary Veins.

Felide, Larynx in, 630-1.

Fermentation, Action of Drugs on, 245.

Ferments

—derived from Solid Organs, uses of, 24.

—Harvey’s pioneer application of, 7d.

—Digestive, uses of, 25.

-Organisms producing, Pasteur’s
coveries concerning, 26,

Fever, Quick Pulse a prominent symptom
of, 455.

-in relation to Temperature, 205 e¢ seq.,
210-11.

Fever and the converse, simulated in
exp-riments with Warm and
Could Blood, 267.

Fick’s Kymographion, see Kymograpbion.

Fifth (Cervical) Nerve,

—effects of division of, (Sinitzin), 444.

~Heart’s action as influenced by, 434.

Finger, congestion of, caused by a liga-

ture, 4383, due to venous
blvod in capillaries, 439.

Fasting as the Action of

dis-

Fire-heat

~'n relief of Burn pain, 449-50.

Fishe, and Frogs

~—Action on, of

—-Casca Bark, 458, 463, various doses,
490-1.

Flushing of Rabbit’s Ear, see Rabbits.

Fontana’s experiments

~on the Organs Es ential to Life, 374.

-on Viper Poison, 381, 385.

Food, see Warm Food.

Foot, see Frog’s foot.

Foot-stools, uses of, 533.

Form of Administration, as affecting the

Action of Drugs, 235.
Michael, and Experimental
Physiology, 8.

Fowls’ blood, experiments on the Nuclei,
or Zooids, of, 147 et seq.

Foxglove, (see Digitalis), 31.

Fraser, (see also Brown, Crum, and
Fraser), researches of, oa
Calabar bean, and their results,
473.

Friedrich’s division of
Pectoris, 191.

Fright, death from, 399.

Foster,

Angina

INLEX,

Frogs, see also Fishes and Frogs, and —
Frésche.

—Action on, of

—Casca, 458, 460, 463 e¢ seq.

—WNitro-glyverine.

-——General, 474 et seq.

—-Special, on various organs, &¢., 477
et seq.

—Artificial circulation in, 319.

—Respiration in, 263.

—as affected by shock, 7//., 401.

—Blood Pressure in

—Action on, of
diag. 502.

—Cireulition of, as affect-d by Nitrite of
Amy], 174, 178.

—difference of muscular sensibility in
different species of, 478.

“Foot of, irritation of the web of, micro-
scopically observed, 445.

~General Action of Condurango on, 340.

—Heurt of, see Electrical Stimulation of
the Frog’s Heart, Effect
of, ¥c.

—Action on, of Casca Bark, 499-501, and
see 525, and of Digitalis, 467-8.

—Simple Method of Demonstrating the
Effect of Heat and Poisons
upon, 455.

—Stannius’s experiment on, described and
explained, 557-8.

—Heart of, (excised), experiments on the

—Action of Drugs on, 804 eé seq.,
all., 305.

—Effect of Warmth on, (Cyon), 205.

—Stopping by Shock, (Goltz), 431-2.

-Lungs of, effect on, of sudden changes
of temperature, il/., 383-4.

—Muscles of

—Artificial oxyzenating of, (Kronecker),
377, 645.

—effect on of joint action of Strychnia
and Nitrite of Amyl, 390-1. —

—Re-vitalizing of (Preyer), 375-6.

—Motor and Sensory Nerves of

—Action on, of Casca, 522, effects of, on
Reflex Excitability, 523-5, <.,
523.

—Pulmonary Capillaries of, Action on, of
Drugs, how observed, ill., 333.

-Skin of, respiration by means of, 651,

Fungi, Action of Drugs on, 245.

Frésche, Beobachtungen tiber deren
Schwimmhaut und JZunge
(Gunning and Cohnheim), 160.

-Wirkung des salpetrig-sauren Amyl-
oxyds auf deren Blut-
strom, 154,

Casca Bark, 6501,

INDEX.

GatyanisM, in Exophthalmic Goitre,
(Meyer), 424-6.

Gunglia, see Cervical Ganzlia an1 others
under names, sze also Nervous
centres.

--of Meduse, producing rhythmical move-
ments of the bell, (Romanes),
572.

Girtner’s Ergostat, 22.

Gases, Action of, on Cells, 249.

~Effect of, on Hemoglobin, 646.

-or Vapours, Artificial Respiration of,
apparatus employei for, 264,
all., 265.

Gaskell, cited on transmission of Stimuli
in the Frog’s Heart, 573, and
Hearts of other Cold Blooded
Animals, 619.

Gastric glands, chemical changes in Blood,
produced by, 23. °

Gefiissnerven, Verinderungen des Ar-
teriendurch-messers von Cen
Errezgungen derselben zum
Theil unabhingig; Versuche
dariiber, 169-60.

Gefiszserwei erung nach Einathmung des
salpetrig-sauren Amylox) ds,
wie herbeigefiihrt, 159.

Gefisswand, Eigenbewegung derselben,
160-1.

—Wirkung des salpetrig-sauren Amyloxyds
auf derselben, 164.

Genitals, see Abdominal Viscera, also
Castration, and Uterus.

Germination, Action on, of Casca Bark,

_ 458, 492.

Germs, in relation te Disease, 26.

Gesicht, plotzliches Erréthen desselben,
von dem salpetrig-sauren Amyl-
oxyd herbeigefiihrt, 154, 159.

Gland-juices, see Pepsin, Thyroid, and
Testicular.

Glands, see Lachrymal, Salivary, Sub- and
supra-maxillary, Sweat, and
Thyroid do

-blood-supply of, increased during secre-
tion, (Bernard), 13.

—digestive. function of, 23.

_-kept alive by Artificial Circulation,
(Ludwig), 376.
Glandular activity and the Heat of the
body, 13.
Giottis, Closed, Griitzner’s picture of,
625.

—-Closure of,

—in Coughing. 562, sneezing, vomiting.
&e., 624, 640, 642

—in relation to fixation of the Thorax,
624, 634, 642.

—by Ventricular bands, 639, 642.

675

Glottis, Closure of (cozt.)

—in Vomiting, 624, in relation to the
development. of the False
vocal cords in different classes
of Animals, 640-2.

Glottic types of Larynx

—Cavernous, 628, 632-5.

—Composite, 623, 630-2.

—Simple, 628, 629-30.

Glutinous and saccharine substances,
action of, in relief of Cough,

562 et seq. :
Glycerine, scion of, in Cough mixture,
566-7.

Goitre, Exophthalmic, Cases of, 414.

—Pathology of, 424.

Goltz, Prof., experiment by, on St»ppage
of a Frogs Heart by Shock,
431-2. .

Graves, observation by, on Exophthalmic
Goitre, 414.

Graves’ Disease, see Thyroid Gland )

Graphic method for measuring Blood-
Pressure, (Ludwig), 9.

Griitzner, picture by, of Closed Glottis,
625.

affecting the Action of

Drugs, 235.

Hemadynamometer, the, of Poiseuille, in
Quantitative Experiments on
the Effects of Drugs, 7.

-the registering, of Setschenow, and its
uses, 52.

Hemoglobin, function of in feeding tissues
with oxygen, 644,

—Effect on, of certain Gases, 646.

-in relation to Fatty Degeneration, 7d.

-Test for presumed alteration of, by
druzs, 647 e¢ seq.

Hemorrhage, collapse from, Transfusion
in, 886-7.

Hemostatic Aa anticipated, of Casca,
473.

Hales, Stephen, first to measure Blood-
pressure in the Arteries, 4,
279.

Haller, on independent
Pulsation, &e., 580.

Hand, steadiness of, in relation to Holding
the Breath, 634.

Hares and Rabbits, Larynx in, 629.

Harnsecretion, Gesch windigkeit Cerselben,
wovon bedingt, (Hermann and
Ludwig), 410.

-Wirkung auf derselben bei Digitalis-
experimenten, 410.

Harveian Oration, The, 1894, 1.

2x 2

HABIT, as

Pulmonary -

676

Harvey, death of, 27, 28.

—-his knowledge of Drugs, used
ternally, 6.

-on the Admixture of Blood from various
parts of the body, 22-3.

—on cures of Diseases of the Circulation, 22.

-on Dilatation of the Vena Cava and
Pulmonary Veivs, 4.

~on Massage for Heart trouble, 21.

ex-

~some Modern Developments of his
Work, 3.
~wishes of, as to Scientific Investiga-

tion, 27.

Hfead and body, mode of supplying with
different kinds of Blood, 298.

Headache, induced by Nitro-glycerine,
478, 480.

—use of Nitrite of Amy] in, 140.

Health, The Standard of, 220. For sub-
heads, see under Experimental
Investigation.

—and Disease, Conditions of, 225.

-different effects of Drugs in, 239.

Heart, see also Cardiac, Frogs, Herz,
Rabbits, Mammalian, and
Electrical Stimulation.

~Accelerating Nerves of, 11.

--Action on, of

—-Casca Bark, 459, 467-8, similar to that
of Digitalis, 473.

—Chloral, 190.

—Drugs, 27.

—Emotion, Harvey on, 9, 10.

—Over-exertion, specially in growing
boys, 18.

—Nux Vomica, as a Stimulant, 561.

—Phyostigma, (glycerine extract of), 528.

—-Strychnia, On the Explanation of
Stannius’s Experiment and on,
(with Theodore Cash, M.D.),
557.

—-as a Stimulant, 561.

—of the Vagus, 10, 11.

—Cat’s, Action on, of Casca Bark, 501.

—Dog’s, Action on, of Casca Bark, small
dose, 505-7, table, 506.

—Frog’s, Action on, of

—Casca Bark, 499-501, and see 525.

—Nitro-glycerine, 479.

—Experiments on the action of Drugs on,
304 e¢ seq., tll., 305.

—Simple Method of Demonstrating the
Effect of Heat and Poisons
upon, 455.

—Stannius’s Experiment on, described
and explained, 557 eé seq.

—~effect, after, of Warmth, in restoring
Pulsation, 558.

—Stoppage of, due to Shock, Goltz’s
experiment on, 431-2.

INDEX,

Heart (cont.)

—Rabbit’s, (see Rabbit’s Heart), stopped by
animal smelling ammonia, 40/7,
439.

Heart,

—Cavities of, see also under names.

—Distension of, pain caused by, explana-
tion of, (Ludwig), 117.

—TInhibitory interaction of, 620.

—Contractions of, in normal and abnormal
conditions, 560.

—sequence of, 529-30.

--Exterior insensibility of, (Harvey), 19.

~Interior sensitiveness, and the pain
caused by pressure, 19-20. _

—Heated, see Electrical Stimulation of the
Frog’s Heart, sub-head (c).

-Inhibitory apparatus of, Action on, of
Atropia, 5238.

—Mammalian,

+——experiments on the action of Drugs
on, 303.

—Infuence of Temperature on the Pulsa-
tions of, and the Action of the
Vagus, 205.

-Modern development of knowledge as
to Diseases of, and Circula-
tion, 3.

—Muscular Fibres of, Paralysis of, 315.

—Nervous System in, diug., 311.

—<Accelerating Ganglia, Stimulation of,
by Drugs, 314.

—Cardiac Ganglia, Co-ordinating appara-
tus of, in quickenel Lieart-
beats, 315.

—-Stimulation of, in the same, 29 t.
—Inhibitory Ganglia, 310, Action of
Drugs on, 311, 314.

—Motor Ganglia, 314—5.

—Paipitation of, in Exophthalmie Goitre,
414 et seq.

—Causes of, three chief, J

—-~Paralysis of the Vagus, 421.

—-—Relaxation of the Arteriole, 7d,

—-Stimulation of the Accelerating
Nerves, 7d.

—Paralysis of, the cause of Death from
Casca poison, (Liebreich), 488.

—caused by inhibition due to Heat,
207.

—Physiological Action of Digitalis on, 49.

—as affecting,

—-Impulse of, 54.

—-Rhythm of, 53.

—-Sounds of, 54.

—Pulsation of, after being cut to pieces, 10,
and after removal from the

body, 11.

—independent of its nerves, 10,

-relation to, of Muscles, 15,

INDEX. 677
Heart (cont.) Heat, &e. (cont.) .
-Sounds of, discovered by Harvey, 5, Electrical Stimulation,
other observers, 5, causes of, | ————Auricular,—

described by Glendinning,
Williams and Todd, 6.

—Stoppage of,

—due to impaired Cardiac Nutrition, 19.

—due to shock, 393-4, 430-3.

—-how caused, 434.

—effect of Quinine in causing, 30.

—effect of, on Respiration, 7d.

-Valvular disease of, bearing on, of the
Contraction of the Pulmonary
Veins and Vena Cava, 530.

Heart’s Action,

—How Quickened by Drugs,

—by Paralysis of the Vagus, 295.

—-of its ends, fibres, and roots, in the
Heart, 295.

—by Stimulation of the Cardiac Gan-
glia, 294.

—direct, of the Sympathetic, id.

—How Retarded by Drugs, 297.

—Irritation of Vagus rvots, #b., e¢ seq.

—indirect, through Blood pressure, 297.

do., through Respiration, 300.

—reflex, 299.

—Irritation of Vagus ends and fibres, 301.

—Increased conducting power of, ib.

—Paralysis of Cardiac Ganglia, 303.

—of the Sympathetic, 7d.

Heart-beats,

—Effect of each, on a Limb, (Mosso), 536.

-Variation of Strength and Rate in,
(Harvey), on, 9.

—Mechanism _ producing, (Weber,
EK. and E., and others), 10.

Heart-disease,

—Diet for, during Rest in Bed, 21.

—Ling’s system of Massage for, ib.

—Symptoms of, 21.

~—Treatment of, rationale of various forms
of, 20 et seq.

Heart-strain, caused by sports in immature
competitors, 18.

Heart and Lungs, the two Essential
Organs to the maintenance
of Life, (Huxley), 374.

Heart and Vessels, the, Determination of
the exact Structures through
which Drugs affect them, 290.

Hleat, see Cold, Heat, and the Action of
Drugs, and Heat and Cold,
infra.

-Action of, in causing Death, author's
view, 212.

~-on the Frog’s Heart.

—~ffect on the Heated Heart of

—Electrical Stimulation, 573,

594, 609, 622-3.

577,

Maximal, 594.

Minimal, 7d.

—-Ventricular,—

Maximal, 594.

Minimal, 593, and on the

Venous Sinus,—

Maximal, 595.

Minimal, 7d. 2

—action of, in relief of Inflammation Pain,
449-50, 454.

~action of, on the refractory period in the
Cardiac cycle, 577.

-application of, to the Cardiac region im
Syncope, 408.

-of the Body,—how maintained, investi-.
gations into, (Ludwig and’
others), 11 et seq.

-of Warm-air bath versus that of Cotton.
Wool in recovering Chloral-
affected animals, 198, 199.

Heat and Cold, action of, on the Heart’s-
pulsations, simple method of
demonstrating, 455-7, <1l., 456.

—Effect of sudden alternations of, on
Frogs’ Lungs, 333.

Heat and Poisons, Effect of, upon the
Heart of the Frog, A Simple-
Method of Demonstrating, 455.

Hedgehog, Larynx in, 629, 635.

Hering, experiment of, in supplying.
different Kinds of Blood to-
Head and Body of a Cat,,
298.

Herz, keine unmittelbare Wirkung auf
dasselbe, von dem salpetrig-
sauren Amyloxyd, 164, 169.

Herzschlag, der, von dem salpetrig-
sauren Amyloxyd beschleunigt,
(Guthrie), 154.

Hill-climbing, in relief of Cardiac pain,
(Ludwig), 17.

Hippopotami, Larynx in, 628.

Holders for Animals to be Experimented
on,

—Bernard’s, 252, ill., 254.

-—Brunton’s, i//., 254, his method of hold-
ing, 338-9.

—Czermak’s, 252, ill., 253.

Holding the Breath, in relation to Steadi-
ness of the Hand, 634.

Hollow Muscular Organs, pain induced
by Distention of, 1u.

Homeopathy, 235.

Horse(s),

—Larynx of, 633.

—Physiological Action of Digitalis on, 39.

—Vomiting in, difficulty of, 640,

678

Howling Apes, Larynx in, 634,

—Ventricular bands in, 635.

Human Pulse, see Pulse, Human.

Hunde, see also Dogs.

-Beobachtungen iiber die Gefiisse deren
Skeletmuskeln, (Sadler), 160.

—Digitalis-experimente an, 410.

Hydrocyanic acid,

—Action of,

—on cough, 563-4.

—in relief of vomiting, 571.

—on Respiratory Centre, 566-7.

—Poisoning by.

_ —Artificial Respiration in, 379, 381.

—Physiological Action of, 381.

Hyena, Larynx in, 631.

Hyoscyamine, a tion of, on the Inhibitory
ganglia of the Heart, 314.

Hyoscyamus and Oxide of Zine, in relief
of Night Sweat in Phthisis, 554.

Hypertrophy as the result of Conges-
tion, 440, case illustrating,

’ (Stirling), 7d.
_ Hypodermic Syringe, the, introduction of
by Wood, 7.

Ics in relief of Vomiting, 571.
Idiosyncrasy, see Constitution and
Independent Pulsation of the Pulmonary
Veinsand Vena Cava, Note on,
(with Sir J. Fayrer, M.D.,
K.0.8.1.), 528.
Induction and maintenance of Anesthesia,
in Animals, 256 et. seq., 337-9.
-Infective Diseases and protective Inocula-
tion, 26.
Inflammation, Action of Drugs on, 248.
—not identical with Congestion, 440, 441,
453-4,
—in relation to Congestion, 438-41.
-period of commencement of, following
Congestion, (Cohnheim and
Paget), 447, 454.
—process of,
—nmicroscopically observed in Frog’s foot-
web, 445.
Influence of Temperature on the Pulsa-
tions of the Mammalian Heart,
and on the Action of the
Vagus, 205.
Infusoria,
'-Action on, of
—Casca Bark, 459, 491-2.
—Drugs, 242, 491-2.
Inhalation, see also Spray and Inhalation.
-of Nitrate of Amyl, effects of, compared
with those following injection
or internal administration,
372-3.

INDEX.

Inhibitory Apparatus of the Heart,

—Action on, of Atropia, 528.

Injection of Drugs, introduced by Wren, 6.
used hy Mezgendie to localise
effects, 7.

—-Fluids, into Blood-Vessels, 260-1.

Inoculation against Infective Diseases, see
Antitoxins.

Instrument, Simp'e, for Examining the
Competency of the Tricuspid
and Mitral Valves, 537.

Instruments needed for Experiments on
Animals, 253.

—Cannule, T.-tubes and Pens, iJ/., ways
of making, il., 255-6.

—Introduction and uses of, 259, 262.

—Valves and stopcocks, ill., 263-5.

Intermittent versus Continuous action,
effects of, on the Body, 18.

Internal Respiration,

—defined, 644.

-Effect on, of action of substances de-
priving Hemoglobin of

oxygen - distributive power,
646.

—of modifications of the Circulation,
644-6.

Intestinal Nerves, Paralysis of, (pre-
sumable), in Cholera, 368,
Moreau’s experimentin relation
to, tl., 362-3.

Intestines,

-Action of Casca on, 461, 465, 495, 498-9.

—Blood in, how chilled and how protected,
various countries, &c., 531.

Intra thoracic pressure in relation to
Vomiting, 640, C41.

Intra-tracheal Pressure, increase of, a
cause of Von iting, 640.

Invertebrata, as affected by Casca Bark,
458, 463, in various doses,
491.

Investigation, Experimental, of the Action
of Medicines, 220, for sub-
heads see under Experimental
Investigation.

Ipecacuanha,

—Solution of,

—Action of, on the respiratory centre,
555.

-Spray of, &c.

—Action of, in relief of Cough, 564.

Ipecacuanha and Squill,

-in relief of Chronic Bronchitis, effect of,
on Cidema of the Legs, 544.

Initants and Counter-Irritants, On, with
Remarks on the Use of Blisters
in Rheumatism, 438.

-benefits of, how produced, 453, 454,

—detinition of, 438,

INDEX.

Irritants (cont.)
-Summary, 453-4.
Irritation of a Sensory Nerve, double
effect of, (Ludwig), 443, 451,
Tron, beneficial in "Heart Palpitation. of
the Anemic, 422; exception
to the application of it, 7d.
Organs, Artificial Circulation
through, (Ludwig and Mosso),
835, do. of different kinds of
Blood, 336.

Tsolated

introdnetion of Vecwuation

by, 26.

Jenner, Sir W., tribute to, 2.

Jenner and Parry, on Causes of Angina
Pectoris, 19.

Joint Action of Drugs, the, within the
Animal Organism, On the
Apparent Production of a New
Effect by, 390.

Joints, Rheumatic aitections of, relieved
by Blisters, 453 -3, 454,

Jugular, the, and other Veins, On Pulsa-
tion, (or Pseudo- Pulsation), i in,
539.

-as affected by Cough, 566.

-unilateral pulsation in, 539, case illus-
trating, 540-1.

Jujubes, probable action of, in relief of

Cough, 553.

JENNER,

Kaneaross, Larynx in, 623, 684-5. ‘

Kaninchen (see also Rabbits), Athem-
bewegungen derselben bei
Einatbmung stark riechender
Dimpfe eingestellt, 155.

-Wirkung des salpetrig-sauren Amyloxyds
auf deren Blutstrom, Versuchs-
anordnung und Resultate, 7/l.,
155 ef. seq.

Kaninchenohr (see also Rabbit’s Ear),
Erréthen desselben, nach
Einathmung = des_ salpeurig-
sauren Amyloxyds, 159.

Kidney-extract, therapeutic use of, 25.

Kidneys,

~Action on, of

_ —Casea, 460, 470.

—Digitalis, 412-3, 471.

—Dogs’,

— Artificial Circulation through, (Ludwig
and Mosso), 335-7.

—Effects on, of Atropia, Carbonic acid
Gas, Chloral hydrate,
tricity, and Nicotine, 336-7.

Knee-jeiats, requirements of, to secure
Rest, 532, 536.

Elec- |

)

679

Kronecker’s experiment in artificially
oxygenating a frog’s muscles,
377. .

Kiihne, Prof., discovery of, concerning
Nuclei of Blood Corpuscles,
147,

Kymographion, the,

—Fick’s spring pattern, 144, <//., 284.

—Ludwig’s, 280-3, 7l/., 281.

~Mode of using, 235.

—Pens for use with, 256.

—Reduction of tracings made by, 286.

—Used in experiments with Digitalis, 141,
144, 145, note.

LACHRYMAL Gland, (Cat’s), action on, of
Casca, 519.

Laennec, Auscultation of the Heart intro-
duced by, 5.

Larynx, Valvular Action of, (in conjunc-
tion with Theodore Cash,
M.D.), 624.

—aspect of, in Retching, 624.

—-Bibliography, 642.

—Comparative anatomy of, €27-35.

—Lxperiments on those of

—A pes, 635, 639.

—Cats, 7b., 637-8.

—Dogs, ib., 638-9.

—Man, ib., 639-40.

—Sheep, 7b., 636-7.

—-—Methods pursued, 635 e¢ seq.

—Human, see Man, Larynx in.

-relation of, to

—Cough, 562.

—Movements, 634-5.

Laryngeal Nerves

-as affecting the Respiratory Centre.

—(a) normally, 324-6.

—(b) when affected by inhalations, 327.

Laryngeal Phthisis, sedatives in re'icf of,
methods of applyir g, 564-5.

Laryngeal variations,

—Anatomical Classification of, proposed
by Mi!ne Edwards, 627-8 et seq.

I. Aglottic type, 628-9.
IT. Simple Glotiic type, 628, 629-30.
III. Composite type, 628, 639-2.
IV. Cavernous type, 621, 632-5.

Laudanzm, (see also Opium), action cf, on
the Heart, 315.

-in experiments on Rabbits’ Hearts and
Temperature, 212.

Leech, Dr. Croonian Lecture by, referred

to, on remedial Treatment and

modification of the Heart, &e.,

by j)rugs, 27.

Legallois’ experiment on the Essentials to
life, 374-5.

680 INDEX.
Legs, Lung(s)—cont.
-action on, of each Heart-bzat, (Mos 0), | —secretion and nutrition of

536.

'-posture of, best suited to relieve swelling
of Fatigue, 535.

~—swelling of,

—in Chronic Bronchitis, 543-4.

—after Fatigue, cause of, 534, how best
removed, 535.

-why drawn up in cold weather and vice
vers, 532.

Leucocytes, Action of Drugs on, 247.

Liebreich, Prof., experiments of, on Casca
Bark, and its action on
Animals, 483.

Life, see Preserving Life.

—processes in which it consists, 224.

—the Tripod of, 377, Huxley cited on, 374.

Life and Health of Cells, 227.

Lifting-Power of Muscle, effect on, of
Casca, 521, 522.

Light, Young’s Undulatory Theory of, 4.

Limb, see Leg.

Linctus, Action of Drugs in, in relief of
Cough, 563 e¢ seq.

Ling system of Massage
Disease, 21.

Lion, Larynx in, 630,

—Ventricular bands in, 635, 642.

Liver, (Dog’s), Amificial Circvlation
through, Ludwig and Mosso,
335.

—(IIuman), Vaso-motor Nerves of, their
course, and connection with
Diabetes, 424, 425, il.

Living Body, the, Cireulation in, 272,

Llaina, Larynx of, 632, 635.

Local Action of Drugs, Magendie’s investi-
gations into, 7.

Localisation of Action, the aim of Experi-
ments with Drugs, 241.

Ludwig, Carl, discoverer cf the action of
the Vaso-dilator muscles, 11.

—experiments of, in preserving activity in
excised glands, 376.

-hypothesis of, as to the heart, and other
pains in Angina Pectoris, 194.

—Kymographion, see Kymographion.

—method of, for testing Drug action on
Frogs’ Hearts, 304.

~Respiration- pump, of, 264.

—work of, and of his pupils in connection
with our knowledge of the Cir-
culation, 8,9 ef seq.

Ludwig and Coats, apparatus of, for re-
search on the Vagus, 307,
ill., 308.

Lung(s), (see also Respiration), experi-
mental introduction into, of
Gases, 264-6.

for Heart

—-action on, of

Nitric acid, 567, 569,

Potash, 569.

—surface of, in relation to Cough, 562-3.

—Frogs’,

—effect on, of sudden changes of tempera.
ture, il/., 333-4.

-Toads’,

—differenceof, from Frogs’, (Sharpey),333.

Lungs and Heart, the two essential orgars
to maintain Lile, (Huxley), Pye

Lymph in the Muscles, in relation to
Fatigue, 534-6.

MaMMALIAN Heart,

-experiments on the Action of Drugs
on, 303.

Influence of Temperature on the Pulsa-
tions of, and on the Action of
the Vagus, 205.

Mammals, see also separate names.

—Artificial Circulation in, 318.

—Artificial Respiistion in, apparatus for,
ill., 262-3.

—General Action on, of

—Casca, 483 e¢ seq.

—Condurango, 312.

—Pisciform, and Ungulate,

—Larynx in, 623, 630.

Man, Action on,of Casca bark, in Angola
ordeals, 481. j

—Larynx in, 639.

—KExperiments on, 635, 639-40.

—Ventricular bands in, 649, 642.

Manometer, the, various forms of (See also
Kymographion), 280-3.

Marey, Prof., Cardiograph of, and its
uses, 203. ‘

-on Electrical Stimulation of the Frog’s
heart, 574, 576, 577, 618, 620.

-law formulated by, on factors of force of
Pulse in Digitalis poisoning, 49.

do. do.

Arterial tension, 46.

—~Pneumograph of, how used, ill., 328.

—Sphygmoscope of, 283.

Marey and Chauveau, method of, fowid res @ -
recording Apex-beat varia-

tions and Pulse curve, 9.
Marmot, Larynx in, 632.

Marshmallow lozenges, probable ation of, a

in relief of Cough, 5638. 2
Marsupialia, Laryngeal cavity in, 628,
634-5.

Massage for Heart Disease, 20.
—modern systems of, 21.

of ratio of Pulse rate and “i

INDEX,

Massage (cont )

-results of, (lunnicliffe), 21-2.

—(J. K. Mitchell), 27.

Meat, raw, first used as a remedy in
Diabetes, 25. 5;

Meatus, Internal Auditory, irritation of,
in relation te Cough, 562.

Medicine(s), (see als» Therapeutics),
Action of, Experimental Inves-
tigat‘on of, 220, for detailed
sub-heads, see Experimental
Investigation.

-Probable use of Casva in, 473.

MedulUa oblongata,

-Action on, of Respiratory Sedatives,
565.

—Influence of, on Vaso-motor and Respi-
ratory movements, 558-560.

—Nerve centres (partly) in, 547-50.

—Cardiac, (Ludwig), 11.

—Cougb, 562.

—Respiratory, (chief seat of), 322 e¢ seq.

—Vomiting, 571.

—Nerves proceeding from,

—Vaso-motor, 13.

—Position in, of the Cardiae Centre, 11.

-Venosity of Blood in, consequences of,
652-3.

Meduszx, observations on, of Romanes,
ll., 572.

Mental emot’on asa cause of death from
Shock, 399.

-and Physical power,

—restorative action on, of

—Nux Vomica and Strychnia in small
doses, 561.

Method, A Simple, of Demonstrating the
Effect of Heat and Poisons
upon the Heart of the
Frog, 455.

Meyer, Adolph Bernard, m.p., (joint-
author), see Action of Digitalis
on the blood- Vessels.

Meyer, R., on the occasional red colour of
Venous Blood, 405 note.

Microbes, discovered by Pasteur, import-
ance of his work, 26.

Milk, diuretic action of, 21.

Milne-Edwards, Anatomical classification
of Laryngeal variations pro-
posed by, 627 et seq.

Milton, on the effect of the Emotions on
Facial Colour, 10.

Minimum Fatal Dose, how ascertained,
251.

Mitchell, Dr. Weir-,

of, 21.

Mitral disease of the Heart, anticipated
use of Casca in, 473.

-Valves, see Tiicuspid and Mitral do.

massage system

681i

Modification by Cold, Heat, anid the
Action of Drugs, of the Effect
of Electrical Stimulation of
the Frog’s Heart, (with Theo-
dore Cash, M.D.), 574, 576.

Monkeys, see Apes and Simians.

Monteiro, Mr., Casca Bark provided by,
for investigation, 463, 473, 481.

Moreau’s experiment, 7//., 362-3.

Morphine, see also Opium.

—Action of, on,

—Cough, in Linctus and Solution, 563-4.

—Digestion, how counterbalazced, 567.

—Respiratory centre, 566-7.

Morphine and starch powder, mode of
applyingin Laryngeal Phthisis,
564-5.

“ Motion as it were in a Circle,” Harvey’s
idea, and its developments, 3,
et seq.

Motor ganglia of the Heart,

—Action on, of

—Stannius’s experiment, 557-8.

—St~ychnia, #fter above, 559.

—Warmth, after the above, 558-559.

—distribution of, 557-8.

—how called into action, 314-5, 559-60.

Motor nerves,

—Action on, of,

—Casca, 466, 522.

—Nitro-glycerine, 478.

Mouth, see Skin and Mouth, and Thirst.

Movements, relation to, of the Larynx,
634-5.

Moxon Medal, awarded to Sir W. Jenner,
1891., 2.

Mucilaginous substances, see Linctus.

Mucin, in relation to the chief constituent
of the Nuclei of Blood Cor-
puscles, (Kiihne), 147.

-results of the author’s experiments con-
cerning, 152-3.

Mucous Membrane.

-Action on, of Spray and Inhalation of
Drugs, in relief of Cough,
564.

—Congestion of, a cause of Cough, 567.

—Nasal, action on, of Digitalis, 60.

Mule, Larynx of, Cuvier cited on, 633.

Miller, Johanres, on

—closure of the Glottis, 624.

~independent Pulsation of the Vena Cara
and Pulmonary veins, 530.

Miiller’s valve, and its uses, 263, 7l/., 265.

Murrell, Dr., proposer of the use of Nitro-
glycerine in place of Nitrite of
Amyl, 480.

Muscarin, (Muscearia), action of, on the

—-Frog’s Heart, 311-3, 487.

—Pulmonary capillaries, 568.

682

Muscle(s), see also Nerves and Muscles.

—Action on, of

—Casca, 462-3, 456, 21-2.

—-Effect on

—— Liftirg Power of, 521, 522.

—Muscle-Curves, 521, 522.

Structure of Muscular ‘issue, 520.

—-~Muscular weakness induced by, 465.

—Nitro-glycerine, 477.

Contracting, sound emitted by, discovered
by Dr. Wollaston, 5

-of Fiogs, effect on, of joint action of
Strychria and Nitrite of
Amy], 390-1.

-relation of, to the Heart, 15.

—waste products of, accumulation of, the
cause of Fatigue, (Kronecker),
533-4.

—how remored, 534.

Muscle-Curves, effect on, of the action of
Casea, 521, 522.

Muscular Action in relation to Blood
Pressure, 15, 16.

—Circulation, ’

—three ways of increasing

—(1) Rest in bed, with Massage, 20-2, 27.

—(2) Graduated exercises of Stationary
Patient, (Schott), 20, 22, 27.

—(8) Graduated exercises in walking
stig climbing, (Oertel), 29, 22,
27.

~Fibres,

—of the Arterioles, independent con-
tractility and the converse, of,
results, 12.

—of the Heart, Paralysis of, 315.

~Tissue, Structure of, Effect on, of Casca,
520, 522.

Camm T of Stimulus to the Hear‘,
573.

—vessels, dilatation of, on irritation of
Peripheral Nerves, 14, 15.

Mustard applications, in Pleurisy, relief
given by, deductions from, 451.

Myosin, coagulation of, the cause of
Rigor Mortis, 376.

Myxeedema, use of Thyroid Gland Extract
in, 25.

Narcotics. Administrati-n of, to Animals
before Expei imenting, 256.

—Action of, 258-9.

—Mode of administering, 259-61.

Nasal Mucous Membrane, Physiological
Action on, of Digitalis, 60.

- Nerves

—as alfecting the Respiratory Centre,

—(a) normally, 324-5.

—(b) when affected by inhalations, 327.

INDEX.

Nauheim Treatment, (Schott), features
20 a

of, 20. J
Nerve-Centres, On the Action of Nitrite —
of Amyl on the Circulation —
and on Active Dilatation and —
Contraction of Arterioles,
independently of, 174.
Nerves, see .
-Chorda Tympani, Depressor, Fifth Cervi- —
cal, rapes Nasal, Respiratory, —
Sciatic, Sensory, Superior Cer:
vical Ganglia, Sympathetic,
Vagus, Vaso-di'ator, Vaso- —
inhibitory, Vaso-motor, see
also Ganglia.
-Division and Stimulat‘on of, in Experi-
ments on Animals, 261. q
~Influence on, of Drugs, reacting on
B ood-pressure, 274, ;
-Contro'ling the Heurt’s Action, (see also —
Heart, nervous system in), 434,
—the principal one, 7d.
-Iufluencing B'ood-pressure,
—Cardiac Ganglia, 274.
—Inhibitory Nerves, 7.
—Quickening do., 275.
—Vaso-inhibitory do., 276.
—Vaso-motor do., 275. 4
-Influencing R-spiratory Centre, 324-7,
all, 325. |
—Cutaneous, 324-5.
—Laryngeal, Superior
32

and Inferior, —

—Nasal, 324-7.

—Pharyngeal, 327.

—*upra-maxillary, 325,

—Vaynus, 324, 326.

—modification of their effect by Drugs, ©

(a) inhaled, 327.
(4) injected, ab.

-Influencing Pulse,

Cutaneous and Visceral, 15, :

-Intestinul, Paralysis of, (presumab’ ay
in Cholera, | 303, Moreau’s —
experiment in relution to, tly 3
362-3. ;

-Peripheral, irritation of, causing dilata-
tiono! Muscular vessels, 14,15, —

-regulating action of, on the diamoter of
vessels, 11.

-secreting, act'on of, on Sweat Glands, 545. A

-Vaso-motor of the Liver, course of, and
connection with Diabetes, 424, —
ill., 425. a

Nerves and Muscles, kept alive by Artifi-
cial Circulat on, 374-6, 4

Nervous Centres, see Cerebral centre, Vaso-
motor and Voluntary centres. ©

—for Cough, location of, 562.

—-for Vomiting, location of, 571.

INDEX.

Nervous (cont.)

-channels of Stimulus to Auricle and
Ventricle, 573.

System, Act‘on on, of Nitro-glycerine,
474,

—in the Heart,

——Accelerating Ganglia, 314.

—TInhibitory Ganglia, 310.

Action of Drugs on, 310-11, 314.

—Motor Ganglia, see that head.

—Physiological Action of Digitalis on, 66.

Neuralgia, use of Nitrite of Amy! in,
140

Newt, Blood-corpuscles of, as affected by
Casca Bark, 493.

Nicotine, (Nicvtia),

-effect of, on the Blood in Art ficial Cir-
culation in Isolated Organs,
336.

—on the Vagus, &c., 310-11, ?12, 314.
—introduced into the Circulation, (a cause
of cold Sweat), 550.

—when used before Muscaria, 312.
Niere, wahrscheinliche Wirkung der Digi-
talis auf deren Nerven, 411.
Night-Sweating in Phthisis, On the
Pathology of, and the Mode of
Action of Strychnia and cther
Remedies in it, 545.
- -consequent exhaustion,
—probable common cause of both, 545.
—Patho'ogy of, 550-1.
—Relief of, by Drugs, 551.
—cases illustrating, 552 e¢ seq.
Nitric acid, action «f, on the
—Secretion in the Lungs, £67, 569.
—Stomach, 567.
Nitric Oxide, action of, on Internal
Respiration, 646.
Nitrite of Amyl, see also Salpetrig-
sauren Amyloxyds.
-action of, contrasted with that of Nitro-
glycerine, 479-80.
-in conjunction with Strychn‘a, effect of,
on Frog’s Muscles, 390-1.
-in Experim nts on Pulse rate and
Arterial Pressure, 145.
.~On the Action of, on the Circulation
[and on Active Dilatation and
Contraction of Arterioles, in-
dependently of Nerve-
Centres], 174.
—Action of, on the Circulation, 174.
—effects of,
Diminished Blood-pressure, 175, 180.
Flushing of the Human face, 174, 176.
of the Rabbits’ ear, 176, 178.
Throbbing of the Carotids, 174.
— experiments on the reason of, diags.,
175-8 4.

683

Nitrite of Amy], &c., experiments (cont.)
on Dogs, 174, 176.
—cn Frogs, 174.
——on Rabbits, 175 et seq.
Results of, and deductions from,
cause of Diminished Biood-pressure
ascertained, 180-4.

independence of Vaso-motor nerves
=o of varying Blood-pressure,
178.

—-On the Emp'orment of, in the Collapse
of Chelera, [with Exp: riments
upon the Pulmonary Circula-
tion ], 359.

—Action of, on

—-blood, 372.

—Circulation, 359.

——Pulmonary Capillaries, 369-73.

——Systemic Capill»ries, 369 ef seq.

— Question of form of Administration,372.

—On the Use of, ir Angina Pectoris, 137,
185.

—Action of, 137.

—case illustrating use of, 185-190.

remarks on,

symptoms, and location of pain, 190.

treatment, 191.

syphymographic tracing, fac simile,

195.

—comments and deductions, 189, 192-6.

—Discoverer and investigators of, 138.

—methods of administering, 139-40.

~other maladies to which it is applicable,
140.

—physiological action of, 138-40.

Nitrites, action of, on Hemoglobin, 646-7.

-other than Nitrite of Amyl, probably
Muscular Poisons, authcr’s
researches on, 391.

Nitro-glycerine, the Physiological Action
of, Preliminary Notes on, (with
E. 8. Tait), 474.

—Action of, on

—Animals,

—Cats, 475 et seq.

—Frogs, 474 et seq.

—Blood, and Blood-pressure, 479.

—Brain, headache induced by, 478, 480.

—Heart, +479.

—Motor Nerves, 478.

—Muscles, 477.

—Nervous system, 474, 477.

—Oxidation, 480.

—Spinal Cord, 478.

~—Poisonous character of, 474.

—Principal effects produced by, 476.

Note(s) on Indeyendent Pulsution of the
Pulmonary Veins and Vena
Cava, (with Sir J. Fayrer,
M.D., K.0.8.1.), 528.

684

Note(s) —cont.

~—Preliminary, on the Physiological Action
of Nitro-Glycerine, (with
E. S. Tait), 474.

—Regarding the LEfiect of Electrical
Stimulation of the Frog’s
Heart, &c., 572.

Nuclei of Blood Corpuscles, the, On
the Chemical Composition
of, 147.

Nux Vomica,

—Action of, as

—as Cardiac Stimulant, 561.

—on the Respiratory Centre, benefits of,
in combating Night-sweats in
Phthisis, 551, 556, cases illus-
trating, 552 ef seq.

Oniiguiry of Position in Relation to
relief of Fatigue, 532-3, 536.
Observations, Some, on the Urine, On
Digitalis, w.th, 29, 77.
(Edema, rationale of tr:atment of, 20.
Oertel method of Treatment fur Heart
Disease, 20, 22.
(Esophagus, Dilatation of its Curdiac
extremity a concomitant cf
Vomiting, 640.
Oil of Almonds in cases of Woorara
Poisoning, 381.
see also Laudanum
Morphia.
—Action of, on the
—Cerebrum, 299-300,
—Cough, in, 563-4,
—Digestion, 565.
—Respiration, 565.
—in relief of Vomiting, 571.
~—as a Narcotic, 257-9 et passim,
Opium and Scrychnine,
~in combination, in relief of Night Sweat
in Phthisis, 554, 555.
Ordeal by Poison, West Africa, plants
used in, how employed, 462,
464-5, 481.
Organs Isolated,
-Artificial Circulation through, (Ludwig
and Mosso), 345.
—different kinds of Blood seat through,
336.
-other than Respiratory, affected by
Cough, 566.
Organism, see Animal Organism.
Uscillations in Blood Pressure,
caused, 273.
of Arteries, consequences
of, 18-19.
Over-exertion, elfect of, on the Heart, 18.

Opium, and

how

Os:ification

INDEX,

“—part of the

Oxidation,

—Action on, of

—Casca Bark, 493-4.

—Drugs, 247.

—Nitro-glycerine, 480.

Oxide of Zine and Hyoscyamus,

—in relief of Night Sweat in Phthisis, 554, ,

Oxygen, inhalation of, in Cholera Collapse,
results with, 360-1.

Oxygen and Carbonic acid, interchange
of, _ constituting Internal ;
Respir ation, 644.

Oxygen-carrying power of Hemoplohiti
644, effects of diminution of,
on Fatty Degeneration, 646.

Oxreenaios of the Blood, importance
of, 377.

Ozonising Power of Blood, 649,

Pacer, Sir James, on Congestion, his —
“sonbriolion of the term, 433.
note, 447. q

Pain—

—of Burns,

—relieved by exposure to Fire heat, 449. —
—-probable reason of relief, 450. 4
—Death from, case of Alice Bruce, 398.
-due to Distension of any hollow mus-—
cular organ, 16, .
—in Inflammation,
—character of, 449.
—probable causes of, 449, 434.
—ways of relieving, 419-50, 451-38, 4540
—-by cold, 449, 454.
——by heat, 449-50, 454.
—internal,
—relieved by external irritation, facts
bearing out, 451. ,
-pinching, biting lips, &c.; as a meatil
of preventing Syncope, 408.
Pain and Painful Impressions, (fright
&e.), Shock induced by, 399,
400, 408. 4
Palpitation of the Heart in Exophthalmie
Goitre, 414. y
—Paralysis of the Vagus, cause of, 421,
422.
Pancreas, ferments formed by, 24.
Pangenesis, Darwin’s theory of, 336,
Paralysis—
-of the Cardiac Ganglia, 303.
Ganglionie
affected, 309, 315.
-of Co-ordinating Apparatus of the Cardiae
Ganglia, 315. M
-ofthe Heart, (see Muscular Fibres infra),
the cause of Death from Casea,
(Liebreich), 482, 482.

Apparatus

INDEX.

Paralysis (cont.)

—of the Intestinal Nerves, (presumable), in
Cholera, 363.

—bearing on, of Moreau’s experiment, ¢/l.,
362-3.

-of the Muscular Fibres of Heart, 315.

—of the Sympathetic, 303.

-of the Vagus, a cause of Heart Palpita-
tion, 421, 422.

' Parturition, collapse or shock after,
probable causes of, 400.

—Digitalis successful in a case of, (Fother-
gill), 409.

Parry, first observer
Goitre, 414.

of Exophthalmic

-cifed on causation of Angina Pec-
toris, 19.

Passive, or Venous Congestion, 439,
453.

Pasteur and his discoveries in Bacteri-
ology, 26.

Pathology, study of, in relation to Thera-
peutics, 222-3.

Pectin, in Digitalis, 36.

Pepsine, formation of, 24,

—introduction of, by Corvisart, 25.

Pepsinogen, enquiries concerning, 24.

Perforation in Stomach or Intestines,
collapse or Shock after, 400.

Pericarditis, aciion of Blisters in, 452,
454.

Pharmazological Uses of Artificial Cir-
culation, 268.

Pharmacology, Study of, 223.

Pharyngeal Nerves, as aifecting Respira-
tion, 327.

Phlebotomy, see also Venesection.

-relief of Pain by, 450-1, 454, drawbacks
to, 450-1.

Phosphorus, action of, on Internal Respi-
ration and Fatty Degenera-
tion, 647.

Phthisis, Bronchitis and, On the Actions
and Use of Certain Remedies
employed in, 562.

—Digitalis in (Crichton), 568-9.

—Night-Sweating in, On the Pathology
of, and the Mode of Action of
Strychnia and other Remedies
in it, 545.

—Laryngeal,

—Sedatives in relief of, mode of apply-
ing, 564-8.

Phyostygma, action of

-on the Vagus ends, 302, and on the
Inhibitory ganglia, 314.

~antagonism of, and of Atropia, bearing
of this on Therapeutics, 313.

-glycerine extract of, action of, on the
Heart, 528.

685

Physiological Action of the Bark of
Erythrophl-um Guinense
(Casca, Cassa, or Sassy Bark),
(with Walter Pye, M.R.C.8.),

458, 481.
Physiological Action in relation to
Chemical Constitution of

Drugs, 240.

—of Condurango, 340.

—of Digitalis

—on Animals, (Horses), 39 e¢ seq., other
animals, and man, 43.

—-on Plants, 39.

—-on various organs in detail.

Blood, 43.

Bowels, 59.

——-Circulation, 44.

Arterial Tension, 54, and see 45.

Capillaries, 55.

Pulse, 46.

Digestion, 57.

—E yes, 67.

Heart, 49.

—Impulse of, 54.

——-Rhythm of, 53.

—-Sounds of, 54.

Nervous System, 66.

Respiration, 57.

Secretions,

Saliva, 59.

Secretion of the Nasal Mucous

Membrane, 60.

—-Sweat, 60.

Temperature of the Body, 65.

Urine, 60, tables, 63 and Appendix.

—— Uterus, and Genital Organs, 68.

— Mode of Action of, 68.

Brunton’s theory, 72.

——Dybkowsky’s theory (and others), 71.

Traube’s theory, 69.

—of Nitro-Glycerine, Preliminary Notes
on, (with E. 8. Tait), 474.

Physiological Chemistry, anticipations
from, 240.
Physiology,

—Experimental, increase of knowledge in
to whom due, 8.

-and the Prevention of Disease, 6.

—study of, precedent to those of Pathology
and Pharmacology, 224.

Picrotoxine, Action of, in relief of Night
Sweats of Phthisis, 555.

Pig, Larynx in, 633-4.

—Ventricular bands in, 635.

Pilo-carpine, Action of, on Salivary and
Sweat Glands, 547.

Pinching of Web of Frog’s Foot, Con-
gestion caused by, 445.

Pinnigrada, Larynx in, 632.

Pisciform Mammals, Larynx in, 628,

686

Plantigrada, Larynx in, 631.

Plants, Physiological Action of Digitalis
on, 39.

Pleura, in relation to Cough, 562.

Pleurisy, relief given in, by external
irritants, deductions from,
451-454.

Pneumograph, Marey’s, method of em-
ploying, é//., 328.

Pneumonia,

—Blister applied to the Chest in, acting as
a Counter Irritant, 438, 454.

—Inaction of Digitalis in, (Thomas), 211.

—Quick breathing in, probable causes

of, 324, 326.

benefits

in, 571

Poiseuille’s Hreemadynamometer, 7.

Poisons, see Cobra, Snake, and others
under names.

-corrosive, action of, on the Stomach
producing Shock or Col-
lapse, 400.

-effect on Frog’s Heart of Atropia and
Muscaria, 457.

-Simple Method of Demonstrating the
Effect of Heat and, upon the
Heart of the Frog, 435.

Poisoning, ¢

—by Curare, (Herrmann), 472.

-by Digitalis, 472.

—Case of,—recovery, 99.

—various forms of, use of Artificial Respi-

, ration in, alone, 379-83, with
Transfusion, 383-7,

—Catarrhal, of Cod-lirer oil

Position

-for patients under Chloroform, impor-
tance of, 432-3, 437.

—suffering from Pain of Inflamma-
tion, 449, 455.
—-from Syncope, 404, 407.
Posture
~as affected by Climate or Season, 531.
—by Fatigue, 532, 535-6.
-as affecting
—Bodily Temperature, 531, 532 e¢ seq.
Potash, action of, on the Lungs, and their
Secretion, 569.
Henry, M.B., F.B.0.3., (joint
author), see Diuretic Action
of Digitalis, and the same in
German.
Preliminary Notes on the Physiological
Action of Nitro-Glycerine,
(with BE. 8. Tait), 474.

Preserving Life, On the Use of Artificial
Respiration and Transfusion
as a Means of, 374.

Power,

Pressure, afforded by a suitable seat, in’

relief of Fatigue, 533, 536.

INDEX.

Pressure of blood, sce Blood Pressure.

Preventing Death from CUhloral, Effect of : 4 f

Warmth in, 197.

Pryer’s experiment in re-vitalising a

Frog’s muscles, 375-6.
Protoplasm, Action of Drugs
242. ’
Protrusion of the Eyeballs, in Exoph-
thalmic Goitre, 414, cases
illustrating, 415 e¢ seq.
-Probable causes of, 4234, if2 , 425.

Pseudo-Pulsation, see Pulsation in the

Jugular.

Pulmonary Artery,

—Embolism of, effect of, on Respiration,
330.

—-Action of Oondurango, (an error
noted), 7A.

Pulmonary Capillaries,

—Contractile power of, Drugs affect-
ing, 568-9.

—Contraction of, effect of, on Respira-

tion, 331.

—-Action of Muscarin in causing, il, — 4

332.
—~Influence of, on Drugs injected, 321.
—Frog's,
observation of the action of Drugs
on, (i//,), 333.

Pulmonary Circulation, the, Experiments

upon, Oa the Employment
of Nitrite of Amyl in the
Collapse of Cholera, with,
359.
~Arrested in Cholera, 365 and note.
—Causes and Consequences of, 366-8.
~—Treatment indicated for, 368 e¢ s2q.

—Nitrite of Amyl for, 359 pros and cons _ |

of, 370-8, diags., 371.

Pulmonary Veins and Vena Cava, Note A

on Independent Pulsation in,
(with Sir J. Fayrer, M.D.,
K.C.8.1.), 528.
—Dilatation of, (Harvey), 4. F
—lIndependent Pulsation of, (Haller and
Senac), 5, 541. 3
—~—Experiments ilustrating, 528-30.
—-Importance of the fact, 530.

—-under what circumstances observed,

542. -
Pulsation, Independent, of the Pulmonary _
Veins and Vena Cava, (Haller

and Senac), 5, Note on, (with — Z

Sir J..Fayrer, M.D., K.C.8.I.),
528. 3
—Jugular,
—-causes assigned to, 539, 541.
—~inference usually made from, 539.
—Unilateral, observed by author, 539-41,
cases illustrating, 540-1. a

INDEX,

>

Pulsations, the, of the Mammalian Heart,
Influence of ‘emperature on,
and on the Action of the Vagus,
205.

Pulse, Animal, Action on, of

-Atropia, (Dogs and Rabbits), 291,
modes of registering, 293-4.

—Casea, (Cats, Dogs and Frogs), when
injected, 513-5.

—Human, Action on, of

—Digitalis, 46.

— Stimulation of the Cutaneous, visceral,
and Muscular Nerves, 15.

—tTemperature, 205 et seq. 210-12.

—Author's, Sphrgmographic Tracing of,
129 et seq.

—in Cholera Collapse, 361, and after, 356,
effect on, of Nitrite of Amyl
and of Oxygen, 359-61.

—Graphic method of measuring, (Volk-

man), 9.

—Quick, a prominent symptom of Fever,
cause of, 455.

—Quickening of, Causes of,

—Muscular exertion, 15.

—-radial, as affected by Nitrite of Amyl,
(Gamgee and Rutherford),
174.

—when induced by Atropia, 291-7.

-after Shock, 395, 401-2.

-Slowing of, under the action of a Drug,
how induced, 2,7.

Pulse Curve, the, as registered by Marey
and Chauveau, 9.

Pulse-rate, in relation to Arterial pressure
and the action of Digitalis and
Nitrite of Amyl, 145, 145.

Pulse-tracings during use of Digitalis,
(author’s own), 129 e¢ seq.

—in Poisoning by Digitalis, 99 e¢ seg.

Pupil, (Cat’s), Action on, of Casca, 519.

Purgatives or Diaphoretics, action of, 24.

Putrefaction, Action of Drugs on, 246,

: Pye, Walter, M.R.C.s., (joint-author), see

Erythrophleum Guinense.

QvassrA, action of, on the Stomach, 567.

Quick Pulse,

—induced by Atropia, causes of, 294-7.

—a prominent symptom of Fever, 465.

Quickened Breathing.

—produced by Drugs.

—-Causes to which it may be due, and
how tested.

Excitement of Voluntary Nervous
Centres, 329.

Increased Temperature, 15,

Venosity of the Blood, 7d,

Irritation of the Vagi, 7d.

687

Quickening Nerves, acting on the Heart,
as affected by Drugs, 275.

Quinine, action of in

-lessening Oxidation in Blood, 651.

-relief of Night Sweats, (Murrell), 555.

-stopping the Heart, 330.

Raseits, see also Harcs and Rabbits and
Kanincten.

—Avstion on, of Atropia, in different Doses,
291

—Cireulation of, as affected by Nitrite of
Amyl, Mole of experimenta-
tion and results, diags. 175 ef
seq.

—Pulsation in, of Pulmonary Veins and
Vena Cava, 541-3.

—do., after death from Cobra Po'son, 523.

—Respiration of, suspended on inhalation
of strong smelling vapours,
155, 175, 300, 324-7, 407, 434.

-Vagus of,

—Experiments on, in relation to effect
of Fever Temperatures, 211-3.

— Motor Action of, 217, and retentioa
of Inhib.to'y action, 219.

Rabbit’s,

—Ear,

—Best part for observing change in size
of Vessels, 319.

——Coogestion and Flushing of, and the
converse, 159, 176, 178, 517.

—-Protracted Hypertrophy caused by,
440

—Heart, see Laudanum, and Mammalian
Heart.

-Skin, Zulzer’s experiments on, as to reflex
movements due to skin irrita-
t.on, 451--2.

Rales of the Lungs, in health and disease,
use of Potash in the latter,
569.

Rattiesnake Poisoning, Artificial Respira-
tion in, (Weir - Mitchell,
Beunton, and Fayrer), 3~1-2.

Red-water Bark, or Doom, in Sierra
Leone and Ashanti Ordeals by
Poison, effects of, 431-2.

Re-duplication of Heart-beat in Electric
Stimulation of Ventric'e, 579,
581, 532 e¢ seq.

Reflex Action, 35).

—Effects on of

—Condurango, 345, 35).

—Nitro-gl. cerine, 478.

-Imperfect, on the Heart, Dangers of,
435, 437.

—Incurred by small doses of Chloro-
form, 436-7.

688

Reflex, Excitability,

—KEffect on, of Casca, acting on the
Sensory Nerves, 523-5.

Reflex movements

—induced by Irritation of the skin, 451.

—Ziilzer’s experiments on, 451-2.

Refractory period, in the

—Cardiae Cycle, 573, 574 & note, 578
ef seq., 619 et seq. moment of,
576, duration of, 577.

—effect on, of

—Cold, protracting, 577.

—Heat, diminishing, 7d.

Rein-Deer, Larynx in, 629.

Relaxation of the Arterioles, a cause of
Heart Palpitation, 421, 422.

Remedies, Certain, employed in Bronchitis
and Phthisis, on the Actions
and Use of, 562.

—Alum. 571.

—Atropine, 568.

—Cascarilla, 567.

—Chloroform, 563-4, 566-7.

—Cod liver oil, 570-1.

—Conium (Vapour), 564.

—Digitalis, 568-9.

—Expectorants, 569-70.

—Glycerine, 566-7.

—Hydrocyanic acid, 563-4, 565-7, 371.

—Vapour of, 564.

—Tce, 571.

—Inhalation, 564-5.

—Ipecacuanha, Spray, 564,

—Linctus, 563 e¢ seq.

—Morphia, 563-5, 566-7.

—Muscarine, 568.

—Nitrie Acid, 567, 569.

—Opium, 563-4, 565, 571.

—Potash, 569.

—Quassia, 566-7.

—Solutions, 564.

—Vapour, 564.

Respiration, see also Artificial Respira-
tion and Circulation and
Respiration.

—Action on, of

—Casca Bark, 472, 498.

-—Chloral, 197, 199.

-—Digitalis, 137.

—Opium, 565.

-—Nitrite of Amyl (inhalation of), 371,

373.

-—as affecting Arterial Tension, 45-6.

—External, 644, 651.

—How accelerated or retarded, 326-7.

-— Accelerated, by drugs,

Causes to which it may be due, and
| how tested.

Excitement of Voluntary Nerve

Centres, 329.

INDEX.

Re: piration of Rabbits, effect on, of a

>

Resp'ration, External, &c. (cont.)

—Accelerated by Drugs,

Causes to which it may be due,

——~Increased Temperature, 7d.

——-Increased Venosity of Blood, id.

———-Irritation of the Vagi, 7b.

—-Retarded by Drugs,

Causes to which it may be due and
how tested.

Contraction of Pulmonary Capil- a
Jaries, 331. .

330.

-Stopping of the Heart, 330.
-Internal, |
—Action on, of the Crake 645.
—defined, 644. ;
~Movements of, Registration of, 327. q
-Rapid, in Pneumonia, probable causes
of, 324, 326. a
in Cells composing the
Higher Organisms, 644. ~ a
Kaninckens, Wirkung darauf,
bei Einathmung stark —
riechender Dimpfe, 155.

Respiration

—des

inhaling strorg smelling
We acy 155, 175, 300, 324-7, —
407, 43 :
Respiration in Unicellular Organisms, 643, _
Respiratory Centre, ,
—Action on, of Drugs, 326. a
—as inhalations, points to be observed q
in, 327, a
—as3 injections, points to be observed in, id,
—as sedatives, 566-7. —
—Action on, of Strychnia, 323. iy
—experiments to determine, 322-6.
—of temperature, 654.
-Healthy Action of,
—in eliminating excess of Carbonic Acic i
from the Blood, and th
reverse, effect of the latter 01 1
Night Sweats of Phthisis,
550-1. "%
—increased excitability of, to combat the ©
above, induced by 51, Cas
and other Drugs, 551, Cas
illustrating, 552 et seq.
—How normally called into action, 560.
—Influence on, of Nerves, 324-6, id. oe
—Location of, 322, 547-9.
Respiratory Movements, 652.
—Activity of, how caused, 653.
-reinduced by Strychnia, after severa:
of Spinal Cord, 323,559,
Respiratory Muscles, 7
-—Action on, of various Drugs, 300. a
—of Atropia, 554, 555-6.
—-Curare, 300.
——Hyoscyamus, 554.

INDEX.

Respiratory Passages, Vapours acting on,
in Relief of Coughs, 564.

Respiratory Sedatives, action of, on the
Cough nerve centre, some
drawbacks to, 565.

Rest,

-Factors necessary for complete, 533.

—Positions most easeful in, in bed,
(Goodsir), 532.

Retching, aspect of the Human Larynx
during, 624, do., of that of the
Cat, il/., 641.

Rheumatism, Blisters in, On Irritants
and Counter-Irritants, with
Remarks on, 438.

-Acute, Blisters useful for young patients,
not so useful for elderly, 452-3,
454.

Rhinoceros, Larynx in, 633.

Rigidity of Arteries, (in age), causing
inability for prolonged exer-
tion, 18-19.

Rigor Mortis, the cause of, 376.

Rodentia, see also Hares and Rabbits,

-—Vomiting in, difficalt or impossible, 640.

Rokitansky, experiments of, demonstrat-
ing the Respiratory Centre in
the Spinal Cord. 323, 559.

Romanes, G. J,, observations of, upon
Meduse, il., 572.

Rosenthal, on the reason for different
Postures in different tempera-
tures, 531.

-(and others), experiments of, on Arti-
ficial Respiration in Strychnia
Poisoning, 383.

Rubbing, see Shampooing.

Riickenmark, Wirkung des salpetrig-
sauren Amyloxyds bei, 7/., 3,
161, 162 e¢ seq.

Ruminants, Larynx in, 629.

-Vomiting in, difficult or impossible, 640,

SACCHARINE substances, see Glutinous
and.

Saliva, secretion of,

—Action on, of

—Atropine, 546.

—Belladonna, 547.

—Culabar Bean, 546-7.

—Digitalis, 59.

—Pilocarpine, 547.

-effects on, of irritating certain nerves, 556.

Salivary Glands, action on, of Atropine,
556.

Salpetrig-sauren Amyloxyds, Ueber die
Wirkung des, aut den Blut-
strom, 154.

-in Angina Pectoris,weshalb gebraucht, 157.

689

Salpetrig-sauren Amyloxyds (cont.)

-von Balard entdeckt, 154.

—Einfluss unter der Verschliessung der
Aorta, figs., 165, et seq.

-Selbstindige bewegungen der Arterien
unter, 159.

—Wirkung auf,

——Blutdriicks, 155, 158.

——Blutgefiisse, 169.

Carotiden, 154.

Erréthen des menschlichen Gesiclits,

154, 159.

——Erréthen des Kanichendhres, 159.

—Gefisswand, 164.

Gesicht, 154.

Herschlag Beschleunigter, 154.

Klopfer der Carotiden, 154.

—Wirkung bei Riickenmark, figs. 161,
162 et seq.

—-Versuche dariiber angestellt, figs. 155-

an Fréschen, 154.

an Kaninchen, 154 et seq.

Resultate und Schliisse.

——-Ursache der Druckminderung festge-
stellt; alleinige Wirkung des
Salpetrig-sauren Amyloxyds
auf die Blutzgefiisse; Keine
unmittelbare Wirkung auf das
Herz, 164, 168-9.

—Versuchsprotocol, 169 et seq.

Sand in the Eye, how it acts, if soon
removed, and if allowed to
lodge, 444.

Sanderson, Dr. Burdon, and Experimental
Physiology, 8.

Santos, on Casca Bark, 481-3.

—on its action on Animals, 483.

Schiff’s experiments in Artificial Respira-
tion, 378-9.

Schott’s method of Treatment for Heart
Disease, 20, 22.

Sciatic nerves, effect of irritation of, in
producing Sweat, (Goltz), 549.

Science of Easy Chairs, On the, 531.

Seal, Larynx, in, 632.

Secreting Nerves, Action of, on Sweat
Glands, 545.

—Action on, of Drugs, 546-7.

Secretions, Physiological
Digitalis on, 59.

Seeds, yeast, and moulds as affected by
Casca, 458, 463.

Setschenow’s registering Haemadynometer,
uses of, 52.

Senac, on the Cardiac Cycle, 5, and on the
Vena Cava, 7d.

Senile Gangrene, causes of, and symptoms
preceding, (Brodie), 18, 19.

-incapacity for sudden overwork, 18, 19.

2Y¥

Action of.

690

Sensitive phase, in the Cardiac Cycle,
576-7.

Sensory Nerves,

—Action on, of Casca, Effect on, of Reflex
excitability, 523-5.

-Irritation of, double effect of, (Ludwig),
443, 451.

-Peripheral ends of, Action on, of sedative
drugs in. Linctus in relief of
Cough, 563-4.

-the Fifth, influence of, on the Heart’s
action, 434.

Shampooing cr rubbing of the Legs, when
Fatigued, proper direction of,
533, 535, 536.

Sharpey, Prof., debt to, of James Blake, 7,
others influenced by him, 8.

Sheep, Larynx of, Experiments on, 635,

6-7.

Shock and Syncope, On the Pathology and
Treatment of, 392.

Shock,

—as a cause of Death under Chloroform,
428.

—two forms of, 430, 433.

-ditto, of Animals under the same, 338.

—Causes of, 398-9, the chief, 407.

—Burns, 400.

—lInjuries to

— Abdominal Viscera and Genitals, 394,
397, 398, 400.

—-Bones, (Crushing and Amputation),
398.

—Mental Emotions, 399.

—Pain and Painful Impressions, 398-9,

400.

-Death from, Astley Cooper’s instance
cited, 393-4.

—Definition of (Savory), 401-2.

—Pathology of, 392, 400.

—Re-action from, 397.

—-Symptoms of, 393-4, 400.

—Pulse weak, arterial tension low, 400.

—Skin coldness, 400, 402.

—Surface pallor, 7.

—Two forms of

—-Erethismic, 396.

—-Torpid, 394.

-Two factors in, as seen in the Frog, 7//.,
402.

-Treatment for, by

—Digitalis, 409.

—Heat, 408.

—Stimulation, 7d.

Sierra Leone, Ordeal by Casea or Red-
water Bark in, 481-2.

Simia, see Apes and Howling Ape or
Monkey.

-Parnisco, Larynx of, 634.

—Sabcea, Larynx of, 70.

INDEX.

Simple Instrument, On a, for Examining
the Competency of the
rb ae and Mitral Valves,
537.

—construction and employment of. 537-8.

Simple Method, A, of Demonstrating the
Effect of Heat and Poisons
upon the Heart of the Frog,
455.

—apparatus used, 455, 71l., 456.

Sinitzin, experiments of, on the effects of
copious Blood-Supply on repair,
444,

Sitting or squatting postures in different
countries, 531.

Skin,

—Action of Irritants on, in producing reflex
movement, 451, 454.

-in Fever, compared with skin after

exercise, 546.

-Functions of, actual and probable, 4.
—Pallor and Coldness of, after Shock, 394,
396, 398, 400, 402.

Skin and Mouth, as affected by Belladonna,

; 547.

Sloth, Larynx in, 629-380.

-Ventricular bands in, 635, 642. .

Smelling Salts, (see also Ammonia), action
of, on the Arterioles, 407.

Snake Poisons, effects of, when swallowed,
386. /

Snake Poisoning, Artificial Respiration in,
381-2, in conjunction with

. Transfusion, 385-6.

Sneezing induced by powdered Casca
Bark, 498.

Snow, Dr., on Deaths under Chloroform,
427.

Solipedes,

—Larynx in, 633,

—Ventricular bands absent in, 635.

—~Vomiting in, difficult or impossible, 640.

Solutions, Action of Drugs in, on Cough,

564.
Sound, (see also Cardiac do.), given out by —
Contracting Muscles, dis- —

covered hy Wollaston, 5. 7
Spanish liquorice, probable action of, in —
relief of Cough, 563.
Spasmodic Asthma, see Asthma.
Sphygmograph, the, the use of, 321-2.
Sphygmographic Tracings, author’s Pulse
129 ef seq.
-in the case of Poisoning by Digi-
talis, 99.
Sphygmoscope, Marey’s, 283.
Spinal Cord
—Action on, of
—Casca, 466.
—Nitro-glycerine, 478.

INDEX.

Spinal Cord (cont.)

-ellect of division of, in experiments with
Nitrite of Amyl on Rabbits,
diags. 181.

—severance of, at Occiput, effect of, on

Vaso-motor reflex, and Respiratory

movements, 559, 560, see
a'so 323.

-how normally called into action, 560.

-Nerve centres partly in, 547-50.

-in relation to the Respiratory Centre,
323.

Spray and Inhalation,

-Action of Drugs in, in relief of Cough,
564-5.

“Spurting,” capacity for, in relation to
Age, 18.

Squill, see Ipecacuanha and

Standard, The, of Health, 220.

-( for sub-heads, see under Experimental
Investigation).

Stannius’s Experiment, On tne Explana-
tion of, and on the Action
of Strychnia on the Heart,
(with Theodore Cash, M-:D.),
557.

Stasis in the Capillaries, following appli-
cation of Caustic to web of
Frog’s foot, 445.

-theories to account for, (Cohnheim and
others), 447.

—that of the Webers, 448-0, 454.

Steno’s experiment on the vital im-
portance of the Circulation,
376.

Stimulation, see also Electrical do.

-of the Accelerating Nerves or Ganglia of
the Heart, 314, 315, a cause of
Palpitation, 421.

-of the Cardiac Ganglia, effect of, on the
Pulse, 294.

-of the Sympathetic, direct, effect of, on
the Pulse, 294.

Stomach, Action on, of Casca, 459, 463,

464-5, 495.

—Congestion oe as inducing vomiting,

571.

—Drugs acting on as tonics, 567.

Stomach and Bladder distention, pain
caused by, 16.

Stopcock, the author’s, i/l., 265.

Stoppage of the Heart,

-a consequence of impaired Cardiac
Nutrition, 19.

-effect of, on Respiration, 330, action of
Quinine in inducing, 7d.

Strangling, see Asphyxia. —

Structures through which Drugs affect
the Heart and Vessels, Deter-
mination of the exact, 290.

691

Strychnine, the Action of, on the Heart,
On the explanation of Stan-
nius’s experiment and on,
(with Theodore Cash, M.D.),
557.

-the Mode of Action of, and of other
Remedies, On the Pathology of
Night-Sweating in Phthisis
and, 545.

—action of,

—as Cardiac Stimulant, 561.

—causes of its symptoms, proved by
Magendie, 7.

—on the Frog’s Heart, 575, 596, 614 ef

seq., 622-8,
—-Effect of Electrical Stimulation
on the Strychnia-injected
Heart.
—Auricular,

——-Maximal, 598, 615.

———Minimal, 598.

Ventricular,

Maximal, 597.

Minimal, 596~7, and on the

Venous Sinus, 617.

——-Maximal, 600.

Minimal, 599.

—on the Respiratory Centres, 323, 326.

-——-benefits of, in combating Night-Sweats

in Phthisis, 551.

—-—cases illustrating, 552 e¢ seq.

—-eases indicating use of, 556.

——drawbacks of, remedied by combining
with Opium, 554.

—-effect of injection of, on the same, and

on the Vaso-motor centres,
after severance of Spinal
Cord, 548-9, 559, see also 323,
326.

—on the Respiratory Muscles, 300.

-Tetanising action of, 330.

Strychnine Poisoning, Artificial Respira-
tion in, (Rosenthal and others),
383.

Strychnine and Nitrite of Amy], joint
effect of, on Frogs’ Muscles,
390-1.

Submaxillary gland, dilatation of, (Bes-
nard), 15.

-secretion of saliva by,

—effects on, of irritation of the Chorda
Tympani nerve, 546.

—of the same, after giving Atropine, id.

Sudden exertion in Heart disease, as a
cause of Cough, 567.

Sugar, in Digitalis, 36.

Superior-cervical ganglion,

~-effects of evulsion of, (Sinitzin), 444.

Supramaxillary Nerves, as affecting
Respiration, 326.

692

Supra-renal capsules, extract of, Thera-
peutic uses of, 25.

Sweat ay

-Causes of, 545.

—Induced by

—-Increased Blood Temperature, (Luch-

singer), 550, 555.
—-Increased Carbonic Acid in the Blood,

(Luchsinger), 550, 555.
—-Nicotine introduced into the Cireula-

tion, (Luchsinger), 550.
—-Physical Exercise, state of the skin

and sweat glands during,
545-6.

-Nerve centres for, position of, 547,
5419-50.

~Physiological Action of Digitalis on, 60.

Sweat glands, Action of,

-as affected by

—Atropine, 546.

—Belladonna, 547.

—Calabar Bean, 546-7.

—Pilocarpine, 547.

—how induced, 545.

Sweat Nerves, Action on, of Atropine, 554,
555.

Swift-running animals, Larynx in, see
Pigs.

Syme, Prof., reasons given by, for success
in the use of Chloroform, 427.

Sympathetic Nerve,

—Paralysis of, 303.

—Stimulation of, in relation to the Pulse,
294.

Syncope, Shock and, On the Pathology
and Treatment of, 392.

—causes of,

—chief (Brunton), 406-7.

—impaired Cardiac Nutrition, 19.

—Death from, case of Alice Bruce, 393.

—an old method of inducing, 403.

—Pathology of, 403.

-Symptoms of, 393.

—Feeble Pulse, 395, 397, 400.

—Low Arterial Tension, 7d.

~Treatment for, by

—Cold Air and Water, 407.

—Prone Position, 404, 407.

—Smelling Salts, 7d.

Syringe, see Hypodermic Syringe.

Systemic Capillaries, (see also Pulmon-
ary), Action on, of Nitrite of
Amyl, 369 e¢ seq.

Systolic sound, the, how produced, 6.

T-tTUBES, to make, 256.

Tables of Pulse and Respiration during
administration of Digitalis,
105-26,

INDEX.

Tables of Urine, &e., taking
Digitalis, 82, 98.

‘Tadema, Sir L. Alma, Postures shown by,
in pictures of the Seasons,
531, 582.

E. §., ’ joint-author,

' Glycerine.

Tannic Acid in Digitalis, 3f.

Tartar Emetic, effect of, on the Respira-

tory Nervous Centre, 654.

Teeth, One of the Causes of Death during

Extraction of, under Chloro-
form, 427.
Temperature,
—Action on, of Casea, 461, 4:72.
—Increased, as possible cause of Quickented
Breathing, 329.

-effect, of, on the Respiratory Nervgus
Centre, 654.

-Influence of, on the Pulsations of Mam-
malian Heart, and on the
Action of the Vagus, 205.

-sudden alternations of, effect of, on
Frogs’ Lungs, 333.

Temperature of the

—Blood, increase of, a cause of Sweat,
550, 555.

while

Tait, see Nitro-

—Body,

—how maintained, 531-3.

—loss of, after taking Chloral, 198, experi-
ments coacerning, 7b. et seq.
(tables), deductions for treat-
ment, 198-9.

—Physiological Action of Digitalis on,
65, 84

‘Testicular extract, Therapeutic use of, by
Brown-Séquard, 25.

Tests for Heemoglobin presumably altered
by action of Drugs, 647 et seq.

Pietanins suggested use of Nitrite of Amyl
in, (Richardson), 140.

—treatment of, by

—Anti-toxin, 21.

—Nitrite of Amy), 140.

Thebaia Poisoning, Artificial Breatbing in,
(Uspensky), 383.

Therapeutic Action of Digitalis in

—Ague, 75.

—Anasarca and kindred maladies, 76.

—Delirium Tremens, 7d. ,

—Epilepsy and some phases of Insanity, i.

—Heemorrhages, 74.

—Inflammatory fevers, 7d.

—Nervous Affections, 75.

—Pneumonia and other Lung Affec-
tions, 7d.

—Rheumatism, 74, 75.

-Typhoid fever, 75.

-Weak hearts, a warning concern.

ing,

INDEX.

Therapeutics,

-Importance of the fact of antagonistic
action of certain Drugs, 313. |

-slow advance of, 30. A

Thirst in Cholera collapse, 360, probable
cause of, 364.

Thiry’s instrument for Artificial Respira-
tion of Gases, 264.

Thorax, (see a/so Intra-thoracic Pressure),
fixation of,in relation to Closure
of the Glottis, 624, 634, 642.

Thyroid Gland,

-enlargement of, in Exopbthalmic Goitre,
414, cases illustrating, 415 e¢

seqg., probable causes of, 423.

~juice of,

—destructive of Anthrax poison, (Wool-
dridge), 27.

—in Myxcedema, 25.

—poisonous if injected into the Blood, 25.

Ticunas poison, see Woorara.

Tiger, Larynx in, 631.

—Ventricular bands in, 635.

Toads’ Lungs, difference of, from Frogs’,
(Sharpey), 333.

Tobacco, cold sweat produced by, in young
smokers, 550.

—Smoke of,

—effect of, when nasally inhaled by a
Rabbit, (Kratschmer), 327.

Tongue, root of, and fauces, in relation to
Cough, 563.

Torture, Death from Syncope induced by,
case of Alice Bruce, 393.

Trachea, (see also Intra-tracheal Pressure),
in relation to Cough, 562.

Transfusion of Blood, evolved from Wren’s
experiments, 7.

—-On the use of Artificial Respiration and,
as a Means of Preserving Life,
374.

-in conjunction with Artificial Respira-
tion, 383-7.

—in Charcoal Poisoning, 383-4, 386.

—Snake Bite, 385-6.

—-Strychnine and other Poisoning, 384,
386.

-objections to, disposed of, 386-7.

‘Lraube’s theory of the mode of Action of
Digitalis, 69.

Treatment of Heart Disease, rationale of
various modes of, 20 et seq.

~aims of

—increase of Heart Power, 20, 27.

—les:ened resistance to overcome, id.

-methods of increasing Muscular Circu-
lation,

—(1) Rest in bed with Massage, 20-2, 27.

—(2) Graduated exercises of stationary
patient (Schott), 20, 22, 27.

693

Treatment of Heart Disease (cont.)

-methods of increasing Muscular Circu-
lation (cont.)

—(3) Graduated exercises in Walking and

: Climbing, (CErtel), 20, 22.

-indicated for Heart Palpitation, in the
Ansemic, 422.

-for Preventing Death from Chloral, see
Warmth.

-of Shock and Syncope, On the Pathology
and, 392.

Tricuspid and Mitral Valves, the, the
Competency of, On a Simple
Instrument for Examining, 537.

Tripod, the, of Life, 377.

-—Huxley cited on, 374,

Utcer, Callous, Blisters applied to, acting
as an Irritant, 438, 453, 454.

Undulatory theory of light, Young’s, 4.

Ungulate Mammals, Larynx in, 630.

Urine, as affected by Digestion, 23.

—effect on, of moderate doses of Casca
Bark, 460, 471-2.

—-On Digitalis, with some Observations,
on, 29.

—Constituents, Amount of, 78.

—Amount of each Excreted, 79,

— Relative Proportions of, 7d.

—Observations on, 77.

——Dietary Table employed, 81.

—-Specific gravity of, 80.

—Physiological Action of Digitalis on, 60,
tables, 61, 64, 82 et seq.

-secretion, in Dogs,

—Action on, of

—Casca, 502, 518, 519, diag., 518.

— Coincident variations of, and of Blood
under influence of Casca, 505,
diag. 518, tables, 503-4,

—Digitalin, 412.

—in Horses, action on, of Digitalis, 42-3.

Use, see Actions and Use.

Uspensky’s experiments on Artificial
Breathing in Strychnia,
Brucia, Thebaia, and Caffeine
Poisoning, 383.

Uterus, Action on, of,

—Casca, 461, 472.

—Digitalis, 168.

VaGotTomy, symptoms induced after, by
Casca Bark, 497.
Vagus (i),
—Action of, on the
—Heart, regulating and retarding, 10, 11,
35.

694

Vagus (i)—cont.

'. -Action of, on the

—Respiratory Centre,
(a) normally, 324, 324.
(b) when affected by injections, 327,

-the Action of, Influence of Temperature —

on the Pulsations of the Mam-
malian Heart and on, 205, see
also 11.

—Action on, of

—Atropine, 295-7.

—Casca, 468.

—Maximum Irritation, 507-9.

—-Minimum do., (peripheral
509-10.

—Irritation of the Fifth Nerve, 434,
reflex action of, in stopping the
Heart's action, 434-5.

-Complex Functions of, 296-7.

+Fibies in, two sets of, affecting Respira-
tion, 324-5.

-Lrritation of,

—effects of, on the Pulse, 298.

ends),

—-portion affected by Drugs, &c.,
298-302.

—as possible cause of Quickened Breath-
ing, 329.

—Paralysis of,

—a cause of Palpitation, 421, 422.

—effects on the Pulse, 295.

— portion of, affected by Atropia, 295-7.

—Respiratory branches of, in relation to

—Cough, 562.

—Vomiting, 571.

Vagus, the Frog’s, effect on, of Heat,
and of Electricity conjoined,
(Schelske), 207.

Vagus, the Rabbit’s, experiments on, in
relation to effect of Fever
Temperatures, 211-3.

-Motor Action of, 217, and retention of
Inhibitory action, 219.

Vagus-roots, Action on, of Casca,
Minimum Excitability of,
510-13.

Valeric acid, (Digitalissic acid), 36.

Valves of the Heart, see Tricuspid and
Mitral Valves.

Valvular Action, The, of the Larynx, (with

Theodore Cash, M.D.), 624.

—Bibliography, 642.
Valvular disease of the Heart, bearing
on, of the contraction of the
Pulmonary Veins and Vena
Cava, 530.

Vapour, action of Drugs in, on Cough, 564.

Variation in Blood-Pressure, Causes
of, 273.

Vaso-dilator Nerves, action of, on the
Arteries, 11.

INDEX.

Vaso-Inhibitory and Vaso-Motor Nerves,
as uffected by Drugs, 275, 276.

Vuso-motor Centres,

—action on, of Casca, 515-6.

-as related to the disease in Bennett's
case of Angina Pectoris, 196.

—construction of, 121, 443.

~how usually called into action, 560.

—position of, 441, 517-9.

-reflex movements, of

—re-induced, after severance of spinal
cord, by Strychnia, 323, 559.

Vaso-motor Ganglia or Nerves, :

-Peripheral, as affected by Casca Bark,
469-70.

Vaso-motor nerves,

—action of, on the Blood Vessels, 441.

—in relation to

—dilatation of Vessels, 11, 441.

—diminished Blood-pressure induced by
Nitrite of Amyl, experiments
concerning, diags., 178.

—vessels of the Intestines and Skin, 13.

-of the Liver, course of, (Cyon and
Aladoff), 424, il., 425.

—in relation to Diabetes, 424, 425.

Vasomotorische Neryen, wahrscheinliche
Wirkung der Digitalis auf
denselben, 411.

Venesection, in Phthisis, 74, 75.

-in Angina, 138-9.

Veins, see also Capillaries, Jugular, Pul- “a

monary and Vena Cava.

-action’on, of Drugs, need of further

knowledge on, 544,
-affected by Cough, 566.
—Contractility in, 542.
—-uses of, 543.
—Contraction, local, of, 541.
Vena Cava,
—Dilatation of, (Harvey), 4. -
-Independent Pulsation in, (Haller, and —
Senac), 5,
Fayrer) ; 528-30, 541. :
-Place of, in the circulatory system,
(Senac), 4, 5. ;
Venosity of
-Blood, what it consists in, 652. tae
-Increased, as possible cause of Quickened —
Breathing, 329.
—Causes of the above, —
—~-Prevention of Air from reaching Blood, _
330. 4
of Blood from reaching Air, 330.
—how this last may be effected by re
Contraction of the Pulmonary ~
Capillaries, 331. y
—-Embolism of the Pulmonary Artery,
330.
Stoppage of the Heart, 330.

(Brunton and

INDEX.

Venous Blood,

-Action of, on Sweat Centre, 551.

—Occasional brightened colour of, 404, 406.

—Meyer’s view, 405 & note.

Venous, or Passive Congestion, 439, 453.

Venous Sinus,

—Action of Drugs on, 311.

—Etfect on, of

—KElectrical Stimulation, 617.

—(qa) in normal condition, 573, 576.

Maximal, 577, 587-8.

Minimal, 577, 586-7.

——(b) under the influence of Cold, 575,
589, diags. 608-9.

— Maximal, 593.

Minimal, 591.

— (ce) under the influence of Heat,

Maximal, 595.

——Minimal, id.

——(d) under the influence of Strychnia,

—Maximal, 600.

Minimal, 599.

-Function ascribed to, 309-10.

-Stimulation of, in relation to the

—Refractory period of the Cardiac Cycle,
574.

Venous Sinus of the Frog’s Heart,

—Function of, in regard to contractions

thereof, &c., 560, 561.

—Stannius’s experiment on, described and
explained, 557 et seq.

Venous System, Dilatation of, by Shock,
431-2.

Ventricles, Ventricular, see also Electrical

Stimulation of the Frog’s
Heart, and Inhibitory
Influence.

—Action of Digitalis on, 315,

-Effect on, of

—Electrical Stimulation,

—(a@) in normal conditions, 573, 576.

Maximal, 577, 581-4,

——Minimal, 577, 578-81.

—~(b) under the influence of Cold,

Maximal, 590.

Minimal, 589.

— (ce) under the influence of Heat,

Maximal, 594.

——Minimal, 593.

—(d) under the influence of Strychnia,

Maximal, 597-8.

Minimal, 596.

—Funetion ascribed to, 309-10.

—Pulsation of, 528-30, 541-2.

Ventricle, Auricle, and Venous Sinus,

-Movements of, under Artificial Stimula-
tion, how studied, 577.

—apparatus employed, 577, 578.

Ventricles of Morgagni, in relation to
Closure of the Glottis. 625-7.

——— = _ _ eo ———

695

Ventricular and Auricular Contractions,

-effect on of Stimulation to Ventricle -

Auricle, &c., researches or, 573.
Ventricular bands of the Larynx,
~-Animalsin which absent and present,634-6
—function cf, in
—Closure of the Glottis, 391, 642.
Veratrine,

—Action of, on
—Accelerating apparatus of the Heart,

314-5.

—Inhibitory ganglia of the Heart, 314.
—Vagus-roots, 298-9. ei
—beneficial in Exophthalmic Goitre, 424.
Vessels, see Blood Vessels.

Vibriones, Action of Drugs on, 244.
Viper, Poison of, Fontana’s experiments

on, 381, 385-6.

Visceral Nerves, effect of Stimulation of,

on the Pulse, 15. 5
“ Vital spirits,” 12.

Vital and Chemical Energy, 224-5.

Vocal cords, see also False do.

-true nature of, (Wyllie), 527.

-want of, cause of ditliculty in Vomiting,

641, 642.

Vocalisation in the Cat tribe, mechanism

of, 632.

Voluntary movements,

—Cerebral Centre for, (Ferrier), 14,
-Voluntary Nervous Centres,
—excitement of, as possible cause of

Quickened Breathing, 329.
-Vomiting, associated with Cough, Drugs

affecting, 57.

—causes of, 640-2.
“in different Animals, relation to, of the
development of the Fals-

Vocal Cords, iil., 640-2.
-effect of, 641.

—Nerve centre for, location of, 571.
Vomiting and Purging,
—induced by Casca Bark, 458, 459, 463-8.

_W-sHarEep Easy Chairs, special advan-

tages of, 533, 536.

Walking on the flat or up-bill, in relation to
Heart-distention, (Ludwig), 17.

Walshe, Dr., definition by, of Angina
Pectoris, 191.

Walz, volatile principles obtained by,
from Digitalis, 36-7.

Warm,

-and Cold Blood, Circulation of, in Inves-
tigations, 267.

—food as an Expectorant, 570.

-rooms and crowded assemblies, dilata-
tion of the Arterioles (and of
the surface veins) in, 404, 405,

696

Warmth,

-Effect of,

—on Cardiac Activity, 558, 559. °

—in Preventing Death: Fromm Chore) 197. 4

— how best applied, 198-9, see also 204.

—on the Pulse, hypothesis as to. the
quickened » Pulse in Fever,
(Budge and Liebermeister),
Experiments concerning, 205
et seq., Cyon’s, on the Frog’s
Heart externalized, 205 e€ seq.,
Panum’s, .on Rabbits’ hearts,
207, the author’ son the latter,
tables, 208, et seq., practicdl
conclusions, 210-12.

Waste products of Muscle, after exertion,

-Effects of, in inducing

—Fatigue (Kronecker), 533-4.

—Sleepiness (Preyer), 534.
Water, elimination’ of, in the Treatment
of Heart disease, 20.
Waterson’s experience of, and experiments
on, Woorara, 379, 385.

Webers, the, discoverers of the Action of
the Vagug, 10.

-theory of, to account for Stasis in
Inflammation, 448-9.

Weir- Mitchell, see Mitchell. Weir-

Wirkung, Diuretische, der Digitalis, (mit
H. Power, M.D.), 410,

—des Salpetrig-sauren Amyloxyds auf den
Blutstrom, 154.

Wolf, (Canis lupus), Larynx in, 630.

-Ventricular bands in, 635.

INDEX.

4

Wolff, aie on the Larynx in Canide and
Felide, &c., 630-1. —
pezestonn Dr. afliscoverer’ of the sound

- emit by Contrasting
5.

Muscles,
Wood, Dr. Alexander, introdustiay by, of
the Hypodermic Syringe, 7
Woorara Poisoning, Artificial Respiration
in, 879-81, 384. _
~Physiological Action ‘of, 380, 384-6.
Wren, Sir Christopher, first to employ -
Drugs by Tnjockions 6, a .
Wyllie, Dr., cited_on,
—Closure of ‘the Glottis, 625-7.
~Experiments of 625, confirmed ie those
of present writers, 627, 642,

YOuNG persons,
-Efficacy of Blisters to» the Joints of,
in Acute Rheumatism, 453,

454,
Young, Thomas, investigator of Capillary
resistance to the Circula-

tion, 4,
—Undulatory theory of, id.

a

Zoorps of Fowls’ blood, aspect of, 148.
-co-agulation (P) of, 149.
-re-actions given by, 150, 151.

-substance contained by, 150, or sugpecha i

in, 151.
Zymogens, 24,

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