A respiratory symptom of tobacco poisoning and its experimental investigation [microform]

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Keprintcd for the Author from the British Medical Jouknal,
June sth, 1897.

A RESPIRATORY SIMPTOM OF TOBACCO

POISONING AND ITS EXPERIMENTAL

INVESTIGATION.*

By WILLIAM S. MOKROW, M.D.,

Lecturer on Physiology, McGill University.

The present paper is written with the object of describing
and, as far as possible, explaining a certain peculiarity of
breathing met with in cases of tobacco poisoning.

In the experience of the writer it is a very common symptom
/of excessive use of the "weed," as he has seen three cases m as
many years exhibiting it to a marked degree, besides several
others in which it was less characteristic. As considerable
difficulty was experienced in finding a description of the
symptom, it would seem to have been overlooked by most
observers, and yet it is believed to be of considerable dia-
gnostic importance. The following are short accounts of the
three cases referred to above in which it was most topical :

Case i.-In December, 1893. a medical student came complaining of
nalnitation on slight exertion. He said he had used tobacco freely since
II years of age. While examining his chest his breathing was observed to
be peculiar. He would take a deep inspiration, and then there would be
little or no breathing for a considerable interval, followed by another
deep inspiration. On inquiry he said he believed he often went a long
time witbout breathing. At any rate, he was often conscious of taking a
very deep inspiration. He was advised to give up tobacco altogether. He
did not do so immediately, and was lost sight of for a time. When seen a
year or more later he had given up the habit, and the peculiarity of
breathing had passed away. It was this case which first drew my attention

*°CASE^n.-L.'T., a boy of 14, small for his age, was first seen in Decem-
ber, 1895. He complained of pain in the left side, extending from the
heart around to the back and down the left arm. It was Eometimes
severe enough to wake him up at night. His mother said he was lescless
and excitable, and ate poorly. He had smoked cigarettes for two years.
While in the office peculiar heaving sighlike inspirations were observed.
On being Questioned he said he often breathed like that. Discontinuance
of tobacco was enforced, it is believed, with success. He was seen at in-
tervals after this, and the breathing did not become norma) for over six
months during which the sighlike inspirations were frequemly observed.
The following case was only diagnosed by the light thrown on it by the

TashT in.-fn December, i8g6, Mr. T., a medical student, came complain-
ing of not being able to take a deep breath. The difficulty had come on
three days before, and was increasing. He said he was not prevented by
pain, but it felt as if the air would not go in. When asked to try, he
seemed to succeed very well, and as he sat m the office he took at inter-
vals deep heaving breaths. He was conscious of effort in doing so. Once
lie remarked that the air seemedjto go in that time. There was no pal-

*Readrbelore the Montreal Medico-Chirurgical Society.

fiitation or pain in the chest or arm. The pulse was 70. He said at first
hat he did not smolce much, but aftorwards admitted that he had smoked
far more than usual during the preceding week. One afternoon he had
smoked seven cigars, and he was not used to smoking more than one or
two. He said also that he chewed the ends of his cigars. He was told to
stop tobacco and to report progress, but he did not return. A brother
practitioner has, however, seen nim since, and tells me that the peculiar
breathing only lasted a few days after the smoking was discontinued.

The only satisfactonr description of this symptom that I
have been able to find is in a paper by Chapman, of Louis-
ville, read at the Mississippi Valley Medical Society in 1891
(abstract published in the Medical Record and in Sajous
Annual.} He described the breathing in a case of tobacco
poisoning as irregular, consisting of several short shallow
respirations^ followed by one deep and gasping. He counted
the respirations, and found them 20 to 22 per minute. I have
to plead guilty myself to having failed to observe the kind of
respiration intervening between the special deep inspirations
to which I am drawing attention. As far as could be judged
from the abstracts at my disposal, Chapman made no attempt
to explain the peculiar breathing he described, and after a
fairly careful search no explanation was found in the English
literature within reach. Such a change in the breathing is in
all probability due to some influence affecting either the
respiratory centre, the pneumogastric nerve, or the blood.

It has been aflirmed by many writers, though denied by
some, that changes do take place in the blood in nicotine
poisoning. It would seem, however, that any such explana-
tion of the symptom in question may be excluded when we
remember that in one of my cases the symptoms persisted
for some months after cessation of the use of the drug.

In order to determine whether the respiratory centre or the

gneumogastric nerve is chiefly afl'ected, a somewhat detailed
nowledge of the effect of tobacco on respiration is required,
and as I could not find answers anywhere to some of the
questions suggested by these cases, I decided to carry out a
few experiments in the hope of settling the matter for my-
self.

Before describing the experiments I will take the liberty of
reminding you in a few words of the principal factors in the
nervous control of the respiration. There is a respiratory
centre in the medulla which is divided physiologically into
an inspiratory and an expiratory centre so distinct from one
another that either one may be afl'ected by stimuli which
fail to influence the other. These centres may or may not be
able to act automatically, bnt they are in any case profoundly
afl'ected by nervous impulses reaching them from the brain
above and by various paths from below, especially by the
pneumogastric nerves. The respiratory centres send their
stimuli to the muscles of respiration by the ordinary spinal
nerves such as the phrenics and intercostals. The experi-
ments were carried out to determine as far as possible which
parts of the nervous mechanism of respiration are aflTected in
tobacco poisoning.

The apparatus used consisted of the well-known arrange-
ment of Marey's tambour, shown in Fig, 71 of the sixth
edition of Foster's Physiology. By this the movements of the
air in and out of the chest can be recorded on a moving sur-
face. A lever scratches curves on a strip of lamp-blacked
paper in such a way that the upstroke of the curve reading
from left to right corresponds to expiration, and the down
stroke to inspiration. The amplitude of the curves is proper-

force of the respirations. The records may be
varnishing the papers on which they are

tionate to the
preserved by
taken.

The first point investigated was the effect of tobacco on the
respiratory curves of rabbits. For this two experiments
were performed, in each of which the rabbit was first
etherised. Tracheotomy was then performed and connection
made with tlie apparatus. The rabbit was then poisoned by
one or more doses of an infusion of tobacco, and then records
were taken of the breathing at intervals. In one case the
tobacco was given in repeated doses hypodermically, and in
the other one large dose was given by enema.

FiGl.

■" *j^

Fig. I. Respiratory curves from a rabbit poisoned witli tobacco:
I. Control— rabbit under etlier. After tliis curve was talcen,
tobacco infusion was injected into tlie bowel, and enough ether
given at intervals to keep the animal quiet. 2. Lengthening of
curves showing slowing of respirations. Taken three minutes
after injection. 3. Taken two minutes after 2 ; and 4, taken three
minutes after 3, show the breathing becoming quicker again.

5. Taken five minutes after 4, shows slowing and change of type.

6. Taken five minutes after s, shows failure of expiration.
Respiration reduced to inspiratory gasp. See also Fig. 4, tracing 4.

General description of figures.— Re&A from left to right. Up stroke cor-
responds to expiration. Down stroke to inspiration. Base line
marks position of lever at rest. In tracing 4, Fig. 3, the base line
Is a fraction of an inch too high. The vertical lines in some of the
figures are through corresponding parts of the curves for com-
paring the rate of respiration.

The effects which followed are shown in Fig. i, and were :

(1) Slowing of respiration; (2) quickening to beyond the
original rate ; (3) slowing again and shallowing ; (4) a change
in type in which expiration became absolutely passive,
and the breathing consisted of an infrequent deep
inspiration, gasping in character.

The next experiment was carried out to determine whether
any of the above effects were due to differing degrees of ether
anaesthesia. The results are seen in Fig. 2, and show that
the preliminary slowing was probably due to the ether par-
tially passing off, but the ether failed to cause the great
quickening seen in the tobacco experiments or the still more
characteristic breathing of the later stages.

The third point investigated was the effect of poisoning
with tobacco after first cutting the pneumogastric nerves (see

Fig. 3). The results were (i) quickening and increased ampli-
tude ; (2) slowing and weakening ; (3) failure of expiration,
and confinement of breathing to active inspiration and purely
passive expiration. This is practically the same series of
changes as with the pneumogastrics intact, showing that the
characteristics effect of tobacco poisoning are not likely to
be due to any effect on the peripheral pneumogastrics.

Fion

Fig. 2. Respiratory tracings in various degrees of ether anjBsthesw.
I Rabbit well under ether. 2 and 3. Partly out, showing resem-
blance to the first slowing in the curves of tobacco poisoning.
4. Partly under again. 5. .Very deeply under. 6. Partly out
again,

Next a rabbit was poisoned as before with tobacco, and the
intact pneumogastrics were stimulated at intervals with a
faradic current (see Fig. 4)- The effect of the stimulation

FiGin.

Via , Tnhacconoisonineaftersectionof both pneumogastric nerves.

^'V^'R.^sStor^tSngs taken after section of these nerves. 2.

A^feraSection of tobacco infusion showing preliminary stimu-

iSion of respiratory centre. 3 and 4. Slowing and weakening, with

failure of expiration before inspiration.

was at first to stop respiration, or in some cases to render it
very shallow and rapid, but towards the end the eftect became
Ss maSed, and iS tie final stage of poisoning stimulation

of the nerve failed to affect respiration to anv "appreciable
deorree although inspirations were still taking place.

This showed that there was loss of irritability either in the
nerve itself, or in th«) nerve roots, or on the sensory side of
the respiratory centre. It is hard to decide for certain which,

Fig IV.

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Vie. 4.-Eflfect of stimulating the pneumogastric nerves at various
stages of tobacco poisoning. In eacli curve (a) marks the point at
which a moderately strong current from a Du Bois-Reymond In-
ductorium was turned into the nerve. At first tlio breathing is
stopped or greatly modified, but in the final stage of poisoning
seen in Tracing 4 the stimulation has no efl'ect.

but I believe that the profound change in the breathing at
this stage may be attributed with reason to all the afferent
impulses being cut off from the centre, so that it was only
stimulated to action in an imperfect way by the impure blood
which reached it. This assumption is borne out by the work
of Loewy, as referred to in Landois and Stirling's Physiology.

FigV.

Fig. ?.— Stages of chloral poisoning, shows weakening and slowing o
respiration following a preliminary quickening. The failure of
inspiration is, if anything, more marked than that of expiration.

He found that on cutting off all possible nervous impulses
from the centre the respiration became extraordinarily slow,
and each individual respiration became deeper. He believes
that these respiratory movements were due to the stimulation

0, the centre Y^hBWoo. "c ^^rh^d.^^H J~
total volume of air i^^^P"^^„^ „oigo„inK, and this has b^'.-n
lVoVn'':o\1"bX%at'w!;rth^opr«mV»trie.t>mu^

°'r.Sf to"q lx&. A r*bjt w., „,.xt^oieoned
With chloral, and ^hej-^cngs taken w" expiration

Fig. 5. These show that „\y«^«f g^^hioral poisoning the
does not ««ff«^"^yheJase After this an experiment was
reverse seems to be the case. ^'"^ j^ , ^y^^ pneumogastnc
performed which showed tha^ the trunKoiip tdbacco.

Ts able to conduct neX^^iftn mSscTe was laid upon the
A frog's nerve connected with » 'J'JJ^'f ^^,. p^^ stimulated
upper%nd of ^^^^ne^og^l^c^^,^^^^^^ show-

with a moderate current {^n|«°8f j^g^ up the trunk of the
ing that a nerve impulse had traveuea up accompany

pneumogastric, and the electncal changes wn ^f^^^

Wry nervous i^«l«« Jj!,n'JS)gS^^^ ^'^""^^

due to escape of current.

FigVI

™.s,/f!.nar.w«-.iss»s!s,i«=r,».

caused contraction «{, ^j^f^jf^XS oned having %en per-
were done on dogs, ^H hitherw ^^^i^igt^red to two dogs, and
formed on rabbits. ^^.V^^'^^ „^°,^jtpa is shown in F g. 6. Al-
tracings taken, of ^^^l^^^ ,°?,^,fXev wSe rea ly among the
though these are de««Pb«^^^T„^eSerience I waited too^long
first performed, and in J^y .^"^^Plhis crobably explains the

before taking my second ^^^^^.^8' ./„ot gho^n but the final
fact that the stage of, quickening ^^ not shown o .^^^

and most characteristic stages of slowing aii y

failure, with deep, ^a«P^°g.^S?oi o '^er Ixp^^^^^ were
purposes of comparison and control Jiner y varying

dwTSf r tKenSSI'of'S pape/they are

only mentioned. . ^oanii fhp following conclusions :

From these experiments we f^^f^^^^P olEl cases reported,

and expiration less.

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Tobacco doeg not produce this charncteriBtic effect through
the peripheral endings of the pneumogaHtric nerves, as ita
action is practically the same after those nerves have been
cut. The same experiment makes it unlikely that it acts
through the trunks of these nerves.

Moreover, they seem capable of conducting nerve impulses
after death from tobacco, and it would be difficult to explain
the diminution which seems to occur in the total volume of
air breathed by any action on these nerves.

I do not deny that the pulmonary branches of the pneumo-
gastrics may be affected in any way. On the contrary, Roy
and Graham Brown have shown that nicotine dilates the
bronchial tubes, presumably through these nerves, but the
characteristic symptom forming the subject of this paper can-
not be explained by any action of the poison on them.

The poison seems to act principally on the respiratory
centre, paralysing the expiratory division of it, and render-
ing the whole centre insensitive to afTerent nervous impulses.
The deep-drawn inspirations seen in my three cases may
correspond exactly to the deep-drawn inspirations seen in the
rabbit and dog in the final stage of poisoning, but from the
fact that respiration may be carried on in a feeble way be-
tween them, and that they are seen in cases of moderate
degrees of poisoning, it seems more likely that they are due
to a less severe interference with the sensory side of the
centre causing a partial failure of response to the ordinary
stimulating influences from above and below. This properly
brings into play direct stimulation of the centre by the blood
^rom partial asphyxia, which explains the subjective feeling of
ack of air complained of in Case iii.

Summary and Application.
A fairly common symptom of tobacco poisoning is a deep
gasping inspiration occurring at intervals, and sometimes
quite audible. This may be practically the only symptom
complained of. It is probably due to a paralysing action of
the drug on the'respiratory centre, affecting especially the ex-
piratory division, but also diminishing the irritability of the
whole centre to afferent impulses. This symptom may per-
sist from a few days to some months after the poison is dis-
continued.

s: