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L'axamplaira film* fut raproduit grdca i la ginirositi da: Medical Library McGill University Montreal Laa imagaa suivantaa ont M raproduitas avac la plua grand aoin. compta tanu da la condition at da la nattati da l'axamplaira fllmi. at an conformiti avac laa conditiona du contrat da fiimaga. Original copiaa In printad papar covara ara filmad baginning with tha front covar and anding on tha laat paga with a printad or illuatratad impraa- sion, or tha back covar whan approprlata. All othar original copiaa ara filmad baginning on tha first paga with a printad or illuatratad Impraa- sion. and anding on tha laat paga with a printad or illustratad impraaaion. Laa axamplairaa originaux dont la couvartura an papiar aat imprimte sont filmte 9n commandant par la pramiar plat at an tarminant soit par la darniAra paga qui comporta una amprainta d'Impraaaion ou d'lilustration. soit par la sacond plat, salon la caa. 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Lorsqua la documant aat trop grand pour dtra raproduit an un saul cllchA. il aat film* i partir da I'angla sup^riaur gaucha, da gaucha d droita. at da haut an baa. an pranant la nombra d'Imagaa nteaasaira. Las diagrammas suivants iilustrant la m^thoda. 1 2 3 32X 1 2 3 4 5 6 ^. /njfmoJ. V/'.S' 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. ^)|(tvw»ViV»»»»vvy»»»»y»www»»V»1W>s^»Wft^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. e g e a y )r re »g ig 10 re 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: