A CONTRIBUTION TO THE PHYSIOLOGICAL STUDY OF VERATRUM MDE AID VERATRIA, (With Experiments on Lower Animals, Made at La Grange 'St. Laboratory, 1839). BY R. AMORY, M.D. S. G; WEBBER, M.D. Reprinted from Boston Medical and Surgical Journal. BOSTON: PRINTED BY DAVID CLAPP & SON. 1 8 69. PREFACE. The experiments which will be related in the following paper were performed with the assistance of Messrs. Wood, Boutelle, Bridge, Spooner, Putnam, Pierce, Brigham and Cutler. Many points of interest still remain uninvestigated ; but, as it may be several months before experiments with this drug can be resumed, and as we think the results thus far obtained are in one or two respects an advance on what has been hitherto recorded, at least in the English language* we venture to present them in this, comparatively, incomplete state. We wish to call attention to the fact, that the historical investigations on this subject were not commenced, until after our expe- riments had been performed. VERATRUM VIRIDE AND YERATRIA. Yrratrum viride was not brought into notice until a little more than two years ago. Several practitioners had used and found this drug to be of great value ; but its advantage was not generally known until Drs. Cutter, Eickard and Ingalls, in behalf of the Middlesex District Medical Society, called the attention of physicians to its use, and prepared an account of their experience with it, which was published in the American Journal of Medical Sciences. Dr. Cutter’s monograph attracted atten- tion in Europe, and the drug was experi- mented upon there. Veratria.—Previously the alkaloid vera- tria had been studied, but this was ob- tained from the seeds of veratrum sabadilla, 6 and seems in some respects only to imper- fectly represent the virtues of veratrum vi- ride. Magendie experimented with an impure veratria in 1820. In 1829 Bardsley pub- lished an article on the Therapeutical Value of Veratria. In 1844 Dr. Gebhard com- pared the action of veratria and strychnia. These are a few of the authors referred to by Van Praag.* A pricking or tingling, especially of the hands and feet, compared by some to the sensation produced by elec- tricity, is mentioned by many ; also, a sense of warmth followed by a feeling of cool- ness. Van Praag noticed in several cases that the animals upon which he experimented had a peculiar spasm, which he likens to St. Vitus’s dance, a stiffness of the limbs which ended in a dancing movement. He states that the cardiac pulsations were first * Yeratrin Toxikologisch-pharmakodynamische Stu- dien von J. Leonides Van Praag, in Virchow’s Archiv. 7, Band, 1854, s. 252. 7 increased and then diminished, irregular and then weak. The respiration was affect- ed only when large doses were taken, when it was embarrassed or ceased entirely. He noticed, also, the weakness of the muscular power, but in his summary this seems not to have attracted his attention so much as the spasms. In some cases the pupils were dilated; there was evidence, also, of pain in the mouth or throat. Nausea and vomit- ings occurred constantly. No inflammation was seen in the primes vice. He performed experiments, also, on.birds, frogs and fishes. His conclusions are : “ The respiration and circulation diminish in intensity. The muscles lose their ten- sion. The irritability of many nerves (espe- cially the peripheric cutaneous nerves) is considerably lowered. After very small doses vomiting follows ; often, also, diar- rhoea, but this more frequently after large doses. The secretion of urine is not nota- bly excited. Salivation is considerably in- creased. * * * The stage of stimulation 8 [.erregungsstadium] is shown by accele- rated respiration, increased frequency of the pulse, cramp-like tension of the muscles, increased irritability of the nerves. Death from veratria poisoning seems to proceed from paralysis of the spinal cord.” He states, also, that veratria acted in a similar manner upon man. In no case did he find any signs of inflammation, and the results of post-mortem examination were en- tirely negative. Veratrum viride.—Much has been written in regard to the use of veratrum viride in different diseases; and, so far as the re- cord of cases gives an insight into the phy- siological action, this agrees with our ex- periments. The therapeutical and pharma- ceutical character and uses of this drug are not, however, the subject of our investiga- tion, and will be entirely disregarded. Drs. Cutter and others investigated its action.* They remark that the benefit de- * American Journal of the Med. Sciences, Oct., 1858. 9 rived from its use is due to its sedative power over the circulation and the nervous system. The reduction of the pulse is mentioned in almost every case (40 to 60 beats per minute in the course of twelve to eighteen hours), as well as the general de- pression from prolonged sedation. Gene- rally there was no nausea after its use, though this symptom is mentioned by other writers. Most of the facts mentioned in this paper are, however, therapeutical, and are not included in the plan of our investi- gation. Another paper* by the same authors gives one or two cases worth referring to. In the first case detailed below, the effect of the drug upon the respiration is noticed. The case was reported by Dr. Minot, of Boston. Case.—A young man, 18 years of age, with acute pericarditis, having an irregular pulse (96-116), took of Thayer’s fl. ext. of * American Jour, of Med. Science, Oct., 1861, p. 400. 10 of veratrum viride gtt. iv. The respirations numbered 30 per min. He became more comfortable during the day. The pulse in the evening was 96. This was October 12th. Date. Pulse. Resp. Remarks. Oct. 13 87 36 Had taken seven doses; stop- ped on acount of vomiting. i( 14 112 36 Resumed the medicine. (( 15 112 30 Six doses taken; dose increas- ed to gtt. V. 16 114 40 Took three doses. “ 17 112 24 (Pleurisy.) gtt. v. ev. 4 firs. <( 18 96 22 Five doses; vomit, after last. 19 96 24 Four “ nausea. (( 20 100 30 Three “ “ (C 21 96 28 Four “ “ (( 23- 22 -25 96 100 Five “ “ The medicine was omitted for a time, and then renewed, hut neither pulse nor respiration were noticed particularly. Another case* is reported by Dr. Forsaith, in which the pulse was reduced from 120 to 40, and the respiration was only 15, an over dose having been accidentally taken. In another case,f reported by Dr. C, S. * Am. Jour, of the Med. Scienees, Oct., 1861, p, 403. f Idem, p. 406. 11 Bishop, of Philadelphia, a medical student who had been injured by fireworks; the pulse, at first 100, was k,ept at 60 for thirty- six hours, and “from the time that the seda- tive influence of the veratrum viride became manifest he felt no pain.”* In the Edinburgh Medical Journalf. Dr. J. Watson gives the results of experiments •» on himself and on several patients, from which we can derive some knowledge of the action of this drug. He took gtt. viij. of a tincture (made according to Dr. Cutter’s direction) at 3 o’clock, P.M. Two hours after, his pulse was unaffected. At 5 o’clock he took another dose, and then had tea. At 6 o’clock his pulse was the same as at 3 o’clock. Towards 7 o’clock he was troubled with flatulence. Some minutes before 7 he began to feel nauseated and would have vomited, but restrained himself. The force and frequency of the pulse be- came diminished There was griping of * Italics in the original, f January, 1864. 12 the bowels, sickness and weakness, with considerable pain in epigastric region ;he had a heavy, dull- headache, with, occa- sionally, painful throbbing in the temples. His pulse, 10 at 8 o’clock, was reduced to 64. The pain in the bowels continued, and he felt himself growing weaker ; but as he wished to experience the full effects, at 1 o’clock he took another dose of eight drops. From he felt about as described above. Soon he became weaker and felt that he must vomit. The pain in his stomach and bowels became much more severe ; a clam- my cold sweat broke out on his bi’ow, and at 71 he vomited with much pain. While vomiting he required all his strength to Support himself; his back became extreme- ly weak ; and, when a fit of retching came on, he felt as if he was going to be as- phyxiated ; he had one or two cold shivers ; his feet and hands became cold and be- numbed, though there was a large fire in the grate ; the cold, numb feeling crept up the legs and arms, and, at last, his whole body felt as if enveloped in cold, damp cloths, and he became quite prostrate. At a little after 8 o’clock his pulse was 40 and very weak. The flatulence contin- ued, till a quarter past eight, when he again vomited slightly. The cold, clammy sweat continued, and the whole surface of the body was numb. At 8f his pulse was 56. After vomiting his face was quite pale, but there was no dilatation of the pupil. He felt prostrated during the evening, but the next day was quite well. This is one of the most valuable experi- ments recorded, and, so far as it goes, agrees with what has been found in ani- mals. Dr. Watson administered the tincture in three cases. In one the patient was suffer- ing from phthisis with a pulse of 120. At quarter to 9 o’clock, gtt. viij. of the tinc- ture were given, which dose was repeated in one half an hour, as no effect had been produced upon the pulse. In half an hour more the pulse was still the same, but in a 14 few minutes she was found retching violent- ly and vomiting. Her pain was intense and her prostration excessive. She contin- ued vomiting at short intervals till within a few minutes of 11 o’clock. A cold, clam- my sweat broke out over her whole body, but especially upon the face. At 10£ the vomiting was diminishing in severity (bran- dy had been given), but the prostration be- came more marked. Just before the vom- iting commenced her pulse was at 120, but at 10£ it had sunk below 60, and was very weak. At a quarter before eleven it was 60, and at 11 o’clock it was 80 after taking wine and morphia. She was very much frightened on account of a dead feeling she experienced, especially in her limbs, and to a certain extent over her whole body. The following table shows the rapidity of her pulse: 9.45, P.M., 120 10 30 “ below 60 10.45 “ 60 11 “ 80 11.15 “ 72 11.30 “ 72 11.45- “ 80 12, midnight, 76 12.15, A.M., 72 12.30 “ 72 12.45 “ 80 1 “ 80 9 “ 120 15 lu this case, the symptoms were essen- tially the same as in the previous experi- ment. In the second case the tincture was given to a young man, aged 16 years, who had undergone amputation of the thigh on ac- count of a tumor. At 7 o’clock, 4 minims were given. At 7.15, he had nausea. At 7.30, he vomited. His pulse was as follows At 7, P.M., 152. 7.15 “ 152. 7.30 “ 136. 7.45 “ 136. Bto 9 “ 132. 9 “4 minims more were taken. 9.15 “ 132; nausea increased. 9.30 “ 124. 9.45 “ 124; vomiting, with great weakness. 10 “ 124; vomiting. The next day, 11, A.M., 150. The following day, 10, A.M., 132. Tincture again taken in the dose of 4 minims. 10.15, A.M., 132; feels sick. 10.30 “ 124. 11.15 “ 124. 11.30, A.M., 120. 11.45 “ 126; 4 minims more. [iting. 12 “ 124 ; great nausea and occasional vom- -12.30, P.M., 124. 1 “ 128. 3 “ 132. The next morning, 160. In the third case, the tincture was given to a man, aged 52, who had a fracture of 16 the thigh-bone. Six weeks after the acci- dent his pulse was high, but the general health of the patient was good. At 7.15, P.M., pulse 100; gave 4 minims. 7.30 “ 100. 8 “ 100; gave 4 minims. 8.15 “ 96; flatulence and nausea. 8.30 “ 92. 8.45 “ 88. 9 “ 100; patient retching. 9.15 “ 94; vomiting over, though gre&t nausea. 9.30 “ 88. 9.45 “ 36; great nausea. 10 “ 86. 11, A.M., 92. On the second day the medicine was again tried. At 10, A.M., pulse 100 ; gave 4 minims. 10.30 “ “ 100. 11 “ “ 96; flatulence. 11.15 “ “ 96; sickness and flatulence. 11.30“ “ 92; 11.45 “ “ 94; another 4 minims. 12, noon, “ 94; flatulence. 12.30, P.M., pulse 94; great nausea. 1 “ “ 90; other 4 min.; great nausea. 1.30 “ “ 96. 2.15 “ severe fit of vomiting, which lasted from 20 to 30 minutes. He complained of a sinking at the heart, pain in the stomach and bowels, and, after the vomiting, of great depression, and of a dead feeling in the limbs. After vomiting, the pulse fell to 80, but at 3 o’clock, after taking stimulants, it was 92, and the next morning it was at 96. In the Medical Times and Gazette* is re- corded by Dr. Edwards a case of accidental poisoning with veratrum viride. A chemist took an over dose of the tinct. ver. vir. for the purpose of testing its ef- fects. He took 5j., equal to about 12 grs. of the powder. He was found sitting in the water-closet, vomiting into the pan. His features were sunken, skin cool and covered with a profuse clammy sweat; his pulse was quite imperceptible. He complained of intense pain in the epigastrium. The vomi- tus, at first, appeared to consist of food and contents of stomach, afterwards of a glairy mucus. He received immediately §jss. of pure brandy, which checked the vomiting. He was removed into a room, and on to a couch in front of the fire. The surface of the body was still very cold, especially of the extremities. The clammy sweat con- * Jan. 3d, 1863, 18 tinned, but the pulse could be indistinctly- felt, beating feebly and with irregularity, about 44 a minute. Under the use of brandy warmth gradually returned to the surface, and the pulse became better in volume and power. He fell asleep, and awoke better. The next day he was well. There was no diarrhoea. He stated after- wards, that before and during the vomiting he had a sense of constriction in the throat, and excessive pain. His mind was calm, though consciousness was clouded for a time. Immense circles of green color were seen around a candle flame, which turned to red on closing the eyes. There was a tendency to cramps in his legs when they were touched. M. Oulmont has published* in a memoir, read before the Academie de Medecine de Paris, the results of his experiments with this drug. He sums up the results of his experiments (which are not related) with veratrum viride, as follows : * Bui. Gen. de Therap., 1868, tome Ixxiv. p. 145. 19 “ Ist. It quickly causes nausea, vomiting and diarrhoea, which two former may last fifteen to twenty hours. “ 2d. The respiration is greatly modified, becoming irregular; sometimes, very rapid, sometimes so retarded, that there may be but one or two respiratory move- ments during a minute ; sometimes in frogs it is completely suspended. “ 3d. The circulation is very rapidly di- minished in frequency ; the pulse, at the end of a quarter or half of an hour, as much as 20, 40, or 60 pulsations a minute. In man not in a febrile state, veratria (in the dose of 1 to 3 centigrammes) causes the pulse to fall thirty to forty beats. “ 4th. Thetemperature follows a descend- ing scale a little less marked ; at the end of half an hour to two hours only, it descends 2°, 3° or even 5° (C.), and may remain there twenty-four hours without death resulting. “sth. The debilitating action of veratrum viride is manifested from the beginning. Fee- bleness and prostration continually increase, 20 and when they have attained the highest point the animal dies. “ 6th. There never results contraction, muscular rigidity or tetanic convulsions. “ 7th. The poisonous dose of veratrum viride for frogs is 20 drops of the tincture, for rabbitsGO to 80, and for dogs 120 to 150.” He concludes from comparative experi- ments that veratrum album is much more unequal in its effects, and more severe in its action. lie thinks that the action of veratrum viride does not depend on the al- kaloid veratria,* as the latter causes mus- cular contractions and spasms. M. Limonf found that the tincture of vera- trum viride causes diminished frequency in the pulse and reduction of temperature. The pulse decreased from 112 to 54, and the temperature from 39 to 37 (C.), He noticed, too, that the sphygmograph showed an in- * According to our experiments, this distinction can- not he maintained. f De Taction du Yer. Yir,, Gaz. Med. de Strasbourg, in Bull. Gen. de Ther., Jan. 30th, 1869. 21 creased arterial tension, when the pulse is reduced in frequency. Its effects passed off rapidly, and there was no cumulative action. He, also, mentioned the vomiting1. Two cases, well reported and observed by MM. Tuber et H. Hirtz, internes aux Hopitaux de Strasbourg, were reported by M. Oulraont to the Society of Therapeutics. The first was a case of pneumonia in a woman, 30 years of age, mother of three children, pregnant with a fourth. She en- tered the hospital on the evening of the 9th of March, on account of pneumonia of the left lung. The temperature was 39° (0.), pulse 112. March 10th.—Temp. 88.8° (C.) ; pulse 108 ; respiration 80. Antimony and bleed- ing had been her treatment. In the even- ing the temperature was 39.2° (0.); the pulse 108 ; respiration 48. March 11th.—Asphyxia seemed immi- nent. Temperature 39.7° (C.) ; pulse 112 ; respiration 76. Yeratrum viride was now ordered in 22 granules containing 1 centigramme of ex- tract. This was first given at 9| o’clock. Hour. Dose. Temp. P. R. ■Remarks. 9.30 1st gran. 39.7°l 116 70 10.30 2d “ 39.4 108 76 * 12 3d “ 38.7 98 68 Vomiting. 1.30 38.1 68 42 3 37.8 64 44 Temp, of vag. 38.6°. 4.30 36.8 64 38 The vomiting which arose after the third granule caused considerable distress, which was of short duration. During the evening the symptoms recurred in severity. March 12th, A.M.—Temperature was 39.2°; pulse 104 ; respiration 80. Yera- trura viride was again given. Hour'. Dose. Temp. Pulse. Resp. Remarks. 10 1st gran. 38.8° 108 74 11 2d “ 38.3 100 50 12 3d “ 37.4 82 50 Vomiting. 1.30 38.3 60 30 2.30 38.6 60 40 3.30 37-7 64 40 4.30 37.5 72 40 .5.30 37 68 28 6.30 37.5 80 40 7.30 37.5 80 36 8.30 37.2 80 36 9.30 37.9 80 36 10.30 38.1 80 36 11.30 36.6 96 40 23 March 13th.—Temperature 38.1° ; pulse 96 ; resp. 32. She gradually recovered. The second case is one of generalized bronchitis in a man 37 years old. We do-not think it worth while to tran- scribe this case, which agrees in every es- sential with the one detailed above. The conclusions in regard to the physio- logical action of veratrum viride, and the alkaloid, veratria, which can be drawn from these experiments and cases recorded by others, confirm those that we have been induced to draw from our own experiments. We need only mention, here, the influence which is exerted upon the nervous system. In some respects resembling the action of woorara, it differs from that poison in less energetic action, in attacking the sen- sory fibres as well as the motor, and in di- minishing the frequency of the cardiac pul- sations. We have not performed any ex- periments to show whether the periphery Summary. 24 or centre of the nervous system is affected, or whether the whole nervous tract is influ- enced. The influence over the cardiac pulsation is, however, such that we are disposed to suspect that the nerves supplying that vis- cus are influenced at their central origin. The reduction in temperature indicates that the metamorphosis of tissue by which the temperature is sustained is interfered with ; but this is most marked in cases of abnor- mal excess of temperature. The reduction of temperature would, also, indicate an in- fluence over the vaso-motor system; the paleness of face, the dilated pupils, which have been sometimes noticed, and the in- crease of the ai’terial tension, observed by Limon, point to the same conclusion. If this be so, the weakness and paralysis may be due to an excessive contraction of the arterioles. Our experiments do not allow us to decide whether it is the spinal cord which is affected by this contraction, or whether it is the nervous trunks, or the 25 terminal fibres of the nerves, or the ner- vous plates, which form the connection be- tween the nerve and the muscle ; but inas- much as the respiratory and cardiac move- ments, the arterial contractility, the motor and sensory powers, and the secretory functions are all more or less affected, it seems more reasonable to refer the disturb- ance to the spinal axis, as that part of the nervous system through which the influ- ence is exerted, and from which all the above-mentioned results are produced. The nausea and vomiting, the sensation of tingling, the prickling in the fingers and toes, and other abnormal sensations in the throat and elsewhere, which seemed to be present even when the drug was admin- istered hypodermically, might be caused by the direct contact of the drug upon these parts as it circulates through them in the blood. A local application produces a numbness and deadens the pain of neural- gia. The deadness and diminished sensi- bility may, likewise, be due to the local 26 contact of the drug; or, both these effects, viz., the loss of sensitiveness and the ab- normal sensation, may be due to its influence over the central nervous system. In one case only, that of accidental poi- soning, does there seem to be a.cloud over the intelligence. These are the conclusions which follow from what has been recorded by others, and it will be well to bear them in mind in considering our experiments, which will now be given. It is proposed to show, by the following experiments, the symptoms produced in various animals by veratria, and at first from a poisonous dose. Exp. I.—Green-colored frog. Before the administration of the poison, the thorax is opened, and the number and force of the cardiac pulsations noticed :—Respiration 10; pulsations 32, Yeratria placed upon the web of the frog’s foot. 27 Hour. Respiration. Pulsation. Remarks. 0.21 0.31 0.36 feeble, very feeble. veratria applied to heart itself. 0.41 nearly ceased. very feeble. 28 the same. heart pale, tetanic spasms; right lung forced out of thoracic opening and rup- tured. 0.58 2.21 2.31 ceased. very feeble, still goes on. tetanic spasms ev- ery few minutes. obliged to leave; muscular fibres contract to stimu- lation. Post Mortem, twenty-one hours after. Continued rigor mortis ; muscles, heart and liver all very pale. No muscular contrac- tility to stimulation or by electricity. Lung tissue contains air. No transverse striae visible by the microscope in cardiac muscu- lar fibres, which seem to be replaced with granular spots. In this experiment it may be noticed that veratria is not very readily absorbed by the skin of a frog ; and, also, that after its topi- cal application to the cardiac muscles, it does not cause paralysis of the heart’s ac- 28 tion, though it does produce cessation of the respiratory function. It produces various muscular spasms, to which the frog, of all animals, is the most liable, and which may, after all, be voluntary movements. Exp. ll.—Eusset-colored frog. As it is stated by some observers, that phenomena produced in the green-frog and in the rus- set-frog are dissimilar, the effects are repro- duced upon the latter that a comparison may be drawn. The tincture of veratrum viride was used in this case. Tinctura veratri viridis gtt. q. s. Subcu- taneous injection to leg. Hour. Pulse. Resp. Remarks 0.07 Thorax opened. 22 0.07 weaker. 0.13 22 0.18 0.3-5 do. very feeble spasms. 0.40 18 0.53 10,irre£. 1.00 12 1.12 10 1.22 12 ceased. • Post-mortem examination ished response to electrics showed dimin- L stimulation in electrical 29 the leg to which the injection was adminis- tered ; striated muscular fibres of this leg somewhat disintegrated, though the strise can be distinguished. This is specially time of the cardiac muscles. Rigor mortis very marked. This last experiment agrees in general with the previous one, but the symptoms and other effects are more intense, proba- bly, because the dose of veratria was larger. Exp. lll.—Frog (green), Tinctura vera- tri viridis gtt. xii; placed under skin of a frog’s leg. When it touched the flesh the frog jumped and kicked. I'. Respiration spasmodic. s'. “ irregular and jerking; vio- lent struggling. 11'. Respiration slower and jerking; vio- lent struggling. 16'. Respiration feeble. I'!'. Convulsive movements; bulging of sides, reminding us of the efforts at vo- miting by a cat under similar circum- stances. 30 24'30". Same effects; resp. ceased for a short time, and was then resumed. I,B'. Muscular quiverings in posterior ex- tremities. i 1.45'. All phenomena of life had ceased, in- cluding those of reflex action. Post mortem.—The muscles near to the place where the veratria had been applied were, in some places, covered with granu- lar degenerations (as it appeared under the microscope), and, in others, extremely fine transverse striee were arranged very near each other; the corresponding muscles of the opposite leg had nothing of this pecu- liarity. The cardiac muscles were easily separated into fibrillse, some showing a coarse striation, others the same granular appearance above referred to. The hearts of each of the two frogs (Exp. 11. and III.) were pale and muscles somewhat contract- ed, each animal having an abundance of fluid blood in its body. These peculiarities were afterwards ex- plained by a more careful examination, 31 made with the use of alcohol and ether, which cleared up the field of observation, leaving the striae more distinctly marked, though the fibrillee were a good deal disin- tegrated and broken up. We were led to suppose that these dubious effects were due to mechanical deposition of the drug, as both the solution of veratria and the tincture of veratrum viride under the microscope had these same spots, and muscles soaked in either of the above were covered with these same globules. This last experiment shows, in a general way, how the respiratory movements in a frog are modified, and that death can be induced by a dose of 12 drops ; also that the post-mortem changes reveal little to show by what cause the vital functions are interrupted. It will be interesting to com- pare these first three experiments, taken from a number made upon frogs, with Exp. IV.—Upon a cat. A small amount of veratria (by estimation 32 3 to 5 centigrammes) on the point of a scalpel was inserted beneath the skin of the back, just over the upper lumbar vertebra. The cat immediately licked the wound. s'. Champing of jaws and salivation ; eyes closed; sneezing and retching; no loss of power over limbs ; continued twitching of tail, occasionally crying ; head held up with her nose in the air. 35'. Another dose (of equal amount) is ad- ministered in the same manner. Seems to cause much pain, from the crying in- duced. Apparent loss of muscular power in posterior extremities ; great uneasi- ness and distress. 40'. Has a dejection ; after which, seems disinclined to move. 1,9', Eyes shut; when opened, pupils ap- pear round and bright. 1.45'. Another defecation. 2.0'. Retching with cries, followed imme- diately by others, which were continued with much violence. 2.5'. Another more violent attack of retch- ing, the cat dragging her face along the floor for six inches. 2.15'. Vomits a small portion of liquid food. Some loss of muscular power in posterior extremities. 33 2.20'. More veratria administered, followed by continuous moaning ; violent spasms, pawing at mouth, loss of muscular con- trol ; respiration very rapid ; violent efforts at vomiting, drawing her up and off her feet. 2.35'. Convulsions and vomiting ; respira- tion diaphragmatic. No loss of sensa- tion. 2.55'. Ejection of urine followed by tetanic spasms and muscular twitchings. 2.55'. No respiration, no cardiac pulsation —death. Post-mortem examination. Heart normal —lungs congested, ecchyraosed and emphy- sematous, the lower lobes covered with white spots. Stomach rather pale ; liver and intestines show no peculiarities ; blad- der empty; muscl.es of heart showed broken- up fibrillaa with the striae somewhat irregu- lar. In a muscle from the thigh the striae were distinct. The first peculiar effect produced by this drug, it may be noticed, is salivation ; and this is followed by retching, movement of the bowels, vomiting, &c. ; after this, the respiratory efforts are hurried, muscular ac- 34 tions are imperfectly performed, spasm of the bladder causes ejection of urine. Final- ly, death occurs, preceded by tetanic spasms Exp. Y.—We will now compare with these another experiment, upon a small rabbit weighing only 15 ounces Troy h.m.s. Resp. Condition Circula- General Symptoms, of Pupil. tion. Remarks, &;c. 0.00 92 carefully examined. 240 1 centigr. inserted under skin of back, which made the ani- mal cry out in a.few seconds. 0.02 Animal now quiet. 0.05 slow contract’d. 144 Champing of jaws. & jerk’g. 0.07 108 0.09 dilated. Large quantity of saliva oozes from the mouth. 0.11 no pulse. Ears very cold and pale. Chest opened; heart pulsates feebly; r. ventricle and au- ricle distended with blood. The contraction of auricle more rapid than that of ventricle (96:48) (120:30). Pulsation of each becomes more and more feeble and irregular. although the heart is kept moist. In 33 min., there • is no pulsation visible. Examination of the body, made immedi- ately, showed the veins turgid, fauces and oesophagus pale, no peristalsis of bowels to stimulation or to galvanic current, very 35 slight contraction of leg muscles on electri- cal stimulation, heart empty, the lungs ec- chymosed (one small haemorrhagic spot in right side), brain normal. An examination of this last experiment, showing that salivation is caused even when the drug is administered hypodermi- cally, would induce us to consider, that it is not local irritation of the buccal mucous membrane which causes the salivary gland to throw out its saliva, but that this effect is probably caused by an irritation of the lingual nerve, or submaxillary ganglion, which Bernard* has shown will cause sali- vation ; but, before we investigate this phe- nomenon, let us compare with these first ex- periments that of the action of veratria on a dog. Exp. YI.—To a vigorous bitch, of about forty-five pounds weight, was given gss. of chloroform until she became quiet. Then ether was used, and the animal bound upon the operating board. * Vide Compt. Ren. de I’Acad. des Sci., 25 Ang. 1862. 36 h.m.s. Pulse. Resp. Remarks. 148 34 Before * the inhalation of chloro- form. 174 56 Imperfect anaesthesia. 142 40 Perfect anaesthesia. 134 40 Veratria gr. 3|, dil. acetic acid, q. s., injected in right leg subcuta- neously. 0.02.00 112 40 0.05.15 120 36 Animal is calm. 0.06.15 112 40 0.08.30 120 36 0.09.30 116 32 0.10.00 116 16 0.12.30 114 15 Muscular quivering in trunk. 0.14.00 108 12 Ether is now removed. 0.16.00 108 10 Abdominal respiration. 0.18.00 102 0.20.30 104 85 Respiration feeble. 0.25.00 102 12| Animal gasps. 0.27.00 88 11 Animal struggles. 0.30.00 36 32 Another gasp. 0.31.30 80 28 Skin is cold. 0.35.00 72 22 0.37.30 84 17 Pulsation stronger. 0.40.00 98 10 Difficult and noisy inspiration* Struggles. 0.45.00 98 14 Expiration slow and noiseless; muscular contraction by electric stimulation feeble, especially in posterior train. 0.49.00 108 0.52.00 120 15 Struggles violently. Irreg. resp. Muse, relaxation; loss of sensat’n. 0.54.00 120 13 0.56.30 126 20 Difficult respiration, with violent movements of neck muscles. 1.00.00 108 12 Respiration very feeble, with mu- cous rales in throat. 1.05.00 128 ceas’d 1.09.00 92 1.09.30 gone. No response to electrical stimula- tion of nerves, though the mus- cular fibres contract when the 1.12.00 poles are applied to these directly 1.15.00 Nerves of neck and forearm ex- posed; electrical stim. does not cause muscular contraction. 37 Post-mortem examination (immediately). —Heart normal in appearance ; clots in left ventricle; fluid blood in right ventricle ; right auricle contains blood which is slightly diffluent; left auricle empty. Lungs apparently healthy ; crepitate between the fingers. Liver, kidneys, spleen and pan- creas all normal. Stomach and intestines show slight arborescent redness. Stomach reddened on the inside, and nearly full of a viscid fluid like saliva. Bladder nearly empty. It may be noticed that chloroform and ether were administered to produce anes- thesia. This was preliminary to an opera- tion to measure the arterial tension which will be described and commented upon elsewhere (Exp. YI. 6). This experiment is related in this place, as it was conducted with great care, and many assistants aided in the taking of observations, which it may be noticed are very accurately described. Attention is called to the fact that the general effect of the drug upon the vital 38 functions agrees with other experiments upon animals not under the effects