RT Journal Article
SR Electronic
T1 STUDIES ON VOMITING
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 139
OP 193
VO 22
IS 3
A1 ROBERT A. HATCHER
A1 SOMA WEISS
YR 1923
UL http://jpet.aspetjournals.org/content/22/3/139.abstract
AB 1. The significance of nausea, and its independence of the vomiting reflex are discussed. 2. The cause of the inability of rodents and certain other animals to vomit is considered and an explanation of this inability is suggested. 3. Experimental evidence is presented showing that nausea affords the cat and the rat a certain degree of protection against poisoning by oral doses of strychnin sulphate. 1. Vomiting was induced after the destruction of the quadrigeminate bodies, the cerebellum, and the area described by Thumas as the vomiting center in the cat, and of the latter area in the dog. 2. Vomiting was not induced after destruction of the sensory nuclei of the vagi in cats, nor after the certain destruction of the nucleus of one side in any of 6 experiments on cats and one on a dog, but it was induced in one such experiment in which the destruction of the nucleus may have been incomplete. 3. The results of these experiments indicate that the sensory nuclei of the vagi are essential for vomiting, however it is induced, in the higher mammals (possibly with exceptions so rare that they do not enter into this discussion). We feel justified, therefore, in stating that the vomiting center is embraced within the sensory nuclei of the vagi. 4. This view finds support in the fact that the vagus supplies the heart, stomach, intestine, and pharynx, from which vomiting can be induced reflexly, the pylorus, which closes when nausea occurs, and the cardia, which must open during the act of vomiting. Also in the fact that it is definitely shown to be concerned with emetic actions of some drugs. 5. It is obvious that the sympathetic makes functional communication (at least) with the vomiting center, wherever it may be, hence vomiting is possible after vagotomy, and it may originate in organs that the vagus does not supply. 6. Vomiting is the result of the orderly sequence of several associated, but independent, reflexes. Injury to the coördinating mechanism may abolish vomiting without interfering with the independent reflexes, such as swallowing. 7. Evidence is afforded for the view that only certain of the cells of the sensory nuclei of the vagi are concerned with the vomiting reflex by the fact that hyperexcitability is induced toward the vomiting act without influencing the associated independent reflexes, except that for respiration, and that is stimulated and inhibited at different periods. 1. Efferent emetic impulses pass from the vomiting center by the vagus and by the spinal cord apparently with equal facility, regardless of the exciting cause. 2. Apomorphin induces emesis by rendering the center hyperexcitable to normal afferent impulses that pass by way of the sympathetic type of nerve (only?) from many organs. It is presumable that other centrally acting emetics behave in the same way as apomorphin. 3. Ergotoxin inhibits the normal afferent emetic impulses from any part of the body from which they may arise, but atropin does not. 4. Afferent emetic impulses induced in an organ by one substance may pass by one path, while those induced in the same organ by a different substance may pass by the other path (e.g., stimulation of the cardiac sympathetic by pilocarpin, of the cardiac vagus by tartar emetic). 5. Afferent emetic impulses induced by a given substance in one organ may pass by one path, and those induced by the same substance in another organ may pass mainly (or exclusively) by another (e.g., tartar emetic stimulates the sympathetic in the duodenum, the vagus in the heart). 6. Afferent emetic impulses induced in an organ by a substance may pass equallly well by both paths (e.g., mercuric chlorid in the stomach). 7. Atropin paralyzes some of the afferent emetic paths in both the vagus and the sympathetic, but it does not paralyze all in either. 8. Ergotoxin paralyzes some of the afferent paths in both nerves, some of which are those paralyzed by atropin, some of which atropin does not affect. It inhibits the action of a greater number of the emetics that we examined than does atropin. 9. If a given substance stimulates both afferent endings about equally, the action of a nearly minimal emetic dose is inhibited by cutting one path. 10. Section of one path does not appear to influence the action of a nearly minimal emetic dose of a poison if the afferent path is intact. We have offered an explanation of the difference in the effect of cutting one path on the passage of afferent and efferent emetic impulses. 11. The influence of vagotomy, section of the spinal cord, atropin, and ergotoxin on the emetic actions of various substances has been studied and the results are tabulated. 12. It is evident that the afferent sympathetic nerve fibers concerned with emesis are in as effective functional communication with the vomiting center in the sensory nuclei of the vagi as the vagi themselves. 13. The vomiting center coördinates many centers. This explains why a few cells in the sensory nuclei of the vagi, which receive impulses from nearly every part of the body, when strongly stimulated exercise a wide range of inhibitions and excitations with convulsive contraction of many muscles. 14. The heart is an important seat of the vomiting reflex induced by many poisons and probably by toxic disease products. 15. Pilocarpin induces defecation by its local action on the intestine and vomiting by its reflex action on the heart, though these phenomena are closely related physiologically, both being frequently induced promptly by the application of minute amounts of poisons to the floor of the fourth ventricle. The behavior of pilocarpin suggests that it acts on ganglion cells; that these differ in the heart, stomach, and intestine; and that it exerts no emetic reflex action on the stomach or intestine. 16. The terms "stimulation" and "depression" are used for the sake of brevity to indicate that afferent emetic impulses are induced or inhibited; similarly the expression "afferent nerve endings" is employed to indicate the peripheral afferent structures without committing us to any view concerning the exact seat of the action. 17. The classification of the afferent nerves now under consideration as sympathetic and parasympathetic is convenient for the purpose of discussion, but we have no evidence that any sharp distinction can be drawn between the two classes either with reference to physiological functions or their pharmacological behavior. Both the sympathetic nerve trunk to the heart and the vagus contain both sympathetic and parasympathetic types of nerves so far as one can distinguish them by their reactions toward drugs. 18. The vomiting reflex affords a convenient means of studying afferent paths and functions because of the ease and certainty with which selected parts of the reflex arc may be stimulated or depressed. and because of the extraordinary extent of the nervous connections of the center. 1. Twenty-seven substances were used in 35 experiments on 28 dogs and 7 cats in which 97 applications were made to the floor of the fourth ventricle just above the obex. 2. Thirteen of the substances induced vomiting in dogs and one in cats. These are, in the order of their activity, with figures which express milligrams, or fractions of a milligram, per kilogram of weight: Apomorphin hydrochlorid, 0.0001; aconitin hydrochlorid, 0.0002 (or less); morphin sulphate, heroin hydrochlorid, and picrotoxin, 0.001; histamin, epinephrin hydrochlorid, nicotin salicylate, and strychnin sulphate, 0.01; brucin sulphate, tyramin, 0.1; emetin sulphate, 0.2; cholin hydrochlorid, sodium salicylate, 1. 3. Apomorphin hydrochlorid increases the excitability of the center, and normal afferent impulses from various organs then induce vomiting. The other substances just mentioned act in the same way, presumably. 4. Atropin sulphate has no inhibitory influence on these normal afferent impulses, put it paralyzes certain of the afferent parasympathetic paths, and probably certain of the sympathetic. 5. Ergotoxin phosphate paralyzes certain of the sympathetic afferent paths and thereby prevents the passage of normal afferent impulses from various peripheral organs to the center, and in this way it inhibits the emetic action of apomorphin. 6. Evidence that these impulses pass up from many different organs is afforded by the fact that apomorphin induces emesis in the eviscerated dog. 7. The vomiting center is sensitive to the depressant action of apomorphin and other substances, and when moderately depressed in this way it is not stimulated by the application of other substances that commonly increase its excitability, but it is still capable of being excited reflexly from the stomach. 8. The intravenous injection of a relatively small dose of mercuric chlorid induces vomiting, probably reflexly from the heart. 9. We have been unable to induce vomiting by the local application to the center of pilocarpin, quinin, tartar emetic, veratrin, or any of the digitalis bodies (previously reported), all of which induce vomiting in the eviscerated dog, and we have been unable to cause vomiting by the application of cocain, caffein, or atropin, toxic doses of which induce vomiting in the intact animal. 10. We were able to demonstrate synergism of action of a centrally acting emetic (apomorphin) and one acting peripherally (ouabain), but we were unable to detect any synergism in the actions of two substances having their seat of emetic reflex action in two different organs. The probable significance of this is discussed. 11. The results of our experiments prove that there is a defecation center in the floor of the fourth ventricle.