S. J. Meltzer

Peristaltic movements of the rabbit's cecum and their inhibition, with demonstration

The rabbits cecum fills nearly one half of the abdominal cavity and is full of food, which has to get into it and leave it again by some moving force. Nevertheless we find in the literature practically no statement on the movements of that organ. There is good reason for it. When the abdominal cavity of a rabbit is opened the cecum as a rule shows no motion. We wish to report that according to our observations, that organ exhibits well marked and quite regular peristaltic movements; but these can be seen only in the normal animal. When a well fed rabbit is fastened on its back on a holder and the hair of the abdomen is removed, as a rule movements of the cecum can be seen sooner or later. The movements are well marked and characteristic in their appearance, and leave no doubt as to the organ in which they take place. We shall mention only a few details in this communication. As a rule, especially in well fed rabbits, the movements begin in the colon and travel towards the small gut, that is, they are antiperistaltic in character. But frequently at the end of an antiperistalsis, after only a short interval, the wave returns and runs from the small gut towards the colon; in other words, the antiperistalsis is often followed by a peristaltic wave. The constriction is preceded by a bulging which is more marked than the former. The degree of the constriction (and bulging) is variable. Weaker waves sometimes do not finish the course. A complete course of a wave in one direction lasts from thirty to fifty seconds. The average rate of the movements is about one per minute, but the rhythm is far from being regular.

Combined action of magnesium and ether; evidence of a central effect of magnesium

We have shown about eight years ago that magnesium sulphate is capable of causing a profound depression in animals. After an injection of a proper dose of a solution of a magnesium salt the animal loses for some time, all reflexes and signs of sensibility, while the respiration remains intact. Several years before it was found (M.) that a condition similar to this can be produced by an intracerebral injection of two or three drops of a 5 per cent. solution of magnesium sulphate, while the injection of hypertonic solutions of other salts caused convulsions. On the basis of both experiences we assumed as a working hypothesis that magnesium favors an inhibition of the entire nervous system. We designated the depressed condition of the animals as anesthesia, which implied that the central nervous system was also affected. This interpretation has not been accepted by Wiki. He called attention to experiments of Binet and of his own to the effect that magnesium salts paralyze the motor nerve endings, and he assumed that in our experiments the animals were merely paralyzed and had not lost any sensation; in short, magnesium acts, according to Wiki, like curare, although he admits the significant difference that curare paralyzes the respiratory motor nerves before the motor nerves of the other parts of the body, while magnesium paralyzes all other motor nerves before it attacks the motor nerves concerned in the respiration. The statement that magnesium paralyzes motor nerve endings is perfectly correct; we have seen it ourselves numerous times. While it is true that many other inorganic salts have also a curarelike action upon the motor nerve endings, it has to be admitted that the effect of magnesium salts upon the motor nerve endings exceeds that of any of the other salts.

A demonstration of the inhibitory effect of magnesium upon normal and artificial peristalsis of the stomach and duodenum

Some years ago J. B. MacCallum 1 made the statement that purgation can be brought about by subcutaneous or intravenous injection of magnesium sulphate. He ascribed the effect to the stimulation of nerve and muscle tissue of the intestines by this salt, which thereby caused increased peristalsis. In a paper by Meltzer and Auer 2 it was stated, however, that magnesium salts not only do not cause peristalsis, but directly inhibit it when normally present or even when aggravated by barium or physostigmin. In opposition to this statement it was asserted in a paper by S. A. Matthews and D. E. Jackson 3 that after injection of magnesium sulphate the peristalsis shows no especial departure from the normal and barium and physostigmin show their usual action.

The prevention of blood clotting by Dakin's sodium hypochlorite solution

It has been shown by Austin and Taylor that Dakins solution dissolves necrotic tissue in wounds and washes away blood clots. Sweet has stated that the dressing of wounds with this solution favored hemorrhage from them. We made experiments to determine whether the solution prevented the clotting of blood in vitro and wish to record some of the facts observed. We found that Dakins solution of sodium hypochlorite added to blood in vitro was able to prevent clotting. If blood of a dog is drawn directly into Dakins solution in the proportion of one part of Dakins to ten of blood, clotting is usually prevented entirely. In a few instances such blood showed the formation of small, soft clots after standing several days. In no case was there any sign of clotting when as much as 1.5 c.c. of Dakins to 10 c.c. of blood were used, even after standing as much as four weeks. There is a slight difference between the blood of different species; thus cat blood is prevented from clotting by rather smaller amounts than are required for the dog, while rabbit blood requires rather more and guinea-pig blood needs about 4 c.c. for each 10 of blood. Dakins solution on standing is said to lose its effectiveness as an antiseptic and its toxicity when injected intraperitoneally. Its power to prevent clotting was found to be reduced to about half in a week and it remained at this point for several weeks. Thus of a certain sample 0.8 C.C. were required to prevent clotting in 10 C.C. of blood when fresh; 1.4C.C. when 10 days old and 1.5 C.C. when 40 days old. Blood preserved from clotting by Dakins solution is not affected by calcium salts but is readily caused to clot by tissue extracts.

Simultaneous graphic registration of gastric and duodenal peristalsis in rabbits; a demonstration

The graphic registration of gastric or intestinal peristalsis is usually obtained from an animal with an opened abdomen while in a saline bath and more or less under the influence of an anesthetic. This method hardly reproduces the normal condition as the act of laparotomy reduces and modifies greatly the peristalsis. In some instances the movements of the stomach have been studied from a gastric or œsophageal fistula and in the rabbit the movements can be studied graphically, as it has been discovered by Auer, in the perfectly normal and unanesthetized animal. In the April meeting of last year we presented some tracings showing the effect of magnesium upon gastric and duodenal peristalsis. At the present time we wish to explain more fully the method we have used and to demonstrate the act of obtaining the peristaltic tracing. This rabbit was operated four days ago. The movements of the stomach and of the duodenum are transmitted to the kymograph by means of catheters which carry at one end small balloons of thin rubber. The balloon end of one catheter is introduced and secured in the pyloric part of the stomach and that of the other in the descending part of the duodenum through openings made directly in each of these parts.

A demonstration of the life-saving action of eserin in poisoning by magnesium

At the May meeting of this Society, one of us (J.) reported that by the use of magnesium, certain toxic effects of physostigmin can be completely overcome. In our present communication we wish to bring out the fact that the antagonism between physostigmin and magnesium is mutual, at least to a certain extent. We wish to show an experiment which demonstrates that physostigmin can overcome certain toxic effects of magnesium and thus save the life of a poisoned animal. Both these rabbits (A and B) received at about the same time 1.2 gram of magnesium sulphate per kilo of body weight. The injections were given intramuscularly in the lumbar region. Rabbit B received in addition one milligram of eserin, also intramuscularly. Rabbit A is already dead. Rabbit B is still alive; although anesthetic and limp, it breathes regularly and apparently is in no danger of death. 1

Experimental pneumonia produced by Streptococcus hemolyticus

Pulmonary lesions were produced by the insufflation of a strain of Streptococcus hemolyticus isolated in Texas and kindly given us by Dr. Avery. The cultures proved to be highly virulent for white mice. A quantity of the culture was insufflated intra-bronchially into twenty-four dogs. The dose varied from 1 to 3 c.c. per kilo. Of these animals nine died in less than twenty-four hours, one died on the third day, and the rest were killed three to fifteen days after the inoculation. Dogs which survived more than two days went on to recovery, although they were ill for several days. Streptococcemia was found in all the animals which died early. It was also found in one of two dogs which was killed on the third day and in one of two killed on the fourth day after injection. Later than the fourth day no streptococci were found in the blood. Blood stained pus was present in the pleural cavity in three dogs, all having streptococci in the hearts blood. One of these animals died on the third day, one was killed on the third day and one on the fourth day. In the rest the pleura was normal. Empyema seemed to have developed before the third day. The pneumonic lesion, in its early stage (twenty-four hours after injection), consisted of intense congestion, edema and small hemorrhages without pleurisy. After forty-eight hours the congestion and edema were still more marked and areas of bronchopneumonia had developed. The solid areas coalesced to some extent, but never became massive. The lungs in these dogs, even on the third day, were never very solid. The lesions involved usually more than one lobe. Resolution had begun on the fourth day, but in one instance there was a distinctly solid area of bronchopneumonia present on the seventh day.

The pulmonary reaction to B. pyocyaneus

Intra-bronchial insufflation of broth cultures of B. pyocyaneus in doses of 10-15 c.c. were more fatal than any other organism thus far used, except B. prodigiosus. The lesion produced was that of a lobular pneumonia with intra-alveolar hemorrhage and fibrinous pleurisy. The bacilli were recovered from the hearts blood and from the lungs. Immunization experiments were successfully carried out, increasing doses of 1 to 15 c.c. being administered. Dogs survived such doses, and developed agglutinins to B. pyocyaneus. In animals which survived ten days or longer, areas of unresolved pneumonia and thickened pleura were the rule.

The development of experimental pneumonia under direct observation of the lungs in the living animal

Experimental pneumonia produced by intra-bronchial insufflation of virulent pneumococci may develop quite rapidly. Thus in the experiments of Lamar and Meltzer it was observed that in one instance seven hours after the injection, nearly complete consolidation affecting the greater part of one lobe was already present. We therefore now made several experiments in which the lungs were under direct observation continuously for several hours after the insufflation of the culture. The procedure has been as follows. The dog was anesthetized by the cone method, and a tube introduced into a bronchus as deep as it could be pushed; the pneumococcus culture was then injected. Immediately after, the tube was withdrawn, so that its lower end was just above the bifurcation, and the arrangement made for continuous intratracheal insufflation. The dog received about “half ether” and was continually under complete anesthesia, The thorax was now widely opened transversely and about two thirds of three or four of the lower ribs on the right side removed; the right lower lobe, which is usually the seat of the inflammation, was now exposed to full view. We shall not enter here upon details. It may suffice to state that we were able to watch the successive stages from the earliest signs of engorgement to complete hepatization. We were also able to establish changes in the auscultation phenomena in the consolidated parts, in some instances even clearly suggesting tubular breathing. We intended to demonstrate such experiments, and we prepared several animals for this purpose. The experiments were successful indeed, but we did not take the lateness of the hour of the meeting sufficiently into account. We prepared the experiments too early and all the animals died before the meeting began. The acute infection, the great loss of heat, the severe operation, and the long-lasting anesthesia are severe factors to contend with.

Experiments with chloroform, administered by intratracheal insufflation, in strychnine poisoning

Soon after the introduction of the method of intratracheal insufflation, experiments were begun to study the control of strychnine poisoning by means of this method. So far three series of investigations were carried out. In the first series Shaklee and Meltzer employed, besides insufflation, curare and intravenous infusions of Ringers solution. In these experiments it was first established that in intravenous injections, 0.4 mgr. of strychnine represents a reliable fatal dose per kilo dog. When using insufflation, curare and Ringers solution quite a large percentage of dogs were saved which received even more than the fatal dose. Out of 6 dogs which received 0.5 mgr. per kilo, 5 were saved, and out of 22 dogs which received 0.8 mgs. p. kilo 13 were saved. In a second series of experiments, carried out by the present authors and communicated at the last meeting of the American Pharmacological Society, ether was substituted for curare. Twenty dogs which received 0.8 mgr. strychnine per kilo, that is, twice the fatal dose, were subsequently treated by intratracheal insufflation, ether and intravenous injections of Ringers solution. All these dogs survived, none died later from after effects and when finally killed the autopsy revealed no abnormal conditions in any of the animals.