John Bruce MacCallum

“ The fact that calcium and magnesium act as inhibitors for both the muscular and secretory activities of the intestine does not imply that they have a similar action in other organs or in all animals. It can only be said with certainty that the chemical conditions under which the intestines of the rabbit live are fairly constant, so that the addition of calcium or magnesium in some way constantly inhibits the activity of both muscular and glandular tissues, and the addition of certain purgative salts constantly stimulates them to greater activity. ”

“ So many unknown conditions exist in such an organ that it is impossible to say what tissue is acted on primarily, whether the nervous system on the one hand, or the glandular and muscular tissues on the other. There are, however, two indicators in the intestine by which the comparative actions of substances can be studied, namely, the muscular movements, and the secretion of fluid, both of which by various chemical substances may be increased or lessened ”

“ What first suggests itself is that the gland cells themselves are made to contract rhythmically by the various conditions which cause rhythmical contractions in muscle. That the stimulus for this must be greater in the case of secretion is shown by the fact that in the intestine peristaltic movements may be maintained in a solution (m/6 NaCl) in which no secretion takes place. It seems not at all improbable that one factor in the production of secretory activity is dependent on a property of the gland cell closely related to muscular contractility. ”

“ My own experiments have given quite uniform results, so much so that the production of increased peristalsis in rabbits by the intravenous injection of one of the saline purgatives has come to be a class experiment with the students in the medical school here. The increased secretion into the intestine produced by the same means requires greater care in protecting the loops from loss of heat and moisture. ”

“ It seems improbable that a change in blood pressure plays any very important rôle, if indeed it has an influence at all. There is much evidence to show that many glands consisting of cells resembling those of the intestine roughly, secrete their characteristic fluids quite independently of blood pressure. ”

“ Saline purgatives produce not only muscular activity, but also increased secretion; and calcium and magnesium are capable of inhibiting both. Atropin also quiets the movements of the intestine, and at the same time is conspicuous in suppressing the secretion. Section of the splanchnic nerves causes not only increased muscular movements, but an increased secretion of fluid in the intestine. These instances could be greatly increased in number. From them it seems that something exists in common in muscular movements and in glandular activity. ”

“ A further factor is suggested by the action of certain diuretics. In the kidney the changes in the quantity of blood flowing through the organ and to some extent changes in blood pressure influence the flow of urine. The diuresis produced by such substances, however, as saponin, digitalin, potassium chlorate, etc., probably depends on an increase in permeability of the capsule of Bowman. As shown [91] recently, these substances produce haemolysis, and are also strong diuretics. Calcium chloride, which inhibits the flow of urine produced by them, inhibits also the haemolysis. ”

“ Rabbits frequently die in a few minutes after an intravenous injection of a quantity relatively small as compared with the amount of Na2SO4 which can be given in this way. Barium chloride is extremely active as a subcutaneous purgative, but should be used with the greatest caution and in very minute quantities on account of its very poisonous character. I can give no idea of the dose that might be given to a human being without danger. A rabbit usually does not recover from a subcutaneous injection of 3 c.c. m/8 BaCl solution. ”

“ The gut is usually relaxed below the bolus, and the general statement [Pg 3] has been made that a stimulation at any point causes a contraction above that point and an inhibition below it. It is generally thought that Auerbach’s plexus is concerned in the propagation of the peristaltic wave since the peristalsis takes place also when the intestine is separated from the central nervous system, and does not occur when nicotine or cocaine is given to paralyze the intrinsic nerves of the intestine. ”

“ In addition to their action on the intestine and in some cases the kidney and salivary gland, these salts produce an interesting condition of the voluntary muscles. As mentioned above, Loeb was able to produce muscular twitchings in the muscle of a frog by immersing the muscle in solutions of these various salts. He also produced muscular twitching in a living frog by injecting sodium citrate into the dorsal lymph sacs. I have found that a subcutaneous injection of 10 c.c. m/1 sodium citrate produces in a rabbit well marked twitchings of the muscles all over the body. ”

“ If a loop such as has been described above be removed from the intestine of a rabbit and placed in m/8-m/6 NaCl solution at body temperature, active movements at once appear. These are regular and rhythmical, resembling those which set in when the nerves to the intestine [Pg 52] are cut in the uninjured animal. If the loop be allowed to lie at the bottom of the solution, it will twist and writhe about in a peculiar worm-like manner. These movements persist in varying intensity for a considerable time, sometimes as long as an hour, usually for 40-45 minutes. They disappear gradually. ”

“ These beakers were kept in a water bath at 39.5° C. It is desirable in these experiments to use loops which contain no faeces, since unknown substances in the faeces might go into solution and disguise the action of the salt being tested. For this reason the upper part of the small intestine was principally used since in the rabbit it is usually empty or can be readily emptied. In each set of experiments the loops must all come from the same rabbit, for there exist considerable differences in irritability in different animals. ”

“ As shown by the following experiments, the fluid secreted by the intestine increases rapidly when m/8 or m/6 NaCl solution is injected into the blood. Without such an injection or other stimulus very little intestinal juice can be gathered in a time as short as that occupied by the experiments. In a rabbit’s small intestine there is usually found between 5 and 10 c.c. fluid, often much less. ”

“ When rectal infusions of NaCl are not retained it is possible by adding CaCl2 to the solution to stop the movements of the rectum which cause their expulsion. Enemata of NaCl containing CaCl2 are retained much better than those of pure NaCl.
The marked action of calcium on the kidney suggests that certain conditions might arise where it could be made use of. In nervous polyuria it can be given with benefit; and although we know practically nothing as to the etiology of diabetes insipidus, it is possible that calcium might be employed with advantage to stop the abnormal flow of urine. ”

“ In the experiments on the rabbit’s intestine, however, calcium and magnesium have been shown to have an action which can only be described as inhibitory. In an animal as highly organized as the rabbit, the intestine is an extremely complex organ ”

“ In all of these solutions twitchings developed in the muscle. Magnesium and strontium act like calcium in inhibiting the muscular twitchings produced by sodium salts. These experiments led Loeb to the conclusion that the presence of [Pg 40] calcium in the body keeps the voluntary muscles from constantly twitching or beating rhythmically in the way the heart does. Calcium, magnesium, and strontium seemed to have a definite inhibitory action on the muscular contractions. ”

“ In this way the quantity of fluid injected could be accurately measured and controlled. The salt solution after passing through the long tube reached the ear at approximately body temperature. It is of the greatest importance to protect the intestinal loops in every way possible from loss of heat or from drying.
In the above experiment the intestinal glycosuria, if such a term may be applied to this phenomenon, appears under circumstances which are exactly the same as those necessary for the production of sugar in the urine by saline infusions. ”

“ It is not possible here to mechanically isolate a part which shall be free from the nervous system as can be done almost completely in the center of the jellyfish and the apex of the heart. We are dealing with an entire organ which must be considered as an indicator by which comparative results may be obtained. ”

“ A still more striking experiment may be made by exposing the intestines and pouring a small quantity of sodium citrate solution on their peritoneal surfaces. Immediately they become extremely active. If now they be washed off with a little NaCl solution and a few c.c. of a solution of calcium chloride be poured on them they will come to rest at once. ”

“ If in the first place it is found that subcutaneous or intravenous injections of saline purgatives are effective in man, there arise in both medical and surgical practice occasions in which these methods of administration would be of the greatest advantage. ”

“ If the animal be placed on the floor it moves with a peculiar incoördinated gait. The hind legs are dragged and very little headway is made. If the rabbit be held up by the ears, the feet tremble, and if touched the legs jerk away violently and usually become rigid. There are sometimes tetanus-like contractions of the [Pg 20] limbs, and occasionally general convulsions of greater or less severity. In one rabbit I gave daily injections of 5 c.c. m/1 sodium citrate subcutaneously throughout one month. ”

“ Even in cases where the control loop is active at first the corresponding loop in the mixture of LiCl and CaCl2 shows no movements. It remains perfectly quiet for 10-15 minutes. Then sharp constrictions appear here and there in the loop. These are followed a second or two later by violent contractions which cause the loop to coil upon itself in a most active manner. These contractions somewhat resemble those caused by BaCl2 in the intact intestine. They follow one another rapidly so that the loop is turned and twisted tightly upon itself. ”

“ The difference in susceptibility to the action of citrate which exists between rabbits on the one hand, and dogs and cats on the other, may be in some way connected with their being herbivorous and carnivorous animals respectively. ”

“ The CaCl2 does not stop the excretion of the haemoglobin by the kidneys, for if the saponin or quillain be given first and the haemoglobinuria established, the subsequent injection of CaCl2 does not stop the excretion of haemoglobin. ”