Although it has long been known that many of the vegetable purgatives act as well when introduced into the circulation as when taken by mouth, it has generally been stated that saline purgatives are inactive when injected either subcutaneously or intravenously. It has even been claimed that they have the opposite effect, causing constipation. Claude Bernard,[22] however, states that sodium sulphate causes purgation when introduced into the circulation, although he gives no experiments to support the assertion. Buchheim[23] believed that intravenous injection of purgative salts produced no purgation. Rabuteau[24] stated that the injection of a large amount of sodium sulphate into the blood caused constipation in a dog, an experiment which he took to prove that the strong solution outside the intestine withdrew fluid from the lumen by its endosmotic power. Headland[25] advanced the view that all medicines act after being absorbed into the blood, and that saline cathartics are first taken up into the circulation and stimulate the intestine in being later excreted by the intestinal glands. Carpenter reported an experiment in which he obtained a purgative action by introducing magnesium sulphate into the stomach after this organ had been separated from the intestine by a ligature. It was further found by Vulpian[26] that small doses of magnesium sulphate, but not of sodium sulphate, acted as purgatives when injected subcutaneously. Hay[27] gives an excellent resumé of the literature on this subject. Although he considers it already proven that purgatives do not act when injected subcutaneously or intravenously, he has made a number of experiments to confirm this idea. He was unable to obtain any purgative effect in dogs and cats by the introduction into the blood of 10% Na2SO4 or 20% MgSO4. With the subcutaneous injection of these salts, however, a purgative action was sometimes produced. This he attributed to the local irritation of the injection. It will be noted that the conditions of these experiments are by no means ideal. Hay injected directly into the blood a solution of Na2SO4, which is approximately twice as strong as a solution of this salt isosmotic with the blood would be. Similarly a solution of MgSO4 isosmotic with the blood would be about 4% (m/6 Soln MgSO4 + 7 H2O = 4.1 g. in 100 c.c.). Hence the solution which Hay introduced directly into the circulation was five times as concentrated as an isosmotic solution. Although it is not clear just what abnormal conditions would be brought about by the injection of such concentrated solutions, it is certain that the normal action of the salt could not be expected under these circumstances. This is further shown by the fact that Hay did obtain a purgative action in some cases when he injected the salt solutions subcutaneously. Here the injury caused by the concentrated solution was only local, and the salt itself was absorbed in small quantities and in more dilute solution into the blood.
In a large number of experiments which have yielded quite constant results I have been unable to confirm the idea generally held and supported by Hay that subcutaneous and intravenous injections of saline purgatives do not exert a purgative action. I have quite constantly found that with proper conditions these salts do produce increased peristalsis and also an increased secretion of fluid into the intestine when introduced directly into the circulation or under the skin. In most cases also an actual passage of faeces was observed.
Several methods were used in testing the action of the salts and it was found that the results could best be studied by observing the loops of intestine directly. In rabbits under the influence of morphine (5 c.c. 1% solution morphine hydrochlorate subcutaneously) the abdominal cavity was laid open and the loops of intestine carefully protected from loss of heat and moisture while under observation. In other cases they were observed under the surface of normal sodium chloride solution, a method devised by van Braam-Houckgeest and used by him in a long series of experiments. In the NaCl solution the intestines normally remain almost quiet and the effect on them of stimulating agents can be readily determined. In addition to this method many experiments were made in which animals were kept in separate cages, some acting as control animals, others for experiment. The amount and character of the faeces were observed during several hours after the administration of the purgative and compared with the control animals. The solutions used were made up as fractions of molecular solutions. Thus to obtain a solution of sodium citrate, for example, approximately isosmotic with the rabbit’s blood, one-sixth molecular weight of the salt in grams (including water of crystallization) was dissolved in 1,000 c.c. distilled water. This gave an m/6 solution, which was taken to be approximately isotonic with the blood. The injections were made usually with a hypodermic needle into the marginal vein of the rabbit’s ear, or into the jugular vein. Subcutaneous injections were made under the loose skin of the back. In most of these experiments small rabbits weighing from 1,200 to 1,500 grams were used.
In studying the purgative action of these salts, two criteria may be considered, namely, the actual passage of faeces, and secondly merely the increase of peristalsis and secretion not necessarily accompanied by defaecation. The former is of course the object of purgation, and unless a salt produces an actual passage of faeces it cannot strictly be termed a purgative. When this has been established, however, it is of much greater advantage to use the other criterion in studying the action of the solutions on the intestine. Any salt which in small doses produces an increased peristalsis will with a more prolonged action and perhaps larger doses produce actual purgation. Therefore in the first rough test as to the action of the salts I have used the actual passage of faeces as the criterion of the action. In this case no morphine is given the animal and its intestines are not exposed as in the other experiments where the movements are directly watched. In these tests the animals were kept in boxes, the bottom of each of which was covered by a large sheet of paper. During a certain time preceding the injection of any solution the animals were watched and the faeces collected and weighed. Half of the animals were kept as controls, and the rest subjected to injections of various solutions. The average weight of the normal faeces was compared with the weight of the faeces passed during the same time by the animals receiving the injections. The faeces were collected and weighed each hour during the first six hours following the first injection. The chief purgative effect usually took place during the first two hours. Although there was considerable individual variation in the rabbits, there was found to be a constant increase in the amount of faeces following the subcutaneous or intravenous injection of one of the salts. This amount varied from two to six times the average normal weight. Sometimes the increase was much greater and in many cases the nature of the faeces was much changed. The normal faeces of the rabbit consist of dry hard definitely formed masses. Following the purgative, they become soft and unformed, and may as in the case of NaF and BaCl2 be semifluid.
The amount of sodium citrate, sulphate, or tartrate necessary to produce purgation is about the same in each case: 10 c.c. m/6 solution injected subcutaneously, followed 10 minutes later by a second injection of 5 c.c. of this solution and 10 minutes after this by a third similar injection, usually produces well marked passages of faeces. Sometimes the result is obtained with a single injection, but a prolonged action of the salt seems to be more favorable. With sodium fluoride and barium chloride much smaller doses are necessary. Sodium fluoride is more poisonous than the citrate or sulphate, but if injected slowly as much as 10 c.c. m/6 solution can be safely introduced under the skin. This produces in a little over an hour well marked purgation, usually with the passage of soft or semifluid faeces. Barium chloride is a well known saline purgative among veterinary surgeons, who always administer it intravenously or subcutaneously. In order to purge a horse weighing 1,000 pounds, O.75 g. BaCl2 is usually given subcutaneously. Its action is very constant. When given to rabbits I have found that 2 c.c. m/6 solution BaCl2, injected under the skin always produces a well marked purgative action with the passage of large quantities of semifluid faeces. When injected intravenously it is better to mix the BaCl2 with about five times its volume of m/6 NaCl. The injection of 1 c.c. of a mixture of 1 c.c. m/6 BaCl2 + 5 c.c. m/6 NaCl produces purgation and a passage of semifluid faeces. This action is much more rapid than with NaF.
These experiments demonstrate the fact that the intravenous or subcutaneous injection of saline purgatives do produce purgation and an actual passage of faeces. In order, however, to study the action of the salts more minutely another method was resorted to, namely, that of opening the abdomen and directly observing the loops of intestine. In a large number of experiments it is not difficult to become quite familiar with the movements normally present, and with the disturbances produced by such external influences as cooling, drying, etc. These influences can by proper precautions be practically eliminated.
By this method it was possible to study the influence of the salts on the two great activities of the intestine, namely, the muscular movements and the glandular activity. Their action on the secretion is treated of in a later chapter and can only be mentioned here. The increase of these two activities by means of a salt is the essential action of a purgative, and leads, if sufficiently prolonged, to purgation and to the passage of faeces. This passage of faeces does not take place so readily when the intestines are exposed and the animal is under the influence of morphine as it does in a normal animal. The exposure of the intestine for an hour or more apparently renders this action difficult, although not uncommonly the actual passage of faeces is observed under these circumstances. This is always the case with BaCl2.
In a rabbit with its intestines visible it was found that the injection of 1-2 c.c. m/8 or m/6 sodium citrate solution into the jugular vein of a rabbit brings about a very marked increase in the peristaltic movements, which begins from 1 to 2 minutes after the injection. The loops are set in active movements and become firm and rounded so that they seem to occupy a greater volume. The movements consist not only of swinging pendulum movements, but of real peristaltic waves which cause the contents of the intestine to move along the gut so that they may be watched through the thin walls. The morphine narcosis of the animal does not seem to interfere with this action of the salt.
When these salt solutions are administered subcutaneously they do not act at once, as in the case of intravenous injections. An interval of 10 to 15 minutes elapses after the subcutaneous injection before any influence on the intestine is noticed. The movements then begin as before, the peristaltic movements and pendulum movements gradually increasing in force. In addition to the greater time required for the action of the salt when administered in this way, it is also necessary to give a larger amount than in intravenous injections; 5-10 c.c. m/8 or m/6 solution of sodium citrate must be introduced subcutaneously in order to produce increased peristalsis.
If the solution be introduced into the stomach or intestine a similar increase in peristalsis is brought about, but only after a considerable interval. Usually no effect is obtained until 10 to 15 minutes after the injection of the salt into the lumen of the gut. The injection may be made by piercing the wall of the intestine or stomach with a hypodermic needle, and forcing the fluid into the lumen. The quantity of the solution necessary to produce increased peristalsis is about the same as when introduced subcutaneously. The movements begin not particularly in the part of the intestine containing the solution, but simultaneously in all parts.