A little later than this it was shown by Moreau[81] and others that solutions of purgative salts placed in loops of intestine which had been tied off caused an increased secretion of fluid into the intestine. Brieger[82] further confirmed this with better methods and showed that the fluid was a real secretion, and not an inflammatory exudate, or a transudation.
Thiry in a series of experiments was unable to produce increased secretion of fluid from a Thiry-Vella fistula by the introduction of sulphate of magnesia. He therefore concludes that the action of saline cathartics is due solely to an increase in peristaltic activity. Radziejewski[83] held a similar theory and made many experiments in an attempt to prove that an increase in peristaltic activity was the main result of the administration of a saline purgative. In connection with this it may be noted that van Braam-Houckgeest[84] concluded from his experiments that saline purgatives do not increase the peristaltic activity of the intestine. It is difficult to imagine how these results could be obtained.
Hay[85] quotes Aubert, Buchheim, and Wagner as holding the theory that in addition to causing an increased peristalsis, the salt is slowly absorbed, and tends to prevent the absorption of fluid from the intestine. This theory was held also by Schmiedeberg,[86] who claimed that the purgative salts were absorbed with difficulty and reached the lower parts of the intestine unchanged. In the large intestine the salts, according to this hypothesis, prevent the faeces from becoming compact by inhibiting the absorption of water from the lumen. This explanation of the action of cathartic salts has been widely accepted and has been supported by Wallace and Cushny,[87] who claim in addition that the salts of acids which form insoluble compounds with calcium are especially active in inhibiting the absorption of fluids from the intestine.
Loeb in studying the action of salts in the production of muscular twitchings in voluntary muscles, and of hypersensitiveness of the skin and nervous elements, recognized the fact that the salts which had these actions included those commonly known as saline purgatives. He says in this connection: “I will not deny the effect of these salts upon the phenomena of absorption of water from the intestine, but it is obvious from our experiments that the same salts must increase the irritability of the nerves and muscles of the intestine, and that this must facilitate the production of peristaltic motions, possibly through the mechanical or contact stimuli of the faeces upon the nerve endings or the muscular wall of the intestine.”[88]
My own experiments which I have described above support this suggestion of Loeb’s. In the first place it was found that the subcutaneous or intravenous injection of one of these salts, especially sodium citrate, caused muscular twitchings in the living rabbit. This had already been done by Loeb in the frog. In both cases the injection of calcium chloride inhibits the twitchings. As shown above, there are produced in a rabbit by such an injection of a purgative salt not only muscular twitchings, but also increased peristaltic movements, and an increased flow of fluid into the intestine. The subsequent injection of calcium chloride was shown to inhibit both the increased secretion and the increased movements of the intestine. There thus seems to be a very distinct analogy between the action of these salts in producing twitchings in voluntary muscles and the production of their purgative effect; and a similar analogy between the suppression of the former and the suppression of the latter by calcium chloride. One is tempted to suppose that these purgative salts act by removing calcium from the tissues, as suggested by Loeb, in the production of muscular twitchings, since they are all calcium precipitants. There is, however, no direct proof of this, and other saline purgatives such as BaCl2 and Hg2Cl2 certainly have an action which is independent of calcium.
There thus seems to be produced by saline purgatives a condition of increased irritability in the intestine analogous to the increased irritability produced in the voluntary muscles. As a result of this the two main activities of the intestine are increased, namely, the peristaltic activity and the secretory activity. The action of the saline purgative, then, as far as we know, consists of two main parts. The peristaltic movements are greatly increased in rapidity and force, and the faeces are carried rapidly from the upper to the lower parts of the intestine. They are thus passed through the large intestine in so short a time that the fluid they already contain has not time in which to be reabsorbed, a process which apparently takes place normally in the large intestine. At the same time there is a much larger quantity of fluid secreted into the lumen of the intestine than takes place in the normal animal. The faeces which are thus forced rapidly through the gut by the increased peristaltic movements are more fluid than normal. This together with the rapid passage of the faeces accounts for their fluid character when a saline purgative is given.
Whether or not the saline purgatives also inhibit the absorption of fluid from the intestine cannot be stated with certainty. The experiments of Wallace and Cushny leave out of account the increased secretion of fluid into the intestine caused by the purgative, a process which undoubtedly takes place. Thus in comparing the amount of NaCl, and the amount of a saline purgative absorbed in a given time from separate loops under the same conditions, it is not surprising that the amount of NaCl solution found in the loop after the experiment is less than the amount of purgative solution left. If the quantities of the two salts were equal in the beginning and an equal amount were absorbed, there would still be more fluid left in the loop containing the purgative on account of the secretion of fluid into the loop which was caused by the purgative, and not by the NaCl.
With regard to the mode in which the salt must be administered it is quite clear that it is not necessary to place it in the stomach or the lumen of the intestine. As shown above, the action is more rapid and more powerful when the solution is injected into the blood, or applied locally to the peritoneal surface of the intestine. Nor is the action due to its being secreted again into the lumen of the intestine, because the action is almost immediate when the solution is poured on the outside of the loops, and only takes place after several minutes when placed in the lumen. If injected into the blood the action is slower than when the solution is applied to the serous surfaces of the intestine. In the former case every opportunity would be afforded for its rapid excretion into the intestine if that were a factor. It is evident that the solution must be absorbed into the blood and bathe the tissues just as a solution surrounds a muscle which is immersed in it.
As to the tissues in the intestine which are primarily affected, it is impossible to make a definite statement. The muscle and glands cannot be at all separated from the complex nervous mechanism of the intestine, and it is necessary to take the whole as an organ made up of many tissues and affected in definite ways by certain solutions.
It is interesting in this connection to again note the effect of these salts on the secretion of urine. It is well known that practically all of them are diuretics, when introduced with a considerable amount of fluid. And even when the flow of urine has been greatly increased by the injection of m/6 NaCl solution, it can be still further augmented by the addition of, e.g., sodium citrate to the injection fluid. These salts constitute the well known class of saline diuretics. All salts do not, however, belong to this class, as is often stated. Calcium chloride, magnesium chloride, and to some extent strontium chloride exert exactly the opposite effect, inhibiting the action of the diuretics and diminishing the flow of urine. These salts might be termed antidiuretics. There is thus an entire analogy between the action of the saline diuretics on the kidney and that of the saline purgatives on the intestine, and also the action of calcium and magnesium is the same in both cases. And the analogy can be traced farther back to the production and inhibition of muscular twitchings in voluntary muscles, which was demonstrated by Loeb.