To any one making these experiments there can be no doubt that the increased peristalsis is the direct result of the injection of the salt. It can be readily proven in the following way: As will be shown in a later chapter, the peristalsis and secretion caused by the saline purgatives can be inhibited by the administration of calcium or magnesium chloride. If now in a rabbit in which the intestine has been set into active motion by the intravenous injection of sodium citrate, a small quantity of m/6 CaCl2 be administered intravenously, all of these movements cease within a minute or two. A second injection of a slightly greater quantity of m/6 sodium citrate will overcome this action and cause active peristalsis to begin again. These actions cannot be due to anything but the solutions introduced.
It is evident also in watching the action of these salts that they produce increased peristalsis much more rapidly and powerfully when introduced intravenously than when placed in the lumen of the stomach or intestine. A much smaller dose also is required to produce this effect. They therefore cannot act because of their presence in the lumen of the gut, or because of their being subsequently secreted into the lumen. When introduced into the stomach or intestine they must first be absorbed into the blood before they can reach the muscular and glandular tissues upon which they act. They therefore act more slowly and only in larger quantities when administered in this way.
Experiments similar to the above were made with a number of salts, including sodium sulphate, fluoride, tartrate, phosphate and oxalate, barium chloride, and magnesium sulphate. It was found that intravenous and subcutaneous injections of all of these were active in producing a greater or less increase in peristalsis. Sodium sulphate acted in this respect very much as sodium citrate did. The latter, however, tended to produce muscular twitchings in the voluntary muscles, a phenomenon which will be spoken of later. Sodium sulphate on the other hand could be introduced into the blood in relatively large quantities without producing any evil effects. The action of sodium sulphate on the intestine was found to be somewhat less than that of sodium citrate; but almost constantly 2-3 c.c. m/6 Na2SO4 injected into the marginal vein of the ear caused a marked increase in the peristaltic movements of the intestine. I cannot at all agree with Hay and earlier writers who affirm that sodium sulphate injected intravenously produces no purgative effect. In all my experiments I have found it to have a very definite effect when introduced in this manner, and I can only attribute their results to the concentrated solutions used, or to other unfavorable conditions.
The injection of solutions of sodium fluoride produces very active movements, although only small quantities can be administered on account of its poisonous nature.
Barium chloride is even more poisonous and only the most minute doses can be given. It is, however, by far the most powerful of all these purgative salts. Its action is extremely rapid and violent. When given intravenously it is best to mix it with about five times its volume of m/6 NaCl solution. Thus 1 c.c. of a mixture of 5 c.c. m/6 NaCl + 1 c.c. m/6 BaCl2 injected into the circulation causes almost immediately most violent intestinal movements. The loops contract so that they resemble white firm cords. They rise up from one another so that they seem to stand erect and the squirming, twisting movements become extremely active. The intestinal contents are hastened on and can be watched through the thin walls moving rapidly from loop to loop. The actual passage of faeces takes place in a very short time. It begins with solid faecal masses, followed quickly by semifluid faeces. The quantity passed is sometimes very considerable. As will be shown in a later chapter, the injection of BaCl2 into the blood causes not only an extensive increase in the peristaltic movements, but brings about also an increase in the quantity of fluid secreted into the intestine.
The subcutaneous injection of 2-3 c.c. m/6 BaCl2 produces in 5-10 minutes an effect quite similar to that described for the intravenous injection of the salt. A rabbit weighing 1,200-1,500 g. does not, however, usually recover from a dose greater than 2.5-3 c.c. m/6 BaCl2 given subcutaneously, and a smaller quantity is sufficient to produce purgation. Boehm[28] gives as the lethal dose of BaCl2 when given intravenously for rabbits O.1-0.2 g., for cats 0.03-0.05 g., for dogs O.1-0.2 g. When given subcutaneously it is O.12-0.18 g. for rabbits and cats and O.3 g. for dogs.
When BaCl2 is taken into the stomach it is absorbed quite slowly, but its effects are similar to those described above. Active peristaltic movements and purgation result, and in many cases vomiting is seen in dogs.
It is clear from these experiments that all salts do not act equally on the intestine. Sodium chloride may be introduced in large quantities into the circulation without causing increased peristalsis or defaecation. Sodium oxalate and phosphate (Na2HPO4) exert only a slight action. Sodium phosphate, according to Bunge, increases the fluid in the intestine. Sodium tartrate produces quite active movements of the intestine and is considerably stronger in its action than either the oxalate or phosphate. Sodium citrate and sulphate as described above are quite constant and vigorous in their action, while barium chloride is by far the most powerful of all these saline purgatives. Sodium fluoride also acts very rapidly.
In addition to their action on the intestine, some of these salts affect the salivary gland. After the injection of BaCl2 there is often so great a flow of saliva that it falls in drops from the mouth. This phenomenon is not constant, however, and seems to follow only large doses. Sodium fluoride has sometimes the same effect. I have not noticed any influence exerted by the other purgative salts upon the salivary secretion. It is further of not infrequent occurrence to have a repeated evacuation of urine after the administration of BaCl2. Although this cannot be attributed to a direct increase of the secretion of urine, it is interesting to note in this connection some later experiments in which it was shown[29] that when the flow of urine in a rabbit had been well established by the injection of m/6 NaCl solution into the circulation, the addition of a minute quantity of BaCl2 to the NaCl solution caused a very considerable increase in the secretion of urine from the kidney. A quantity of not more than ¹⁄₈ c.c. m/8 BaCl2, must be given intravenously to produce this effect. If 1 c.c. m/8 BaCl2 be injected intravenously at one time the flow of urine suddenly stops. This seems to be due either to a sudden constriction of the musculature of the urinary passages and pelvis of the kidney by which the lumen is cut off, or to a similar constriction of the blood vessels of the kidney. In either case the action of BaCl2 in stopping the secretion is mechanical and has to do with its power of causing violent muscular contractions rather than with its capacity for increasing the secretory activity. Although there is apparently one action for BaCl2 on the flow of urine when given in small doses and quite the opposite action when it is given in larger quantities, the two actions are in reality quite distinct, one being exerted on the secretory cells of the kidney and the other on the musculature of either the urinary passages or of the blood vessels of the kidney.
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. These are very noticeable in the gluteal region. They begin almost immediately in the neighborhood of the injection, but only after an interval of 20 to 25 minutes on the opposite side of the body. 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 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. For some time after the injections had been discontinued the hypersensitiveness seemed to persist. It seemed possible from this that a chronic state of increased irritability might be produced. No conclusion, however, can be drawn from this one experiment since the irritation caused by the repeated injections might have had some influence. It is a subject which is of interest for further experiment, on account of the similarity such a chronic condition bears to the various chronic hypersensitive conditions found in human beings.