Bodily changes in pain, hunger, fear, and rage

THE HASTENING OF THE COAGULATION OF BLOOD IN PAIN AND GREAT EMOTION

In the foregoing chapter evidence was presented that the intravenous injection of minute amounts of adrenin hastens the clotting of blood. The amounts used did not vary much above or below the amounts discharged by the adrenal glands after brief stimulation of the splanchnic nerves, as found by H. Osgood in the Harvard Laboratory, and may therefore be regarded as physiological. Since injected adrenin is capable of shortening the coagulation time, may not the increased secretion of the adrenals likewise have that effect? The answer to this question was the object of an investigation by W. L. Mendenhall and myself.[1]

The blood was taken and its coagulation was recorded graphically in the manner already described. In some instances the cats were etherized, in others they were anesthetized with urethane, or were decerebrated. The splanchnic nerves always were stimulated after being cut away from connection with the spinal cord. Sometimes the nerves were isolated unilaterally in the abdomen; sometimes, in order to avoid manipulation of the abdominal viscera, they were isolated in the thorax and stimulated singly or together. A tetanizing current was used, barely perceptible on the tongue and too weak to cause by spreading any contraction of skeletal muscles.

Coagulation Hastened by Splanchnic Stimulation

That splanchnic stimulation accelerates the clotting of blood, and that the effects vary in different animals, are facts illustrated in the following cases:

Oct. 25.—A cat was etherized and maintained in uniform ether anesthesia. After forty minutes of preliminary observation the left splanchnic nerves were stimulated in the abdomen. Following are the figures which show the effects on the coagulation time:

In this instance at least ten minutes elapsed between the end of stimulation and the beginning of faster clotting. The period of faster clotting, however, lasted for about a half-hour, during which the coagulation time averaged 2.1 minutes, only forty-three per cent of the previous average of 4.8 minutes. It is noteworthy that the curve (see Fig. 29), while lower, shows oscillations not unlike those which follow injection of adrenin (see p. 155).

The primary delay of the effect is not always, indeed it is not commonly, present:

Nov. 6.—A cat was anesthetized (1.40 p.m.) with urethane, and later (3.05) its brain was pithed. The following observations on the coagulation time show the prompt effect of splanchnic stimulation:

In Fig. 30 is presented the original record of the shortening of the coagulation after stimulation of the left splanchnic nerve (Nov. 8) in a cat with brain pithed.

In the foregoing instances the coagulation time was reduced after splanchnic stimulation to less than half what it was before. The reduction was not always so pronounced.

Nov. 7.—A cat[*] maintained in uniform ether anesthesia with artificial respiration had the following changes in the clotting time of its blood as the result of stimulating the left splanchnic nerve in the thorax:

In this case the average for about fifteen minutes before stimulation was slightly over five minutes, and for twenty-five minutes thereafter it was four minutes.

In all cases thus far the period of shortened coagulation lasted from ten to thirty minutes. In other cases, however, the effect was seen only in a single observation. If this had occurred only once after splanchnic stimulation, it might be attributed to accident, but it was not an infrequent result, e. g.:

Oct. 28.—A cat was etherized and decerebrated, and the splanchnic nerves were isolated in the thorax. Following are two instances of brief shortening of coagulation after splanchnic stimulation:

In the foregoing instance it is noteworthy that the degree of acceleration is not so great after the second stimulation of the splanchnics as it was after the first. This reduction of effect as the nerves were repeatedly stimulated was frequently noted. The following case presents another illustration:

Nov. 12.—A cat was etherized (2.35 p.m.) and the medulla was punctured (piqûre) at 3.12. The operation was without effect. The loss or lessening of effectiveness on second stimulation of the left splanchnic nerves is to be compared with the persistence of effectiveness on the right side:

The experiments above recorded show that stimulation of the splanchnic nerves results immediately, or after a brief period, in a shortening of the coagulation time of the blood—an effect which in different animals varies in duration and intensity, and diminishes as the stimulation is repeated. The next question was whether this effect is produced through the adrenal glands.

Coagulation Not Hastened by Splanchnic Stimulation if the Adrenal Glands are Absent

The manner in which splanchnic stimulation produces its effects is indicated in the following experiments:

Nov. 28.—A cat was etherized, and through the orbit the central nervous system was destroyed to the midthorax. The blood vessels of the left adrenal gland were then quickly tied and the gland removed. The readings for a half hour before the left splanchnic nerve was stimulated averaged seven minutes, then—

Dec. 4.—A cat was etherized and pithed through the orbit to the neck region. The right and left splanchnic nerves were tied and cut in the thorax. The left adrenal gland was then carefully removed. These operations consumed about a half-hour. The following records show the effect of stimulating the left and right splanchnic nerves:

The results in this experiment are represented graphically in Fig. 31.

Elliott’s evidence that in the cat the splanchnic innervation of the adrenals is not crossed has already been mentioned. If the gland is removed on one side, therefore, stimulation of the nerves on that side causes no discharge from the opposite gland. As the above experiments clearly show, splanchnic stimulation on the glandless side results in no shortening of the coagulation time; whereas, in the same animals, stimulation of the nerves on the other side (still connected with the adrenal gland) produces a sharp hastening of the clotting process.

The splanchnics innervate the intestines and liver even though the adrenal gland is removed. The foregoing experiments indicate that the nerve impulses delivered to these organs do not influence them in any direct manner to accelerate the speed of coagulation. Indeed, in one of the experiments (Dec. 4, see Fig. 31) a high reading about ten minutes after splanchnic stimulation on the glandless side suggests the possibility of an opposite effect. Direct stimulation of the hepatic nerves on one occasion was followed by a change of the clotting time from 4.5, 5, 4.5, 4.5 minutes during twenty-five minutes before stimulation to 4.5, 7, and 6 minutes during twenty minutes after stimulation.

Since with the adrenals present stimulation of hepatic nerves induces alteration of glycogen in the liver and quick increase of blood sugar,[2] just as splanchnic stimulation does, the failure of the blood to clot faster after stimulation of the hepatic nerves confirms the evidence already offered that faster clotting when adrenin is increased in the blood is not due to a larger amount of sugar present (see p. 159).

The liver and intestines cannot be made to shorten clotting time by stimulation of their nerves, but, as has already been shown (see p. 157), neither can adrenin act by itself to hasten the clotting process. Apparently the effect is produced by coöperation between the adrenals and the liver (and possibly also the intestines). Somewhat similar coöperation is noted in the organization of sugar metabolism; splanchnic stimulation in the absence of the adrenal glands does not increase blood sugar,[3] and in the absence of the liver adrenin is without influence.[4]

The variations of effect noted after splanchnic stimulation can be accounted for by variations in the adrenin content of the glands. Elliott[5] found, as previously stated, that animals newly brought into strange surroundings may have a considerably reduced amount of adrenin in their adrenals. The animals used in our experiments had been for varying lengths of time in an animal house in which barking dogs were also kept, and were therefore subject to influences which would be likely to discharge the glands.

The evidence that stimulation of splanchnic nerves, with accompanying increase of adrenal secretion, results in more rapid clotting of blood is especially interesting in relation to the experiments previously described, which showed that in pain and emotional excitement there is an increased secretion of adrenin into the blood. Does the adrenin thus liberated have any effect on the rate of coagulation? The observations here recorded were made in order to obtain an answer to that question.

Coagulation Hastened by “Painful” Stimulation

In the experiments on the action of stimuli which in the unanesthetized animal would cause pain, it will be recalled that faradic stimulation of a large nerve trunk (the stump of the cut sciatic) and operation under light anesthesia were the methods used to affect the afferent nerves. Elliott[6] found that repeated excitation of the sciatic nerve was especially efficient in exhausting the adrenal glands of their adrenin content, and also that this reflex persisted after removal of the cerebral hemispheres. It was to be expected, therefore, that with well-stored glands, sciatic stimulation, even in the decerebrate animal, would call forth an amount of adrenal secretion which would decidedly hasten clotting. The following case illustrates such a result:

Dec. 12.—A cat was anesthetized with ether at 3.45 and the left sciatic nerve was bared. Decerebration was completed at 3.57. The clotting time of the blood began to be tested six minutes later:

The results obtained in this case, which were similar to results in other cases, are represented graphically in Fig. 32. The coagulation time was becoming gradually more prolonged, but each excitation of the sciatic nerve was followed by a marked shortening. The strength of stimulation was not determined with exactness, but it is worthy of note that the current used in the first and the third stimulations was weaker than could be felt on the tongue, whereas that used in the second was considerably stronger, though it did not produce reflex spasms.

Mere tying of the nerve is capable of producing a marked shortening of coagulation, as the following figures show:

Oct. 21.—10.57 cat under ether, and urethane given:

Stimulation of the crural nerve had similar effects, reducing the clotting time in one instance from a succession of 3, 3, and 3.5 minutes to 1.5 minutes shortly after the application of the current, with a return to 3.5 minutes at the next test.

Operative procedures performed under light anesthesia (i. e., with the more persistent reflexes still present), or reduction of anesthesia soon after operation, resulted in a remarkable shortening of the coagulation time:

Nov. 8.—A cat was etherized and tracheotomized. The abdomen was then opened and a ligature was drawn around the hepatic nerves. The operation was completed at 2.25. At 2.50 the etherization became light and the rate of clotting began to be faster:

Nov. 11.—A female cat, very quiet, was placed in the holder at 1.55. The animal was not excited. At 2.10 etherization was begun; the animal was then tracheotomized, and the femoral artery was exposed.

The results of this experiment are shown graphically in Fig. 33.

Nov. 13.—A cat was etherized at 1.55, tracheotomized, and the femoral artery laid bare. As soon as these preparations were completed, the ether was removed and anesthesia became light. The blood clotted thus:

In the foregoing and in other similar instances, a condition of surgical injury, whether just made or being made, was accompanied by more rapid clotting of blood when the degree of anesthesia was lessened. This condition was one which, if allowed to go further in the same direction, would result in pain. Both direct electrical stimulation and also surgical operation of a nature to give pain in the unanesthetized animal result, therefore, in faster clotting.

It is worthy of note that after decerebration clotting apparently occurred no faster because the abdomen had been opened, although in the decerebrate state etherization was suspended. The mechanism for reflex control of the adrenals may not be higher than the corpora quadrigemina, as Elliott has shown, but the discharge from the glands seems to be more certain to occur when the cerebrum is present and is permitted even slightly to operate.

Coagulation Hastened in Emotional Excitement

The evidence for emotional secretion of the adrenal glands has already been presented. As was noted in my earlier observations on the motions of the alimentary canal (see p. 14), cats differ widely in their emotional reaction to being bound; some, especially young males, become furious; others, especially elderly females, take the experience quite calmly. This difference of attitude was used with positive results, the reader will recall, in the experiments on emotional glycosuria; there seemed a possibility likewise of using it to test the effect of emotions on blood clotting. To plan formal experiments for that purpose was not necessary, because in the ordinary course of the researches here reported, the difference in effects on the blood between the violent rage of vigorous young males and the quiet complacency of old females was early noted. Indeed, the rapid clotting which accompanied excitement not infrequently made necessary an annoying wait till slower clotting would permit the use of experimental methods for shortening the process.

The animals used on November 11 and 13 (see pp. 175, 176) are examples of calm acceptance of being placed on the holder; and furthermore, these animals were anesthetized without much disturbance. As the figures indicate, the clotting from the first occurred at about the average rate.

In sharp contrast to these figures are those obtained when a vigorous animal is angered:

Oct. 30.—A very vigorous cat was placed on the holder at 9.08. It at once became stormy, snarling, hissing, biting, and lashing its big tail. At 9.12 etherizing was begun and that intensified the excitement. By 9.15 the femoral artery was tied. The clotting time of the blood for an hour after the ether was first given was as follows:

Twenty-four observations made during the hour showed that the clotting time in this enraged animal averaged three-fourths of a minute and was never longer than a minute and a half. The clots were invariably a solid jelly. The persistence of the rapid clotting for so long a period after anesthesia was started may have been in part due to continued, rather light, etherization, for Elliott[7] found that etherization itself could reduce the adrenin content of the adrenal glands.

The shortened clotting did not always persist so long as in the foregoing instance. The brief period of faster clotting illustrated in the following case was typical of many:

Nov. 18.—A cat that had been in stock for some time was placed on the holder at 2.13, and was at once enraged. Two minutes later etherization was started. The hairs on the tail were erect. The clotting was as follows:

It seems probable that in this case just as in some of the cases in which the splanchnic nerves were stimulated (see p. 166), the adrenals had been well-nigh exhausted because of the cat’s being caged near dogs, and that the emotional flare-up practically discharged the glands, for repeated attempts later to reproduce the initial rapid clotting by stimulation of the splanchnic nerves were without result.

Evidence presented in previous chapters makes wholly probable the correctness of the inference that the faster coagulation which follows emotional excitement is due to adrenal discharge from splanchnic stimulation. In this relation the effect of severance of the splanchnics on emotional acceleration of the clotting process is of interest. The following cases are illustrative:

Oct. 29.—A cat was left on the holder for ten minutes while the femoral artery was uncovered under local anesthesia. The blood removed was clotted in a half-minute. The animal was much excited. It was now quickly etherized and the brain pithed forward from the neck. The tests resulted as follows:

The original record of this case is given in Fig. 34.

Nov. 5.—A cat was etherized at 2.35. At 2.39 artificial respiration by tracheal cannula was begun, the air passing through an ether bottle. The clotting occurred thus:

Nov. 7.—A cat was etherized at 1.55 under excitement and with tail hairs erect. At 2.13 the animal was showing reflexes. The figures show the course of the experiment:

In this instance the subsequent stimulation of the splanchnic nerves resulted again in faster clotting—a reduction from 5.5 minutes to 3.5 minutes (see experiment Nov. 7, p. 164). The results from this experiment are expressed graphically in Fig. 35.