It was in 1891 that Jacobi[1] described nerve fibres derived from the splanchnic trunks which were distributed to the adrenal glands. Six years later Biedl[2] found that these nerves conveyed vasodilator impulses to the glands, and he suggested that they probably conveyed also secretory impulses. Evidence in support of this suggestion was presented the following year by Dreyer,[3] who demonstrated that electrical excitation of the splanchnic nerves produced in the blood taken from the adrenal veins an increased amount of a substance having the power of raising arterial blood pressure, and that this result was independent of accompanying changes in the blood supply to the glands. The conclusion drawn by Dreyer that this substance was adrenin has been confirmed in various ways by later observers. Tscheboksaroff[4] repeated Dreyer’s procedure and found in blood taken from the veins after splanchnic stimulation evidences of the presence of adrenin that were previously absent. Asher[5] observed a rise of blood pressure when the glands were stimulated in such a manner as not to cause constriction of the arteries—the rise was therefore assumed to be due to secreted adrenin. Dilation of the pupil was used by Meltzer and Joseph[6] to prove secretory action of the splanchnics on the adrenal glands; they found that stimulation of the distal portion of the cut splanchnic nerve caused the pupil to enlarge—an effect characteristic of adrenin circulating in the blood. Elliott[7] repeated this procedure, but made it a more rigorous proof of internal secretion of the adrenals by noting that the effect failed to appear if the gland on the stimulated side was removed. Additional proof was brought by myself and Lyman[8] when we found that the typical drop in arterial pressure produced in cats by injecting small amounts of adrenin could be exactly reproduced by stimulating the splanchnic nerves after the abdominal blood vessels, which contract when these nerves are excited, were tied so that no changes in them could occur to influence the rest of the circulation.
The problem of splanchnic influence on the adrenal glands Elliott attacked by a still different method. Using, as a measure, the graded effects of graded amounts of adrenin on blood pressure, he was able to assay the quantity of adrenin in adrenal glands after various conditions had been allowed to prevail. The tests were made on cats. In these animals each adrenal gland is supplied only by the splanchnic fibres of its own side, and the two glands normally contain almost exactly the same amount of adrenin. Elliott[9] found that when the gland on one side was isolated by cutting its splanchnic supply, and then impulses were sent along the intact nerves of the other side, either by disturbing the animal or by artificial excitation of the nerves, the gland to which these fibres reached invariably contained less adrenin, often very much less, than the isolated gland. Results obtained by the method employed by Elliott have been confirmed with remarkable exactness in results obtained by Folin, Denis and myself,[10] using a highly sensitive color test after adding the gland extract to a solution of phosphotungstic acid.
All these observations, with a variety of methods, and by a respectable number of reliable investigators, are harmonious in bringing proof that artificial stimulation of the nerves leading to the adrenal glands will induce secretory activity in the adrenal medulla, and that in consequence adrenin will be increased in the blood. The fact is therefore securely established that in the body a mechanism exists by which these glands can be made to discharge this peculiar substance promptly into the circulation.
The Question of Adrenal Secretion in Emotional Excitement
As we have already seen, the phenomena of a great emotional disturbance in an animal indicate that sympathetic impulses dominate the viscera. When, for example, a cat becomes frightened, the pupils dilate, the activities of the stomach and intestines are inhibited, the heart beats rapidly, the hairs of the back and tail stand erect—from one end of the animal to the other there are abundant signs of nervous discharges along sympathetic courses. Do not the adrenal glands share in this widespread subjugation of the viscera to sympathetic control?
This question, whether the common excitements of an animal’s life might be capable of evoking a discharge of adrenin, was taken up by D. de la Paz and myself in 1910. We made use of the natural enmity between two laboratory animals, the dog and the cat, to pursue our experiments. In these experiments the cat, fastened in a comfortable holder (the holder already mentioned as being used in X-ray studies of the movements of the alimentary canal), was placed near a barking dog. Some cats when thus treated showed almost no signs of fear; others, with scarcely a movement of defense, presented the typical picture. In favorable cases the excitement was allowed to prevail for five or ten minutes, and in a few cases longer. Samples of blood were taken within a few minutes before and after the period.
The Method of Securing Blood from Near the Adrenal Veins
The blood was obtained from the inferior vena cava anterior to the opening of the adrenal veins, i. e., at a point inside the body near the level of the notch at the lower end of the sternum. To get the blood so far from the surface without disturbing the animal was at first a difficult problem. We found, however, that by making anesthetic with ethyl chloride the skin directly over the femoral vein high in the groin, the vein could be quickly bared, cleared of connective tissue, tied, and opened without causing any general disturbance whatever. A long, fine, flexible catheter (2.4 millimeters in diameter) which had previously been coated with vaseline inside and out, to lubricate it and to delay the clotting of blood within it, was now introduced into the opening in the femoral vein, thence through the iliac and on into the inferior cava to a point near the level of the sternal notch. A thread tied around this tube where, after being inserted to the proper distance, it disappeared into the femoral vein, marked the extent of insertion, and permitted a later introduction to the same extent. This slight operation—a venesection, commonly practised on our ancestors—consumed only a few minutes, and as the only possibility of causing pain was guarded against by local anesthesia, the animal remained tranquil throughout. Occasionally it was necessary to stroke the cat’s head gently to keep her quiet on the holder, and under such circumstances I have known her to purr during all the preparations for obtaining the blood, and while the blood was being taken.
The blood (3 or 4 cubic centimeters) was slowly drawn through the catheter into a clean glass syringe. Care was taken to avoid any marked suction such as might cause collapse of the vein near the inner opening of the tube. As soon as the blood was secured, the catheter was removed and the vein tied loosely, to prevent bleeding. The blood was at once emptied into a beaker, and the fibrin whipped from it by means of fringed rubber tubing fitted over a glass rod. Since this defibrinated blood was obtained while the animal was undisturbed, it was labelled “quiet blood.”
The animal was then exposed to the barking dog, as already described, and immediately thereafter blood was again removed, from precisely the same region as before. This sample, after being defibrinated, was labelled “excited blood.” The two samples, the “quiet” and the “excited,” both obtained in the same manner and subsequently treated in the same manner, were now tested for their content of adrenin.