The Hastening of Coagulation by Adrenin Not a Direct Effect on the Blood
As previously stated, von den Velden has contended that shortening of coagulation time by adrenin is due to exudation of tissue juices resulting from vasoconstriction. The amount of adrenin which produces markedly faster clotting in the cat, is approximately 0.001 milligram per kilo. As Lyman and I[12] showed, however, this amount when injected slowly, as in the present experiments, results in brief vasodilation rather than vasoconstriction. Von den Velden’s explanation can therefore not be applied to these experiments.
He has claimed, furthermore, that adrenin added to blood in vitro makes it clot more rapidly, but, as already noted, he gives no account of the conditions of his experiments and no figures. It is impossible, therefore, to criticise them. His claim, however, is contrary to Wiggers’s[13] earlier observations that blood with added adrenin coagulated no more quickly than blood with an equal amount of added physiological salt solution. Also contrary to this claim are the following two experiments: (1) Ligatures were tied around the aorta and inferior vena cava immediately above the diaphragm, and thus the circulation was confined almost completely to the anterior part of the animal. Indeed, since the posterior part ceases to function in the absence of blood supply, the preparation may be called an “anterior animal.” When such a preparation was made and 0.5 cubic centimeter of adrenin, 1:100,000 (half the usual dose, because, roughly, half an animal), was injected slowly into one of the jugulars, coagulation was not shortened. Whereas for a half-hour before the injection the clotting time averaged 4.6 minutes, for an hour thereafter the average was 5.3 minutes—a prolongation which may have been due, not to any influence of adrenin, but to failure of the blood to circulate through the intestines and liver.[14] In another experiment after the gastro-intestinal canal and liver had been removed from the animal, the average time for coagulation during twenty-five minutes before injecting adrenin (0.23 cubic centimeter, 1:100,000, in an animal weighing originally 2.3 kilos) was 5.5 minutes, and during forty minutes after the injection it was 6.8 minutes, with no case shorter than 6 minutes. In the absence of circulation through the abdominal viscera, therefore, adrenin fails to shorten the clotting time. (2) The cannulas were filled with adrenin, 1:1,000, and emptied just before being introduced into the artery. The small amount of adrenin left on the walls was thus automatically mixed with the drawn blood. Alternate observations with these cannulas wet by adrenin and with the usual dry cannulas showed no noteworthy distinction.
| Feb. 19. | 2.21 | 6 | minutes, | with | usual | cannula |
| .30 | 6.5 | “ | “ | “ | “ | |
| .36 | 6.5 | “ | “ | adrenin | “ | |
| .49 | 6 | “ | “ | “ | “ | |
| .56 | 7 | “ | “ | usual | “ | |
| 3.04 | 6 | “ | “ | adrenin | “ |
The results of these experiments have made it impossible for us to concede either of von den Velden’s claims, i. e., that clotting occurs faster because adrenin is added to the blood, or because adrenin by producing vasoconstriction causes tissues to exude coagulant juices.
Vosburgh and Richards found that coagulation became more rapid as the blood sugar increased. Conceivably faster clotting might result from this higher percentage of blood sugar. Against this assumption, however, is the fact that clotting is greatly accelerated by 0.001 milligram adrenin per kilo of body weight, much less than the dose necessary to increase the sugar content of the blood.[15] And furthermore, when dextrose (3 cubic centimeters of a 10 per cent solution) is added to the blood of an anterior animal, making the blood sugar roughly 0.3 per cent, the coagulation time is not markedly reduced. Adrenin appears to act, therefore, in some other way than by increasing blood sugar.
Since adrenin makes the blood clot much faster than normally in the intact animal, and fails to have this effect when the circulation is confined to the anterior animal, the inference is justified that in the small doses here employed adrenin produces its remarkable effects, not directly on the blood itself, not through change in the extensive neuro-muscular, bony, or surface tissues of the body, but through some organ in the abdomen.
That exclusion of the liver from the bodily economy, by ligature of its vessels or by phosphorus poisoning, will result in great lengthening of the coagulation time has been clearly shown. The liver, therefore, seems to furnish continuously to the blood a factor in the clotting process which is being continuously destroyed in the body. It is not unlikely that adrenin makes the blood clot more rapidly by stimulating the liver to discharge this factor in greater abundance. But proof for this suggestion has not yet been established.
REFERENCES
[1] Vosburgh and Richards: American Journal of Physiology, 1903, ix, p. 39.