Figure 27.—A, Primary lengthening followed by shortening of the coagulation time when adrenin, 0.5 cubic centimeter 1:10,000 (0.05 milligram), was injected slowly at 2:43. B, Lengthening of the coagulation time without shortening when the same dose was injected rapidly at 10:08.
If a strong solution, i. e., 1:10,000, is injected rapidly, the process may be prolonged as above, but not followed as above by shortening, thus:
| Nov. 28. | 9.59 | 3 | minutes |
| 10.03 | 3 | “ | |
| .08 | Adrenin, 0.5 cubic centimeter, 1:10,000. | ||
| .10 | 3 | minutes | |
| .14 | 3.5 | “ | |
| .18 | 3.5 | “ | |
| .22 | 3.5 | “ | |
| .26 | 3 | “ | |
| .29 | 3 | “ | |
| .33 | 3 | “ | |
There was in this case no decrease in coagulation time at any test for a half-hour after the injection, but instead a lengthening (see [Fig. 27], B). Howell[9] has reported the interesting observation that repeated massive doses of adrenin given to dogs may so greatly retard coagulation that the animals may be said to be hemophilic. These two instances show that on coagulation large doses have the contrary effect to small, just as Hoskins[10] showed was true for intestinal and Lyman and I[11] showed was true for arterial smooth muscle.
In a few experiments the brain and the cord to midthorax were destroyed through the orbit. Artificial respiration then maintained the animal in uniform condition. Under these circumstances, adrenin intravenously had more lasting effects than when given to the usual decerebrate animals with intact cord. [Fig. 28] illustrates such a case. For thirty minutes before injection the clotting time averaged 5.4 minutes. Then, about ten minutes after one cubic centimeter of adrenin, 1:50,000, had been slowly injected, clotting began to quicken; during the next twenty minutes the average was 3.4 minutes, and during the following forty-five minutes the average was 1.9 minutes—only 35 per cent as long as it had been before the injection.
Figure 28.—Persistent shortening of the coagulation time after injecting (in an animal with brain and upper cord pithed) adrenin, 1 cubic centimeter, 1:50,000 (0.02 milligram), at 11:01–02. The dash lines represent averages.
In another case in which the brain and upper cord were similarly destroyed, the clotting time, which for a half-hour had averaged 3.9 minutes, was reduced by one cubic centimeter of adrenin, 1:100,000, to an average for the next hour and forty minutes of 2.3 minutes, with 1.5 and 3 minutes as extremes. During the first forty minutes of this period of one hour and forty minutes of rapid clotting all of eight tests except two showed a coagulation time of 2 minutes or less. The explanation of this persistent rapid clotting in animals with spinal cord pithed is not yet clear.
As indicated in Figs. 26, 27 and 28, the records of coagulation show oscillations. Some of these ups and downs are, of course, within the limits of error of the method, but in our experience they have occurred so characteristically after injection of adrenin, and so often have appeared in a rough rhythm, that they have given the impression of being real accompaniments of faster clotting. It may be that two factors are operating, one tending to hasten, the other to retard the process, and that the equilibrium disturbed by adrenin is recovered only after interaction to and fro between the two factors.
The oscillations in coagulation time after the injections suggest that clotting might vary with changes in blood pressure, for that also commonly oscillates after a dose of adrenin (see, e. g., [Fig. 23]). Simultaneous recording of blood pressure and determining of coagulation time have revealed that each may vary without corresponding variation in the other. Within ordinary limits, therefore, changes of blood pressure do not change the rate of clotting.