The Effects of Subcutaneous Injections of Adrenin
The first observations were of this class.
Oct. 27. A cat weighing about 3 kilos was given 3 cubic centimeters of adrenin 1:1,000, i. e., 1 milligram per kilo, under the skin. The animal, in this instance, was kept in uniform ether anesthesia. Following is a record showing when blood was taken, and the coagulation time in each instance:
| 2.56 | Injection made | |
| .59 | 6 | minutes |
| 3.07 | 5.5 | “ |
| .13 | 5 | “ |
| .20 | 6.5 | “ |
| —— | ||
| Average | 5.7 | minutes |
| 3.27 | 3.5 | minutes |
| .44 | 2 | “ |
| .55 | 2.5 | “ |
| 4.07 | 3 | “ |
| .20 | 2 | “ |
| —— | ||
| Average | 2.6 | minutes |
| 4.44 | 6 | minutes |
| 5.00 | 4.5 | “ |
| 5.50 | 5 | “ |
| —— | ||
| Average | 5.2 | minutes |
In this case the coagulation time remained at its usual level for about 20 minutes after the subcutaneous injection.[*] Thereafter for about an hour the coagulation time averaged 45 per cent of its previous duration. And widely separated tests made during the following hour indicated that approximately the initial rate of clotting had been regained.
[*] This period is longer than is expected after the subcutaneous injection of any drug. As will be shown later, strong doses of adrenin, if injected rapidly, may not at first shorten the clotting process. Probably in some instances of subcutaneous injection of these strong doses, the drug enters the circulation more rapidly than in others and in consequence coagulation is not at first accelerated.
The rather long period (nearly 30 minutes), in the case just cited, between the injection and the first appearance of rapid clotting was not the rule. As the following figures show, the coagulation time may become shortened quite promptly after subcutaneous injection.
| Oct. 29. | 3.30 | 5.5 | minutes |
| .36 | 5.5 | “ | |
| .44 | Adrenin, 3 cubic centimeters, 1:1,000, injected subcutaneously. | ||
| .46 | 5.5 | minutes | |
| .53 | 4 | “ | |
| 4.01 | 3.5 | “ | |
| .08 | 3.5 | “ | |
| .16 | 4.5 | “ | |
| .23 | 5 | “ | |
| .30 | 5.5 | “ | |
In this case nine minutes after the injection the change in the rate of clotting had begun, and it continued more rapid for the subsequent half-hour.
We did not attempt to find the minimal subcutaneous dose which would shorten clotting. A dose of 0.01 milligram per kilo, however, has proved effective, as shown by the following figures:
| Feb. 3. | 11.34 | 10 | minutes |
| .45 | 9 | “ | |
| .50 to .52 | Adrenin, 2.8 cubic centimeters, 1:100,000, injected under skin of groin in cat weighing 2.8 kilos. | ||
| .55 | 10 | minutes | |
| 12.06 | 7 | “ | |
| .14 | 4 | “ | |
| .19 | 5.5 | “ | |
| .31 | 6 | “ | |
| .37 | 7 | “ | |
| .45 | 9 | “ | |
As will be shown later, the dose in this instance was ten times the minimal effective intravenous dose. On the basis of these figures, less than a milligram of adrenin given subcutaneously would be necessary to shorten clotting to a marked degree in a man of average weight (70 kilograms).
Not many observations were made by us on the effects of adrenin administered subcutaneously. The amount reaching the vascular system and the rate of its entrance into the blood could be so much more accurately controlled by intravenous than by subcutaneous introduction that most of our attention was devoted to the latter method.