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. 3.11.3410minutes
.45 9
.50 to .52Adrenin, 2.8 cubic centimeters, 1:100,000, injected under skin of groin in cat weighing 2.8 kilos.
.5510minutes
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.

The Effects of Intravenous Injections

In this procedure a glass cannula was fastened in one of the external jugular veins and filled with the same solution as that to be injected. A short rubber tube was attached and tightly clamped close to the glass. Later, for the injection, the syringe needle was inserted through the rubber and into the fluid in the cannula, the clip on the vein was removed, and the injection made.

The solutions employed intravenously were adrenin 1:10,000, 1:50,000, and 1:100,000, in distilled water.

The smallest amount which produced any change in clotting time was 0.1 cubic centimeter of a dilution of 1:100,000 in a cat weighing two kilos, a dose of 0.0005 milligram per kilo. Four tests previous to the injection averaged 5 minutes, and none was shorter than 4 minutes. Immediately after the injection the time was 2 minutes, but at the next test the effect had disappeared. Doubling the dose in the same cat—i. e., giving 0.2 cubic centimeter (0.001 milligram per kilo)—shortened the coagulation time for about 40 minutes:

Dec. 23.10.304 minutes
.354
.414
.46 Adrenin, 0.001 milligram per kilo.
.472.5minutes
.503
.533.5
11.001.5
.051.5
.103
.152
.204
.264.5
.315