A QUANTITATIVE STUDY OF THE EFFECTS OF ADRENALIN ON THE PUPILS OF RABBITS AFTER REMOVAL OF A SUPERIOR CERVICAL GANGLION.
It has been shown by these experiments that after the removal of one superior cervical ganglion of a rabbit, 1/50 of a cubic centimeter of a 1:1,000 adrenalin solution (=0.02 of a milligram of adrenalin) per kilo of body weight injected intravenously, is practically the minimum amount that will produce in nearly all cases a perceptible dilatation of the pupil. In one out of eight animals this dose failed to give a definite effect, while in two others the effect was slight. Six experiments with injections of 1/50 of a cubic centimeter of adrenalin per kilo of body weight gave the following averages: a maximum dilatation of 1.62 millimeters, which showed the first sign of decreasing in four minutes and had disappeared entirely in ten minutes after the injection. Six experiments with 1/30 of a cubic centimeter per kilo gave the following averages: a maximum dilatation of 2.25 millimeters, which began to disappear in eight minutes and had entirely disappeared in twenty-eight minutes. For thirteen experiments with 1/20 of a cubic centimeter of adrenalin per kilo these averages were: a maximum dilatation of 3.61 millimeters, a beginning recovery from dilatation in six minutes, with complete recovery of the pupil in thirty-seven minutes. With 1/10 of a cubic centimeter of adrenalin per kilo (eight experiments) the averages were: a maximum dilatation of 3.87 millimeters, a beginning recovery in ten minutes, with complete recovery of the pupil in forty-five minutes. Finally, eleven experiments with 2/10 of a cubic centimeter of adrenalin per kilo gave averages as follows: a maximum dilatation of 4.38 millimeters, a beginning recovery from dilatation in twenty minutes, with complete recovery only after one hundred minutes or more. The time between the injection and the appearance of the maximum dilatation of the pupil varied somewhat according to the dose of adrenalin. In the series of experiments with 1/50 of a cubic centimeter of adrenalin per kilo of body weight the average for this interval was one minute; in the series with 1/30, 1/20, and 1/10 of a cubic centimeter the average length of this interval was about three minutes, while the experiments with 2/10 of a cubic centimeter give us an average for this interval of six and a half minutes, with individual instances in which the maximum dilatation was seen only after fourteen, seventeen, and twenty-two minutes after the injection. In those animals in which the maximum pupil dilatation was especially delayed, there were almost always more or less alarming symptoms of general prostration for a short time after the injection, and the maximum dilatation appeared as these symptoms gradually disappeared. In other words, with an increase in the size of the dose of adrenalin, there was a gradual increase in the following: (1) the time between the injection and the appearance of the maximum dilatation; (2) the amount of dilatation produced; (3) the interval between the injection and the beginning of recovery from dilatation; and (4) in the total time between the injection and the return of the pupil to its normal size. After removal of the ganglion a certain time must elapse before the increase in the sensitiveness develops. During the first ten to fifteen hours there is practically no increase in the sensitiveness. After eighteen hours a moderate effect can be obtained which rapidly increases so that by twenty to twenty-four hours after the removal of the ganglion any given dose of adrenalin produces practically as great a dilatation as it will give at any later time. The experiments teach us that, on account of the individual variation in the degree of dilatation produced by a given dose of adrenin, we may not determine with exactness from any given degree of dilatation of the pupil the quantity of adrenin injected into the blood stream, and that we can not state with absolute exactness either the smallest dose that will constantly cause a dilatation, or mention the exact amount of adrenin which will in no case cause a dilatation of the pupil. However, the results permit the general statement that very small doses of adrenin on entering the circulation cause a fairly prolonged definite dilatation of a deganglionized pupil. Since this is true, there are then at least two ways in which a rabbit from which one superior cervical ganglion has been previously removed may be used for determining qualitatively the amount of adrenin present. If, for example, we have a solution which may or may not contain adrenin, and upon injecting it obtain a dilatation of the deganglionized pupil only while the pupil on the normal side remains unchanged in size, we are justified in assuming that the solution contains adrenin. Again, if after stimulation of the peripheral end of a splanchnic nerve or other procedure upon the animal body under conditions that exclude the possibility of reflex effects, a dilatation of the deganglionized pupil results, while its normal mate remains unchanged, the assumption is warranted, though not absolutely proved, that some adrenin has been thrown into the circulation. This test for the presence of adrenin has the advantage over other tests, that the pupil on the normal side will always act as a control.
Joseph
D R
DR
Department of Physiology and Pharmacology of The Rockefeller Institute for Medical Research, New York.