Wilenko’s conclusion fails to account readily for the disappearance of glycogen from the liver in adrenin glycosuria. Furthermore, Lusk[25] has recently reported that the subcutaneous administration of adrenin (one milligram per kilo body weight) to dogs, simultaneously with 50 grams of glucose by mouth, interferes not at all with the use of the sugar—the respiratory quotient remains for several hours at 1.0; i. e., at the figure which glucose alone would have given. In other words, Lusk’s results with dogs are directly contradictory to Wilenko’s results with rabbits. Nevertheless, Wilenko’s conclusion might be quite true for the glycosuria produced by adrenin alone (which must be excessive), and yet have no bearing whatever on the glycosuria produced physiologically by splanchnic stimulation, even though some adrenin is thereby simultaneously liberated.
The amount of injected adrenin used to produce adrenin glycosuria is enormous. Osgood has studied in the Harvard Physiological Laboratory the effects on blood pressure of alternately stimulating the left splanchnic nerves (with the splanchnic vessels eliminated) and injecting adrenin, and by this method of comparison[26] has shown that the amount secreted after five seconds of stimulation varies between 0.0015 and 0.007 milligram. If 0.005 milligram is taken as a rather high average figure, and doubled (for two glands), the amount would be 0.01 milligram. To produce adrenin glycosuria, an animal weighing two kilos would be injected with two hundred times this amount. It is granted that more adrenin would be secreted if the nerves were stimulated longer than five seconds, and that with injection under the skin or into the abdominal cavity (to produce glycosuria), the amount of adrenin in the blood at one time would not be so great as if the injection were into a vein; but even with these concessions the amount of adrenin in the blood, when it has been injected to produce glycosuria, is probably very much above the amount following physiological stimulation of the glands.
Other evidence that the amount of adrenin discharged when the glands are stimulated is not so great as the amount needed to produce glycosuria when acting alone is presented in experiments by Macleod.[27] He found that if the nerve fibres to the liver were destroyed, stimulation of the splanchnic, which would cause increased adrenal secretion, did not increase the blood sugar. The increased blood sugar due to splanchnic stimulation, therefore, is a nervous effect, dependent, to be sure, on the presence of adrenin in the blood, but the amount of adrenin present is not in itself capable of evoking increase.
Furthermore, the increased blood sugar following splanchnic stimulation may long outlast the stimulation period. The adrenals, however, as has been demonstrated by Osgood, are soon fatigued, and fail to respond to repeated stimulation. They seem to be incapable of prolonged action.
Again, as Macleod[28] has shown, a rise in the sugar content of the blood can be induced, if the adrenals are intact, merely by stimulating the nerves going to the liver. The increased blood sugar of splanchnic origin, therefore, is not due to a disturbance of the use of sugar in the body, as Wilenko claims for the increase after adrenin injection, but is a result of a breaking down of the stored glycogen in the liver and is of nervous origin.
We may conclude, therefore, that since the conditions of Wilenko’s observations are not comparable with emotional conditions, his inferences are not pertinent to the present discussion; that when both adrenin and sugar are increased in the blood as a result of excitement, the higher percentage of sugar is not due to adrenin inhibiting the use of sugar by the tissues, and that there is no evidence at present to show that the brief augmentation of adrenal discharge, following excitement or splanchnic stimulation, affects in any deleterious manner the utilization of sugar as a source of energy. Indeed, the observation of Wilenko and of Patterson and Starling, above mentioned, that adrenin increases the use of sugar by the heart, may signify that a physiological discharge of the adrenals can have a favorable rather than an unfavorable effect on the employment of sugar by the tissues.
The Vascular Changes Produced by Adrenin Favorable to Supreme Muscular Exertion
Quite in harmony with the foregoing argument that sugar and adrenin, which are poured into the blood during emotional excitement, render the organism more efficient in the physical struggle for existence, are the vascular changes wrought by increased adrenin, probably in coöperation with sympathetic innervations. The studies of volume changes of parts of the body, made by Oliver and Schäfer, have already been mentioned. Their observations, it will be remembered, showed that injected adrenin drove the blood from the abdominal viscera into the organs called upon in emergencies—into the central nervous system, the lungs, the heart, and the active skeletal muscles. The absence of effective vasoconstrictor nerves in the brain and the lungs, and the dilation of vessels in the heart and skeletal muscles during times of increased activity, make the blood supply to these parts dependent on the height of general arterial pressure. In pain and great excitement, as we have already noted, this pressure is likely to be much elevated, and consequently the blood flow through the unconstricted or actually dilated vessels of the body will be all the more abundant.
Adrenin has a well-known stimulating effect on the isolated heart—causing an increase both in the rate and the amplitude of cardiac contraction. This effect accords with the general rule that adrenin simulates the action of sympathetic impulses. It is commonly stated, however, that if the heart holds its normal relations in the body, adrenin causes slowing of the beat.[29] This view is doubtless due to the massive doses that have been employed, which are quite beyond physiological limits and which induce such enormous increases of arterial pressure that the natural influence of adrenin on heart muscle is overcome by mechanical obstacles to quick contractions and by inhibitory impulses from the central nervous system. Hoskins and Lovellette have recently shown that when the precaution is taken to inject adrenin into a vein in a manner resembling the discharge from the adrenal glands, not only is there increased blood pressure, but generally, also, an acceleration of the pulse.[30] At the same time, therefore, that a greater amount of work, from increased arterial pressure, is demanded of the heart, blood is delivered to the heart in greater abundance, and the muscle is excited to more rapid and vigorous pulsations. The augmentation of the heart beat is thus coördinate with the other adaptive functions of the adrenal glands in great emergencies.