RELATION SUPRARENAL GLANDS TO CIRCULATION 193 



neural junction substance is not clear. It is quite possible that Straub's 

 principle as regards the action of drugs holds here, namely, that a given 

 substance may exert its influence merely by the process of penetrating 

 the effector cells. That is, it is inactive either when prevented from pass- 

 ing into the cell or after its passage. Favoring this supposition is the 

 fact that it is not possible by a single dose of epinephrin administered 

 intravenously to produce more than a very brief reaction. If the action 

 of the drug is due, however, merely to its transit into the cell, we must 

 assume that epinephrin is destroyed in the myoneural receptive substance. 

 This follows from the fact that it is possible by continuous infusion to 

 maintain elevated blood-pressure for hours. If the drug were not being 

 continuously destroyed, equilibrium would be quickly established within 

 and without and passage of the drug then cease. 



Destruction of Epinephrin in the Body 



Such considerations as the foregoing raise the question', How is epi- 

 nephrin destroyed in the body? No very satisfactory answer can be of- 

 fered. That it is not excreted as such is generally believed. It is not 

 found in the urine except in traces after the administration of large doses. 

 It has not been recognized in any of the other excretory fluids in man, 

 though it has been found in the dermal secretion of a West Indian toad 

 (Abel). 



The fact that epinephrin is readily oxidized suggests that it is by this 

 means that destruction of the substance occurs. But against this con- 

 ception several objections may be raised. If mere oxidation were the 

 method involved, passage through the lungs, with exposure there to maxi- 

 mal oxygen tension, should lead to partial or complete destruction. As 

 a matter of fact, epinephrin can be passed through the pulmonary capil- 

 laries with little or no reduction of its concentration in the blood. Epi- 

 nephrin, when added to aerated, defibrinated blood kept at body tempera- 

 ture, persists with relatively little diminution for hours. It is this fact that 

 renders possible comparative assaying of epinephrin in the blood. Fur- 

 thermore, it appears fairly clear that epinephrin, as a matter of fact, is 

 destroyed in the tissues that have a reducing rather than an oxidizing 

 tendency. Also, epinephrin is much more unstable in alkaline than in acid 

 solutions. Active tissues are constantly producing acid metabolites; hence 

 epinephrin would supposedly meet augmented acidity upon its passage from 

 the peripheral capillaries. Kretschmer has reported that he was able to 

 prolong the hypertensive reaction to epinephrin very materially by intra- 

 venous administration of acid. This result, however, the writer was quite 

 unable to corroborate by the use of acid in any quantity even remotely 

 approaching the maximal amount that could be formed in the normal liv- 



