148 



G. K STEWAKT 



increase o concentration is always observed when the blood flow in the 

 cava is slowed from any cause whatever, provided that the epinephrin 

 output continues unchanged, or is diminished less than the rate of the 

 blood flow. 



It was demonstrated by Stewart and Rogoff(n) (1919) that the pre- 

 dominant and by far the most durable action of nicotin, whether adminis- 

 tered intravenously or hypodermically, upon the epinephrin output is 

 a depressant or paralyzing action. The maximum diminution of the out- 

 put is rather rapidly reached and then there is a more gradual recovery, 



Fig. 19. Intestine tracings. At 29, 33 and 35, Ringer's solution was replaced by 

 venous blood collected after injection of nicotin into a cat; and this at 30 by venous 

 blood to which was added "adrenalin" to make a concentration of 1:660,000; at 34 by 

 a suprarenal blood specimen, collected immediately after injection of nicotin; at 36 by 

 venous blood to which was added "adrenalin"' to make a concentration of 1:330,000. 

 All the blood specimens were diluted with 3 volumes Ringer's solution (the "adrenalin 

 bloods" after adding the "adrenalin"). From these and other curves it was shown 

 that the suprarenal specimen had an epinephrin concentration of fully 1:300,000, 

 corresponding to an output of 0.002 mgm. per kgm. per minute, or 20 times the output 

 represented by a specimen taken before the administration of nicotin. (Reduced to 

 one-half.) (After Stewart and Rogoff 5 J. Pharm. d Exper. Therap.} 



which, when the dose is not too large, proceeds until the original output 

 is approximately attained. At the time of maximum depression no epi- 

 nephrin at all may be detected in the suprarenal vein blood. The depres- 

 sant action is preceded by a transient stage of excitation, lasting as a 

 rule not longer than from half a minute to less than a minute (Fig. 19). 

 In this stage the rate of epinephrin output is markedly increased (from 

 2 or 3 to 10 or 15 times the original output, or even more). With intra- 

 venous injection of the drug the transient augmentation of the output 

 begins practically at once. In some of the experiments there was evidence 

 that the latent period could not have exceeded a few seconds. The brief 

 stage of excitation passes rather abruptly into the much more durable 

 stage of depression (Figs. 20, 21). The changes in the rate of epinephrin 



