16 K. G. HOSKINS 



augments activity, as in case of the heart ; whereas in organs deriving their 

 inhibitory innervation from the sympathetic system the effect is depression 

 of function, as in the gastro-intestinal tract. That the pharmacodynamic 

 effects of epinephrin are not due solely to peripheral action, however, has 

 recently been shown by Hartman and his collaborators. These observers 

 have noted that various of the reactions, and especially vasodilatation, can 

 be evoked by the application of epinephrin to the sympathetic ganglia. 



That the well-known pharmacodynamic effects that follow the injec- 

 tion of epinephrin represent merely an exaggeration of the normal func- 

 tions of the suprarenals has been widely assumed. The assumption is still 

 made the basis for a considerable amount of clinical theorizing. A con- 

 sideration of the quantitative factors, however, renders this very dubious. 

 Xo reliable evidence has ever been reported that epinephrin can be found 

 under normal conditions in the arterial blood in sufficient concentration 

 to bring about such functional perturbations as rise of blood pressure, 

 glycosuria, and the other well-known reactions to large doses of the drug. 

 The most recent investigations, in which the best available technique has 

 been employed, have indicated an output of epinephrin from the supra- 

 renal glands of only approximately 0.0002 milligram per kilogram of 

 body weight per minute, and this output has been obtained under con- 

 ditions of trauma and anesthesia that in all probability markedly augment 

 the discharge. 



That the sympathetic nervous system is under constant minimal epi- 

 nephrin stimulation is the basis of the so-called tonus theory of suprarenal 

 function. Following Oliver and Schafer's classic experiments with supra- 

 renal extracts, the tcnus theory was propounded and widely adopted. A 

 number of observations, however, render the theory highly dubious or, 

 indeed, in the opinion of many competent investigators, quite untenable. 

 The theory has been applied more particularly to the control of blood 

 pressure. It assumes that the suprarenals are constantly supplying to 

 the blood stream enough secretion to stimulate the pressor mechanisms, 

 If this were true the addition of a slightly greater quantity of the drug 

 by vein should augment the pressor influence and send the tension higher. 

 As a matter of fact, quite the opposite occurs. Such injections charac- 

 teristically lower the blood pressure. This observation was made by 

 Moore and Purinton as early as 1900, but the depression was ascribed 

 to impurities in the material injected. In 1912 lioskins and McClure 

 reinvestigated the matter, using a supposedly pure drug. Their experi- 

 ments were made on dogs. The depressor effect was easily demonstrated. 

 In one striking instance, by the infusion into a vein of a dilute solution 

 of epinephrin, the blood pressure was reduced by several millimeters and 

 held at this lower level for ten minutes until the infusion was discon- 

 tinued, when the pressure promptly returned to its former height, The 

 depressor effect of small doses was confirmed by Cannon and Lyman 



