KELATION 'SUPKAKENAL GLANDS TO CIKCULATION 191 



ways but nothing further of fundamental significance was added. The 

 isolation of epinephrin permitted more satisfactory quantitative studies. 

 It was found that the threshold dosage for pressor effects from intra- 

 venous injections is as low as 0.0005 mg. and that doses of the magnitude 

 of 0.001 mg. per kilo, never fail in a normal test animal to give clean-cut 

 pressor reaction of such magnitude, for example, as 25 mm. of mercury. 

 With larger doses pressures of 250 to 300 mm. were found to be easily 

 obtained and such as are not elicitable by any other known means (Biedl). 

 As Oliver and Schafer pointed out, the effects of even maximal single doses 

 are brief, but Biedl reported that he was able to maintain for hours 

 a pressure of 140 to 160 mm. by constant infusion of epinephrin in mam- 

 mals, even after total destruction of the central nervous system. Maximal 

 effects are obtainable with such doses as 0.1 mg. Further augmentation 

 of the quantity injected, it was found, is likely to lead to immediate dis- 

 astrous effects, such as ventricular fibrillation or pulmonary edema. 



That the pressor effect of epinephrin is due to its action partly on the 

 heart and partly on the peripheral blood-vessels was recognized by the 

 earlier investigators. While cardiac depression may result from vagus 

 stimulation incident to the high blood-pressure following the administra- 

 tion of large doses of epinephrin, it is not to be supposed that the sustain- 

 ing influence of the drug upon the heart is in abeyance. Without this 

 influence, a given elevation of arterial pressure would result in materially 

 greater cardiac depression. 



The vaso-constrictor effect of epinephrin can be recognized by inspec- 

 tion of the tissue upon which it acts. Blanching the conjunctiva or nasal 

 mucosa by use of this substance is a well-known clinical procedure. A 

 small quantity of dilute solution introduced intracutaneously results in an 

 area of alabaster whiteness. Cybulski and Szymonowicz, as previously 

 mentioned, believed that the vasoconstriction is due to the action of the 

 drug on the medulla oblongata. Oliver and Schafer's report, however, 

 that the effect is readily elicited after destruction of the nervous system 

 was early and abundantly confirmed. Indeed, if the animal remains 

 alive following the denervation of a given organ, the irritability of the 

 tissues to epinephrin becomes materially augmented. That the vaso- 

 motor effect is exerted largely on the arterioles was deduced from the fact 

 that the large arteries may even enlarge during the time the blood-pres- 

 sure is at its height. This expansion of the arteries is due, however, to 

 relative rather than absolute lack of response to injected epinephrin. This 

 can readily be shown by exposing rings of isolated artery to the action 

 of the drug. Some degree of contraction is noted in almost every case. 

 While the greater part of the pressor effect is due to direct cardiovascu- 

 lar stimulation, it is probable that the vasoconstrictor centers are also stim- 

 ulated to a minor extent. Biedl found that the introduction of epinephrin 

 into the carotid artery resulted in the immediate increase of blood-pres- 



