PHARMACOLOGY AND TOXICOLOGY OF SUPRARENALS 251 



the femoral artery of the opposite leg after it was fatigued by tetanization. 

 Gruber has shown that epinephrin will overcome the effects of fatigue 

 produced artificially by injection of lactic acid and phosphates. Indeed, 

 Gruber and Fellows have been able to restore the irritability of nerve- 

 muscle in animals which have been dead from one to three hours (Fig. 5). 

 Toxic Effects of Epinephrin. Foa and Pellacani appear to have 

 been the first to observe toxic effects from suprarenal extracts. Intra- 

 venous injection produced dyspnea, agitation and more rapid heart rate, 

 to be followed later by a slowing of the rate. The temperature rose to 



Fig. 5. Records of a muscle in a cat dead one hour. Upper, muscular contraction, 

 time record just below (5 sec.) Lowest, rate of perfusion. 1, Epinephrin 1 c.c., 

 1:100,000; 2, Epinephrin 0.5 c.c., 1:1,000. (After Gruber, Endocrin.) 



41.2C, but gradually returned. Great prostration ensued. Death fol- 

 lowed within a few hours after the injection. 



Oliver and Schafer have shown that the paralysis produced from 

 suprarenal extract is central because stimulation of the nerve muscle prep- 

 aration elicits a normal contraction after apparent paralysis. 



Large doses of epinephrin (suprarenal extract, Vincent (a)) frequently 

 cause bleeding from the mouth and nostrils, also hematuria, probably 

 due to rupture of capillaries as a result of high blood pressure. Elliott (&) 

 makes the statement that epinephrin produces hemorrhages in the cortex 

 of the suprarenal sooner than elsewhere. The harmful effects of large 

 doses of epinephrin may be due to excessive blood pressure and to a 

 direct toxic action. The changes in the kidney of an animal which has 

 died from epinephrin injection are striking but variable. These may be 

 anything from simple congestion to parenchymatous nephritis with des- 

 quamation of the cells of the tubules (Drummond). Such changes may 



