252 FKANK A. HAETMAK 



result in death from a single dose or from several doses given at intervals. 

 Frequently the liver shows patches of necrosis although the liver changes 

 are so inconstant that some cases show no definite change in this 'organ. 



The glycogen content of the liver may or may not he affected. In 

 chronic poisoning it is not necessarily changed while in acute poisoning the 

 glycogen is diminished if the animal lives long enough after the injection 

 (Drummond and Paton). 



Convulsions are frequent in animals before death from epinephriii. 

 These may he asphyxial in nature as a result of acute edema of the lungs 

 (Batelli (<?)). The congestion may be intense and even hemorrhagic in 

 character. 



Daily injections of epinephrin even in comparatively moderate amounts 

 in time cause atheroma of the aorta and coronary arteries (Loeper(fr)) 

 although this is said not to be the case in young animals (Pic and Bon- 

 namour). 



Whether significant or not it is interesting to note that the guinea 

 pig has great resistance to epinephrin so that large doses are required 

 to produce death. Likewise the guinea pig has a larger cortex in pro- 

 portion to its size than has any other animal. 



. The lethal dose of natural levo-epinephrin is much less than that for 

 dextro-epinephrin (Schultz, Abderhalden and Slavu). Likewise the 

 former possesses a greater physiological activity. 



A much greater amount of epinephrin is required subcutaneously than 

 intravenously to produce death. When given by the mouth great quantities 

 are tolerated. No doubt a large portion of such a dose is destroyed be- 

 fore it reaches the circulation (Falta(a)). 



Location of Epinephrin Action. It seems that epinephrin produces 

 its effect only through mediation of the nervous system or its closely as- 

 sociated structures, especially through the sympathetic portion. Tissues 

 without sympathetic innervation are unaffected by it, therefore we con- 

 clude that it has no direct action on muscles. 



Myoneural Junctions. Dixon was able to paralyze the structures 

 through which epinephrin acts upon the blood vessels by means of apoco- 

 dein. The smooth muscle itself was still irritable to barium chlorid. 

 Apocodein, at least in moderate doses, does not paralyze every epinephrm- 

 sensitive tissue in the body. The epinephrm-sensitive tissue of the blad- 

 der is such an exception. The effect of apocodein must be a true paralysis 

 rather than a chemical antagonism for if it were the latter all epmephrin- 

 sensitive tissues of the body should be affected equally. Moreover, stim- 

 ulation of vasoconstrictor fibers paralyzed with apocodein is without 

 effect. 



Brodie and Dixon have shown that the excitability of the vascon- 

 strictor nerve trunks to electrical stimulation is lost within two to three 

 hours after death, but that the reaction to epinephrin persists a few 



