TISSUE FUNCTIONS 711 



epinephrine, although 3 mM weakens it, and Nickerson and Nomaguchi 

 (1950) also found 0.5 mM arsenite to be without effect on the chronotropic 

 response to epinephrine. Actually, the situation is probably this: the initial 

 stimulation by epinephrine may not be appreciably reduced by arsenite 

 (assuming that the heart is not too much depressed), but the stimulation 

 is temporary and actually promotes more rapid failure, as is the case with 

 a variety of inhibitors as well as anoxia. Frog hearts depressed by arsenite 

 are also stimulated by Ca++ but further depressed by K+ (Zondek, 1920). 

 Some slight progress has been made toward an understanding of the 

 possible mechanisms involved by investigating the changes in the electrical 

 activity of the heart. Electrocardiographic disturbances, including prolon- 

 gation of the qrs interval, lowering of the st segment, and ectopic activity, 

 have been noted in human arsenical poisoning (Zettel, 1943), and in rabbits 

 poisoned with arsenite one finds electrocardiographic alterations corre- 

 sponding to cardiac damage (Petrucci and Boggio-Gilot, 1955). It is, of 

 course, difficult to interpret such changes in terms of direct actions on the 

 heart, since many secondary effects may be involved, but it seems likely 

 that at least some of the electrocardiographic effects are direct. Goldenberg 

 and Kothberger (1937) studied the electrical activity of dog hearts depressed 

 by the perfusion with 1-2.5 mM arsenite, and claimed that there is a tend- 

 ency for aberrant after-potentials to occur following relatively normal 

 action potentials. It is clear from their records, however, that the true 

 action potential is shortened and reduced in amplitude, although the period 

 of electrical variation may be prolonged. Recording intracellularly with 

 microelectrodes in the rat atrium, it has been found that the effects on 

 membrane potentials are not marked when the contractile activity is 

 quite severely depressed (see accompanying tabulation) (Webb and Hol- 



% Change from 1 mM arsenite 

 Parameter , ^ ^.i ^rv • \ 



(at 21-40 mm) 



lander, 1959). Of all the metabolic inhibitors examined, arsenite produced 

 the most specific contractile depression; that is, since little of the contractile 

 change can be attributed to alteration in the characteristics of the membrane 



