710 6. AKSENICALS 



effects of the arsenicals on blood vessels will be dicussed in a later section 

 (page 726). 



Heart 



The depressant action of arsenite on the hearts of frogs and mammals 

 was first observed by Sklarek (1866) and Cunze (1866), who showed that 

 although the heart is depressed in vivo, the atria are less sensitive than the 

 ventricles and may continue to beat for several hours after death. Einger 

 and Murrell (1878) confirmed that the heart continues to beat after death 

 and concluded that it is more resistant than the central nervous system 

 to arsenite. Unterberger and Boehm (1874) then demonstrated that the 

 injection of arsenite into dogs and cats slows the heart directly and not 

 by an effect mediated through the cardiac nerves, and that it does not 

 significantly alter the cardiac response to vagal stimulation. Lesser (1878 a) 

 reported a progressive slowing of hearts in arsenite-poisoned frogs, the 

 hearts stopping in diastole; however, in several minutes the ventricles may 

 begin to beat with a rhythm of their own. The injection of arsenite in small 

 doses into rabbits and dogs may produce an initial elevation of the cardiac 

 rate, while the contractile amplitude is only depressed, the depression oc- 

 curring also when the vagi are cut (Lesser, 1878 b). 



There is a disconcerting variation in the reported responses of the iso- 

 lated frog heart to arsenite. Loewi (1897) found the heart to be depressed 

 by concentrations as low as 0.0077 mM, and to be stopped in 100 min 

 by 0.039 mM, in 50 min by 0.15 milf, and in 30 min by 1.5 mM. In con- 

 trast, Sivertsev (1938) claimed that 0.1 mM arsenite does not affect either 

 rate or output, while 0.3-0.7 mM reduces the output by 65%. In some 

 instances the rate is readily depressed (Holzbach, 1912), but in most work 

 the contractile amplitude is reduced with little or no change in the rate, 

 at least until terminal failure (Lesser, 1878 a; Loewi, 1897; Joachimoglu, 

 1915; Sivertsev, 1938). There is general agreement that the heart stops 

 in diastole, even with high concentrations of arsenite (Vogt, 1930), but it 

 may be put into contracture by electrical stimulation (Mendez, 1946). 

 Almost all workers have found the effects to be irreversible. An initial and 

 temporary stimulation of the heart by arsenite has been reported in isolated 

 preparations from frogs (Zondek, 1920; Vogt, 1930), silkworm (Campbell, 

 1926), and rat (Webb and Hollander, 1959). This is rather characteristic of 

 SH reagents but the mechanism is unknown. 



The stimulating effect of epinephrine on the rate of the frog heart, both 

 in vivo and isolated, was claimed to be blocked by arsenite (Holzbach, 

 1912). The injection of epinephrine into poisoned frogs temporarily raises 

 the blood pressure but does not change the cardiac rate, while isolated 

 hearts depressed by arsenite have their output restored by epinephrine 

 even though the rate remains low. On the other hand, Vogt (1930) reported 

 that 0.77 mM arsenite does not interfere with the stimulatory action of 



