Cardiac effects of ethacrynic acid, a Na+, K+-ATPase inhibitor

To test hypotheses relating positive inotropic effects of cardiac glycosides (CG) to inhibitory effects on Na,K-ATPase, cardiac actions of other inhibitors were examined. Ethacrynic acid was studied using microelectrode recordings of dog Purkinje fibers (DP) and cat papillary muscle (CP), and isometric recordings of CP at Lmax stimulated at 1/sec (36.5 degrees C). Results with all doses (20-200 gamma/ml) were similar, differing only in latency. Actions of ethacrynic acid on electrical activity of DP and CP were, chronologically: increase in duration of the action potential (AP), and decrease in dV/dt, overshoot, and resting potential. In CP an initial increase (2-5 min) in contractility (10-15 percent) was followed by decreased in active tension and dP/dt with parallel increases in resting tension and duration of contraction. ATP levels were unchanged, eliminating the possibility of ethacrynic acid acting as a metabolic poison. Simultaneous recording of contractions and AP in CP showed that the positive inotropic effect was always associated with a lengthening of the AP. In a series of CP, ouabain (2 gamma/ml) always increased contractility when ethacrynic acid had already reduced it by 75 percent. These results suggest that Na,K-ATPase inhibition is not responsible for the inotropic effects of CG.