Effects of an inhibitor of glycolysis on electrical toxicity of acetylstrophanthidin

The effects of iodoacetate (IAA), an inhibitor of glycolysis, on the electrical toxicity of acetylstrophanthidin (AS) were assessed with standard microelectrode techniques in rabbit Purkinje fibers. IAA (0.1 mM) decreased the amplitudes of AS-induced oscillatory afterpotentials (OAP) at all basic cycle lengths (BCL) tested (200-1000 msec). IAA also decreased the incidence of triggered activity. However, when OAP were induced by high (Ca²⁺), OAP amplitudes were decreased by IAA only at short BCLs. Possible dependence of Na-pump inhibition by digitalis on glycolysis was evaluated by measuring post-pacing hyperpolarization (PPH). IAA did not affect PPH by itself, and did not alter inhibition of PPH by AS. However, in IAA treated tissues, AS caused greater decrease in action potential duration (APD), greater depression of the action potential plateau phase, but less depolarization with rapid stimulation. The results suggest that inhibition of glycolysis decreases the amplitudes of OAP, incidence of triggered activity, and magnitude of depolarization induced by toxic concentrations of digitalis but these effects are not mediated via prevention of Na-pump inhibition. Abbreviation of APD and depression of action potential plateau in presence of glycolytic inhibition might decrease Ca²⁺ load and thereby attenuate digitalis toxicity. In addition, decreased depolarization during rapid stimulation may contribute to the decrease in OAP amplitude since OAP are voltage-dependent.