EFFECTS OF AMILORIDE ON THE MECHANICAL, ELECTRICAL AND BIOCHEMICAL ASPECTS OF ISCHEMIA-REPERFUSION INJURY

Although many causal factors have been proposed for the ischemia-reper fusion injury, the exact mechanisms for interdependent derangements of mechanical, electrical and metabolic events remains unclear. For this purpose, the Langendorff-perfused rat, hearts were subjected to regio nal brief ischemia followed by reperfusion to study the protective eff ects of amiloride, an inhibitor of Na+-H+ exchange. Amiloride (0.1 mM) attenuated the rise in tissue Na+ and Ca2+, both duration and inciden ce of arrhythmias (p < 0.05 vs. control), sarcolemmal injury (assessed by Na-K ATPase) and lipid peroxidation (assessed by malonedialdehyde formation) during reperfusion. Treatment of hearts with monensin, a so dium inophore, reversed the protective effects of amiloride. Reduction in transsarcolemmal Na+ and pH gradients during ischemia exhibited pr otective effects similar to those seen with amiloride. These results s uggest that cardiac dysfunction, sarcolemmal injury and triggered arrh ythmias during ischemia-reperfusion are due to the occurrence of intra cellular Ca2+ overload caused by the activation of Na+-H+ exchange and Na+-Ca2+ exchange systems in the myocardium.