Effects of amiloride on the mechanical, electrical and biochemical aspects of ischemia-reperfusion injury

Although many causal factors have been proposed for the ischemia-reperfusion 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 regional brief ischemia followed by reperfusion to study the protective effects of amiloride, an inhibitor of Na⁺-H⁺ exchange. Amiloride (0.1 mM) attenuated the rise in tissue Na⁺ and Ca²⁺, both duration and incidence 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 sodium inophore, reversed the protective effects of amiloride. Reduction in transsarcolemmal Na⁺ and pH gradients during ischemia exhibited protective effects similar to those seen with amiloride. These results suggest that cardiac dysfunction, sarcolemmal injury and triggered arrhythmias during ischemia-reperfusion are due to the occurrence of intracellular Ca²⁺ overload caused by the activation of Na⁺-H⁺ exchange and Na⁺-Ca²⁺ exchange systems in the myocardium.