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.