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

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Abstract

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.

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Yano, Ki., Maruyama, T., Makino, N. et al. Effects of amiloride on the mechanical, electrical and biochemical aspects of ischemia-reperfusion injury. Mol Cell Biochem 121, 75–83 (1993). https://doi.org/10.1007/BF00928702

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