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.
Department of Bioclimatology and Medicine, Kyushu University 69, Beppu, Japan.
K
K
Yano
T
T
Maruyama
N
N
Makino
H
H
Matsui
T
T
Yanaga
D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy; D002118:Calcium / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects
D000584:Amiloride; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium