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

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.
AuthorsK Yano, T Maruyama, N Makino, H Matsui, T Yanaga
JournalMolecular and cellular biochemistry (Mol Cell Biochem) Vol. 121 Issue 1 Pg. 75-83 (Apr 07 1993) ISSN: 0300-8177 [Print] Netherlands
PMID8389983 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Amiloride
  • Sodium
  • Sodium-Potassium-Exchanging ATPase
  • Calcium
Topics
  • Amiloride (pharmacology)
  • Animals
  • Arrhythmias, Cardiac (drug therapy)
  • Calcium (metabolism)
  • Heart (drug effects)
  • Heart Rate (drug effects)
  • Hydrogen-Ion Concentration (drug effects)
  • Male
  • Myocardial Reperfusion Injury (physiopathology)
  • Rats
  • Rats, Wistar
  • Sodium (metabolism)
  • Sodium-Potassium-Exchanging ATPase (drug effects)

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