Involvement of sodium in the protective effect of 5-(N,N-dimethyl)-amiloride on ischemia-reperfusion injury in isolated rat ventricular wall.
During reperfusion in the isolated right ventricular wall of the rat after 60 min of ischemia, developed tension and resting tension were 35 +/- 4 and 221 +/- 12%, respectively, of preischemic values. Including 35 microM ouabain in the perfusate before and after ischemia resulted in more severe cardiac dysfunction during reperfusion than in drug-untreated hearts. Introduction of the Na(+)-H+ exchange inhibitor, 5-(N,N-dimethyl)-amiloride (DMA), could effectively protect the right ventricular wall against ischemia-reperfusion dysfunction in the presence or absence of ouabain. The ion content in the right ventricular wall was measured with atomic absorbance spectrophotometry. Before ischemia, Na+,Ca++ and K+ content were 53.4 +/- 6.4, 2.70 +/- 0.22 and 262 +/- 7.7 mumol/g of dry weight tissue, respectively. After 60 min of ischemia and 6 min of reperfusion, Na+,Ca++ and K+ content were 73.4 +/- 7.2, 3.79 +/- 0.31 and 180 +/- 15 mumol/g of dry weight tissue, respectively (P less than .05). Introduction of 20 microM DMA normalized ion content in the muscles which was consistent with the contractile function recovery during reperfusion. The data suggest that a rise in intracellular Na+ in the early stage of reperfusion represents a crucial or primary step for the development of cardiac contractile dysfunction. DMA, which protects against severe reperfusion-induced cardiac contractile dysfunction, appears to act via a normalization of tissue sodium levels. This action is consistent with its proposed role as a blocker of transsarcolemmal Na(+)-H+ exchange.
Meng
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Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada.
Pierce
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D000584:Amiloride / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D003327:Coronary Disease / Q000628:therapy; D006321:Heart / Q000187:drug effects; D006352:Heart Ventricles; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000032:analysis / Q000502:physiology*; D013054:Spectrophotometry, Atomic
C039465:5-dimethylamiloride; D010042:Ouabain; D000584:Amiloride; D012964:Sodium; D011188:Potassium