Possible involvement of Na(+)-H+ exchange in the early phase of reperfusion in myocardial stunning.

Calcium overload during reperfusion after prolonged ischemia has been associated with the Na(+)-Ca2+ exchange system. It has been proposed that the promotion of Na(+)-Ca2+ exchange at reperfusion may be mediated by Na(+)-H+ exchange. To evaluate whether this hypothesis is applicable for stunned myocardium, we examined the influence of temporary suppression of Na(+)-H+ and/or Na(+)-Ca2+ exchange during early reperfusion in isolated rat hearts. Myocardial stunning was produced by global ischemia for 15 min at 37 degrees C. The initial reperfusate was given during the subsequent 10 min after ischemia, and followed by reperfusion with normal Krebs-Henseleit buffer solution for 40 min. Hemodynamic indices, creatine kinase in coronary effluent, and myocardial water content were measured during reperfusion. The functional recovery of stunned myocardium was improved with higher extracellular Na+ concentration and/or lower Ca2+ concentration of the initial reperfusate. Aortic flow recovery of group II (135 mM Na(+)-0.5 mM Ca2+) was 77.0 +/- 3.4%, which was substantially greater (P < 0.05) than that of other groups: group I (control, 135 mM Na(+)-1.5 mM Ca2+), 68.2 +/- 2.4%; group III (25 mM Na(+)-0.5 mM Ca2+), 48.7 +/- 2.9%; group IV (25 mM Na(+)-1.5 mM Ca2+), 21.6 +/- 1.5%. Administration of amiloride, an inhibitor of Na(+)-H+ exchange, in the initial reperfusate ameliorates cardiac damage and improved aortic flow recovery in a dose-dependent manner (10(-6) M, 70.1 +/- 3.7%; 10(-5) M, 77.3 +/- 1.7%; 10(-4) M, 82.0 +/- 2.1% vs control 68.2 +/- 2.4%).(ABSTRACT TRUNCATED AT 250 WORDS)