EFFECT OF METHYLISOBUTYL AMILORIDE ON [NA+](I), REPERFUSION ARRHYTHMIAS, AND FUNCTION IN ISCHEMIC RAT HEARTS

With 2 mu M methylisobutyl amiloride (MIA), an inhibitor of Na+/H+ exc hange, we tested the hypothesis that ion imbalance due to H+/Na+/Ca2exchange exacerbates reperfusion injury and arrhythmias. Isolated rat hearts were subjected to 25-min global ischemia and 30-min reperfusion . In the MSA-treated group, MIA was added throughout the perfusion pro tocol. Left ventricular pressure (LVP), arrhythmias, myocardial Na+ an d K+ content, Ca-45(2+) uptake, and the levels of energy metabolites w ere analyzed. The recovery of LV developed pressure (LVDP) and +dP/dt and -dP/dt were improved in the MIA group (53 vs. 80, 71 vs. 86, 77 vs . 94%: each p < 0.05). MIA inhibited the increase in Na+ content and t he decrease in K+ content that occurred at the end of the ischemic pha se and reduced Ca-45(2+) uptake after reperfusion (28.6 vs. 17.1, 248 vs. 296, 2.79 vs. 1.36 mu M/g dry weight of tissue; each p < 0.05), Th e incidence of ventricular tachycardia (VT) or ventricular fibrillatio n (VF) was lower in the MIA group [VT 11 of 20 (55%) vs. 4 of 20 (20%) , p < 0.05; VF 13 of 20, (65%) vs. 6 of 20 (30%), 0.05 < p 0.1], altho ugh the incidence of VF just escaped statistical significance, ATP lev el was higher in the MIA group after the ischemic phase and reperfusio n (5.3 vs. 9.9, 12.3 vs. 14.7 mu M/g dry weight of tissue; each p < 0. 05). Our results suggest that MIA reduced reperfusion arrhythmias and improved functional recovery in isolated rat hearts subjected to globa l ischemia apparently by preserving high-energy phosphates during isch emia and by inhibiting Na+/H+ exchange, with attenuated cellular imbal ance between Na+ and Ca2+.