A Na+-H+ exchange inhibitor (SM-20550) protects from microvascular deterioration and myocardial injury after reperfusion

Na+-H+ exchange inhibitors may reduce myocardial damage after reperfusion. However, their effects on microvascular deterioration are not known. We exa mined the potency of a novel Na+-H+ exchange inhibitor, SM-30550 [ N-(Amino iminomethyl)-1,4-dimethyl-1H-indole-2-carboxamide methanesulfonate], and it s effects on microvascular damage after reperfusion. In an in vitro study. the Na+-H+ exchange inhibiting activity of SM-20550 was about 10 times grea ter than that of ethylisopropyl amiloride. In in vivo experiments, we occlu ded the left circumflex coronary artery in 29 dogs for 2 h and then reperfu sed for 5 h. SM-20550 was administered either before ischemia (n = 11) or b efore reperfusion (n = 7). Another 11 dogs served as controls. We found tha t SM-20550 not only improved coronary vasodilator responses to acetylcholin e and adenosine after reperfusion, but also reduced infarct size (P < 0.01) . Intramyocardial bleeding, which should reflect microvascular damage, was not found in dogs with SM-20550 treatment. Infarct size was correlated inve rsely with collateral blood flow in control (both, P < 0.01) but not in SM- 20550-treated animals. Furthermore, SM-20550 significantly suppressed ventr icular fibrillation during both ischemia and reperfusion. These results sug gest that protective effects of Na+-H+ exchange inhibitors on reperfused my ocardium are due at least in part to microvascular protection. (C) 1999 Els evier Science B.V. All rights reserved.