Reduction of myocardial infarct size by SM-20550, a novel Na+/H+ exchange inhibitor, in rabbits

The effects of N-(aminoiminomethyl)-1,4-dimethyl-1H-indole-2-carboxamide methanesulfonic acid (SM-20550): a novel potent Na+/H+ exchanger, and nicorandil, a K+ channel opener with nitrate-like activity, were studied in a myocardial ischemia acid reperfusion injury model. Anesthetized rabbits underwent occlusion of the coronary artery (30 min) followed by reperfusion (5 h). Intravenous administration of SM-20550 before ischemia reduced the infarct size by approximately 30-70% in a dose-dependent manner, with a significant reduction in serum creatine phosphokinase activity. Similarly, intravenous administration of nicorandil before ischemia reduced the infarct size by 33% with a significant reduction in serum creatine phosphokinase activity. Moreover, intravenous administration of SM-20550 after ischemia resulted in a significant, approximately 20-40% reduction in the infarct size, but the administration of nicorandil after ischemia did not reduce the infarct size. These results indicate that SM-20550 reduced myocardial necrosis when administered either before or after ischemia. (C) 2000 Elsevier Science B.V. All rights reserved.