Reduction by ATP-sensitive potassium channel opener, YM934, of experimental myocardial infarct size in anesthetized dogs

The present study was undertaken to examine whether the ATP-sensitive potas sium channel opener, YM934, would be effective in reducing infarct size in a model of myocardial infarction in anesthetized dogs. For this purpose the effects of nifedipine, a calcium channel blocker, and hydralazine, a vasod ilator with unknown mechanisms, were also investigated for comparison. Seve re, irreversible myocardial injury was produced by a 90-min occlusion of th e proximal left anterior descending coronary artery followed by 5 h of repe rfusion. Infusion of YM934 (0.1 mu g/kg/min i.c.) during the last 15 min of pre-ischemia reduced the myocardial infarct size and attenuated the releas e of creatine kinase MB eluted from the hearts without alteration in hemody namic parameters including regional myocardial blood flow. In contrast, the other vasodilators, hydralazine and nifedipine, did not reduce myocardial infarct size under the same coronary vasodilatory conditions, These observa tions indicate that intracoronary YM934 is cardioprotective and that this e ffect is independent of alterations in regional myocardial blood flow.