REDUCTION IN MYOCARDIAL INFARCT SIZE BY THE NEW POTASSIUM CHANNEL OPENER BIMAKALIM

We examined the effect of a new potassium channel opener, bimakalim, o n myocardial infarct size (IS) in dogs. Barbital-anesthetized dogs wer e subjected to 90 min of left circumflex coronary artery (LCX) occlusi on followed by 5-h reperfusion. Bimakalim (3 mug/kg bolus followed by 0.1 mug/kg/min intravenously, i.v.) was initiated either 15 min before LCX occlusion and continued throughout the experiments in one group o f animals or initiated 5 min before and throughout reperfusion in a se cond group. A third group of dogs received i.v. vehicle (control) 15 m inutes before LCX occlusion and throughout the remainder of the experi ment. IS was determined by triphenyltetrazolium histochemical staining , regional myocardial blood flow (RMBF) by the radioactive microsphere technique, and neutrophil migration by measurement of tissue myeloper oxidase (MPO) activity. Bimakalim reduced mean aortic blood pressure ( MBP, 25 mm Hg) during the occlusion and reperfusion periods in the gro up of dogs that received the drug throughout the experiment and reduce d in BP, during reperfusion when administered immediately before the r eperfusion period. In addition, bimakalim increased LCX coronary arter y blood flow (CBF) and increased regional myocardial blood flow (RMBF) primarily during reperfusion in both drug-treated groups, with the gr eatest increase to the subepicardial region. During occlusion, however , bimakalim had no effect on collateral blood flow to the ischemic reg ion. In all three groups, left ventricular (LV) mass, area at risk (AA R) mass, and percentage of the left ventricle at risk were similar. As compared with the control group, bimakalim reduced myocardial IS (31% reduction) as a percentage of the AAR when administered during both t he occlusion and reperfusion periods (32 +/- 1 vs. 46 +/- 3), although it had no beneficial effect when administered during the reperfusion period only (41 +/- 7). Bimakalim also reduced MPO activity in tissue bordering the infarcted region when administered by either treatment p rotocol. Bimaklim is effective at reducing myocardial IS in dogs. The mechanism of this beneficial effect may be a result of decreased oxyge n consumption during ischemia and/or a direct cardioprotective action secondary to myocardial K(ATP) channel activation.