흰쥐에서의 관상동맥 결찰/재관류도 유도된 심근경색에 대한 칼륨통로 개방제 KR-30450의 약리학적 효과

The Pharmacological Effects of KR-30450, A Potassium Channel Opener on Coronary Artery Occlusion/Reperfusion-Induced Myocardial Infarction in the Rat

The pharmacological effects of benzopyran potassium channel openers (lemakalim, KR-30450 and KR-30818) on the occlusion/reperfusion-induced myocardial infarction were investigated. In anesthetized rats, subjected to 45-min occlusion of the left anterior descending coronary artery (LAD) followed by 90-min reperfusion, the infarct size was measured by calculating the ratio of infarct zone to area at risk (IZ/AAR) with the Evans blue/TTC technique. Rats were intravenously given vehicle (1% DMSO), lemakalim, KR-30450, and KR-30818 alone or in combination with a selective KATP blacker glibenclamide, 30 min prior to coronary occlusion. Compared to vehicle, lemakalim (30 mcg/kg i.v.), the active enantiomer of cromakalim, had a tendancy to decrease infarct size. KR-30450(30 mcg/kg, i.v.). the newly synthetized potassium channel openers (PCOs), caused a reduction of infarct size (from 70+/-4%to 57+/-5%). but KR-30818 (30mcg/kg, i.v.), a metabolite of KR-30450. did not modify infarct size. It seem ed likely that glibenclamide (0.3mcg/kg, i.v.), given in combination, reduced the effects of these PCOs, especially KR-30450 (30mcg/kg, i.v.) on the infarct size. These results indicate that. in the coronary occluded rat model of ischemia, lemakalim and KR-30450 may exert cardioprotective activity through a reduction of infarct size, the effect being considered related to the opening of KATP channel.