K_(ATP)通道开放剂KRN2391对离体大鼠心肌梗死范围的影响

Effects of A K_(ATP) Channel Opener KRN 2391 on Myocardial Infarct Size of Isolated Rat Heart

目的 :探讨 ATP敏感性钾通道 (KATP通道 )开放剂 KRN2 391(KRN)对离体大鼠心功能及心肌梗死范围的影响。方法 :用 L angendorff装置 ,观察不同浓度 KRN对冠脉灌流量及左心室压力的影响。应用离体大鼠双冠脉分别灌流模型 ,行 45 m in缺血及 2 h再灌注 ,观察药物对心肌梗死面积的影响。结果 :KRN在达到 1μmol/L 浓度后冠脉灌流量明显增加 ,达 2 0 μm ol/L 时左室收缩压明显下降 ,用 1μmol/L KRN在缺血前 +缺血中或缺血时单独应用均可缩小心肌梗死范围 ,此作用可被格列本脲完全阻断 ,而单独应用格列本脲未见明显变化。结论 :KATP通道开放剂 KRN有明显冠脉扩张作用 ,大剂量应用可降低心脏收缩功能 ,用不影响心功能的剂量可减少缺血后心肌梗死范围 ,此作用与 ATP敏感性钾通道开放有关。

Objective:Our purpose was to study the influence of K ATP channel opener KRN2391(KRN) on cardiac function and myocardial infarct size of isolated rat heart. Methods:We studied the effect of KRN in different concentration on the flow of coronary artery and the pressure of left ventricle with the langendorff apparatus. The effect of KRN on infarction size was observed on the isolated rats double coronary arteries perfusion model. Results:KRN(1 μmol/L) increased the flow of coronary artery obviously. When the concentration reached 20 μmol/L , KRN decreased the systolic pressure of left ventricle. KRN(1 μmol/L) reduced the myocardial infarct size when it was administrated during both preischemic and ischemic period or only during ischemic period. This effect could be completely blocked by glibenclamide, but glibenclamide administrated alone had no obvious effect on infarct size. Conclusion:K ATP channel opener KRN could dilate coronary artery obviously. KRN decreased cardiac systolic function when administrated at high doses. KRN decreased the infarct size after ischemia when administrated at doses that can not affect cardiac function. These effects were related with the opening of K ATP channel.