KB-R7943对大鼠离体心脏缺血/再灌注的后适应保护作用

目的研究钠钙交换抑制剂KB-R7943对大鼠离体心脏缺血/再灌注损伤的后适应保护作用,探索给药的最佳时机。方法大鼠麻醉后,取心脏,置Langendorff灌流装置上以台氏液灌流,结扎冠状动脉左前降支制备大鼠离体心脏缺血(30min)/再灌注(120min)模型,监测心功能,测定心肌梗死面积。结果KB-R79431μmol·L-1于再灌注开始前1min至再灌注14min给药可改善心功能各项指标,心肌梗死面积较对照组缩小约77%(P<0·01),与钠氢交换抑制剂cariporide 1μmol·L-1及其与KB-R7943联合于再灌注早期给药产生的心肌保护作用差异无显著性。同浓度KB-R7943于再灌注全程灌流也具有一定的心肌保护作用,再灌注后期给药则对心肌缺血/再灌注损伤无保护作用。结论KB-R7943对大鼠离体心脏缺血/再灌注损伤具有药理性后适应保护作用,最佳给药时机为再灌注早期用药。

Postconditioning protective effect of KB-R7943 on cardiac ischemia/reperfusion injury in isolated rat heart

Aim This study aimed at investigating the postconditioning protective effect of KB-R7943 and the proper administration time on cardiac ischemia-reperfusion injury in isolated rat heart. Methods Rat heart was isolated quickly when the animal was anesthetized. With Langendorff perfusion, the left anterior descending coronary artery was ligated for 30 min, then released for 120 min in isolated rat heart. Left ventricular function (LVF) and the infarct size of left ventricle were determined. Result Compared with control, KB-R7943 at 1 μmol·L-1 perfused during the early period of the reperfusion prevented the post-ischemic depression of LVF, decreased the infarct size by 77 %(P<0.01). These protective effects were similar to those of the Na+/H+ exchange inhibitor, cariporide, and the concomitant use of KB-R7943 and cariporide given during the early period of reperfusion. 1 μmol·L-1 KB-R7943 produced protective effects on ischemia/reperfusion heart injury to a certain extent when perfused during the whole reperfusion period but had no protective effect on myocardium when given during the late period of reperfusion. Conclusion KB-R7943 had noticeable postconditioning protective effect on rat myocardium subjected to ischemia/reperfusion injury. The proper time for administration was the early period of reperfusion.