缺血后处理与缺血预处理联合应用对长时程心肌缺血/复灌损伤的保护作用

目的:研究缺血后处理与缺血预处理联合应用对长时程缺血引起的缺血/复灌(I/R)损伤的改善作用及其作用机制。方法:采用离体大鼠心脏Langendorff灌流方法,全心停灌60 m in,复灌120 m in复制长时程心肌缺血的I/R模型,测定心室动力学指标和复灌各时间点冠脉流出液中乳酸脱氢酶(LDH)含量。实验结束测定心肌组织form azan含量的变化。结果:在长时程心肌缺血的I/R模型中,缺血后处理能提高心肌细胞的form azan含量,降低复灌期间冠脉流出液中LDH含量,但对心室血流动力学无明显改善。缺血后处理与缺血预处理联合应用不仅能提高心肌细胞的form azan含量,降低复灌期间冠脉流出液中LDH含量,而且能明显改善心室血流动力学各项指标。钙激活钾通道阻断剂pax illine减弱了两者联合应用的作用。结论:在大鼠离体心脏灌流模型上,缺血后处理与缺血预处理联合应用产生加强的心肌保护作用,其机制可能与激活钙激活钾通道的开放有关。

Cardioprotective effect of ischemic postconditioning and preconditioning against prolonged ischemia and reperfusion indued injury in isolated rat heart

Objective: To explore the cardioprotection effect of co-treatment with ischemic postconditioning and preconditioning in ischemia/reperfusion(I/R) injury and the related mechanism.Methods: Male Sprague-Dawley rats were used for Langendorff isolated heart perfusion.The hearts were subjected to global ischemia for 60 min followed by 120 min of reperfusion.The cardiomyocyte viability was measured by MTT-formazan method,and the cardiac injury was evaluated by the levels of lactate dehydrogenase(LDH) in the coronary effluent.Ventricular hemodynamic parameters were also measured.Results: In 60 min of ischemia and 120 min of reperfusion group,ischemic postconditioning increased formazan content,reduced LDH release,but hemodynamic parameters did not improved.Co-treatment with ischemic postconditioning and preconditioning during the prolonged ischemia further improved the hemodynamic parameters.The calcium activated potassium channel antagonist paxilline attenuated the effect of co-treatment with ischemic postconditioning and preconditioning.Conclusion: Ischemic postconditioning and preconditioning may synergically protect myocardium from severe ischemia injury,which may be related to calcium-activated potassium channel.