羟苯氨酮保护大鼠心脏对抗心肌缺血-再灌注损伤

Protection of oxyphenamone on myocardium against ischemia-reperfusion injury in rat heart

目的 研究强心扩血管新药羟苯氨酮(oxyphenamone)对心肌缺血再灌注损伤的保护作用。方法 对离体或在体大鼠心脏,阻断冠脉前降支10min后行再灌注15min(离体)或30min(在体),形成心肌缺血再灌注损伤模型,从心电图、心肌酶学与心肌超微结构等方面观察药效。结果 羟苯氨酮(离体心脏灌流1 -10μmol·L-1,或静脉注射0 1-1 0mg·kg-1 )剂量依赖性地明显减少再灌注时的心律失常,对抗损伤所致心肌CPK,LDH与MDA的变化,减轻心肌超微结构损伤。结论 羟苯氨酮明显保护离体和在体大鼠心肌对抗冠脉阻断所致缺血再灌注损伤。

Aim To study the protective effect of oxyphenamone, a novel inodilator against myocardial ischemia-reperfusion injury. Methods A model of regional myocardial ischemia-reperfusion injury was established by ligating the left anterior desending coronary artery (LAD) in rat heart 10 min followed by reperfusion 15 min in vitro or 30 min in vivo. The protective effects of oxyphenamone were evaluated from the incidence of arrhythmia and the changes of myocardial creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) activities, malondialdehyde (MDA) content, and myocardial ultrastructure. Results In preparations of rat Langendorff hearts,infusion of oxyphenamone (1-10 μmol·L^-1) diminished the incidence of ventricular fibrillation, decreased the activities of CPK and LDH in coronary efflux, and antagonized the increase of MDA content in ischemic myocardium significantly. The ischemia-reperfusion injury in anesthetized rats produced severe ventricular arrhythmia, decrease of CPK in myocar￣dium, increase of CPK in serum, increase both of LDH and MDA both in myocardium and in serum,and severe damage of myocardial ultrastructure. Intravenous injection of oxyphenamone 0.1-1.0 mg·kg^-1 ~5 min before ischemia ameliorated dose-dependently ventricular arrhythmia, antagonized the changes of CPK, LDH and MDA in both myocardium and serum induced by ischemia-reperfusion. It even maintained these parameters at normal level. The effects were somewhat similar to that of verapamil 1.0 mg·kg^-1. Intravenous injection of oxyphenamone 0.5 or 1.0 mg·kg^-1 5 min after ligation of LAD also antagonized the ischemia-reperfusion induced changes in CPK, LDH and MDA in myocardium and serum significantly, and ameliorated the damage of myocardial ultrastructure markedly. The therapeutic effects of oxyphenamone were similar to that of propranolol 2.0 mg·kg^-1. Conclusion From the examination of ECG, myocardial enzymes and ultrastructure, it appears that oxyphenamone can protect myocardium against ischemia-reperfusion injury induced by occlusion of LAD both in vitro and in vivo.