卡维地洛与培哚普利联合干预心肌梗死后心力衰竭对心肌细胞凋亡和肌浆网Ca^2＋泵活性的影响

目的：探讨β受体阻滞剂卡维地洛与血管紧张素转换酶抑制剂培哚普利联合干预心肌梗死（MI）后慢性心力衰竭对心肌细胞凋亡和肌浆网（SR）Ca^2＋泵活性的影响及意义．方法：通过结扎大鼠左冠脉建立慢性心力衰竭模型，术后1wk开始分别给予卡维地洛6mg／（kg·d）]、培哚普利4ms／（kg·d）]、特拉唑嗪2mg／（kg·d）]、卡维地洛6mg／（kg·d）]及培哚普利4mg／（kg·d）]联合干预9wk，对照观察血流动力学、左室心肌细胞凋亡、SR Ca^2＋泵活性的变化．结果：与假手术组（SH组）相比，心力衰竭组（HF组）左室舒张末压（LVEDP）显著升高（P〈0．01），＋dp／dtmax,-dp／dtmax显著降低（P〈0．01），心肌细胞凋亡指数增高，SR Ca^2＋泵活性显著降低（P〈0．01）．卡维地洛、培哚普利单独及联合干预均降低LVEDP（P〈0．01），升高＋dp／dtmax，-dp／dtmax（P〈0，01），使左室心肌细胞凋亡比例降低，并使左室心肌SR Ca^2＋泵活性增高（P〈0．01），联合干预变化更明显（P〈0．01）．特拉唑嗪组（Ter组）对上述指标无明显影响．结论：卡维地洛和培哚普利长期联合干预MI后慢性心力衰竭，能够改善血流动力学，抑制心肌细胞凋亡，并改善心肌SR Ca^2＋泵活性，优于任何单一药物干预．

Effect of combined carvedilol and perindopril on cardiomyocyte apoptosis and Ca~(2+) pump activity of myocardial sarcoplasmic reticulum in rats with myocardial infarction caused chronic heart failure

AIM： To study the effects of combined administration of carvedilol and perindopril on cardiomyocyte apoptosis and Ca^2＋ pump activity of myocardial sarcoplasmic reticulum （SR） for the prevention and treatment of chronic heart failure （HF） caused by myocardial infarction. METHODS： After the rat model of chronic heart failure was established by ligating the left coronary artery, the rats were divided into 4 groups： group treated with carvedilol 6 mg/（ kg · d）], group treated with ACE inhibitor perindopril 4 mg/（ kg · d）], group treated with α1-adrenergic receptor blocker terazosin 2 mg/（ kg · d） ], and group treated with a combined administration of carvedilol 6 mg/（ kg · d）] and perindopril 4 mg/（ kg · d）] for 9 weeks respectively. Another 12 rats were employed as control with sham operation （group SH）. Hemodynamic parameters, apoptosis index and the activity of SR Ca^2＋ pump were determined. RESULTS. Compared with those in shame-operated group, the left ventricular end-diastolic pressure （LVEDP） and apoptosis index increased （P 〈0.01 ） in HF groups, while ＋ dp/dtmax, - dp/dtmax and the activity of SR Ca^2＋ pump significantly decreased （P 〈 0.01 ）. Both monotherapy and combined therapy of carvedilol and perindopril attenuated the increase in LVEDP and apoptosis index, but increased ＋ dp/dtmaxdp/dtmax, and the activity of SR Ca^2＋ pump （P 〈 0.01 ）. Better effect was observed in group of combined treatment compared with that in group of monotherapy. No obvious effect was observed in the group of Terazosin. CONCLUSION： Compared with monotherapy, long-term combined treatment with β-blocker earvedilol and ACE inhibitor perindopril for myocardial infarction caused chronic heart failure more effectively improves the hemodynamic parameters and the SR Ca^2＋ pump activity, and decreases apoptosis index.