Effect of combined carvedilol and perindopril on cardiomyocyte apoptosis and Ca2+ 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 Ca2 + 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 Ca2+ 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 Ca2+ 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/dtmax,- dp/dtmax and the activity of SR Ca2+ 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 carvedilol and ACE inhibitor perindopril for myocardial infarction caused chronic heart failure more effectively improves the hemodynamic parameters and the SR Ca2 + pump activity,and decreases apoptosis index.