Effects of Carvedilol at different dose on cardiac myocyte apoptosis and apoptosis-associated gene during heart failure subsequent to myocardial infarction in rats

Objective:To study the effects and mechanisms of carvedilol (CAR) at different dose on cardiac myocyte apoptosis during congestive heart failure (CHF) subsequent to myocardial infarction (MI) in rats.Methods:Using a animal model of MI, induced by the left coronary artery ligation in male waistar rats, hemodyanmics parameters, cardiac myocyte apoptosis, the expression of mRNA of Fas, FasL and Bcl 2 were investigated in the untreated experimental group (MI group) at 8 week after operation and treated experimental groups in which rats were treated with CAR at a higher dose (HCAR group, 60 mg.kg -1 .day -1 ,n=10) and at a lower dose (LCAR group, 6 mg.kg -1 .day -1 , n=10) for 7 weeks since 1 week after operation. The sham operated rats served as control (SH group, n=10).Results:Both of CAR at a higher and at a lower dose can improved heart function and decrease apoptosis index in rats with MI. The number of myocytes apoptosis and the level of mRNA of Fas were significantly lower and Bcl 2 was markedly higher in HCAR group than those in LCAR group.Conclusion:CAR can effectively decrease myocardiocyte apoptosis, prevent and cure CHF. The effect is dose dependent, associates with changes of the expression of apoptosis associated gene.