Effects of carvedilol at different dose on oxidative stress and cardiac myocyte apoptosis in heart failure rats

AIM: To study the effects and mechanisms of carvedilol (CAR) in different doses on cardiac myocyte apoptosis during congestive heart failure (CHF) subsequent to myocardial infarction in rats. METHODS: An animal model of myocardial infarction(MI) was used which was induced by the left coronary artery ligation in male Waistar rats. Twenty-seven rats with MI were divided into three groups, the untreated experimental group ( n =10), the group treated with CAR in a higher dose for seven weeks right after the operation (HCAR group, 60 mg·kg -1·d -1, n =10) and the group treated in a lower dose (LCAR group, 6 mg·kg -1·d -1, n =7). The sham-operated rats served as the control ( n =10). Hemodyanmic parameters, cardiac myocyte apoptosis, the concentration of malondialdehyde (MDA) and total antioxidation capacity (TAOC) were investigated eight weeks after the operation. RESULTS: CAR either in a higher and or in a lower dose improved heart function and decreased apoptosis index and the concentration of MDA, increased the TAOC level in rats with MI. The number of myocytes apoptosis was significantly lower (4.6%±1.1% vs 8.0%±2.0%) and the TAOC level was markedly higher(1.92±0.20 U· mg -1 vs 1.59±0.12 U· mg -1) in the HCAR group than in the LCAR group. CONCLUSION: CAR can effectively decrease cardiomyocyte apoptosis, and can prevent and cure CHF. The effect of CAR is dose-dependent, which may be due to its maintenance of protective antioxidants in myocardium.