Comparison of metoprolol with low, middle and high doses of carvedilol in prevention of postinfarction left ventricular remodeling in rats.

Abstract

The dose-related beneficial effects of carvedilol on survival in heart failure have been verified, however, the effects on left ventricular remodeling (LVRM) after acute myocardial infarction (AMI) have not been defined. This experiment was designed to compare the effects of low, middle, and high doses of carvedilol (LD-car, MD-car, and HD-car) with metoprolol (Meto) in preventing postinfarction LVRM in rats. After the left coronary artery was ligated, 177 surviving female SD rats were randomized to: (1) AMI (n = 35), (2) LD-car (0.1 mg x kg(-1) x d(-1), n = 35), (3) MD-car (1 mg x kg(-1) x d(-1), n = 35), (4) HD-car (10 mg x kg(-1) x d(-1), n = 37) and (5) Meto (2 mg x kg(-1) x d(-1), n = 35) groups. A sham-operated group (n = 16) was also randomly selected. Gastric gavage therapy lasted for 4 weeks. After hemodynamic studies, the rat hearts were fixed and pathologically analyzed. After exclusion of rats which died or had an infarct size < 35% or > 55%, complete data were obtained in 69 rats, comprising AMI (n = 11), LD-car (n = 11), MD-car (n = 12), HD-car (n = 12), Meto (n = 11) and sham (n = 12) groups. There were no significant differences in MI size among the five AMI groups (44.5-46.3%, all P > 0.05). Compared with the sham group, left ventricular (LV) end-diastolic pressure (LVEDP), volume (LVV), weight (LVW) and septal thickness (STh) were all significantly increased, while +/- dp/dt was significantly decreased in the AMI group (all P < 0.001). Compared with the AMI group, heart rate was significantly decreased in all except the LD-car treatment groups (P < 0.05-0.01); LVEDP, LVV, LVW, and STh in the four treatment groups were also significantly decreased (P < 0.05-0.001) except LVW and STh in the Meto group (both P > 0.05)(LVEDP: 14.5 +/- 4.6, 12.1 +/- 2.4, 7.7 +/- 1.9 and 13.0 +/- 6.7 mmHg vs 24.1 +/- 5.2 mmHg; LVV: 0.82 +/- 0.1, 0.79 +/- 0.1, 0.72 +/- 0.1 and 0.72 +/- 0.1 mL vs 0.92 +/- 0.1 mL; LVW: 666 +/- 57, 622 +/- 70, 589 +/- 57 and 699 +/- 78 mg vs 730 +/- 79 mg; STh: 1.14 +/- 0.12, 1.18 +/- 0.21, 1.19 +/- 0.15 and 1.35 +/- 0.20 mm vs 1.33 +/- 0.29 mm; P < 0.05-0.001); while +/- dp/dt was significantly increased in each therapy group (P < 0.05-0.001). There were dose-effect relations in LVEDP and LVV in the carvedilol groups. The results indicate that low, middle and high dose carvedilol has dose-related effects in the prevention of postinfarction LVRM with respect to volume expansion and segmental hypertrophy in rats, while metoprolol prevents only LV dilatation but not hypertrophy.