Comparative effects of carvedilol, losartan and their combination in preventing left ventricular remodeling after acute myocardial infarction in rats
Yang, Y.; Tang, Y.; Ruan, Y.; Li, Y.; Gao, R.; Chen, Z.
Zhonghua Nei Ke Za Zhi 40(12): 811-814
2001
ISSN/ISBN: 0578-1426 PMID: 16206669 Document Number: 528549
To compare the effects of carvedilol, losartan and their combination in preventing from left ventricular remodeling (LVRM) after acute myocardial infarction(AMI) in rats. Twenty-four hours after ligating left coronary artery, 100 surviving AMI female SD rats were randomly assigned to: (1) AMI control (n = 25), (2) carvedilol (1 mg x kg(-1) x d(-1)) (C1) (n = 25); (3) losartan (3 mg x kg(-1) x d(-1)) (L3)(n = 25); and (4) carvedilol (1 mg x kg(-1) x d(-1)) + losartan (3 mg x kg(-1) x d(-1)) (C1 + L3) (n = 25) groups. Sham-operated group (n = 17) were selected randomly as non-infarction control. After 4 weeks of therapy with the drugs by gastric gavage, hemodynamic studies were performed, then the rat hearts were fixed and pathologically analyzed. Exclusive of the rats with MI size < 35% or > 55%, complete data were obtained in 65 rats, which were comprised of AMI control (n = 13), C1 (n = 12), L3 (n = 13), C1 + L3 (n = 14) and sham-operated (n = 13) groups. There were no significant differences in MI size among the four AMI groups (45.8% - 46.7%, P > 0.05) . Compared with sham-operated group, Left ventricular (LV) end diastolic pressure (LVEDP), volume (LVV), weight (LVW), septal thickness (STh) and right ventricular weight (RVW) were all significantly increased (all P < 0.01 ) in AMI group, while the left ventricular pressure maximal rate of rise and fall (dp/dt) were significantly decreased (all P < 0.01). In comparison with AMI group, LVEDP, LVV, LVW, STh and RVW were all significantly decreased (all P < 0.01), while +/- dp/dt and +/- dp/dt/LVSP were significantly increased (P < 0.05 - 0.01) in all three therapy groups, with LVEDP decreasing more in the combination and L3 groups than in C1 group (P < 0.05 - 0.01) and STh decreasing more in the combination group than in C1 group (P < 0.01), but there were no significant differences in other variables among the three therapy groups. Carvedilol, losartan and their combination all can prevent from LVRM after AMI in rats, improve hemodynamics and LV function, with the combination superior.