Comparative effects of cilazapril,carvedilol and their combination in preventing from left ventricular remodelling after acute myocardial infarction in rats

Objectives

To compare the effects of cilazapril, carvedilol and their combination in preventing left ventricular remodelling (LVRM) after acute myocardial infarction (AMI) in rats.

Methods

Twenty-four hours after left coronary artery ligation, 100 surviving AMI female Sprague-Dawley rats were randomly assigned to: (1) AMI control (n=25); (2) cilazapril (Cila, 1 mg/kg/day) (n=25); (3) carvedilol (Car, 1 mg/kg/day) (n=25), and (4) cilazapril (1 mg/kg/day)+ carvedilol (1 mg/kg/day) (combination) (n=25) groups. A sham-operated group (n=17) was selected randomly as a non-infarction control. After four weeks of therapy with the drugs given by gastric gavage, haemodynamic studies were performed, following which the rat hearts were fixed and pathologically analysed. Rats with MI size <35% or >55% were excluded. Complete data were obtained in 64 rats, comprising AMI control (n=13), Cila (n=12), Car (n=12), Combination (n=14), and sham-operated (n=13) groups.

Results

There were no significant differences in MI size between the four AMI groups (45.2—46.7%, p>0.05). Compared with the 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<0.001) in the AMI group, while the LV pressure maximal rate of rise and fall (±dp/dt) was significantly decreased (all p<0.001). In comparison with the AMI group, LVEDP, LVV, LVW, STh and RVW were all significantly decreased, while ±dp/dt was significantly increased in the Cila, Car, and combination groups, with LVEDP and STh decreasing more in the combination group than in the two monotherapy groups (p<0.05—0.01). There were no significant differences in other variables between the three therapy groups.

Conclusions

Cilazapril, carvedilol and their combination are all effective in preventing LVRM after AMI in rats, and in improving haemodynamics and LV function, with the combination therapy being superior to monotherapy in all respects.