Low-dose combination therapy with metoprolol and captopril for congestive heart failure in mice

We assessed the therapeutic efficacy of a low-dose combination of metoprolol and captopril given orally to C3H/Hej mice that developed dilated and hypertrophied hearts after being inoculated with the encephalomyocarditis virus. Mice were randomly assigned to one of six 8-week oral regimens: 1 mg/kg/day of metoprolol (group 1); 10 mg/kg/day of metoprolol (group 2); 1.2 mg/kg/day of captopril (group 3); 12 mg/kg/day of captopril (group 4); 1 mg/kg/day of metoprolol plus 1.2 mg/kg/day of captopril (group 5); or distilled water (control group). Group 4 exhibited a significantly lower survival rate and body weight than the control group (p < 0.01). Survival rates and body weights were similar in groups 1, 2, 3, 5, and the control group. Low-dose metoprolol plus captopril is superior to low-dose metoprolol, high-dose metoprolol, and low-dose captopril with regard to heart weight and the heart weight/body weight ratio. The left and right ventricular cavity dimensions as well as myocardial necrosis, calcification, and fibrosis were less severe in groups 4 and 5 than in the control group. The left ventricular free wall showed significantly more thinning in group 4 than in the control group (p < 0.01). Our results show that the administration of low-doses of metoprolol and captopril given in combination was effective in this animal model of congestive heart failure and was associated with a reduction in biventricular cavity dimensions and myocardial necrosis.