Direct Effects of 3 Combinations of Enalapril, Metoprolol, and Spironolactone on Cardiac Remodeling in Dilated Cardiomyopathic Hamsters

Abstract

In congestive heart failure, enalapril (E), metoprolol (M), and spironolactone (S) improve survival. Their direct effects on cardiac remodeling, when administered in combination, remain to be assessed. One hundred and five cardiomyopathic hamsters were divided into 5 groups (control, E, E-M, E-S, E-M-S) and treated from 150 to 240 days of age (E: 3 mg/kg, M: 1 mg/kg, S: 20 mg/kg). Cardiac and systemic hemodynamics, and cardiac remodeling were investigated. There was no difference between groups on blood pressure. Compared with C, both S-treated groups significantly increased cardiac index (E-S: +49%; E-M-S: +46%). Compared with C, E significantly decreased left ventricular (LV) cavity area (-10%). Compared with E, all combinations significantly decreased LV cavity area (E-M: -13%, E-S: -22%, E-M-S: -19%) and right ventricular (RV) collagen density (E-M: -18%, E-S: -30%, E-M-S: -34%), and the tri-therapy significantly decreased LV collagen density (-18%). Compared with bi-therapies, the tri-therapy significantly decreased LV (-19% vs. E-M, -16% vs. E-S) and RV (-20% vs. E-M) collagen densities. At subdepressor doses, both bi-therapies induced similar effects on myocardial remodeling, enhancing the effects of E on LV cavity area and reducing RV collagen density. Compared with bi-therapies, the tri-therapy induced additional effects on LV and RV collagen densities.