Eplerenone in combination with ACE inhibitor reduces post-myocardial infarction LV remodeling and maintains function

Abstract

Effects of the selective aldosterone receptor antagonist, eplerenone, on LV remodeling were examined 28 days after myocardial infarction (MI) in S-D rats. Rats underwent either sham or coronary ligation and were randomized as SHAM+vehicle (VEH), MI+VEH, MI+eplerenone (EPL), MI+enalapril (ACEi), or MI+EPL in combination with ACEi for 28 days of treatment. Ventricular remodeling was manifested in MI rats as marked increases in left ventricular end diastolic volume (EDV), left ventricular end diastolic pressure (EDP), and a significant shift in the diastolic pressure/volume relationship. Myocardial function was also impaired as evidenced by reduced +dP/dt in MI+VEH treated rats. Neither EPL alone, nor ACEi alone significantly impacted EDV, EDP, or the pressure/volume relationship. In contrast, animals treated with combination therapy showed a significant attenuation of remodeling based on EDV, EDP and passive pressure/volume data compared with MI-VEH animals. Eplerenone treatment alone reduced thinning of the infarcted LV free wall, however, animals treated with ACEi or combination therapy did not show a significant reduction in wall thinning. Treatment with EPL, ACEi, or combination therapy significantly reduced plasma ANP levels compared to animals treated with vehicle. No significant differences in body weight, heart weight, mean arterial blood pressure, +dP/dt, collagen volume fraction, or infarct size were demonstrated among the groups. Thus, administration of EPL in combination with ACEi diminished LV remodeling and maintained LV function after MI in rats. (See Table)