Aldosterone antagonists attenuate myocyte apoptosis and prevent ventricular remodeling in post-infarct rat hearts

Abstract

Background: Aldosterone antagonists have been reported to prevent ventricular remodeling after myocardial infaction (MI) via its action to extracellular matrix (ECM). However, it remains largely unknown whether aldosterone antagonists directly attenuate myocyte loss in remodeling process. This study examined whether aldosterone antagonists prevent myocyte apoptosis and improve post-infarct ventricular remodeling. Methods and Results: MI was achieved by permanent occlusion of left coronary artery. Administration of spironolactone (Sp: 100mg/kg/day) was started on the first day after MI. Sprague-Dawley rats were divided into four groups; 1)Sham group, 2)Sham+Sp group, 3)MI group, 4)MI+ Sp group. Systolic BP was not significantly different among 4 groups. Echocardiographic parameters (LVDd, %FS) were not significantly different between MI group and MI+Sp group on the 2nd and 7th day. In contrast, echocardiographic parameters, hemodynamic parameters (+dp/dt, -dp/dt, LVEDP),and collagen accumulation quantitated by Masson's Trichrome staining were significantly improved in MI+ Sp group on the 14th day, compared to MI group. Moreover, the percentage of myocyte apoptosis evaluated by TUNEL assay was significantly decreased in MI+Sp group on the 2nd and 7th days, compared to MI group. Conclusions: The present study demonstrates that, in addition to the effect on ECM, early administration of aldosterone antagonists can inhibit myocyte apoptosis and prevent post-infarct ventricular remodeling, which may account for the important clinical efficacy of aldosterone antagonists against acute MI.