Effects of captopril therapy after late reperfusion on left ventricular remodeling after experimental myocardial infarction

Abstract

Reperfusion that is too late to salvage ischemic myocardium reduces early infarct expansion, and captopril therapy favorably alters long-term left ventricular remodeling. To study whether the beneficial effects of these two therapies are additive, we examined the effects of captopril therapy after late reperfusion on left ventricular remodeling after acute myocardial infarction. Female Sprague-Dawley rats ( n = 67) were randomly assigned to one of four groups: group 1, sham surgery and no treatment; group 2, left coronary artery ligation and no treatment (myocardial infarction [r MI]; group 3, left coronary artery ligation, reperfusion 2 hours later, and no treatment (late reperfusion [LR]); and group 4, left coronary artery ligation, reperfusion 2 hours later, and captopril treatment (LR-Cap). Captopril therapy (2 gm/L of drinking water) was begun in the LR-Cap group in the immediate post-operative period and continued for 20 days. Twenty-one days postoperatively, hemodynamic measurements were made before and after volume loading. The rats were killed, their hearts were removed, and passive pressure-volume curves were obtained. The hearts were then fixed at a constant pressure for morphometric analysis. Compared with the MI group, the LR group had a lower expansion index and a higher thinning ratio. There were no differences in hemodynamics, left ventricular volumes, or other morphometric indexes between the two groups. Compared with the MI and LR groups, the LR-Cap group had lower peak left ventricular end-diastolic pressure, lower left ventricular volume, lower left and right ventricular weights, and a leftward shift of pressure-volume curves. There were no differences in the expansion index or the thinning ratio between the LR and LR-Cap groups. Thus captopril therapy after late reperfusion additionally improves hemodynamics, attenuates left ventricular cavity dilation, attenuates an increase in left and right ventricular weights, and alters the pressure-volume relationship of the left ventricle.