Effect of left ventricular unloading with captopril on remodelling and function during healing of anterior transmural myocardial infarction in the dog

Abstract

Objective: To determine whether left ventricular (LV) unloading with captopril between two days and six weeks during healing after transmural anterior acute myocardial infarction might prevent further LV remodelling and preserve function in the canine model.

Design: Serial LV topographic and functional parameters (two-dimensional echocardiograms) and hemodynamics over six weeks and scar topography (planimetry) and collagen (hydroxyproline) at six weeks were measured in 34 chronically instrumented dogs; 24 with anterior transmural acute myocardial infarction (coronary artery ligation and collateral obliteration) that had been randomized at two days post infarction to therapy with oral 50 mg bid placebo (n = 12) or captopril (n = 12) for six weeks, and 10 with sham infarction.

Main results: At six weeks, captopril and placebo groups had similar scar mass (7.7 versus 8.1% LV), infarct hydroxyproline and transmurality but the captopril group showed significantly less (P less than or equal to 0.05) infarct expansion and thinning, cavity dilation, epicardial and endocardial bulge. Between two days and six weeks, captopril decreased mean left atrial and arterial pressures compared to placebo or sham. Echocardiograms at two days showed similar LV asynergy, ejection fraction, infarct expansion and thinning with placebo and captopril. In contrast, echocardiograms between two days and six weeks showed that: further expansion and thinning occurred with placebo but not captopril; LV volumes increased with placebo but decreased with captopril; total LV asynergy was unchanged with placebo but decreased with captopril; and LV ejection fraction was unchanged with placebo but increased with captopril. At six weeks, LV ejection fraction was 10% higher (45 versus 35%, P less than 0.001) and LV aneurysm was less frequent (33 versus 100%, P less than 0.005) with captopril compared to placebo.

Conclusions: Chronic LV unloading with captopril therapy during healing after canine transmural anterior acute myocardial infarction limits further remodelling, decreases aneurysm formation and improves function.