Early angiotensin converting enzyme inhibitor therapy after experimental myocardial infarction prevents left ventricular dilation by reducing infarct expansion: a possible mechanism of clinical benefits

Objective To examine the effects of early angiotensin-converting enzyme (ACE) inhibitor therapy after myocardial infarction on infarct expansion in an experimental rat model. Background ACE inhibitor therapy within 24 h of acute myocardial infarction (AMI) reduces mortality by unknown mechanism(s). Methods Rats underwent permanent coronary artery occlusion. A treated group received enalapril (1.9 +/- 0.2 mg/kg) daily in drinking water beginning 2 h after coronary artery occlusion, a time too late to reduce infarct size. Rats were sacrificed 2 days or 2 weeks after myocardial infarction. Hearts were arrested and fixed at a constant pressure, then sectioned and photographed for morphometric analysis. Results Infarcts in the control group expanded between 2 days and 2 weeks after myocardial infarction (expansion index 0.7 +/- 0.1 versus 2.5 +/- 0.4, P < 0.05). However, infarct expansion remained unchanged in the enalapril group between 2 days and 2 weeks after myocardial infarction (expansion index 0.8 +/- 0.1 versus 1.3 +/- 0.1, NS). Two weeks after myocardial infarction, the enalapril group had fewer expanded infarcts than the control group (expansion index 1.3 +/- 0.1 versus 2.5 +/- 0.4, P < 0.05). While left ventricular volume increased in the control group between 2 days and 2 weeks after myocardial infarction (0.17 +/- 0.01 ml versus 0.36 +/- 0.03 ml, P < 0.05), it remained constant in the enalapril group (0.22 +/- 0.02 ml versus 0.25 +/- 0.03 ml, NS). Two weeks after myocardial infarction, the left ventricles were larger in the control group than in the enalapril group (0.36 +/- 0.03 ml versus 0.25 +/- 0.03 ml, P < 0.05). Conclusions Treatment with enalapril initiated 2 h after AMI prevented left ventricular dilation by limiting infarct expansion. This may explain the mechanism by which ACE inhibitor therapy started within 24 h of an AMI improves survival 5-6 weeks after infarction. Coronary Artery Dis 9:815-821 (C) 1998 Lippincott Williams & Wilkins.