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.
Ali
S M
SM
Department of Medicine, Bronx-Lebanon Hospital Center, New York 10457, USA.
Brown
E J
EJ
Nallapati
S R
SR
Alhaddad
I A
IA
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D004656:Enalapril / Q000627:therapeutic use*; D005260:Female; D017379:Hypertrophy, Left Ventricular / Q000517:prevention & control*; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D020257:Ventricular Remodeling / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril