Early angiotensin converting enzyme inhibitor therapy enhances the benefits of late coronary artery reperfusion on infarct expansion.

Abstract

Individually, both late reperfusion and early angiotensin converting enzyme (ACE) inhibitor treatment prevent infarct expansion after acute myocardial infarction. To examine the effect and mechanism of early post-myocardial infarction ACE inhibitor treatment, when used in combination with late coronary artery reperfusion, on infarct expansion. Sprague-Dawley rats underwent 8 h of coronary occlusion followed by permanent reperfusion. The treatment group received enalapril, started 1 h after coronary occlusion and continued for 13 days. A control group received placebo. Two weeks after acute myocardial infarction, hemodynamic, morphometric and histologic analyses were performed. Hemodynamic parameters were similar in both groups (P = NS). Infarct size was similar in the ACE inhibitor and placebo treatment groups (44 +/- 4% compared with 39 +/- 4%, P = NS). Septal thickness was also similar in the two groups (2.8 +/- 0.3 mm compared with 2.7 +/- 0.3 mm, P = NS). The ACE inhibitor-treated group had thicker infarcts than those in the placebo-treated group (0.93 +/- 0.07 mm compared with 0.76 +/- 0.04 mm, P < 0.05) and these infarcts were less expanded (expansion index 1.17 +/- 0.12 compared with 1.57 +/- 0.12, P < 0.05). ACE inhibitor treatment was associated with hypertrophy of viable myocytes within the scar compared with placebo treatment (cell diameter 11.1 +/- 0.5 microns compared with 8.9 +/- 0.4 microns, P < 0.01). Early post-myocardial infarction ACE inhibitor treatment enhances the benefits of late coronary reperfusion on infarct expansion. The benefits may be related to hypertrophy of still-viable myocytes within the infarcted zone.