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Effects of late coronary artery reperfusion on left ventricular remodeling persist for 10 weeks after experimental rat myocardial infarction and are associated with improved survival

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Abstract

Objective: To test the hypothesis that coronary artery reperfusion performed too late to reduce infarct size improves survival by altering left ventricular remodeling and preventing progressive left ventricular dilation.Background: Several clinical trials have suggested that late coronary artery reperfusion without infarct size reduction is associated with a survival benefit. Although the mechanism is not known, survival benefits could be related to decreased infarct expansion associated with late coronary artery reperfusion. Decreased infarct expansion results in decreased left ventricular volume, and the resulting decreased wall stress could prevent or attenuate progressive left ventricular dilation and improve survival.Methods: Rats (n=84) were randomized to undergo sham operation, permanent left coronary artery ligation, or 2 hours of left coronary artery ligation followed by reperfusion. Ten weeks later, hemodynamic measurements were made before and after volume loading. The rats were killed, the hearts were removed, and passive pressurevolume curves were obtained. The hearts were fixed at a constant pressure and analyzed morphometrically.Results: When examined 10 weeks after experimental myocardial infarction, late reperfusion's effects on left ventricular remodeling resulted in reduced left ventricular volume when compared to hearts with infarcts supplied by a permanently occluded coronary artery (1.9 ± 0.1 ml/kg vs. 2.1 ± 0.2 ml/ kg; p < 0.01). Although there was a trend toward less thinning (0.95 ± 0.13 mm vs. 1.00 ± 0.10 mm; p=NS) and less expansion (2.3 ± 0.4 vs. 2.8 ± 0.9; p=NS) in reperfused hearts compared to hearts with a permanently occluded coronary artery, changes in infarct shape 10 weeks after infarction were not significantly different. Reperfusion's beneficial effects on remodeling of noninfarcted myocardium were associated with improved survival. Mortality was higher in the permanently occluded rats than in the reperfused rats (35% vs. 12%; p < 0.05).Conclusion: Late coronary artery reperfusion has a beneficial effect on remodeling of noninfarcted myocardium that results in reduced left ventricular volume in rat hearts examined 10 weeks after infarction. These beneficial effects on left ventricular remodeling are associated with improved survival.

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Mallavarapu, C., Ross, P.L., Langenback, E.G. et al. Effects of late coronary artery reperfusion on left ventricular remodeling persist for 10 weeks after experimental rat myocardial infarction and are associated with improved survival. J Thromb Thrombol 1, 55–62 (1994). https://doi.org/10.1007/BF01061997

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