Hypercholesterolemia exacerbates ventricular remodeling in the rat model of myocardial infarction

Background: Detrimental left ventricular (LV) remodeling is exacerbated in hypercholesterolemic patients with myocardial infarction; however, this could result from either larger infarcts or more extensive remodeling itself in this population. Therefore, we sought to investigate whether high cholesterol feeding exacerbates LV remodeling and heart failure in rats with myocardial infarction independently from its influence on infarct size. Methods and Results: Myocardial infarction was induced by permanent ligation of left coronary artery in rats fed normal and high-cholesterol diet and the animals were followed for 8 weeks. Hypercholesterolemic rats were matched with normocholesterolemic animals for infarct size 24 hours after infarction and exhibited more pronounced LV dilation at 8 weeks after infarction (LV systolic/diastolic diameter 8.1 +/- 0.2/10.2 +/- 0.3 versus 6.7 +/- 0.2/8.9 +/- 0.2, respectively, measured by echocardiography, P < .05 each). Pressure-volume curves obtained in isolated Langendorff-perfused hearts revealed higher diastolic LV volumes (1677 +/- 102 versus 1385 +/- 46 mu L/kg body weight, P < .05) and hemodynamic examination demonstrated higher LV end-diastolic pressure (21.8 +/- 0.7 versus 18.7 +/- 1.0 mm Hg, P < .05) in hypercholesterolemic rats compared with normocholesterolemic animals. Conclusion: In a rat model of myocardial infarction, LV remodeling and heart failure are more pronounced in rats fed high-cholesterol diet in comparison to animals fed normal chow. This effect is independent from effect of hypercholesterolemia on infarct size.