Postinfarct remodeling causes insulin resistance and defects in substrate oxidation

Aims: Post infarction left ventricular remodeling leads to hypertrophy and dilatation. Little is known about substrate metabolism in this setting, although defects in substrate oxidation may cause contractile dysfunction and insulin resistance is an independent predictor of heart failure. Objective: We investigated substrate oxidation rates and insulin responsiveness of isolated rat hearts after LAD ligation. Methods: The LAD was ligated through a lateral thoracotomy in adult rats (200–350g, n=5) to induce an anterior infarction. After two weeks cardiac size and function were assessed with echocardiography. Hearts were then perfused in the working mode using radioactive tracers to assess fatty acid and glucose oxidation rates and insulin sensitivity. Results: Two weeks after LAD ligation, hearts were dilated (LVEDD in mm: 0.21±0.03 vs. 1.6±0.1; p≤0.05) and had reduced contractile function (FS in%: 24.4±4.78 vs. 45.87±2.23; p≤0.05). Compared to control, the infarcted hearts generated less power as isolated hearts (CP in mW/g dry weight: 19.05±5.81 vs. 36.61±2.53; p≤0.05) and oxidized less fatty acids (µmol/min/g dry weight: 0.63±0.1 vs. 1.04±0.06; p≤0.05) and glucose (0.35±0.1 vs. 0.56±0.04; p≤0.05). The response to insulin was significantly blunted (change of GO/FAO in%: 352±130 vs. 772±105; p≤0.05). Insulin did not affect contractile function of the isolated hearts. Conclusions: Postinfarct remodeling causes insulin resistance and substantial defects in energy substrate utilization. These findings may have therapeutic and/or prognostic relevance.