Exogenous substrate preference of the post-ischaemic myocardium

Myocardial exogenous substrate preference was studied under conditions of increased plasma lactate concentration before and after a severe (halving of tissue ATP concentration, sixfold increase in tissue lactate concentration) but reversible (<1% necrosis on reperfusion) global ischaemic stress produced by continuous hypothermic electromechanical arrest of the heart of four hours duration by aortic cross clamping and multidose potassium cardioplegia. Fatty acid oxidation was studied using l-l4C-palmitate under steady state conditions and under similar isovolumic fixed pressure conditions with the heart at a constant rate using a left ventricular intracavitary balloon. Exogenous free fatty acid oxidation during the pre-ischaemic period with an increased lactate concentration (3.9-5.8 mmol·litre–1) was 0.62(0.21) µmol·min–1·100 g–1 (mean (SEM)). This represented a mean of 32% of the total carbon dioxide produced in contrast to a post-ischaemia free fatty oxidation rate of 2.67(0.87) µmol·min–1·100 g–1, in the presence of even further increased plasma lactate concentrations (8.47-11.17 mmol·litre–1), representing a mean of 82% of the total carbon dioxide output. These data suggest that the substrate preference of the myocardium, under conditions of increased plasma lactate concentration, shifts to greater oxidation of exogenous free fatty acids after ischaemic stress.