Enhanced glucose uptake via GLUT4 fuels recovery from calcium overload after ischaemia-reperfusion injury in sevoflurane-but not propofol-treated hearts

Background. So far, no study has explored the effects of sevoflurane, propofol, and Intralipid on metabolic flux rates of fatty acid oxidation (FOX) and glucose oxidation (GOX) in hearts exposed to ischaemia-reperfusion. Methods. Isolated paced working rat hearts were exposed to 20 min of ischaemia and 30 min of reperfusion. Peri-ischaemic sevoflurane (2 vol%) and propofol (100 mu M) in the formulation of 1% Diprivan (R) were assessed for their effects on oxidative energy metabolism and intracellular diastolic and systolic Ca(2+) concentrations. Substrate flux was measured using [(3)H] palmitate and [(14)C] glucose and [Ca(2+)] using indo-1AM. Western blotting was used to determine the expression of the sarcolemmal glucose transporter GLUT4 in lipid rafts. Biochemical analyses of nucleotides, ceramides, and 32 acylcarnitines were also performed. Results. Sevoflurane, but not propofol, improved the recovery of left ventricular work (P=0.008) and myocardial efficiency (P=0.008) compared with untreated ischaemic hearts. This functional improvement was accompanied by reduced increases in post-ischaemic diastolic and systolic intracellular Ca(2+) concentrations (P=0.008). Sevoflurane, but not propofol, increased GOX (P=0.009) and decreased FOX (P=0.019) in hearts exposed to ischaemia-reperfusion. GLUT4 expression was markedly increased in lipid rafts of sevoflurane-treated hearts (P=0.016). Increased GOX closely correlated with reduced Ca(2+) overload. Intralipid alone decreased energy charge and increased long-chain and hydroxyacylcarnitine tissue levels, whereas sevoflurane decreased toxic ceramide formation. Conclusions. Enhanced glucose uptake via GLUT4 fuels recovery from Ca(2+) overload after ischaemia-reperfusion in sevoflurane-but not propofol-treated hearts. The use of a high propofol concentration (100 mu M) did not result in similar protection.