title: Enhanced glucose uptake via GLUT4 fuels recovery from calcium overload after ischaemia-reperfusion injury in sevoflurane- but not propofol-treated hearts.
abstract: 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 µM) in the formulation of 1% Diprivan(®) 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 µM) did not result in similar protection.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Cardiovascular Research Centre, Department of Pediatrics, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Lucchinetti
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: K W S
authors.initials: KW
authors.lastname: Ko
authors.forename: H
authors.initials: H
authors.lastname: Troxler
authors.forename: M
authors.initials: M
authors.lastname: Hersberger
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: M A
authors.initials: MA
authors.lastname: Omar
authors.forename: G D
authors.initials: GD
authors.lastname: Lopaschuk
authors.forename: A S
authors.initials: AS
authors.lastname: Clanachan
authors.forename: M
authors.initials: M
authors.lastname: Zaugg
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects; D051275:Glucose Transporter Type 4 / Q000502:physiology*; D006321:Heart / Q000187:drug effects; D008297:Male; D021962:Membrane Microdomains / Q000378:metabolism; D008738:Methyl Ethers / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism; D009924:Organ Culture Techniques; D015742:Propofol / Q000494:pharmacology; D011494:Protein Kinases / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism*; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D008738:Methyl Ethers; C495694:Slc2a4 protein, rat; D000077149:Sevoflurane; D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases; D002118:Calcium; D015742:Propofol