title: Metabolic profiling of hearts exposed to sevoflurane and propofol reveals distinct regulation of fatty acid and glucose oxidation: CD36 and pyruvate dehydrogenase as key regulators in anesthetic-induced fuel shift.
abstract: BACKGROUND
  Myocardial energy metabolism is a strong predictor of postoperative cardiac function. This study profiled the metabolites and metabolic changes in the myocardium exposed to sevoflurane, propofol, and Intralipid and investigated the underlying molecular mechanisms.
  
  
  METHODS
  Sevoflurane (2 vol%) and propofol (10 and 100 microM) in the formulation of 1% Diprivan (AstraZeneca Inc., Mississauga, ON, Canada) were compared for their effects on oxidative energy metabolism and contractility in the isolated working rat heart model. Intralipid served as a control. Substrate flux through the major pathways for adenosine triphosphate generation in the heart, that is, fatty acid and glucose oxidation, was measured using [H]palmitate and [C]glucose. Biochemical analyses of nucleotides, acyl-CoAs, ceramides, and 32 acylcarnitine species were used to profile individual metabolites. Lipid rafts were isolated and used for Western blotting of the plasma membrane transporters CD36 and glucose transporter 4.
  
  
  RESULTS
  Metabolic profiling of the hearts exposed to sevoflurane and propofol revealed distinct regulation of fatty acid and glucose oxidation. Sevoflurane selectively decreased fatty acid oxidation, which was closely related to a marked reduction in left ventricular work. In contrast, propofol at 100 microM but not 10 microM increased glucose oxidation without affecting cardiac work. Sevoflurane decreased fatty acid transporter CD36 in lipid rafts/caveolae, whereas high propofol increased pyruvate dehydrogenase activity without affecting glucose transporter 4, providing mechanisms for the fuel shifts in energy metabolism. Propofol increased ceramide formation, and Intralipid increased hydroxy acylcarnitine species.
  
  
  CONCLUSIONS
  Anesthetics and their solvents elicit distinct metabolic profiles in the myocardium, which may have clinical implications for the already jeopardized diseased heart.
authors.affiliation: Department of Anesthesiology and Pain Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Lianguo
authors.initials: L
authors.lastname: Wang
authors.forename: Kerry W S
authors.initials: KW
authors.lastname: Ko
authors.forename: Eliana
authors.initials: E
authors.lastname: Lucchinetti
authors.forename: Liyan
authors.initials: L
authors.lastname: Zhang
authors.forename: Heinz
authors.initials: H
authors.lastname: Troxler
authors.forename: Martin
authors.initials: M
authors.lastname: Hersberger
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Omar
authors.forename: Elena I
authors.initials: EI
authors.lastname: Posse de Chaves
authors.forename: Gary D
authors.initials: GD
authors.lastname: Lopaschuk
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Clanachan
authors.forename: Michael
authors.initials: M
authors.lastname: Zaugg
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology; D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D005227:Fatty Acids / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D055442:Metabolome / Q000187:drug effects / Q000502:physiology; D008738:Methyl Ethers / Q000494:pharmacology*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology*; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane
chemical_list: D018686:Anesthetics, Intravenous; D018955:CD36 Antigens; C008132:Cd36 protein, rat; D005227:Fatty Acids; D008738:Methyl Ethers; D011768:Pyruvate Dehydrogenase Complex; D000077149:Sevoflurane; D005947:Glucose; D015742:Propofol