title: Activation of adenosine-monophosphate-activated protein kinase abolishes desflurane-induced preconditioning against myocardial infarction in vivo.
abstract: OBJECTIVE
  Myocardial ischemia is accompanied by a rapid activation of adenosine-monophosphate-activated protein kinase (AMPK). However, it is unclear whether this represents a potentially beneficial or detrimental event in the course of ischemic injury. The role of AMPK activation in the cardioprotective setting of desflurane-induced preconditioning has not been investigated to date. Hence, the current study was undertaken to address the role of AMPK activation during desflurane-induced preconditioning in vivo.
  
  
  METHODS
  A prospective randomized vehicle-controlled study.
  
  
  METHODS
  A university research laboratory.
  
  
  METHODS
  Male New Zealand white rabbits (n = 44).
  
  
  METHODS
  The animals were subjected to a 30-minute coronary artery occlusion (CAO) followed by 3 hours of reperfusion. Desflurane (1.0 minimum alveolar concentration) was administered for 30 minutes and discontinued 30 minutes prior to CAO. Different groups of animals received the AMPK activator, 5-aminoimidazole-4-carboxamide-1-b-riboside (AICAR), alone or in combination with desflurane. Infarct size was determined gravimetrically; AMPK activity and myocardial glycogen content were measured using specific assays. Phosphorylation of the AMPK substrate, acetyl-CoA carboxylase, was assessed by immunoblotting. Data are mean ± standard error of the mean.
  
  
  RESULTS
  Desflurane significantly reduced the myocardial infarct size (36.7 ± 1.9%, p < 0.05) compared with the control group (61.6% ± 3.0%), concomitant with increased myocardial tissue levels of glycogen (2.09 ± 0.07 μg, p < 0.05). Activation of the AMPK by AICAR alone did not protect against ischemic injury (65% ± 3.3), but did abolish the cardioprotection elicited by desflurane (61.8% ± 4.2%) at the same time as increasing myocardial glycogen consumption (1.42 ± 0.15 μg/mL).
  
  
  CONCLUSIONS
  The results obtained show that the pharmacologic activation of AMPK abolishes cardioprotection elicited by desflurane.
authors.affiliation: Department of Anesthesiology, Bayerische Julius-Maximilians-Universitaet, Würzburg, Germany.
authors.forename: Christopher
authors.initials: C
authors.lastname: Lotz
authors.forename: Beate
authors.initials: B
authors.lastname: Fisslthaler
authors.forename: Andreas
authors.initials: A
authors.lastname: Redel
authors.forename: Thorsten M
authors.initials: TM
authors.lastname: Smul
authors.forename: Jan
authors.initials: J
authors.lastname: Stumpner
authors.forename: Joanna
authors.initials: J
authors.lastname: Pociej
authors.forename: Norbert
authors.initials: N
authors.lastname: Roewer
authors.forename: Ingrid
authors.initials: I
authors.lastname: Fleming
authors.forename: Franz
authors.initials: F
authors.lastname: Kehl
authors.forename: Markus
authors.initials: M
authors.lastname: Lange
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000627:therapeutic use*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002316:Cardiotonic Agents; D000077335:Desflurane; D004562:Electrocardiography / Q000187:drug effects; D004789:Enzyme Activation; D006003:Glycogen / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology; D047468:Immunoprecipitation; D019157:Ischemic Preconditioning, Myocardial; D007530:Isoflurane / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D011817:Rabbits; D012265:Ribonucleotides / Q000494:pharmacology
chemical_list: D018685:Anesthetics, Inhalation; D002316:Cardiotonic Agents; D007004:Hypoglycemic Agents; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D006003:Glycogen; D000077335:Desflurane; D007530:Isoflurane; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide