title: Mitochondrial adenosine triphosphate-regulated potassium channel opening acts as a trigger for isoflurane-induced preconditioning by generating reactive oxygen species.
abstract: BACKGROUND
  Whether the opening of mitochondrial adenosine triphosphate-regulated potassium (K(ATP)) channels is a trigger or an end effector of anesthetic-induced preconditioning is unknown. We tested the hypothesis that the opening of mitochondrial K(ATP) channels triggers isoflurane-induced preconditioning by generating reactive oxygen species (ROS) in vivo.
  
  
  METHODS
  Pentobarbital-anesthetized rabbits were subjected to a 30-min coronary artery occlusion followed by 3 h reperfusion. Rabbits were randomly assigned to receive a vehicle (0.9% saline) or the selective mitochondrial K(ATP) channel blocker 5-hydroxydecanoate (5-HD) alone 10 min before or immediately after a 30-min exposure to 1.0 minimum alveolar concentration (MAC) isoflurane. In another series of experiments, the fluorescent probe dihydroethidium was used to assess superoxide anion production during administration of 5-HD or the ROS scavengers N-acetylcysteine or N-2-mercaptopropionyl glycine (2-MPG) in the presence or absence of 1.0 MAC isoflurane. Myocardial infarct size and superoxide anion production were measured using triphenyltetrazolium staining and confocal fluorescence microscopy, respectively.
  
  
  RESULTS
  Isoflurane (P < 0.05) decreased infarct size to 19 +/- 3% (mean +/- SEM) of the left ventricular area at risk as compared to the control (38 +/- 4%). 5-HD administered before but not after isoflurane abolished this beneficial effect (37 +/- 4% as compared to 24 +/- 3%). 5-HD alone had no effect on infarct size (42 +/- 3%). Isoflurane increased fluorescence intensity. Pretreatment with N-acetylcysteine, 2-MPG, or 5-HD before isoflurane abolished increases in fluorescence, but administration of 5-HD after isoflurane only partially attenuated increases in fluorescence produced by the volatile anesthetic agent.
  
  
  CONCLUSIONS
  The results indicate that mitochondrial K(ATP) channel opening acts as a trigger for isoflurane-induced preconditioning by generating ROS in vivo.
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226, USA.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Tanaka
authors.forename: Dorothee
authors.initials: D
authors.lastname: Weihrauch
authors.forename: Lynda M
authors.initials: LM
authors.lastname: Ludwig
authors.forename: Judy R
authors.initials: JR
authors.lastname: Kersten
authors.forename: Paul S
authors.initials: PS
authors.lastname: Pagel
authors.forename: David C
authors.initials: DC
authors.lastname: Warltier
mesh_terms: D000251:Adenosine Triphosphatases / Q000502:physiology*; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D004996:Ethidium; D005456:Fluorescent Dyes; D016166:Free Radical Scavengers / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D015640:Ion Channel Gating / Q000502:physiology*; D019157:Ischemic Preconditioning, Myocardial; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D018613:Microscopy, Confocal; D008929:Mitochondria, Heart / Q000201:enzymology* / Q000502:physiology; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D015221:Potassium Channels / Q000502:physiology*; D011650:Pulmonary Alveoli / Q000378:metabolism; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D018685:Anesthetics, Inhalation; D005456:Fluorescent Dyes; D016166:Free Radical Scavengers; D015221:Potassium Channels; D017382:Reactive Oxygen Species; D007530:Isoflurane; D000251:Adenosine Triphosphatases; D004996:Ethidium