title: Sevoflurane confers additional cardioprotection after ischemic late preconditioning in rabbits.
abstract: BACKGROUND
  Sevoflurane exerts cardioprotective effects that mimic the early ischemic preconditioning phenomenon (EPC) by activating adenosine triphosphate-sensitive potassium (KATP) channels. Ischemic late preconditioning (LPC) is an important cardioprotective mechanism in patients with coronary artery disease. The authors investigated whether the combination of LPC and sevoflurane-induced preconditioning results in enhanced cardioprotection and whether opening of KATP channels plays a role in this new setting.
  
  
  METHODS
  Seventy-three rabbits were instrumented with a coronary artery occluder. After recovery for 10 days, they were subjected to 30 min of coronary artery occlusion and 120 min of reperfusion (I/R). Controls (n = 14) were not preconditioned. LPC was induced in conscious animals by a 5-min period of coronary artery occlusion 24 h before I/R (LPC, n = 15). Additional EPC was induced by a 5-min period of myocardial ischemia 10 min before I/R (LPC+EPC, n = 9). Animals of the sevoflurane (SEVO) groups inhaled 1 minimum alveolar concentration of sevoflurane for 5 min at 10 min before I/R with (LPC+SEVO, n = 10) or without (SEVO, n = 15) additional LPC. The KATP channel blocker 5-hydroxydecanoate (5-HD, 5 mg/kg) was given intravenously 10 min before sevoflurane administration (LPC+SEVO+5-HD, n = 10).
  
  
  RESULTS
  Infarct size of the area at risk (triphenyltetrazolium staining) was reduced from 45 +/- 16% (mean+/-SD, control) to 27 +/- 11% by LPC (P < 0.001) and to 27 +/- 17% by sevoflurane (P = 0.001). Additional sevoflurane administration after LPC led to a further infarct size reduction to 14 +/- 8% (LPC+SEVO, P = 0.003 vs. LPC; P = 0.032 vs. SEVO), similar to the combination of LPC and EPC (12 +/- 8%; P = 0.55 vs. LPC+SEVO). Cardioprotection induced by LPC+SEVO was abolished by 5-HD (LPC+SEVO+5-HD, 41 +/- 19%, P = 0.001 vs. LPC+SEVO).
  
  
  CONCLUSIONS
  Sevoflurane administration confers additional cardioprotection after LPC by opening of KATP channels.
authors.affiliation: Klinik für Anaesthesiologie, Universitätsklinikum, Duesseldorf, Germany.
authors.forename: Jost
authors.initials: J
authors.lastname: Müllenheim
authors.forename: Dirk
authors.initials: D
authors.lastname: Ebel
authors.forename: Mirco
authors.initials: M
authors.lastname: Bauer
authors.forename: Florian
authors.initials: F
authors.lastname: Otto
authors.forename: André
authors.initials: A
authors.lastname: Heinen
authors.forename: Jan
authors.initials: J
authors.lastname: Frässdorf
authors.forename: Benedikt
authors.initials: B
authors.lastname: Preckel
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schlack
mesh_terms: D018528:ATP-Binding Cassette Transporters; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003331:Coronary Vessels / Q000502:physiology; D003652:Decanoic Acids / Q000494:pharmacology; D006331:Heart Diseases / Q000517:prevention & control*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006880:Hydroxy Acids / Q000494:pharmacology; D019157:Ischemic Preconditioning, Myocardial; D054086:KATP Channels; D008738:Methyl Ethers / Q000494:pharmacology*; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D000077149:Sevoflurane; D014655:Vascular Resistance / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D018528:ATP-Binding Cassette Transporters; D018685:Anesthetics, Inhalation; D003652:Decanoic Acids; D006880:Hydroxy Acids; D054086:KATP Channels; D008738:Methyl Ethers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; C092520:uK-ATP-1 potassium channel; D000077149:Sevoflurane; C052853:5-hydroxydecanoic acid