title: Sevoflurane preconditioning attenuates myocardial ischemia/reperfusion injury via caveolin-3-dependent cyclooxygenase-2 inhibition.
abstract: BACKGROUND
  The inhaled anesthetic sevoflurane has been demonstrated to protect against myocardial ischemia/reperfusion (MI/R) injury via mechanisms involving AMP-activated protein kinase (AMPK) and caveolin-3 (Cav-3). However, the relative contributions of AMPK and Cav-3 to sevoflurane preconditioning (SF-PreCon)-mediated cardioprotection and their precise underlying mechanisms of action remain incompletely understood.
  
  
  RESULTS
  SF-PreCon (consisting of 3 cycles of 15-minute exposure to 2% sevoflurane before 30 minutes of MI) decreased MI/R injury in wild-type mice (caspase-3 activity, -29.1%; infarct size, -20.2%; and left ventricular end diastolic pressure, -33.8%). In cardiac-specific AMPKα2 dominant-negative overexpressing mice, the cardioprotective effect of SF-PreCon was largely retained (caspase-3 activity, -26.7%; infarct size, -16.7%; and left ventricular end-diastolic pressure, -25.9%; P<0.01). In contrast, SF-PreCon failed to significantly protect Cav-3 knockout mice against MI/R injury (P>0.05). SF-PreCon significantly decreased MI/R-induced superoxide generation in wild-type (-43.6%) and AMPK dominant-negative overexpressing mice (-35.5%; P<0.01) but not in Cav-3 knockout mice. SF-PreCon did not affect nicotinamide adenine dinucleotide phosphate oxidase expression but significantly inhibited cyclooxygenase-2 expression in wild-type (-38.7%) and AMPK dominant-negative overexpressing mice (-35.8%) but not in Cav-3 knockout mice.
  
  
  CONCLUSIONS
  We demonstrate for the first time SF-PreCon mediates cardioprotection against MI/R injury via caveolin-3-dependent cyclooxygenase-2 inhibition and antioxidative effects.
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital (J.Z., Y.Z., L.J., L.W., B.L.), Department of Pathophysiology (F.W.), and Department of Physiology, Key Laboratory of Cellular Physiology, Ministry of Education (Y.W.), Shanxi Medical University, Taiyuan, China; Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA (W.B.L., X.-L.M., Y.W.); and Center for Translational Research, Temple University, Philadelphia, PA (E.G., W.J.K.).
authors.forename: Jianli
authors.initials: J
authors.lastname: Zhao
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Zhang
authors.forename: Liyuan
authors.initials: L
authors.lastname: Jiao
authors.forename: Wayne Bond
authors.initials: WB
authors.lastname: Lau
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.forename: Baojiang
authors.initials: B
authors.lastname: Liu
authors.forename: Erhe
authors.initials: E
authors.lastname: Gao
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Koch
authors.forename: Xin-Liang
authors.initials: XL
authors.lastname: Ma
authors.forename: Yajing
authors.initials: Y
authors.lastname: Wang
mesh_terms: D018685:Anesthetics, Inhalation / Q000627:therapeutic use; D000818:Animals; D051244:Caveolin 3 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D008738:Methyl Ethers / Q000627:therapeutic use*; D051379:Mice; D018345:Mice, Knockout; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D051244:Caveolin 3; D052246:Cyclooxygenase 2 Inhibitors; D008738:Methyl Ethers; D000077149:Sevoflurane
keywords: caveolin; preconditioning; reperfusion injury; signal transduction
references.citation: Circ Res. 1986 Dec;59(6):612-9
references.pmid: 3028671
references.citation: Circulation. 2009 Sep 15;120(11 Suppl):S10-5
references.pmid: 19752353
references.citation: Eur J Anaesthesiol. 2012 Dec;29(12):561-9
references.pmid: 22965457
references.citation: Am J Physiol Endocrinol Metab. 2009 Aug;297(2):E384-91
references.pmid: 19470831
references.citation: Anesth Analg. 2009 Aug;109(2):405-11
references.pmid: 19608810
references.citation: Circulation. 2009 Feb 17;119(6):835-44
references.pmid: 19188503
references.citation: Circ Res. 2010 Dec 10;107(12):1445-53
references.pmid: 20966393
references.citation: Exp Biol Med (Maywood). 2011 Dec;236(12):1427-36
references.pmid: 22075552
references.citation: J Cell Sci. 2012 Jan 15;125(Pt 2):295-309
references.pmid: 22331353
references.citation: Anesthesiology. 2010 May;112(5):1136-45
references.pmid: 20418694
references.citation: Eur J Anaesthesiol. 2008 Mar;25(3):230-6
references.pmid: 17894911
references.citation: Arterioscler Thromb Vasc Biol. 2012 Apr;32(4):934-42
references.pmid: 22328772
references.citation: J Cardiovasc Pharmacol. 2007 Jun;49(6):416-8
references.pmid: 17577107
references.citation: Anesth Analg. 2005 Nov;101(5):1252-1260
references.pmid: 16243977
references.citation: Anesthesiology. 2005 Dec;103(6):1174-82
references.pmid: 16306729
references.citation: Circ Res. 2010 Feb 5;106(2):409-17
references.pmid: 19940263
references.citation: Circulation. 2008 Nov 4;118(19):1979-88
references.pmid: 18936328
references.citation: Am J Physiol Cell Physiol. 2005 Jun;288(6):C1317-31
references.pmid: 15689413
references.citation: Br J Anaesth. 2010 Feb;104(2):191-200
references.pmid: 20086064
references.citation: J Mol Cell Cardiol. 2008 Jan;44(1):123-30
references.pmid: 18054955
references.citation: Cardiovasc Res. 2010 May 1;86(2):219-25
references.pmid: 20202978