title: Differential role of Pim-1 kinase in anesthetic-induced and ischemic preconditioning against myocardial infarction.
abstract: BACKGROUND
  Ischemic preconditioning (IPC) and anesthetic-induced preconditioning against myocardial infarction are mediated via protein kinase B. Pim-1 kinase acts downstream of protein kinase B and was recently shown to regulate cardiomyocyte survival. The authors tested the hypothesis that IPC and anesthetic-induced preconditioning are mediated by Pim-1 kinase.
  
  
  METHODS
  Pentobarbital-anesthetized male C57Black/6 mice were subjected to 45 min of coronary artery occlusion and 3 h of reperfusion. Animals received no intervention, Pim-1 kinase inhibitor II (10 microg/g intraperitoneally), its vehicle dimethyl sulfoxide (10 microl/g intraperitoneally), or 1.0 minimum alveolar concentration desflurane alone or in combination with Pim-1 kinase inhibitor II (10 microg/g intraperitoneally). IPC was induced by three cycles of 5 min ischemia-reperfusion each, and animals received IPC either alone or in combination with Pim-1 kinase inhibitor II (10 microg/g intraperitoneally). Infarct size was determined with triphenyltetrazolium chloride, and area at risk was determined with Evans blue (Sigma-Aldrich, Taufkirchen, Germany). Protein expression of Pim-1 kinase, Bad, phospho-Bad, and cytosolic content of cytochrome c were measured using Western immunoblotting.
  
  
  RESULTS
  Infarct size in the control group was 47 + or - 2%. Pim-1 kinase inhibitor II (44 + or - 2%) had no effect on infarct size. Desflurane (17 + or - 3%) and IPC (19 + or - 2%) significantly reduced infarct size compared with control (both P < 0.05 vs. control). Blockade of Pim-1 kinase completely abrogated desflurane-induced preconditioning (43 + or - 3%), whereas IPC (35 + or - 3%) was blocked partially. Desflurane tended to reduce cytosolic content of cytochrome c, which was abrogated by Pim-1 kinase inhibitor II.
  
  
  CONCLUSIONS
  These data suggest that Pim-1 kinase mediates at least in part desflurane-induced preconditioning and IPC against myocardial infarction in mice.
authors.affiliation: Department of Anaesthesia and Critical Care, University of Würzburg, Würzburg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Stumpner
authors.forename: Andreas
authors.initials: A
authors.lastname: Redel
authors.forename: Anna
authors.initials: A
authors.lastname: Kellermann
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Lotz
authors.forename: Christoph A
authors.initials: CA
authors.lastname: Blomeyer
authors.forename: Thorsten M
authors.initials: TM
authors.lastname: Smul
authors.forename: Franz
authors.initials: F
authors.lastname: Kehl
authors.forename: Norbert
authors.initials: N
authors.lastname: Roewer
authors.forename: Markus
authors.initials: M
authors.lastname: Lange
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D045304:Cytochromes c / Q000378:metabolism; D003627:Data Interpretation, Statistical; D000077335:Desflurane; D004789:Enzyme Activation / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D019157:Ischemic Preconditioning, Myocardial; D007530:Isoflurane / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000201:enzymology* / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D051573:Proto-Oncogene Proteins c-pim-1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D015427:Reperfusion Injury / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D051025:bcl-Associated Death Protein / Q000378:metabolism
chemical_list: D018685:Anesthetics, Inhalation; D051025:bcl-Associated Death Protein; D045304:Cytochromes c; D000077335:Desflurane; D007530:Isoflurane; D051573:Proto-Oncogene Proteins c-pim-1