title: Desflurane-induced and ischaemic postconditioning against myocardial infarction are mediated by Pim-1 kinase.
abstract: BACKGROUND
  Anaesthetic-induced (APOST) and ischaemic postconditioning (IPOST) against myocardial infarction are mediated via phosphatidylinositol-3-kinase/Akt. Pim-1 kinase is acting downstream of Akt and has recently been demonstrated to enhance cardiomyocyte survival. We tested the hypothesis that both APOST and IPOST are mediated by Pim-1 kinase.
  
  
  METHODS
  Pentobarbital-anaesthetized male C57BL/6 mice were subjected to 45-min coronary artery occlusion (CAO) and 3-h reperfusion. Animals received either no intervention, the Pim-1 kinase inhibitor II (10 μg/g intraperitoneally) or its vehicle dimethy sulfoxide (10 μl/g intraperitoneally). Three minutes prior to the end of CAO, 1.0 minimum alveolar concentration desflurane was administered for 18 min alone or in combination with Pim-1 kinase inhibitor II. IPOST was induced by three cycles of each 10-s ischaemia/reperfusion, and animals received either IPOST alone or in combination with Pim-1 kinase inhibitor II. Infarct size was determined with triphenyltetrazolium chloride and area at risk with Evans blue. Protein expression of Pim-1 kinase, Bad, phospho-Bad(Ser112)  and B-cell lymphoma 2 was determined using Western immunoblotting analysis.
  
  
  RESULTS
  Infarct size in control animals (CON) was 46 ± 3%. Dimethylsulfoxide (47 ± 3%) and Pim-1 kinase inhibitor II (44 ± 5%) did not significantly reduce infarct size. Desflurane (16 ± 2%*; *P < 0.05 vs. CON) and IPOST (21 ± 2%*) significantly reduced infarct size compared with CON. Inhibition of Pim-1 kinase abolished desflurane-induced postconditioning (46 ± 4%) and IPOST (44 ± 5%). Western blot analysis revealed that only desflurane enhances phosphorylation of Bad at serine 112 that was abrogated by Pim-1 kinase inhibitor II.
  
  
  CONCLUSIONS
  These data suggest that Pim-1 kinase mediates both desflurane-induced postconditioning and IPOST in mice.
authors.affiliation: Department of Anaesthesia and Critical Care, University of Würzburg, Würzburg, Germany. stumpner_j@klinik.uni-wuerzburg.de
authors.forename: J
authors.initials: J
authors.lastname: Stumpner
authors.forename: T M
authors.initials: TM
authors.lastname: Smul
authors.forename: A
authors.initials: A
authors.lastname: Redel
authors.forename: T
authors.initials: T
authors.lastname: Hilz
authors.forename: T
authors.initials: T
authors.lastname: Tischer-Zeitz
authors.forename: H
authors.initials: H
authors.lastname: Eisenbarth
authors.forename: M A
authors.initials: MA
authors.lastname: Schick
authors.forename: F
authors.initials: F
authors.lastname: Kehl
authors.forename: N
authors.initials: N
authors.lastname: Roewer
authors.forename: M
authors.initials: M
authors.lastname: Lange
mesh_terms: D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000077335:Desflurane; D005786:Gene Expression Regulation / Q000187:drug effects; D019254:Genes, bcl-2; D007274:Injections, Intraperitoneal; D057775:Ischemic Postconditioning / Q000379:methods*; D007530:Isoflurane / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D051573:Proto-Oncogene Proteins c-pim-1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D011897:Random Allocation; D015398:Signal Transduction / Q000187:drug effects; D051025:bcl-Associated Death Protein / Q000096:biosynthesis / Q000235:genetics
chemical_list: C576263:2-hydroxy-3-cyano-4-phenyl-6-(3-bromo-6-hydroxyphenyl)pyridine; D018685:Anesthetics, Inhalation; C494820:Bad protein, mouse; D047428:Protein Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D011725:Pyridines; D051025:bcl-Associated Death Protein; D000077335:Desflurane; D007530:Isoflurane; C496636:Pim1 protein, mouse; D051573:Proto-Oncogene Proteins c-pim-1