title: Role of 70-kDa ribosomal protein S6 kinase, nitric oxide synthase, glycogen synthase kinase-3 beta, and mitochondrial permeability transition pore in desflurane-induced postconditioning in isolated human right atria.
abstract: BACKGROUND
  Desflurane during early reperfusion has been shown to postcondition human myocardium. Whether it involves "reperfusion injury salvage kinase" pathway remains incompletely studied. The authors tested the involvement of 70-kDa ribosomal protein S6 kinase, nitric oxide synthase, glycogen synthase kinase (GSK)-3beta, and mitochondrial permeability transition pore in desflurane-induced postconditioning.
  
  
  METHODS
  The authors recorded isometric contraction of human right atrial trabeculae suspended in an oxygenated Tyrode's solution (34 degrees C, stimulation frequency 1 Hz). After a 30-min hypoxic period, desflurane 6% was administered during the first 5 min of reoxygenation. Desflurane was administered alone or with pretreatment of rapamycin, a 70-kDa ribosomal protein S6 kinase inhibitor, NG-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, and atractyloside, the mitochondrial permeability transition pore opener. GSK-3beta inhibitor VII was administered during the first few minutes of reoxygenation alone or in the presence of desflurane 6%, rapamycin, NG-nitro-L-arginine methyl ester, and atractyloside. Developed force at the end of a 60-min reoxygenation period was compared (mean +/- SD). Phosphorylation of GSK-3beta was measured using blotting.
  
  
  RESULTS
  Desflurane 6% (84 +/- 4% of baseline) enhanced the recovery of force after 60 min of reoxygenation when compared with the control group (54 +/- 4%, P < 0.0001). Rapamycin (68 +/- 8% of baseline), NG-nitro-L-arginine methyl ester (57 +/- 8%), atractyloside (52 +/- 7%) abolished desflurane-induced postconditioning (P < 0.001). GSK-3beta inhibitor-induced postconditioning (84 +/- 5%, P < 0.0001 vs. control) was not modified by desflurane (78 +/- 6%), rapamycin (81 +/- 6%), and NG-nitro-L-arginine methyl ester (82 +/- 10%), but it was abolished by atractyloside (49 +/- 6%). Desflurane increased the phosphorylation of GSK-3beta (3.30 +/- 0.57-fold increase in desflurane vs. control; P < 0.0001).
  
  
  CONCLUSIONS
  In vitro, desflurane-induced postconditioning protects human myocardium through the activation of 70-kDa ribosomal protein S6 kinase, nitric oxide synthase, inhibition, and phosphorylation of GSK-3beta, and preventing mitochondrial permeability transition pore opening.
authors.affiliation: Laboratory of Experimental Anesthesiology and Cellular Physiology EA3212, Institut Fédératif de Recherche ICORE146 Université de Caen Basse Normandie, Caen, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Lemoine
authors.forename: Lan
authors.initials: L
authors.lastname: Zhu
authors.forename: Gallic
authors.initials: G
authors.lastname: Beauchef
authors.forename: Olivier
authors.initials: O
authors.lastname: Lepage
authors.forename: Gérard
authors.initials: G
authors.lastname: Babatasi
authors.forename: Caline
authors.initials: C
authors.lastname: Ivascau
authors.forename: Massimo
authors.initials: M
authors.lastname: Massetti
authors.forename: Philippe
authors.initials: P
authors.lastname: Galera
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Gérard
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Hanouz
mesh_terms: D016280:Atrial Function, Right / Q000187:drug effects* / Q000502:physiology*; D000077335:Desflurane; D038362:Glycogen Synthase Kinase 3 / Q000502:physiology*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007530:Isoflurane / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D033681:Mitochondrial Membrane Transport Proteins / Q000502:physiology*; D000083162:Mitochondrial Permeability Transition Pore; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D019001:Nitric Oxide Synthase / Q000502:physiology*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000502:physiology*; D013997:Time Factors
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D000077335:Desflurane; D007530:Isoflurane; D019001:Nitric Oxide Synthase; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D038362:Glycogen Synthase Kinase 3