title: Signaling pathways involved in desflurane-induced postconditioning in human atrial myocardium in vitro.
abstract: BACKGROUND
  Isoflurane and sevoflurane have been shown to elicit myocardial postconditioning, but the effect of desflurane remain unknown. The authors studied the mechanisms involved in desflurane-induced myocardial postconditioning.
  
  
  METHODS
  Contracting isolated human right atrial trabeculae (34 degrees C, stimulation frequency 1 Hz) were exposed to 30-min hypoxia followed by 60-min reoxygenation. Desflurane at 3%, 6%, and 9% was administered during the first 5-min of reoxygenation. Postconditioning with 6% desflurane was studied in the presence of 1 microM calphostin C, a protein kinase C inhibitor; 800 mm 5-hydroxydecanoate, a mitochondrial adenosine triphosphate-sensitive potassium channels antagonist; 1 microM Akt inhibitor; 20 microM PD89058, an extracellular-regulated kinase 1/2 inhibitor; and 1 microM SB 202190, a p38 mitogen-activated protein kinase inhibitor. The force of contraction at the end of the 60-min reoxygenation period was compared (mean +/- SD). The p38 mitogen-activated protein kinase phosphorylation was studied using Western blotting.
  
  
  RESULTS
  Desflurane at 3% (77 +/- 10% of baseline), 6% (90 +/- 14% of baseline), and 9% (86 +/- 11% of baseline) enhanced the recovery of force after 60 min of reoxygenation as compared with the control group (51 +/- 9% of baseline; P < 0.001). Calphostin C (55 +/- 3% of baseline), 5-hydroxydecanoate (53 +/- 3% of baseline), Akt inhibitor (57 +/- 8% of baseline), PD89058 (64 +/- 6% of baseline), and SB 202190 (61 +/- 3% of baseline) abolished desflurane-induced postconditioning. Western blot analysis showed that 6% desflurane increased p38 mitogen-activated protein kinase phosphorylation.
  
  
  CONCLUSIONS
  In vitro, desflurane postconditioned human atrial myocardium through protein kinase C activation, opening of mitochondrial adenosine triphosphate-sensitive potassium channels, Akt and extracellular-regulated kinase 1/2 activation, and p38 mitogen-activated protein kinase phosphorylation.
authors.affiliation: Laboratory of Experimental Anesthesiology and Cellular Physiology, Department of Cardiac and Thoracic Surgery, Centre Hospitalier Universitaire Caen, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Lemoine
authors.forename: Gallic
authors.initials: G
authors.lastname: Beauchef
authors.forename: Lan
authors.initials: L
authors.lastname: Zhu
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Renard
authors.forename: Olivier
authors.initials: O
authors.lastname: Lepage
authors.forename: Massimo
authors.initials: M
authors.lastname: Massetti
authors.forename: André
authors.initials: A
authors.lastname: Khayat
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: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077335:Desflurane; D006325:Heart Atria / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D007530:Isoflurane / Q000031:analogs & derivatives* / Q000494:pharmacology; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
chemical_list: D000077335:Desflurane; D007530:Isoflurane