title: Mechanisms involved in the desflurane-induced post-conditioning of isolated human right atria from patients with type 2 diabetes.
abstract: BACKGROUND
  Desflurane triggers post-conditioning in the diabetic human myocardium. We determined whether protein kinase C (PKC), mitochondrial adenosine triphosphate-sensitive potassium (mitoK(ATP)) channels, Akt, and glycogen synthase kinase-3β (GSK-3β) were involved in the in vitro desflurane-induced post-conditioning of human myocardium from patients with type 2 diabetes.
  
  
  METHODS
  The isometric force of contraction (FoC) of human right atrial trabeculae obtained from patients with type 2 diabetes was recorded during 30 min of hypoxia followed by 60 min of reoxygenation. Desflurane (6%) was administered during the first 5 min of reoxygenation either alone or in the presence of calphostin C (PKC inhibitor) or 5-hydroxydecanoate (5-HD) (mitoK(ATP) channel antagonist). Phorbol 12-myristate 13-acetate (PKC activator) and diazoxide (a mitoK(ATP) channel opener) were superfused during early reoxygenation. The FoC at the end of the 60 min reoxygenation period was compared among treatment groups (FoC(60); mean and sd). The phosphorylation of Akt and GSK-3β was studied using western blotting.
  
  
  RESULTS
  Desflurane enhanced the recovery of force [FoC(60): 79 (3)% of baseline] after 60 min of reoxygenation when compared with the control group (P>0.0001). Calphostin C and 5-HD abolished the beneficial effect of desflurane-induced post-conditioning (both P<0.0001). Phorbol 12-myristate 13-acetate and diazoxide enhanced the FoC(60) when compared with the control group (both P<0.0001). Desflurane increased the level of phosphorylation of Akt and GSK-3β (P<0.0001).
  
  
  CONCLUSIONS
  Desflurane-induced post-conditioning in human myocardium from patients with type 2 diabetes was mediated by the activation of PKC, the opening of the mitoK(ATP) channels, and the phosphorylation of Akt and GSK-3β.
authors.affiliation: Laboratory of Experimental Anaesthesiology and Cellular Physiology EA3212, Institut Fédératif de Recherche ICORE146, Université de Caen Basse Normandie, Caen, France. sand.lemoine2@wanadoo.fr
authors.forename: S
authors.initials: S
authors.lastname: Lemoine
authors.forename: L
authors.initials: L
authors.lastname: Zhu
authors.forename: C
authors.initials: C
authors.lastname: Buléon
authors.forename: M
authors.initials: M
authors.lastname: Massetti
authors.forename: J-L
authors.initials: JL
authors.lastname: Gérard
authors.forename: P
authors.initials: P
authors.lastname: Galera
authors.forename: J-L
authors.initials: JL
authors.lastname: Hanouz
mesh_terms: D000368:Aged; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D015153:Blotting, Western; D003652:Decanoic Acids / Q000494:pharmacology; D000077335:Desflurane; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D003981:Diazoxide / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria; D006801:Humans; D006880:Hydroxy Acids / Q000494:pharmacology; D000860:Hypoxia / Q000473:pathology; D057775:Ischemic Postconditioning / Q000379:methods*; D007530:Isoflurane / Q000031:analogs & derivatives* / Q000494:pharmacology; D054086:KATP Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control; D009281:Naphthalenes / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013318:Stroke Volume / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D018685:Anesthetics, Inhalation; D003652:Decanoic Acids; D000077335:Desflurane; D003981:Diazoxide; D004791:Enzyme Inhibitors; D006442:Glycated Hemoglobin; D038362:Glycogen Synthase Kinase 3; D006880:Hydroxy Acids; D007530:Isoflurane; D054086:KATP Channels; D009281:Naphthalenes; D011493:Protein Kinase C; D051057:Proto-Oncogene Proteins c-akt; D013755:Tetradecanoylphorbol Acetate; C052853:5-hydroxydecanoic acid; C058819:calphostin C