title: Effect of helium pre- or postconditioning on signal transduction kinases in patients undergoing coronary artery bypass graft surgery.
abstract: The noble gas helium induces pre- and postconditioning in animals and humans. Volatile anesthetics induce cardioprotection in humans undergoing coronary artery bypass graft (CABG) surgery. We hypothesized that helium induces pre- and postconditioning in CABG-patients, affecting signaling molecules protein kinase C-epsilon (PKC-ε), p38 mitogen activated protein kinase (p38 MAPK), extracellular signal-regulated kinase 1/2 (ERK-1/2) and heat shock protein 27 (HSP-27) within cardiac tissue, and reducing postoperative troponin levels.
  
  
  
  After ethical approval and informed consent, 125 elective patients undergoing CABG surgery were randomised into this prospective, placebo controlled, investigator blinded, parallel arm single-centre study. Helium preconditioning (3 × 5 min of 70 % helium and 30 % oxygen) was applied before aortic cross clamping; postconditioning (15 min of helium) was applied before release of the aortic cross clamp. Signaling molecules were measured in right atrial appendix specimens. Troponin-T was measured at 4, 12, 24 and 48 h postoperatively.
  
  
  
  Baseline characteristics of all groups were similar. Helium preconditioning did not significantly alter the primary outcome (molecular levels of kinases PKC-ε and HSP-27, ratio of activated p38 MAPK or ERK ½). Postoperative troponin T was 11 arbitrary units [5, 31; area-under-the-curve (interquartile range)] for controls, and no statistically significant changes were observed after helium preconditioning [He-pre: 11 (6, 18)], helium postconditioning [He-post: 11 (8, 15)], helium pre- and postconditioning [He-PP: 14 (6, 20)] and after sevoflurane preconditioning [APC: 12 (8, 24), p = 0.13]. No adverse effects related to study treatment were observed in this study.
  
  
  
  No effect was observed of helium preconditioning, postconditioning or the combination thereof on activation of p38 MAPK, ERK 1/2 or levels of HSP27 and PKC-ε in the human heart. Helium pre- and postconditioning did not affect postoperative troponin release in patients undergoing CABG surgery. Clinical trial number Dutch trial register ( http://www.trialregister.nl/ ) number NTR1226.
authors.affiliation: Laboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), Department of Anesthesiology, Academic Medical Centre (AMC), Meibergdreef 9, 1100 DD, Amsterdam, The Netherlands.
authors.forename: Kirsten F
authors.initials: KF
authors.lastname: Smit
authors.affiliation: Laboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), Department of Anesthesiology, Academic Medical Centre (AMC), Meibergdreef 9, 1100 DD, Amsterdam, The Netherlands.
authors.forename: Daniel
authors.initials: D
authors.lastname: Brevoord
authors.affiliation: Department of Anesthesiology, Ghent University, Ghent, Belgium.
authors.forename: Stefan
authors.initials: S
authors.lastname: De Hert
authors.affiliation: Department of Cardiothoracic Surgery, Academic Medical Centre (AMC), Amsterdam, The Netherlands.
authors.forename: Bas A
authors.initials: BA
authors.lastname: de Mol
authors.affiliation: Laboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), Department of Anesthesiology, Academic Medical Centre (AMC), Meibergdreef 9, 1100 DD, Amsterdam, The Netherlands.
authors.forename: Raphaela P
authors.initials: RP
authors.lastname: Kerindongo
authors.affiliation: Laboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), Department of Anesthesiology, Academic Medical Centre (AMC), Meibergdreef 9, 1100 DD, Amsterdam, The Netherlands.
authors.forename: Susan
authors.initials: S
authors.lastname: van Dieren
authors.affiliation: Laboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), Department of Anesthesiology, Academic Medical Centre (AMC), Meibergdreef 9, 1100 DD, Amsterdam, The Netherlands.
authors.forename: Wolfgang S
authors.initials: WS
authors.lastname: Schlack
authors.affiliation: Laboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), Department of Anesthesiology, Academic Medical Centre (AMC), Meibergdreef 9, 1100 DD, Amsterdam, The Netherlands.
authors.forename: Markus W
authors.initials: MW
authors.lastname: Hollmann
authors.affiliation: Laboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), Department of Anesthesiology, Academic Medical Centre (AMC), Meibergdreef 9, 1100 DD, Amsterdam, The Netherlands. n.c.hauck@amc.uva.nl.
authors.forename: Nina C
authors.initials: NC
authors.lastname: Weber
authors.affiliation: Laboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), Department of Anesthesiology, Academic Medical Centre (AMC), Meibergdreef 9, 1100 DD, Amsterdam, The Netherlands.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Preckel
mesh_terms: D000368:Aged; D001026:Coronary Artery Bypass; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D003710:Demography; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins; D006371:Helium / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D057775:Ischemic Postconditioning; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones; D010766:Phosphorylation / Q000187:drug effects; D051744:Protein Kinase C-epsilon / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D020107:Troponin T / Q000097:blood; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D020107:Troponin T; D006371:Helium; D011494:Protein Kinases; D051744:Protein Kinase C-epsilon; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: CABG surgery; ERK1/2; HSP-27; Helium; Noble gases; P38 MAPK; PKC-ε; Postconditioning; Preconditioning; Translation