PMID- 27737678 OWN - NLM STAT- MEDLINE DCOM- 20171016 LR - 20201209 IS - 1479-5876 (Electronic) IS - 1479-5876 (Linking) VI - 14 IP - 1 DP - 2016 Oct 14 TI - Effect of helium pre- or postconditioning on signal transduction kinases in patients undergoing coronary artery bypass graft surgery. PG - 294 LID - 294 AB - BACKGROUND: 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-epsilon), 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. METHODS: 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 x 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. RESULTS: Baseline characteristics of all groups were similar. Helium preconditioning did not significantly alter the primary outcome (molecular levels of kinases PKC-epsilon and HSP-27, ratio of activated p38 MAPK or ERK (1/2)). 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. CONCLUSIONS: 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-epsilon 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. FAU - Smit, Kirsten F AU - Smit KF AD - 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. FAU - Brevoord, Daniel AU - Brevoord D AD - 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. FAU - De Hert, Stefan AU - De Hert S AD - Department of Anesthesiology, Ghent University, Ghent, Belgium. FAU - de Mol, Bas A AU - de Mol BA AD - Department of Cardiothoracic Surgery, Academic Medical Centre (AMC), Amsterdam, The Netherlands. FAU - Kerindongo, Raphaela P AU - Kerindongo RP AD - 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. FAU - van Dieren, Susan AU - van Dieren S AD - 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. FAU - Schlack, Wolfgang S AU - Schlack WS AD - 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. FAU - Hollmann, Markus W AU - Hollmann MW AD - 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. FAU - Weber, Nina C AU - Weber NC AD - 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. FAU - Preckel, Benedikt AU - Preckel B AD - 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. LA - eng GR - L30 TR001226/TR/NCATS NIH HHS/United States PT - Clinical Trial PT - Journal Article DEP - 20161014 PL - England TA - J Transl Med JT - Journal of translational medicine JID - 101190741 RN - 0 (HSP27 Heat-Shock Proteins) RN - 0 (HSPB1 protein, human) RN - 0 (Heat-Shock Proteins) RN - 0 (Molecular Chaperones) RN - 0 (Troponin T) RN - 206GF3GB41 (Helium) RN - EC 2.7.- (Protein Kinases) RN - EC 2.7.11.13 (Protein Kinase C-epsilon) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) SB - IM MH - Aged MH - *Coronary Artery Bypass MH - Cytosol/drug effects/enzymology MH - Demography MH - Extracellular Signal-Regulated MAP Kinases/metabolism MH - Female MH - HSP27 Heat-Shock Proteins/metabolism MH - Heat-Shock Proteins MH - Helium/*pharmacology MH - Hemodynamics/drug effects MH - Humans MH - *Ischemic Postconditioning MH - Ischemic Preconditioning, Myocardial MH - Male MH - Middle Aged MH - Molecular Chaperones MH - Phosphorylation/drug effects MH - Protein Kinase C-epsilon/metabolism MH - Protein Kinases/*metabolism MH - Signal Transduction/*drug effects MH - Troponin T/blood MH - p38 Mitogen-Activated Protein Kinases/metabolism PMC - PMC5064802 OTO - NOTNLM OT - CABG surgery OT - ERK1/2 OT - HSP-27 OT - Helium OT - Noble gases OT - P38 MAPK OT - PKC-epsilon OT - Postconditioning OT - Preconditioning OT - Translation EDAT- 2016/10/16 06:00 MHDA- 2017/10/17 06:00 PMCR- 2016/10/14 CRDT- 2016/10/15 06:00 PHST- 2016/06/13 00:00 [received] PHST- 2016/10/03 00:00 [accepted] PHST- 2016/10/15 06:00 [entrez] PHST- 2016/10/16 06:00 [pubmed] PHST- 2017/10/17 06:00 [medline] PHST- 2016/10/14 00:00 [pmc-release] AID - 10.1186/s12967-016-1045-z [pii] AID - 1045 [pii] AID - 10.1186/s12967-016-1045-z [doi] PST - epublish SO - J Transl Med. 2016 Oct 14;14(1):294. doi: 10.1186/s12967-016-1045-z.