Effect of helium pre- or postconditioning on signal transduction kinases in patients undergoing coronary artery bypass graft surgery

Journal of Translational Medicine

Research

Stefan De Hert¹  Bas A. de Mol²  Wolfgang S. Schlack³  Nina C. Weber³  Benedikt Preckel³  Kirsten F. Smit³  Daniel Brevoord³  Susan van Dieren³  Markus W. Hollmann³  Raphaela P. Kerindongo³ 

[1] Department of Anesthesiology, Ghent University, Ghent, Belgium;Department of Cardiothoracic Surgery, Academic Medical Centre (AMC), Amsterdam, The Netherlands;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;

关键词: Noble gases;    Helium;    Preconditioning;    Postconditioning;    Translation;    CABG surgery;    P38 MAPK;    ERK1/2;    HSP-27;    PKC-ε;   

DOI  :  10.1186/s12967-016-1045-z

 received in 2016-06-13, accepted in 2016-10-03,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundThe 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.MethodsAfter 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.ResultsBaseline 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.ConclusionsNo 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

【 授权许可】

CC BY   
© The Author(s) 2016