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




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Journal of Translational Medicine

, 14:294

Pain, Critical Care andAnesthesia

Abstract

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

KeywordsNoble gases Helium Preconditioning Postconditioning Translation CABG surgery P38 MAPK ERK1-2 HSP-27 PKC-ε AbbreviationsAPCanesthetic preconditioning

CABGcoronary artery bypass grafting

CPBcardiopulmonary bypass

ERK1-2extracellular signal-regulated kinase 1-2

He-Posthelium postconditioning

He-PPhelium pre- and postconditioning

He-Prehelium preconditioning

HSP-27heat shock protein 27

p38 MAPKmitogen activated protein kinase 38

MACminimal alveolar concentration

PKC-εprotein kinase C-epsilon

TBS-Ttris-buffered saline containing tween

Kirsten F. Smit and Daniel Brevoord contributed equally to this work

Electronic supplementary materialThe online version of this article doi:10.1186-s12967-016-1045-z contains supplementary material, which is available to authorized users.

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Author: Kirsten F. Smit - Daniel Brevoord - Stefan De Hert - Bas A. de Mol - Raphaela P. Kerindongo - Susan van Dieren - Wolfg

Source: https://link.springer.com/







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