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

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Abstract
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-e 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-e in the human heart. Helium pre-and postconditioning did not affect postoperative troponin release in patients undergoing CABG surgery.
Keywords
Noble gases, Helium, Preconditioning, Postconditioning, Translation, CABG surgery, P38 MAPK, ERK1/2, HSP-27, PKC-epsilon, HEART IN-VIVO, CARDIOPULMONARY BYPASS, CARDIAC-SURGERY, RAT-HEART, INDUCED CARDIOPROTECTION, VOLATILE ANESTHETICS, HUMAN MYOCARDIUM, NOBLE-GASES, XENON, MECHANISM

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Chicago
Smit, Kirsten F, Daniel Brevoord, Stefan De Hert, Bas A de Mol, Raphaela P Kerindongo, Susan van Dieren, Wolfgang S Schlack, Markus W Hollmann, Nina C Weber, and Benedikt Preckel. 2016. “Effect of Helium Pre- or Postconditioning on Signal Transduction Kinases in Patients Undergoing Coronary Artery Bypass Graft Surgery.” Journal of Translational Medicine 14.
APA
Smit, K. F., Brevoord, D., De Hert, S., de Mol, B. A., Kerindongo, R. P., van Dieren, S., Schlack, W. S., et al. (2016). Effect of helium pre- or postconditioning on signal transduction kinases in patients undergoing coronary artery bypass graft surgery. JOURNAL OF TRANSLATIONAL MEDICINE, 14.
Vancouver
1.
Smit KF, Brevoord D, De Hert S, de Mol BA, Kerindongo RP, van Dieren S, et al. Effect of helium pre- or postconditioning on signal transduction kinases in patients undergoing coronary artery bypass graft surgery. JOURNAL OF TRANSLATIONAL MEDICINE. 2016;14.
MLA
Smit, Kirsten F et al. “Effect of Helium Pre- or Postconditioning on Signal Transduction Kinases in Patients Undergoing Coronary Artery Bypass Graft Surgery.” JOURNAL OF TRANSLATIONAL MEDICINE 14 (2016): n. pag. Print.
@article{8500035,
  abstract     = {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-e 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-e in the human heart. Helium pre-and postconditioning did not affect postoperative troponin release in patients undergoing CABG surgery.},
  articleno    = {294},
  author       = {Smit, Kirsten F and Brevoord, Daniel and De Hert, Stefan and de Mol, Bas A and Kerindongo, Raphaela P and van Dieren, Susan and Schlack, Wolfgang S and Hollmann, Markus W and Weber, Nina C and Preckel, Benedikt},
  issn         = {1479-5876},
  journal      = {JOURNAL OF TRANSLATIONAL MEDICINE},
  keywords     = {Noble gases,Helium,Preconditioning,Postconditioning,Translation,CABG surgery,P38 MAPK,ERK1/2,HSP-27,PKC-epsilon,HEART IN-VIVO,CARDIOPULMONARY BYPASS,CARDIAC-SURGERY,RAT-HEART,INDUCED CARDIOPROTECTION,VOLATILE ANESTHETICS,HUMAN MYOCARDIUM,NOBLE-GASES,XENON,MECHANISM},
  language     = {eng},
  pages        = {13},
  title        = {Effect of helium pre- or postconditioning on signal transduction kinases in patients undergoing coronary artery bypass graft surgery},
  url          = {http://dx.doi.org/10.1186/s12967-016-1045-z},
  volume       = {14},
  year         = {2016},
}

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