title: Xenon triggers pro-inflammatory effects and suppresses the anti-inflammatory response compared to sevoflurane in patients undergoing cardiac surgery.
abstract: BACKGROUND
  Cardiac surgery encompasses various stimuli that trigger pro-inflammatory mediators, reactive oxygen species and mobilization of leucocytes. The aim of this study was to evaluate the effect of xenon on the inflammatory response during cardiac surgery.
  
  
  METHODS
  This randomized trial enrolled 30 patients who underwent elective on-pump coronary-artery bypass grafting in balanced anaesthesia of either xenon or sevoflurane. For this secondary analysis, blood samples were drawn prior to the operation, intra-operatively and on the first post-operative day to measure the pro- and anti-inflammatory cytokines interleukin-6 (IL-6), interleukin-8/C-X-C motif ligand 8 (IL-8/CXCL8), and interleukin-10 (IL-10). Chemokines such as C-X-C motif ligand 12/ stromal cell-derived factor-1α (CXCL12/SDF-1α) and macrophage migration inhibitory factor (MIF) were measured to characterize xenon's perioperative inflammatory profile and its impact on migration of peripheral blood mononuclear cells (PBMC).
  
  
  RESULTS
  Xenon enhanced the postoperative increase of IL-6 compared to sevoflurane (Xenon: 90.7 versus sevoflurane: 33.7 pg/ml; p = 0.035) and attenuated the increase of IL-10 (Xenon: 127.9 versus sevoflurane: 548.3 pg/ml; p = 0.028). Both groups demonstrated a comparable intraoperative increase of oxidative stress (intra-OP: p = 0.29; post-OP: p = 0.65). While both groups showed an intraoperative increase of the cardioprotective mediators MIF and CXCL12/SDF-1α, only MIF levels decreased in the xenon group on the first postoperative day (50.0 ng/ml compared to 23.3 ng/ml; p = 0.012), whereas it remained elevated after sevoflurane anaesthesia (58.3 ng/ml to 53.6 ng/ml). Effects of patients' serum on chemotactic migration of peripheral mononuclear blood cells taken from healthy volunteers indicated a tendency towards enhanced migration after sevoflurane anaesthesia (p = 0.07).
  
  
  CONCLUSIONS
  Compared to sevoflurane, balanced xenon anaesthesia triggers pro-inflammatory effects and suppresses the anti-inflammatory response in cardiac surgery patients even though the clinical significance remains unknown.
  
  
  BACKGROUND
  This clinical trial was approved by the European Medicines Agency (EudraCT-number: 2010-023942-63) and at ClinicalTrials.gov ( NCT01285271 ; first received: January 24, 2011).
authors.affiliation: Department of Anaesthesiology, University Hospital of the RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany. tbreuer@ukaachen.de.|Department of Intensive and Intermediate Care, University Hospital of the RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany. tbreuer@ukaachen.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Breuer
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, University Hospital of the RWTH Aachen, Aachen, Germany. cemontzpohl@ukaachen.de.|Institute of Biochemistry and Molecular Cell Biology, University Hospital, RWTH Aachen University, Pauwelsstr. 30, 52074, Aachen, Germany. cemontzpohl@ukaachen.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Emontzpohl
authors.affiliation: Department of Anaesthesiology, University Hospital of the RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany. mcoburn@ukaachen.de.
authors.forename: Mark
authors.initials: M
authors.lastname: Coburn
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, University Hospital of the RWTH Aachen, Aachen, Germany. cbenstoem@ukaachen.de.
authors.forename: Carina
authors.initials: C
authors.lastname: Benstoem
authors.affiliation: Department of Anaesthesiology, University Hospital of the RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany. rrosaint@ukaachen.de.
authors.forename: Rolf
authors.initials: R
authors.lastname: Rossaint
authors.affiliation: Department of Intensive and Intermediate Care, University Hospital of the RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany. gmarx@ukaachen.de.
authors.forename: Gernot
authors.initials: G
authors.lastname: Marx
authors.affiliation: Department of Anaesthesiology, University Hospital of the RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany. gschaelte@ukaachen.de.
authors.forename: Gereon
authors.initials: G
authors.lastname: Schälte
authors.affiliation: Institute of Biochemistry and Molecular Cell Biology, University Hospital, RWTH Aachen University, Pauwelsstr. 30, 52074, Aachen, Germany. jbernhagen@ukaachen.de.
authors.forename: Juergen
authors.initials: J
authors.lastname: Bernhagen
authors.affiliation: Department of Intensive and Intermediate Care, University Hospital of the RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany. cbruells@ukaachen.de.
authors.forename: Christian S
authors.initials: CS
authors.lastname: Bruells
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, University Hospital of the RWTH Aachen, Aachen, Germany. agoetzenich@ukaachen.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Goetzenich
authors.affiliation: Department of Anaesthesiology, University Hospital of the RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany. christian.stoppe@gmail.com.|Department of Thoracic and Cardiovascular Surgery, University Hospital of the RWTH Aachen, Aachen, Germany. christian.stoppe@gmail.com.|Institute of Biochemistry and Molecular Cell Biology, University Hospital, RWTH Aachen University, Pauwelsstr. 30, 52074, Aachen, Germany. christian.stoppe@gmail.com.
authors.forename: Christian
authors.initials: C
authors.lastname: Stoppe
mesh_terms: D018685:Anesthetics, Inhalation / Q000009:adverse effects*; D054441:Cell Migration Assays, Leukocyte; D054377:Chemokine CXCL12 / Q000097:blood; D001026:Coronary Artery Bypass / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced* / Q000209:etiology; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008738:Methyl Ethers / Q000009:adverse effects*; D010084:Oxidation-Reduction / Q000187:drug effects; D000077149:Sevoflurane; D014978:Xenon / Q000009:adverse effects*
chemical_list: D018685:Anesthetics, Inhalation; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D015850:Interleukin-6; D016209:Interleukin-8; D008738:Methyl Ethers; D016753:Interleukin-10; D000077149:Sevoflurane; D014978:Xenon