title: Sub-anesthetic Xenon Increases Erythropoietin Levels in Humans: A Randomized Controlled Trial.
abstract: BACKGROUND
  The licensed anesthetic xenon, which exerts organ protective properties, was recently added by the World Anti-Doping Agency to the list of prohibited substances. Xenon is supposed to trigger the production of hypoxia-inducible factor 1α (HIF-1α) and subsequently erythropoietin, but data are limited to in vivo experimental work. Therefore we evaluated the effect of xenon on erythropoietin levels in healthy persons.
  
  
  METHODS
  Twenty-four healthy volunteers were randomly assigned either to a group spontaneously breathing xenon 30 % (Xe/O230 %/60 %) or a group breathing control gas (N2/O240 %/60 %) for 45 min. Primary outcome parameters were erythropoietin levels at several time-points after exposure. Secondary outcome parameters were serum levels of testosterone, cytokines, and growth factors as well as concentrations of xenon in blood and exhalation samples measured at several time-points after exposure. In addition, hemodynamic safety parameters were monitored during exposure.
  
  
  RESULTS
  The administration of xenon significantly increased erythropoietin levels 8 h after exposure (1.34 [±0.368]; p = 0.008), peaking at 24 h compared to the baseline values (1.45 [±0.498]; p = 0.01) and remained traceable in blood and exhalation probes until 24 h after exposure. In contrast, no significant change was observed in the control group. Measurement of stromal cell-derived factor 1 (SDF-1) revealed a significant increase of SDF-1 levels (p = 0.005), whereas no differences were observed with respect to growth factors, cytokines, or androgens. In an in vitro chemotaxis assay, endothelial progenitor cells (EPCs) showed a trend towards increased migration in serum samples received from participants after xenon exposure (p = 0.080).
  
  
  CONCLUSIONS
  The present study presents first evidence about a xenon-induced effect on increased erythropoietin levels in healthy volunteers. The study was registered at the European Medicines Agency (EudraCT-number: 2014-000973-38) and at ClinicalTrials.gov (NCT number: 02129400).
authors.affiliation: Department of Anaesthesiology, University Hospital RWTH, Pauwelsstrasse 30, 52074, Aachen, Germany. christian.stoppe@gmail.com.|Institute of Biochemistry and Molecular Cell Biology, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany. christian.stoppe@gmail.com.
authors.forename: Christian
authors.initials: C
authors.lastname: Stoppe
authors.affiliation: Department of Anaesthesiology, University Hospital RWTH, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Ney
authors.affiliation: Department of Anaesthesiology, University Hospital RWTH, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Brenke
authors.affiliation: Department of Thoracic, Cardiac and Vascular Surgery, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Goetzenich
authors.affiliation: Institute of Biochemistry and Molecular Cell Biology, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Emontzpohl
authors.affiliation: Department of Anaesthesiology, University Hospital RWTH, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: Gereon
authors.initials: G
authors.lastname: Schälte
authors.affiliation: Department of Anaesthesiology, University Hospital RWTH, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Grottke
authors.affiliation: Institute of Hygiene and Environmental Medicine, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Moeller
authors.affiliation: Department of Anaesthesiology, University Hospital RWTH, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Rossaint
authors.affiliation: Department of Anaesthesiology, University Hospital RWTH, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: Mark
authors.initials: M
authors.lastname: Coburn
mesh_terms: D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D054377:Chemokine CXCL12 / Q000097:blood; D004300:Doping in Sports; D004921:Erythropoietin / Q000378:metabolism*; D006801:Humans; D014978:Xenon / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology*
chemical_list: D018685:Anesthetics, Inhalation; D054377:Chemokine CXCL12; D004921:Erythropoietin; D014978:Xenon