Sub-anesthetic Xenon Increases Erythropoietin Levels in Humans: A Randomized Controlled Trial
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ORIGINAL RESEARCH ARTICLE
Sub-anesthetic Xenon Increases Erythropoietin Levels in Humans: A Randomized Controlled Trial Christian Stoppe1,3 • Julia Ney1 • Martin Brenke1 • Andreas Goetzenich2 • Christoph Emontzpohl3 • Gereon Scha¨lte1 • Oliver Grottke1 • Manfred Moeller4 Rolf Rossaint1 • Mark Coburn1
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Ó Springer International Publishing Switzerland 2016
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 1a (HIF-1a) 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/O2 30 %/60 %) or a group breathing control gas (N2/O2 40 %/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 C. Stoppe and J. Ney contributed equally as first authors.
Electronic supplementary material The online version of this article (doi:10.1007/s40279-016-0505-1) contains supplementary material, which is available to authorized users. & Christian Stoppe [email protected] 1
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). Conclusion 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).
Department of Anaesthesiology, University Hospital RWTH, Pauwelsstrasse 30, 52074 Aachen, Germany
Key Points
Department of Thoracic, Cardiac and Vascular Surgery, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany
Xenon triggers erythropoietin level increase in serum of healthy participants.
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Institute of Biochemistry and Molecular Cell Biology, Univ
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