title: Selenium prevents microparticle-induced endothelial inflammation in patients after cardiopulmonary resuscitation.
abstract: BACKGROUND
  Microparticles are elevated in patients after successful cardiopulmonary resuscitation (CPR) and may play a role in the development of endothelial dysfunction seen in post-cardiac arrest syndrome (PCAS), a life threatening disease with high mortality. To identify mechanisms of endothelial activation and to develop novel approaches in the therapy of PCAS, the impact of selenium, a trace element with antioxidative properties, was characterized in endothelial dysfunction induced by microparticles of resuscitated patients. Additionally, course of plasma selenium levels was characterized in the first 72 hours post-CPR.
  
  
  METHODS
  Endothelial cells were exposed to microparticles isolated of the peripheral blood of resuscitated patients, and leukocyte-endothelial interaction was measured by dynamic adhesion assay. Expression of adhesion molecules was assessed by immunoblotting and flow chamber. Blood samples were drawn 24, 48 and 72 hours after CPR for determination of plasma selenium levels in 77 resuscitated patients; these were compared to 50 healthy subjects and 50 patients with stable cardiac disease and correlated with severity of illness and outcome.
  
  
  RESULTS
  Microparticles of resuscitated patients enhance monocyte-endothelial interaction by up-regulation of ICAM-1 and VCAM-1. Selenium administration diminished ICAM-1 and VCAM-1-mediated monocyte adhesion induced by microparticles of resuscitated patients, suggesting that selenium has anti-inflammatory effects after CPR. Lowered selenium plasma levels were observed in resuscitated patients compared to controls and selenium levels immediately and 24 hours after CPR, inversely correlated with clinical course and outcome after resuscitation.
  
  
  CONCLUSIONS
  Endothelial dysfunction is a pivotal feature of PCAS and is partly driven by microparticles of resuscitated patients. Administration of selenium exerted anti-inflammatory effects and prevented microparticle-mediated endothelial dysfunction. Decline of selenium was observed in plasma of patients after CPR and is a novel predictive marker of ICU mortality, suggesting selenium consumption promotes inflammation in PCAS.
authors.affiliation: Department of Emergency Medicine, University hospital of Freiburg, Sir-Hans-A.-Krebs-Str., 79106, Freiburg im Breisgau, Germany. katrin.fink@uniklinik-freiburg.de.
authors.forename: Katrin
authors.initials: K
authors.lastname: Fink
authors.affiliation: Department of Cardiology and Angiology I, University Heart Center Freiburg, Hugstetter Str. 55, 79106, Freiburg im Breisgau, Germany. monica.moebes@uniklinik-freiburg.de.
authors.forename: Monica
authors.initials: M
authors.lastname: Moebes
authors.affiliation: Department of Cardiology and Angiology I, University Heart Center Freiburg, Hugstetter Str. 55, 79106, Freiburg im Breisgau, Germany. caroline.vetter@universitaets-herzzentrum.de.
authors.forename: Caroline
authors.initials: C
authors.lastname: Vetter
authors.affiliation: Department of Cardiology and Angiology I, University Heart Center Freiburg, Hugstetter Str. 55, 79106, Freiburg im Breisgau, Germany. nataschabourgeois@googlemail.com.
authors.forename: Natascha
authors.initials: N
authors.lastname: Bourgeois
authors.affiliation: Department of Emergency Medicine, University hospital of Freiburg, Sir-Hans-A.-Krebs-Str., 79106, Freiburg im Breisgau, Germany. bonaventura.schmid@uniklinik-freiburg.de.
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Schmid
authors.affiliation: Department of Cardiology and Angiology I, University Heart Center Freiburg, Hugstetter Str. 55, 79106, Freiburg im Breisgau, Germany. christoph.bode@universitaets-herzzentrum.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Bode
authors.affiliation: Department of Cardiology and Angiology I, University Heart Center Freiburg, Hugstetter Str. 55, 79106, Freiburg im Breisgau, Germany. thomas.helbing@universitaets-herzzentrum.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Helbing
authors.affiliation: Department of Emergency Medicine, University hospital of Freiburg, Sir-Hans-A.-Krebs-Str., 79106, Freiburg im Breisgau, Germany. hans-joerg.busch@uniklinik-freiburg.de.
authors.forename: Hans-Jörg
authors.initials: HJ
authors.lastname: Busch
mesh_terms: D000975:Antioxidants / Q000627:therapeutic use*; D016887:Cardiopulmonary Resuscitation; D016022:Case-Control Studies; D002448:Cell Adhesion / Q000187:drug effects; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D009000:Monocytes / Q000502:physiology; D012643:Selenium / Q000097:blood / Q000627:therapeutic use*; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D000975:Antioxidants; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D012643:Selenium