title: Postresuscitation syndrome: potential role of hydroxyl radical-induced endothelial cell damage.
abstract: OBJECTIVE
  After out of hospital cardiac arrest, it has been reported that endothelium dysfunction may occur during the postresuscitation syndrome. However, the consequences of the reperfusion phase on endothelial reactive oxygen species production and redox homeostasis have not been explored in out of hospital cardiac arrest patients.
  
  
  METHODS
  Prospective, observational study.
  
  
  METHODS
  Medical intensive care unit in a university hospital.
  
  
  METHODS
  Twenty successfully resuscitated out of hospital cardiac arrest patients, seven septic shock patients, and ten healthy volunteers.
  
  
  METHODS
  Plasma was collected from patients at admission and 12, 24, 36, 48, and 72 hrs after cardiac arrest. We studied the production of reactive oxygen species and cell survival during plasma perfusion using perfused endothelial cells (human umbilical vein endothelial cells) as a model. Cell antioxidant response was studied by measuring superoxide dismutase, glutathione peroxidase, and glutathione reductase activities and reduced and oxidized glutathione levels. Mitochondrial respiratory chain activity was assessed by measuring complex I, II, III, and IV activities and anaerobic glycolysis by measuring glucose-6-phosphate dehydrogenase activity.
  
  
  RESULTS
  Using perfused endothelial cells as a model, we demonstrate that plasma from out of hospital cardiac arrest patients induced on naive human umbilical vein endothelial cells a significant and massive cell death compared to plasma from septic shock patients and healthy volunteers. An increase of reactive oxygen species production with a decrease in antioxidant defenses (superoxide dismutase, glutathione peroxidase, and glutathione reductase activities, reduced and oxidized glutathione levels) was observed. The metabolic consequence of plasma exposure showed that mitochondrial respiratory chain activity was significantly impaired and anaerobic glycolysis was significantly increased. Inhibiting hydroxyl radical production significantly decreased cell death, suggesting that plasma from out of hospital cardiac arrest induced significant cell death by triggering the Fenton reaction.
  
  
  CONCLUSIONS
  Plasma from out of hospital cardiac arrest induces major endothelial toxicity with an acute pro-oxidant state in the cells and impairment of mitochondrial respiratory chain activity. This toxicity could be due to hydroxyl radical production by activation of the Fenton reaction.
authors.affiliation: Réanimation Médicale, Université Paris Descartes, Hôpital Cochin-Port Royal, Assistance Publique des Hopitaux de Paris, Paris, France. olivier.huet@bakeridi.edu.au
authors.forename: Olivier
authors.initials: O
authors.lastname: Huet
authors.forename: Laurent
authors.initials: L
authors.lastname: Dupic
authors.forename: Frédéric
authors.initials: F
authors.lastname: Batteux
authors.forename: Corine
authors.initials: C
authors.lastname: Matar
authors.forename: Marc
authors.initials: M
authors.lastname: Conti
authors.forename: Christiane
authors.initials: C
authors.lastname: Chereau
authors.forename: Virginie
authors.initials: V
authors.lastname: Lemiale
authors.forename: Anatole
authors.initials: A
authors.lastname: Harrois
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Mira
authors.forename: Eric
authors.initials: E
authors.lastname: Vicaut
authors.forename: Alain
authors.initials: A
authors.lastname: Cariou
authors.forename: Jacques
authors.initials: J
authors.lastname: Duranteau
mesh_terms: D000328:Adult; D000368:Aged; D016887:Cardiopulmonary Resuscitation / Q000009:adverse effects; D016923:Cell Death; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism* / Q000502:physiology; D005260:Female; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006019:Glycolysis / Q000502:physiology; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000503:physiopathology; D058687:Out-of-Hospital Cardiac Arrest / Q000097:blood* / Q000503:physiopathology; D015427:Reperfusion Injury / Q000097:blood / Q000503:physiopathology; D012772:Shock, Septic / Q000097:blood / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000378:metabolism; D055815:Young Adult
chemical_list: D017665:Hydroxyl Radical; D005954:Glucosephosphate Dehydrogenase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005978:Glutathione