title: Nitrosative and oxidative stresses contribute to post-ischemic liver injury following severe hemorrhagic shock: the role of hypoxemic resuscitation.
abstract: OBJECTIVE
  Hemorrhagic shock and resuscitation is frequently associated with liver ischemia-reperfusion injury. The aim of the study was to investigate whether hypoxemic resuscitation attenuates liver injury.
  
  
  METHODS
  Anesthetized, mechanically ventilated New Zealand white rabbits were exsanguinated to a mean arterial pressure of 30 mmHg for 60 minutes. Resuscitation under normoxemia (Normox-Res group, n = 16, PaO(2) = 95-105 mmHg) or hypoxemia (Hypox-Res group, n = 15, PaO(2) = 35-40 mmHg) followed, modifying the FiO(2). Animals not subjected to shock constituted the sham group (n = 11, PaO(2) = 95-105 mmHg). Indices of the inflammatory, oxidative and nitrosative response were measured and histopathological and immunohistochemical studies of the liver were performed.
  
  
  RESULTS
  Normox-Res group animals exhibited increased serum alanine aminotransferase, tumor necrosis factor--alpha, interleukin (IL) -1β and IL-6 levels compared with Hypox-Res and sham groups. Reactive oxygen species generation, malondialdehyde formation and myeloperoxidase activity were all elevated in Normox-Res rabbits compared with Hypox-Res and sham groups. Similarly, endothelial NO synthase and inducible NO synthase mRNA expression was up-regulated and nitrotyrosine immunostaining increased in animals resuscitated normoxemically, indicating a more intense nitrosative stress. Hypox-Res animals demonstrated a less prominent histopathologic injury which was similar to sham animals.
  
  
  CONCLUSIONS
  Hypoxemic resuscitation prevents liver reperfusion injury through attenuation of the inflammatory response and oxidative and nitrosative stresses.
authors.affiliation: 3rd Department of Critical Care Medicine, University of Athens Medical School, Athens, Greece. edouzin@med.uoa.gr
authors.forename: Emmanuel E
authors.initials: EE
authors.lastname: Douzinas
authors.forename: Olga
authors.initials: O
authors.lastname: Livaditi
authors.forename: Marios-Konstantinos
authors.initials: MK
authors.lastname: Tasoulis
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Prigouris
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Bakos
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Goutas
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Vlachodimitropoulos
authors.forename: Ilias
authors.initials: I
authors.lastname: Andrianakis
authors.forename: Alex
authors.initials: A
authors.lastname: Betrosian
authors.forename: George D
authors.initials: GD
authors.lastname: Tsoukalas
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D016207:Cytokines / Q000097:blood; D000860:Hypoxia / Q000150:complications* / Q000628:therapy; D008099:Liver / Q000201:enzymology / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D018384:Oxidative Stress; D010100:Oxygen / Q000627:therapeutic use; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D015427:Reperfusion Injury / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D012771:Shock, Hemorrhagic / Q000150:complications*
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D026361:Reactive Nitrogen Species; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D000410:Alanine Transaminase; D010100:Oxygen