Nitrosative and oxidative stresses contribute to post-ischemic liver injury following severe hemorrhagic shock: the role of hypoxemic resuscitation

• Published in: PloS one 2012-03, Vol.7 (3), p.e32968-e32968
• Main Authors: Douzinas, Emmanuel E, Livaditi, Olga, Tasoulis, Marios-Konstantinos, Prigouris, Panagiotis, Bakos, Dimitrios, Goutas, Nikolaos, Vlachodimitropoulos, Dimitrios, Andrianakis, Ilias, Betrosian, Alex, Tsoukalas, George D
• Format: Article
• Language: English
• Subjects: Alanine; Alanine transaminase; Alanine Transaminase - blood; Animals; Biochemistry; Biology; Blood pressure; Chemistry; Critical care; Cytokines - blood; Forensic medicine; Gene expression; Group dynamics; Hemorrhage; Hepatitis; Hypoxemia; Hypoxia - complications; Hypoxia - therapy; Inflammation; Inflammatory response; Injury prevention; Interleukin; Interleukin 6; Interleukins; Ischemia; Lipid peroxidation; Liver; Liver - enzymology; Liver - injuries; Liver - metabolism; Liver - pathology; Liver diseases; Male; Malondialdehyde; Medical schools; Medicine; Meningitis; Neutrophils; Nitric Oxide Synthase Type II - genetics; Nitric Oxide Synthase Type III - genetics; Nitric-oxide synthase; Nitrotyrosine; Oxidative Stress; Oxygen; Oxygen - therapeutic use; Pancreatic cancer; Peroxidase; Peroxidase - metabolism; Phosphatase; Phosphorylation; Polymerase chain reaction; Rabbits; Reactive Nitrogen Species - metabolism; Reactive oxygen species; Reperfusion; Reperfusion Injury - complications; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; Reperfusion Injury - prevention & control; Resuscitation; RNA; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; Shock; Shock, Hemorrhagic - complications; Toxicology; Ventilation
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0032968

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. 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. 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. Hypoxemic resuscitation prevents liver reperfusion injury through attenuation of the inflammatory response and oxidative and nitrosative stresses.