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PLoS By Category | Recent PLoS Articles
Chemistry - Critical Care and Emergency Medicine - Gastroenterology and Hepatology - Surgery

Nitrosative and Oxidative Stresses Contribute to Post-Ischemic Liver Injury Following Severe Hemorrhagic Shock: The Role of Hypoxemic Resuscitation
Published: Monday, March 05, 2012
Author: Emmanuel E. Douzinas et al.

by Emmanuel E. Douzinas, Olga Livaditi, Marios-Konstantinos Tasoulis, Panagiotis Prigouris, Dimitrios Bakos, Nikolaos Goutas, Dimitrios Vlachodimitropoulos, Ilias Andrianakis, Alex Betrosian, George D. Tsoukalas

Purpose

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, PaO2?=?95–105 mmHg) or hypoxemia (Hypox-Res group, n?=?15, PaO2?=?35–40 mmHg) followed, modifying the FiO2. Animals not subjected to shock constituted the sham group (n?=?11, PaO2?=?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) -1ß 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.

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