Abstract
PurposeHemorrhagic 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.MethodsAnesthetized, 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.ResultsNormox-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.ConclusionsHypoxemic resuscitation prevents liver reperfusion injury through attenuation of the inflammatory response and oxidative and nitrosative stresses.
Highlights
Hemorrhagic shock and resuscitation initiates an inflammatory response characterized by the up-regulation of cytokine expression and accumulation of neutrophils in a variety of tissues [1,2]
Ischemia/ reperfusion (I/R) injury caused significant exhaustion of the hepatic antioxidant defense in Normox-Res group as observed by the significant reduction in the reduced glutathione (GSH) of hepatic tissue compared with both Hypox-Res and sham groups (p,0.05, Figure 2B) in which it was maintained
Hepatic tissue GSH-to-total GSH (GSH+2 oxidized, GSSG) ratio (Figure 2C) was significantly lower in Normox-Res group compared with both Hypox-Res and sham groups (p,0.05)
Summary
Hemorrhagic shock and resuscitation initiates an inflammatory response characterized by the up-regulation of cytokine expression and accumulation of neutrophils in a variety of tissues [1,2]. Liver with its crucial involvement in metabolism and homeostasis is among the most frequently affected organs [3] These processes are triggered when liver is transiently deprived of oxygen and reoxygenated. This occurs in a number of clinical settings associated with low flow states resulting in insufficient perfusion, such as hemorrhagic and other types of shock, diverse surgical procedures, or during the organ procurement for transplantation [4,5]. Animal studies have shown that early in the reperfusion period, tissue damage appears to be associated with a decreased amount of endothelial nitric oxide (NO) synthase (e-NOS) derived NO related to e-NOS down-regulation [6].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
