3rd Department of Critical Care Medicine, University of Athens Medical School, Athens, Greece.
PLoS One. 2012;7(3):e32968. doi: 10.1371/journal.pone.0032968. Epub 2012 Mar 5.
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.
失血性休克和复苏常伴有肝脏缺血再灌注损伤。本研究旨在探讨低氧复苏是否能减轻肝脏损伤。
麻醉、机械通气的新西兰白兔放血至平均动脉压 30mmHg 持续 60 分钟。随后进行常氧（Normox-Res 组，n=16，PaO2=95-105mmHg）或低氧（Hypox-Res 组，n=15，PaO2=35-40mmHg）复苏，调节 FiO2。未休克的动物构成假手术组（n=11，PaO2=95-105mmHg）。测定炎症、氧化和硝化反应的指标，并对肝脏进行组织病理学和免疫组织化学研究。
与 Hypox-Res 和假手术组相比，Normox-Res 组动物的血清丙氨酸氨基转移酶、肿瘤坏死因子-α、白细胞介素（IL）-1β和 IL-6 水平升高。与 Hypox-Res 和假手术组相比，Normox-Res 兔的活性氧生成、丙二醛形成和髓过氧化物酶活性均升高。同样，内皮型一氧化氮合酶和诱导型一氧化氮合酶 mRNA 表达上调，硝基酪氨酸免疫染色增加，表明硝化应激更严重。低氧复苏动物的组织病理学损伤较轻，与假手术动物相似。
低氧复苏通过减轻炎症反应、氧化应激和硝化应激来预防肝脏再灌注损伤。
