Anti-inflammatory adjuvant in resuscitation fluids improves survival in hemorrhage.
Anti-inflammatory adjuvant in resuscitation fluids improves survival in hemorrhage.
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DOI：
10.1097/ccm.0b013e31819b8237
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发表时间：
2009-03
影响因子：
8.8
通讯作者：
Ulloa L
中科院分区：
文献类型：
--
作者：
Cai B;Chen F;Lin X;Miller E;Szabo C;Deitch EA;Ulloa L
尽管重症监护取得了进展，但严重出血仍是常见的死亡原因。传统的复苏液被设计用于重建组织灌注，但它们不能防止致命的炎症反应。我们以前的研究表明，丙酮酸乙酯（EP）抑制巨噬细胞产生肿瘤坏死因子（TNF）。在这里，我们分析是否EP可以提供一个治疗抗炎价值复苏液。实验动物实验。大学医学院动物研究实验室。成年雄性Sprague-Dawley大鼠致死性出血超过15分钟，达到35-40 mm Hg的平均动脉血压，随后再维持该平均动脉血压15分钟。复苏限制为15 mL/kg Hextend（有或无EP）。用补充EP的Hextend复苏使所有动物免于致死性出血。与常规液体不同，EP抑制炎症和心血管因子如TNF和高迁移率族B蛋白-1的产生。从药理学的角度来看，EP复苏特别有效地抑制了脾脏和心脏中TNF的产生。与其他抗炎策略不同，EP通过独立于脾脏的机制减轻全身炎症。在分子水平上，EP抑制聚ADP-核糖聚合酶和p65 RelA DNA结合，而不影响IκBα活化。EP可能是一种很有前途的抗炎补充剂，以提高复苏期间的生存在重症监护。(Crit Care Med 2009; 37：860-868）
Severe hemorrhage is a common cause of death despite the recent advances in critical care. Conventional resuscitation fluids are designed to reestablish tissue perfusion, but they fail to prevent lethal inflammatory responses. Our previous studies indicate that ethyl pyruvate (EP) inhibits tumor necrosis factor (TNF) production from macrophages. Here, we analyze whether EP can provide a therapeutic anti-inflammatory value to resuscitation fluids. Laboratory animal experiments. Animal research laboratory at university medical school. Adult male Sprague-Dawley rats. Lethal hemorrhage over 15 minutes to reach a mean arterial blood pressure of 35–40 mm Hg and subsequent maintenance of this mean arterial blood pressure for another 15 minutes. Resuscitation was limited to 15 mL/kg Hextend with or without EP. Resuscitation with Hextend supplemented with EP rescued all the animals from lethal hemorrhage. Unlike conventional fluids, EP inhibited the production of inflammatory and cardiodepressant factors such as TNF and high mobility group B protein-1. From a pharmacologic perspective, resuscitation with EP was particularly effective inhibiting TNF production in the spleen and the heart. Unlike other anti-inflammatory strategies, EP mitigated systemic inflammation through a mechanism independent of the spleen. At the molecular level, EP inhibited both poly(ADP-ribose) polymerase and p65RelA DNA binding without affecting IκBα activation. EP may be a promising anti-inflammatory supplement to improve survival during resuscitation in critical care. (Crit Care Med 2009; 37:860–868)