Tsai Hsin-Jung, Tsao Cheng-Ming, Liao Mei-Hui, Ka Shuk-Man, Liaw Wen-Jinn, Wu Chin-Chen
Department of Pharmacology, Institute of Pharmacology, National Defence Medical Centre, Taipei, Republic of China, Taiwan.
Blood Coagul Fibrinolysis. 2012 Mar;23(2):118-26. doi: 10.1097/MBC.0b013e32834ee170.
Liver injury developing in patients with sepsis may lead to an increased risk of mortality. Thrombelastography (TEG) is generally applied to evaluate hemostatic disturbance in patients undergoing liver transplantation or cardiopulmonary bypass. The aim of this study was to investigate the development of liver injury and coagulopathy in a lipopolysaccharide (LPS)-induced animal model and to assess the relationship between TEG variables and liver injury. Male Wistar rats received LPS (30 mg/kg over a 4-h intravenous infusion) to induce experimental liver injury or isotonic saline as a control. Variables of hemodynamics and liver biochemistry were measured during the subsequent 6 h after the start of infusion. TEG variables (R-time, K-time, α-angle and maximal amplitude), thrombin-antithrombin complex and plasminogen activator inhibitor-1 were also measured. After LPS infusion, liver injury [examined by biochemical variables (e.g. alanine aminotransferase, ALT) and histological studies] was developed and inflammatory cytokines (tumor necrosis factor-α and interleukin-6) were raised. At the initial period of LPS infusion, R-time was shortened and α-angle was increased. Thereafter, α-angle and maximal amplitude were decreased progressively, demonstrating that endotoxin induced coagulation disturbances. Furthermore, there were strong positive correlation between K-time and natural log (Ln)(ALT) (r = 0.823, P = 0.001); also, there were strong negative correlations between α-angle and Ln(ALT) (r = -0.762, P = 0.002) as well as maximal amplitude and Ln(ALT) (r = -0.732, P = 0.004) at 6 h after LPS infusion. These results demonstrated that TEG could be a potential tool to evaluate the development of liver injury in endotoxemia.
脓毒症患者发生的肝损伤可能会导致死亡风险增加。血栓弹力图(TEG)通常用于评估肝移植或体外循环患者的止血功能紊乱。本研究的目的是在脂多糖(LPS)诱导的动物模型中研究肝损伤和凝血病的发展,并评估TEG变量与肝损伤之间的关系。雄性Wistar大鼠接受LPS(4小时静脉输注30mg/kg)以诱导实验性肝损伤,或接受等渗盐水作为对照。在输注开始后的6小时内测量血流动力学和肝脏生化指标。还测量了TEG变量(R时间、K时间、α角和最大振幅)、凝血酶-抗凝血酶复合物和纤溶酶原激活物抑制剂-1。输注LPS后,出现了肝损伤(通过生化指标如丙氨酸转氨酶(ALT)和组织学研究进行检测),炎症细胞因子(肿瘤坏死因子-α和白细胞介素-6)升高。在LPS输注初期,R时间缩短,α角增大。此后,α角和最大振幅逐渐降低,表明内毒素诱导了凝血功能紊乱。此外,K时间与自然对数(Ln)(ALT)之间存在强正相关(r = 0.823,P = 0.001);同样,在LPS输注6小时后,α角与Ln(ALT)之间存在强负相关(r = -0.762,P = 0.002),最大振幅与Ln(ALT)之间也存在强负相关(r = -0.732,P = 0.004)。这些结果表明,TEG可能是评估内毒素血症中肝损伤发展的一种潜在工具。