Gallos George, Jones Dean R, Nasr Samih H, Emala Charles W, Lee H Thomas
Department of Anesthesiology, Columbia University, 630 West 168th Street, New York, NY 10032-3784, USA.
Anesthesiology. 2004 Oct;101(4):902-11. doi: 10.1097/00000542-200410000-00015.
Mortality from sepsis frequently results from multiple organ injury and dysfunction. Cecal ligation and puncture is an established murine model of septic peritonitis that produces septic shock characterized by an initial hyperinflammatory response. In addition to their anesthetic properties, local anesthetics have been shown to attenuate inflammatory responses both in vivo and in vitro. In the current study, the ability of local anesthetic infusions to protect against sepsis-induced mortality, as well as renal and hepatic dysfunction after cecal ligation and puncture, was investigated.
C57BL/6 mice received mini-osmotic pumps containing saline (vehicle), 10% lidocaine, or 1% bupivacaine and were subjected to cecal ligation and puncture. Twenty-four hours after cecal ligation and puncture, renal and hepatic functions were assessed as well as markers of inflammation (proinflammatory cytokine protein and mRNA concentrations and myeloperoxidase activity). Renal apoptosis and 7-day survival was also assessed.
Mice treated with lidocaine or bupivacaine infusion showed improved survival and had significantly lower plasma creatinine, aspartate aminotransferase, and alanine aminotransferase concentrations compared with mice receiving vehicle alone. Significant reduction in plasma tumor necrosis factor-alpha and keratinocyte-derived chemokine, as well as reductions in myeloperoxidase activity, intracellular adhesion molecule-1 protein expression, mRNA concentrations of proinflammatory markers, and apoptosis were observed in renal cortices from both local anesthetic groups.
The current data demonstrate that local anesthetic infusions confer a protective effect in mice from septic peritonitis by attenuating the hyperacute inflammatory response. This suppression resulted in improved mortality and less progression to acute kidney and liver injury and dysfunction.
脓毒症导致的死亡常常源于多器官损伤和功能障碍。盲肠结扎穿孔术是一种公认的脓毒性腹膜炎小鼠模型,可引发以初始高炎症反应为特征的脓毒性休克。除了具有麻醉特性外,局部麻醉药已被证明在体内和体外均能减轻炎症反应。在本研究中,探究了局部麻醉药输注对盲肠结扎穿孔术后脓毒症诱导的死亡以及肾和肝功能障碍的保护作用。
C57BL/6小鼠接受含有生理盐水(载体)、10%利多卡因或1%布比卡因的微型渗透泵,并进行盲肠结扎穿孔术。盲肠结扎穿孔术后24小时,评估肾功能和肝功能以及炎症标志物(促炎细胞因子蛋白和mRNA浓度以及髓过氧化物酶活性)。还评估了肾细胞凋亡和7天生存率。
与仅接受载体的小鼠相比,接受利多卡因或布比卡因输注治疗的小鼠生存率提高,血浆肌酐、天冬氨酸转氨酶和丙氨酸转氨酶浓度显著降低。在两个局部麻醉药组的肾皮质中均观察到血浆肿瘤坏死因子-α和角质形成细胞衍生趋化因子显著降低,以及髓过氧化物酶活性、细胞间黏附分子-1蛋白表达、促炎标志物mRNA浓度和细胞凋亡减少。
目前的数据表明,局部麻醉药输注通过减轻超急性炎症反应,对脓毒性腹膜炎小鼠具有保护作用。这种抑制作用导致死亡率降低,急性肾损伤和肝损伤及功能障碍的进展减少。