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首页> 外文期刊>Shock: Molecular, cellular, and systemic pathobiological aspects and therapeutic approaches = The official journal of the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies >Effects of intra-abdominal administration of recombinant tissue plasminogen activator on coagulation, fibrinolysis and inflammatory responses in experimental polymicrobial peritonitis.
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Effects of intra-abdominal administration of recombinant tissue plasminogen activator on coagulation, fibrinolysis and inflammatory responses in experimental polymicrobial peritonitis.

机译：腹腔管理的影响重组组织纤溶酶原激活物凝固,纤维蛋白溶解和炎症反应实验polymicrobial腹膜炎。

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摘要

Peritonitis represents a procoagulant state because of activated coagulation and inhibited fibrinolysis. Intra-abdominal fibrin deposition-entrapping bacteria-prevents bacterial spread but impairs bacterial clearance. Activating intra-abdominal fibrinolysis by recombinant tissue-type plasminogen activator (r-tPA) early during peritonitis may enhance bacterial clearance and reduce inflammation. This study examines effects of abdominal r-tPA lavage on local and distant coagulation, fibrinolysis, and inflammatory responses in experimental polymicrobial peritonitis. Twenty-four hours after cecal ligation and puncture, mice were exposed to therapeutic abdominal lavage with varying doses of r-tPA or saline (controls). Coagulation, fibrinolysis, and inflammation were assessed in abdominal, systemic, and pulmonary compartments (n = 6 per group per time point). Survival was assessed during 96 h (n = 16 per group). Highest-dose (2 mg/mL) r-tPA lavage caused immediate death. High-dose (0.5 mg/mL) r-tPA lavage increased fibrinolysis, demonstrated by low abdominal plasminogen activator inhibitor 1 levels and elevated pulmonary tPA levels, resulting in reduced abdominal bacterial load, chemokine levels, leukocyte influx, and thrombin generation, along with less pulmonary fibrin depositions and organ damage on histological examination (P < 0.05 vs. saline lavage). Low-dose (0.05 mg/mL) r-tPA lavage showed hardly any effect compared with saline lavage. Adversely, abdominal and plasma interleukin (IL) 12 were elevated, whereas IL-10 levels were decreased after high-dose r-tPA lavage (P < 0.05 vs. saline). Survival rate was not affected by any dose of r-tPA lavage compared with saline lavage. Delayed local stimulation of fibrinolysis by peritoneal r-tPA lavage enhanced intra-abdominal bacterial clearance and reduced intra- and extra-abdominal coagulation responses in a dose-dependent manner. Survival rate was unaffected likely due to adverse changes in IL-12 and IL-10 levels.
机译：腹膜炎代表促凝血的状态因为凝血激活和抑制纤维蛋白溶解。deposition-entrapping bacteria-prevents细菌传播,但损害细菌清除率。激活腹内的纤维蛋白溶解的组织类型重组纤溶酶原激活物(r-tPA)早期腹膜炎期间可能会加强细菌的间隙,减少炎症。研究了影响腹部r-tPA灌洗在地方和遥远的凝固,纤维蛋白溶解,在实验和炎症反应polymicrobial腹膜炎。盲肠的结扎和穿刺后,老鼠暴露于治疗腹腔灌洗不同剂量的r-tPA或生理盐水(控制)。凝固、纤维蛋白溶解和炎症评估在腹部,系统性和肺隔间(n = 6 /组/时间点)。生存是在96 h (n = 16 /评估组)。导致立即死亡。r-tPA洗胃增加纤维蛋白溶解,证明由低腹部纤溶酶原激活物抑制剂1水平和肺tPA水平升高,导致减少腹部细菌负荷,趋化因子水平,白细胞涌入,凝血酶代,还有少肺纤维蛋白口供,在组织器官损伤检查(P < 0.05与生理盐水灌洗)。低剂量(0.05毫克/毫升)r-tPA灌洗显示几乎没有任何影响而盐水洗胃。不利,腹部和血浆白介素(IL)12人升高,而il - 10水平减少后高剂量r-tPA灌洗(P < 0.05)比生理盐水)。任何剂量的r-tPA较生理盐水灌洗灌洗。由腹膜r-tPA灌洗增强腹内的细菌清除和减少内部和腹外凝血反应剂量依赖性的方式。可能由于不良变化il - 12的影响和il - 10水平。

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