Nebulized Anticoagulants Limit Pulmonary Coagulopathy, But Not Inflammation, in a Model of Experimental Lung Injury
Nebulized Anticoagulants Limit Pulmonary Coagulopathy, But Not Inflammation, in a Model of Experimental Lung Injury
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DOI：
10.1089/jamp.2009.0779
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发表时间：
2010-04-01
影响因子：
3.4
通讯作者：
Schultz, Marcus J.
中科院分区：
文献类型：
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作者：
Hofstra, Jorrit J.;Vlaar, Alexander P.;Schultz, Marcus J.
背景：肺凝血异常可能导致肺损伤的不良结局。采用大鼠内毒素血症肺损伤模型，观察局部抗凝治疗对内毒素血症肺损伤大鼠支气管肺泡和全身止血的影响。方法：给雄性SD大鼠静脉注射脂多糖(LPS)，同时给予雾化生理盐水(安慰剂)、重组人活化蛋白C(APC)、血浆源性抗凝血酶(AT)、肝素或达那普利治疗。结果：静脉注射LPS可导致肺损伤，并伴有肺组织凝血酶-抗凝血酶复合体(TATc)水平升高；安慰剂组为6.9+/-0.8 ng/毫升，健康对照组为0.5+/-0.2 ng/毫升(p<；纤维蛋白降解产物(FDP)水平升高，分别为555+/-74 ng/mLvs 27+/-12 ng/mLvs27+/-12 ng/mL(p<；0.01)。雾化吸入APC、AT和达那普利都显著限制了TATc、1.5+/-0.2、3.8+/-0.7和3.2+/-0.9 ng=毫升(均为安慰剂)和纤维蛋白降解产物，243+/-77、113+/-20、317+/-74和300+/-42 ng=毫升(均为P<；0.01与安慰剂组)的上升。肝素和达那普利对全身凝血障碍也有显著影响。但雾化吸入抗凝剂不影响肺组织炎症反应[中性粒细胞进入肺内、肺泡髓过氧化酶水平、肺泡肿瘤坏死因子、白介素6和CINC-3水平]，也不影响肺组织病理学。结论：APC、AT、肝素或达那普利局部治疗对内毒素血症肺损伤大鼠肺内凝血障碍有减轻作用，但不影响炎症反应。
Background: Pulmonary coagulopathy may contribute to an adverse outcome in lung injury. We assessed the effects of local anticoagulant therapy on bronchoalveolar and systemic haemostasis in a rat model of endotoxemia-induced lung injury.Methods: Male Sprague-Dawley rats were intravenously challenged with lipopolysaccharide (LPS) and treated with nebulized normal saline (placebo), recombinant human-activated protein C (APC), plasma-derived antithrombin (AT), heparin, or danaparoid.Results: Intravenous administration of LPS resulted in lung injury associated with elevated bronchoalveolar levels of thrombin-antithrombin complex (TATc), 6.9 +/- 0.8 ng/mL (placebo) versus 0.5 +/- 0.2 ng/mL (healthy control) (p < 0.01), and elevated bronchoalveolar levels of fibrin degradation products (FDP), 555 +/- 74 ng/mL versus 27 +/- 12 ng= mL (p < 0.01). Nebulized APC, AT, and danaparoid all significantly limited the rise of bronchoalveolar levels of TATc, 2.4 +/- 0.7 ng/mL), 1.5 +/- 0.2, 3.8 +/- 0.7, and 3.2 +/- 0.9 ng= mL, respectively (all p < 0.01 vs. placebo), and fibrin degradation products, 243 +/- 77, 113 +/- 20, 317 +/- 74, and 300 +/- 42 ng= mL (all p < 0.01 vs. placebo). Heparin and danaparoid also significantly affected systemic coagulopathy. However, pulmonary inflammatory responses [neutrophil influx into the lungs, bronchoalveolar levels of myeloperox-idase, and bronchoalveolar levels of tumor necrosis factor (TNF), interleukin (IL)-6 and CINC-3], and histopathology of lungs were not affected by nebulization of anticoagulants.Conclusions: In conclusion, local treatment with APC, AT, heparin, or danaparoid attenuate pulmonary coagulopathy, but not inflammation, in rats with endotoxemia-induced lung injury.