Laboratory of Experimental Intensive Care and Anesthesiology (LEICA), Academic Medical Center, University of Amsterdam , Amsterdam, The Netherlands.
J Aerosol Med Pulm Drug Deliv. 2010 Apr;23(2):105-11. doi: 10.1089/jamp.2009.0779.
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.
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.
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 myeloperoxidase, 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.
In conclusion, local treatment with APC, AT, heparin, or danaparoid attenuate pulmonary coagulopathy, but not inflammation, in rats with endotoxemia-induced lung injury.
肺凝血障碍可能导致肺损伤的不良后果。我们评估了局部抗凝治疗对脂多糖（LPS）诱导的肺损伤大鼠模型中肺泡和全身止血的影响。
雄性 Sprague-Dawley 大鼠静脉内给予 LPS，并给予雾化生理盐水（安慰剂）、重组人活化蛋白 C（APC）、血浆源性抗凝血酶（AT）、肝素或达那肝素。
静脉内给予 LPS 导致肺损伤，与肺泡中凝血酶-抗凝血酶复合物（TATc）水平升高相关，6.9±0.8ng/mL（安慰剂）与 0.5±0.2ng/mL（健康对照组）相比（p<0.01），肺泡中纤维蛋白降解产物（FDP）水平升高，555±74ng/mL 与 27±12ng/mL 相比（p<0.01）。雾化 APC、AT 和达那肝素均显著限制了肺泡中 TATc 水平的升高，分别为 2.4±0.7ng/mL、1.5±0.2ng/mL、3.8±0.7ng/mL 和 3.2±0.9ng/mL（均 p<0.01 与安慰剂），纤维蛋白降解产物为 243±77ng/mL、113±20ng/mL、317±74ng/mL 和 300±42ng/mL（均 p<0.01 与安慰剂）。肝素和达那肝素也显著影响全身凝血障碍。然而，抗凝剂雾化对肺部炎症反应[中性粒细胞浸润肺部、肺泡中髓过氧化物酶水平和肺泡中肿瘤坏死因子（TNF）、白细胞介素（IL）-6 和 CINC-3 水平]和肺组织病理学没有影响。
总之，在 LPS 诱导的肺损伤大鼠中，局部应用 APC、AT、肝素或达那肝素可减轻肺凝血障碍，但不能减轻炎症。
