Nebulized Anticoagulants Limit Pulmonary Coagulopathy, But Not Inflammation, in a Model of Experimental Lung Injury

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