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

Abstract

Abstract

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 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.

Conclusions:

In conclusion, local treatment with APC, AT, heparin, or danaparoid attenuate pulmonary coagulopathy, but not inflammation, in rats with endotoxemia-induced lung injury.