• J Aerosol Med Pulm Drug Deliv · Apr 2010

    Nebulized anticoagulants limit pulmonary coagulopathy, but not inflammation, in a model of experimental lung injury.

    • Jorrit J Hofstra, Alexander P Vlaar, Alexander D Cornet, Barry Dixon, Joris J Roelofs, Goda Choi, Tom van der Poll, Marcel Levi, and Marcus J Schultz.
    • Laboratory of Experimental Intensive Care and Anesthesiology (LEICA), Academic Medical Center, University of Amsterdam , Amsterdam, The Netherlands. j.j.hofstra@amc.uva.nl
    • J Aerosol Med Pulm Drug Deliv. 2010 Apr 1;23(2):105-11.

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

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