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, Marcus J Schultz

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    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.

    Original languageEnglish
    Pages (from-to)105-11
    Number of pages7
    JournalJournal of aerosol medicine and pulmonary drug delivery
    Volume23
    Issue number2
    DOIs
    Publication statusPublished - Apr-2010

    Keywords

    • Administration, Inhalation
    • Animals
    • Anticoagulants
    • Blood Coagulation Disorders
    • Bronchoalveolar Lavage Fluid
    • Disease Models, Animal
    • Endotoxemia
    • Hemostasis
    • Inflammation
    • Lipopolysaccharides
    • Lung
    • Lung Injury
    • Male
    • Nebulizers and Vaporizers
    • Rats
    • Rats, Sprague-Dawley

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