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

Hofstra, J. J., Vlaar, A. P., Cornet, A. D., Dixon, B., Roelofs, J. J., Choi, G., van der Poll, T., Levi, M. & Schultz, M. J., Apr-2010, In : Journal of aerosol medicine and pulmonary drug delivery. 23, 2, p. 105-11 7 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • 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

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
Issue number2
Publication statusPublished - Apr-2010


  • 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

ID: 29061102