title: Nebulized anticoagulants limit pulmonary coagulopathy, but not inflammation, in a model of experimental lung injury.
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.
authors.affiliation: Laboratory of Experimental Intensive Care and Anesthesiology (LEICA), Academic Medical Center, University of Amsterdam , Amsterdam, The Netherlands. j.j.hofstra@amc.uva.nl
authors.forename: Jorrit J
authors.initials: JJ
authors.lastname: Hofstra
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Vlaar
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Cornet
authors.forename: Barry
authors.initials: B
authors.lastname: Dixon
authors.forename: Joris J
authors.initials: JJ
authors.lastname: Roelofs
authors.forename: Goda
authors.initials: G
authors.lastname: Choi
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
authors.forename: Marcel
authors.initials: M
authors.lastname: Levi
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Schultz
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000494:pharmacology*; D001778:Blood Coagulation Disorders / Q000188:drug therapy* / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000150:complications; D006487:Hemostasis / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy* / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000187:drug effects / Q000473:pathology; D055370:Lung Injury / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D009330:Nebulizers and Vaporizers; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000925:Anticoagulants; D008070:Lipopolysaccharides