Nebulized anticoagulants limit pulmonary coagulopathy, but not inflammation, in a model of experimental lung injury.
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.
Hofstra
Jorrit J
JJ
Laboratory of Experimental Intensive Care and Anesthesiology (LEICA), Academic Medical Center, University of Amsterdam , Amsterdam, The Netherlands. j.j.hofstra@amc.uva.nl
Vlaar
Alexander P
AP
Cornet
Alexander D
AD
Dixon
Barry
B
Roelofs
Joris J
JJ
Choi
Goda
G
van der Poll
Tom
T
Levi
Marcel
M
Schultz
Marcus J
MJ
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
D000925:Anticoagulants; D008070:Lipopolysaccharides