PMID- 20073557
OWN - NLM
STAT- MEDLINE
DCOM- 20100702
LR  - 20220310
IS  - 1941-2703 (Electronic)
IS  - 1941-2711 (Linking)
VI  - 23
IP  - 2
DP  - 2010 Apr
TI  - Nebulized anticoagulants limit pulmonary coagulopathy, but not inflammation, in a 
      model of experimental lung injury.
PG  - 105-11
LID - 10.1089/jamp.2009.0779 [doi]
AB  - 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.
FAU - Hofstra, Jorrit J
AU  - Hofstra JJ
AD  - Laboratory of Experimental Intensive Care and Anesthesiology (LEICA), Academic 
      Medical Center, University of Amsterdam , Amsterdam, The Netherlands. 
      j.j.hofstra@amc.uva.nl
FAU - Vlaar, Alexander P
AU  - Vlaar AP
FAU - Cornet, Alexander D
AU  - Cornet AD
FAU - Dixon, Barry
AU  - Dixon B
FAU - Roelofs, Joris J
AU  - Roelofs JJ
FAU - Choi, Goda
AU  - Choi G
FAU - van der Poll, Tom
AU  - van der Poll T
FAU - Levi, Marcel
AU  - Levi M
FAU - Schultz, Marcus J
AU  - Schultz MJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Aerosol Med Pulm Drug Deliv
JT  - Journal of aerosol medicine and pulmonary drug delivery
JID - 101475057
RN  - 0 (Anticoagulants)
RN  - 0 (Lipopolysaccharides)
MH  - Administration, Inhalation
MH  - Animals
MH  - Anticoagulants/administration & dosage/*pharmacology
MH  - Blood Coagulation Disorders/*drug therapy/physiopathology
MH  - Bronchoalveolar Lavage Fluid
MH  - Disease Models, Animal
MH  - Endotoxemia/complications
MH  - Hemostasis/drug effects
MH  - Inflammation/*drug therapy/physiopathology
MH  - Lipopolysaccharides/toxicity
MH  - Lung/drug effects/pathology
MH  - Lung Injury/*drug therapy/physiopathology
MH  - Male
MH  - Nebulizers and Vaporizers
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 2010/01/16 06:00
MHDA- 2010/07/03 06:00
CRDT- 2010/01/16 06:00
PHST- 2010/01/16 06:00 [entrez]
PHST- 2010/01/16 06:00 [pubmed]
PHST- 2010/07/03 06:00 [medline]
AID - 10.1089/jamp.2009.0779 [doi]
PST - ppublish
SO  - J Aerosol Med Pulm Drug Deliv. 2010 Apr;23(2):105-11. doi: 
      10.1089/jamp.2009.0779.