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Nebulized Anticoagulants Limit Coagulopathy but not Inflammation in Pseudomonas aeruginosa-induced Pneumonia in Rats.
MedLine Citation:
PMID:  21897338     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: Disturbed alveolar fibrin turnover is a characteristic feature of pneumonia. Inhibitors of coagulation could exert lung-protective effects via anticoagulant (inhibiting fibrin deposition) and possibly anti-inflammatory pathways, but could also affect host defense. METHODS: In this randomized controlled in vivo laboratory study, rats were challenged intra-tracheally with Pseudomonas aeruginosa, inducing pneumonia, and randomized to local treatment with normal saline (placebo), recombinant human activated protein C (rh-APC), plasma-derived antithrombin (AT), heparin or danaparoid. RESULTS: Induction of P. aeruginosa pneumonia resulted in activation of pulmonary coagulation and inhibition of pulmonary fibrinolysis, as reflected by increased pulmonary levels of thrombin-antithrombin complexes (TATc), fibrin degradation products (FDP), and decreased pulmonary levels plasminogen activator activity (PAA). P. aeruginosa pneumonia was accompanied by systemic coagulopathy, since systemic levels of TATc increased and systemic levels of PAA decreased. While rh-APC and plasma-derived AT potently limited pulmonary coagulopathy, neither heparin nor danaparoid affected net pulmonary fibrin turnover. rh-APC also displayed systemic anticoagulant effects. Neither bacterial clearance nor pulmonary inflammation was affected by anticoagulant therapy. CONCLUSION: Nebulization of rh-APC or plasma-derived AT attenuated pulmonary coagulopathy, but not bacterial clearance or inflammation, in a rat model of P. aeruginosa pneumonia.
Authors:
Alexander D Cornet; Jorrit J Hofstra; Alexander P Vlaar; Floor E van den Boogaard; Joris J Roelofs; Tom van der Poll; Marcel Levi; A B Johan Groeneveld; Marcus J Schultz
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-8-18
Journal Detail:
Title:  Shock (Augusta, Ga.)     Volume:  -     ISSN:  1540-0514     ISO Abbreviation:  -     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-9-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9421564     Medline TA:  Shock     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands: 1Laboratory of Experimental Intensive Care and Anesthesiology (L·E·I·C·A) 2Department of Intensive Care Medicine 3Department of Internal Medicine 4Department of Pathology 5Center for Experimental and Molecular Medicine (CEMM) 6HERMES Critical Care Group, Amsterdam, The Netherlands VU University Medical Center, Amsterdam, The Netherlands 7Department of Intensive Care Medicine.
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