title: Nebulized anticoagulants limit coagulopathy but not inflammation in pseudomonas aeruginosa-induced pneumonia in rats.
abstract: 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. In this randomized controlled in vivo laboratory study, rats were challenged intratracheally 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. Induction of P. aeruginosa pneumonia resulted in activation of pulmonary coagulation and inhibition of pulmonary fibrinolysis, as reflected by increased pulmonary levels of thrombin-AT complexes and fibrin degradation products and decreased pulmonary levels plasminogen activator activity. Pseudomonas aeruginosa pneumonia was accompanied by systemic coagulopathy, since systemic levels of thrombin-AT complexes increased, and systemic levels of plasminogen activator activity decreased. Although rh-APC and plasma-derived AT potently limited pulmonary coagulopathy, neither heparin nor danaparoid affected net pulmonary fibrin turnover. Recombinant human APC also displayed systemic anticoagulant effects. Neither bacterial clearance nor pulmonary inflammation was affected by anticoagulant therapy. 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: Laboratory of Experimental Intensive Care and Anesthesiology (LEICA), Academic Medical Center, University of Amsterdam, the Netherlands.
authors: Alexander D
authors: AD
authors: Cornet
authors: Jorrit J
authors: JJ
authors: Hofstra
authors: Alexander P
authors: AP
authors: Vlaar
authors: Floor E
authors: FE
authors: van den Boogaard
authors: Joris J
authors: JJ
authors: Roelofs
authors: Tom
authors: T
authors: van der Poll
authors: Marcel
authors: M
authors: Levi
authors: A B Johan
authors: AB
authors: Groeneveld
authors: Marcus J
authors: MJ
authors: Schultz
mesh_terms: D000818:Animals; D000925:Anticoagulants; D000991:Antithrombins / Q000627:therapeutic use; D001777:Blood Coagulation / Q000187:drug effects; D002809:Chondroitin Sulfates / Q000627:therapeutic use; D003871:Dermatan Sulfate / Q000627:therapeutic use; D005342:Fibrinolysis / Q000187:drug effects; D006493:Heparin / Q000627:therapeutic use; D006497:Heparan Sulfate / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy*; D008297:Male; D011014:Pneumonia / Q000188:drug therapy* / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000472:pathogenicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D006493:Heparin; D006497:Heparan Sulfate; C035838:danaparoid