title: Antithrombin inhibits bronchoalveolar activation of coagulation and limits lung injury during Streptococcus pneumoniae pneumonia in rats.
abstract: OBJECTIVE
  Alveolar fibrin deposition is a hallmark of pneumonia. It has been proposed that natural inhibitors of coagulation, including activated protein C, antithrombin, and tissue factor pathway inhibitor, exert lung-protective effects via anticoagulant and possibly anti-inflammatory pathways. We investigated the role of these natural anticoagulants in Streptococcus pneumoniae pneumonia.
  
  
  METHODS
  A controlled in vivo laboratory study.
  
  
  METHODS
  Research laboratory of a university hospital.
  
  
  METHODS
  Total of 98 male Sprague-Dawley rats.
  
  
  METHODS
  Rats were challenged intratracheally with S. pneumoniae (serotype 3, 10(6) colony forming units), inducing pneumonia. Rats were randomized to intravenous treatment with normal saline, activated protein C, antithrombin, tissue factor pathway inhibitor, heparin, or tissue-type plasminogen activator.
  
  
  RESULTS
  Rats infected with S. pneumoniae had increased thrombin-antithrombin complexes in bronchoalveolar lavage fluid, with decreased levels of antithrombin activity and fibrin degradation products. Administration of activated protein C, antithrombin, and tissue factor pathway inhibitor significantly limited these procoagulant changes. Furthermore, antithrombin treatment resulted in less bacterial outgrowth of S. pneumoniae and less histopathologic damage in lungs.
  
  
  CONCLUSIONS
  Anticoagulant treatment attenuates pulmonary coagulopathy during S. pneumoniae pneumonia. Antithrombin seems to exert significant lung-protective effects in pneumococcal pneumonia in rats.
authors: Department of Intensive Care Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. godachoi@mail.com
authors: Goda
authors: G
authors: Choi
authors: Jorrit-Jan H
authors: JJ
authors: Hofstra
authors: Joris J T H
authors: JJ
authors: Roelofs
authors: Anita W
authors: AW
authors: Rijneveld
authors: Paul
authors: P
authors: Bresser
authors: Jaring S
authors: JS
authors: van der Zee
authors: Sandrine
authors: S
authors: Florquin
authors: Tom
authors: T
authors: van der Poll
authors: Marcel
authors: M
authors: Levi
authors: Marcus J
authors: MJ
authors: Schultz
mesh_terms: D000818:Animals; D000991:Antithrombins / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects*; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D008297:Male; D011014:Pneumonia / Q000097:blood / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D011018:Pneumonia, Pneumococcal / Q000097:blood / Q000150:complications* / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology
chemical_list: D000991:Antithrombins