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.

DESIGN:

A controlled in vivo laboratory study.

SETTING:

Research laboratory of a university hospital.

SUBJECTS:

Total of 98 male Sprague-Dawley rats.

INTERVENTIONS:

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.

MEASUREMENTS AND MAIN 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: Goda Choi, Jorrit-Jan H Hofstra, Joris J T H Roelofs, Anita W Rijneveld, Paul Bresser, Jaring S van der Zee, Sandrine Florquin, Tom van der Poll, Marcel Levi, Marcus J Schultz
• Journal: Critical care medicine (Crit Care Med) Vol. 36 Issue 1 Pg. 204-10 (Jan 2008) ISSN: 1530-0293 [Electronic] United States
• PMID: 18090375 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antithrombins

Topics

• Animals
• Antithrombins (therapeutic use)
• Blood Coagulation (drug effects)
• Bronchoalveolar Lavage Fluid (microbiology)
• Colony Count, Microbial
• Disease Models, Animal
• Male
• Pneumonia (blood, drug therapy, etiology, pathology)
• Pneumonia, Pneumococcal (blood, complications, drug therapy, microbiology, pathology)
• Rats
• Rats, Sprague-Dawley
• Respiratory Distress Syndrome (blood, drug therapy, etiology, pathology)