Antithrombin inhibits bronchoalveolar activation of coagulation and limits lung injury during Streptococcus pneumoniae pneumonia in rats.
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.
Choi
Goda
G
Department of Intensive Care Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. godachoi@mail.com
Hofstra
Jorrit-Jan H
JJ
Roelofs
Joris J T H
JJ
Rijneveld
Anita W
AW
Bresser
Paul
P
van der Zee
Jaring S
JS
Florquin
Sandrine
S
van der Poll
Tom
T
Levi
Marcel
M
Schultz
Marcus J
MJ
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
D000991:Antithrombins