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DOI: 10.1055/s-0038-1650402
A Novel Platelet Activating Factor Antagonist, SM-12502, Attenuates Endotoxin-induced Disseminated Intravascular Coagulation and Acute Pulmonary Vascular Injury by Inhibiting TNF Production in Rats
Publikationsverlauf
Received 20. Oktober 1995
Accepted after resubmission 27. Februar 1996
Publikationsdatum:
27. Juli 2018 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/199606/lookinside/thumbnails/10-1055-s-0038-1650402-1.jpg)
Summary
Adult respiratory distress syndrome and disseminated intravascular coagulation are important pathologic conditions affecting the outcome of patients with sepsis. To elucidate the possible therapeutic efficacy of SM-12502, a novel platelet activating factor antagonist, on acute lung injury and disseminated intravascular coagulation in sepsis, we investigated the effect of SM-12502 on an endotoxin (ET)-induced septic model in rats. SM-12502 prevented ET-induced increases in pulmonary vascular permeability and ET-induced histologic changes, such as leukocyte infiltration and pulmonary interstitial edema, 6 h following the administration of ET (5 mg/kg). SM-12502 also inhibited the decrease in fibrinogen and the increase in fibrin and fibrinogen degradation products observed following ET administration. SM-12502 prevented increases in the serum concentration of tumor necrosis factor (TNF) 90 min following ET administration in vivo, and significantly inhibited the production of TNF-α by ET-stimulated monocytes in vitro.
These findings suggest that SM-12502 attenuates the actions of endotoxin by the inhibition of TNF production
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