EFFECT OF NAFAMOSTAT MESILATE ON PULMONARY VASCULAR INJURY-INDUCED BYLIPOPOLYSACCHARIDE IN RATS

Nafamostat mesilate (NM) is a synthetic protease inhibitor that is cap able of inhibiting the various coagulation factors such as factor VIIa and thrombin. To determine whether NM may also be useful in treating adult respiratory distress syndrome (ARDS) related in sepsis, we inves tigated the effect of NM on lipopolysaccharide (LPS)-induced pulmonary vascular injury in rats. The intraperitoneal administration of NM pre vented the pulmonary vascular injury and coagulation abnormalities ind uced by LPS. DEGR-factor VIIa, a selective inhibitor of factor VIIa, p revented the coagulation abnormalities, but not the pulmonary vascular injury, induced by LPS. NM did not reduce LPS-induced increase in pul monary accumulation of leukocytes. NM did not inhibit the increase in the plasma concentration of tumor necrosis factor-alpha (TNF-alpha) ob served after administration of LPS. NM did not inhibit the function of activated neutrophils in vitro. Plasma values of total serum hemolyti c complement (CH50) were markedly decreased after the administration o f LPS. NM inhibited the LPS-induced decrease in plasma CH50 values. Fi ndings suggest that NM may reduce the pulmonary vascular injury as wel l as the coagulation abnormalities induced by LPS. The former effect m ay be independent of the anticoagulant effect but dependent on the inh ibitory effect of the activation of the complement system in rats admi nistered LPS.