Am. J. Respir. Crit. Care Med., Vol 155, No. 2, 02 1997, 711-718.
Effect of nafamostat mesilate on pulmonary vascular injury induced by lipopolysaccharide in rats
M Uchiba, K Okajima, K Murakami, H Okabe and K Takatsuki
Department of Medicine, Kumamoto University Medical School, Japan.
Nafamostat mesilate (NM) is a synthetic protease inhibitor that is capable
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 investigated the
effect of NM on lipopolysaccharide (LPS)-induced pulmonary vascular injury
in rats. The intraperitoneal administration of NM prevented the pulmonary
vascular injury and coagulation abnormalities induced by LPS. DEGR-factor
VIIa, a selective inhibitor of factor VIIa, prevented the coagulation
abnormalities, but not the pulmonary vascular injury, induced by LPS. NM
did not reduce LPS- induced increase in pulmonary accumulation of
leukocytes. NM did not inhibit the increase in the plasma concentration of
tumor necrosis factor-alpha (TNF-alpha) observed after administration of
LPS. NM did not inhibit the function of activated neutrophils in vitro.
Plasma values of total serum hemolytic complement (CH50) were markedly
decreased after the administration of LPS. NM inhibited the LPS-induced
decrease in plasma CH50 values. Findings suggest that NM may reduce the
pulmonary vascular injury as well as the coagulation abnormalities induced
by LPS. The former effect may be independent of the anticoagulant effect
but dependent on the inhibitory effect of the activation of the complement
system in rats administered LPS.
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Copyright © 1997 American Thoracic Society
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