Summary
We have evaluated the effects of the xanthine derivate HWA 138 in rat endotoxemia
in order to 1) prevent coagulation disturbances and other endotoxin-induced physiological
abnormalities and 2) to reduce mortality. We performed two studies using two different
models (sensitized vs non-sensitized rats) with a similar mortality but different
severity of coagulation disturbances: a) LPS (15 mg/kg) alone or with HWA 138 (80
mg/kg) as a treatment modality 30 min pre LPS, b) galactosamine (500 mg/ kg) simultaneously
with LPS (100 µg/kg) with or without HWA 138 (80 mg/kg) pretreatment. Experiments
c) and d) employed D-galactosamine and/or LPS similar to experiments a) and b), while
HWA 138 was applied simultaneously. We found significant 1) amelioration of life-threatening
coagulation disturbances in non-sensitized rats, 2) prevention of liver dysfunction
in sensitized rats, 3) reduction of TNF formation in both models, and 4) improvement
of survival in all groups receiving HWA 138. Our data indicate protective effects
of HWA 138 against clotting disturbances either directly via reduced LPS-induced formation
of procoagulant activity or indirectly via reduced TNF formation.
