A novel fibrinolytic
enzyme,
FII(a), was isolated from Agkistrodon acutus
venom, which can degrade
fibrin/
fibrinogen and dissolve
thrombus without activating
plasminogen or influencing the activities of
tissue plasminogen activator (t-PA) and
plasminogen activator inhibitor type-1 (PAI-1). In this study, we evaluated the effect of
FII(a) on
lipopolysaccharide (LPS)-induced experimental
disseminated intravascular coagulation (
DIC) in rabbits, through the continuous infusion of 100-microg/kg/h LPS for a period of 6 h. Seven groups were established: LPS control,
FII(a) (0.1, 0.3, and 0.6 mg/kg/h, respectively),
heparin control (100 IU/kg/h),
heparin +
FII(a) (
heparin 100 IU/kg/h associated with
FII(a) 0.3 mg/kg/h), and a saline control group. A continuous injection of LPS induced a gradual impairment in
hemostatic parameters, kidney
fibrin deposition, and a high mortality rate. The
intravenous administration of
FII(a) improved the concentration of
fibrinogen, the activities of
protein C,
plasminogen, t-PA,
antithrombin III (ATIII), and
PAI-1. Kidney
fibrin deposition and the mortality also decreased. In the in vitro experiments,
FII(a) can degrade
fibrin/
fibrinogen and high-dose
FII(a) enhanced the activity of
protein C. These findings suggest that the effects of
FII(a) on LPS-induced
DIC were from
fibrinogen degradation and enhanced
protein C activity. The simultaneous administration of
FII(a) and
heparin further improved all the
hemostatic parameters, including decreased kidney
fibrin deposition, and none of the rabbits died within 24 h, which indicates that the effects were mediated by degradation of
fibrin/
fibrinogen together with
thrombin inhibition. We conclude that
FII(a) may be useful in the treatment of
DIC.