Arterial
thrombosis in the rabbit was established as a novel model to evaluate the effects of
antithrombotic agents. Endothelial injury was produced by applying electrical stimulation to the femoral artery. The process of primary endothelial injury, and subsequent platelet activation and
fibrin formation were confirmed by electron microscopy. In this model, vessel occlusion occurred within 30 min after stimulation without changes in heart rate and blood pressure. Using this model, several agents were evaluated for their antithrombotic activities:
aspirin (30 mg/kg, p.o.),
ticlopidine (10-100 mg/kg, p.o.),
heparin (300 unit/kg, i.v.),
PPACK (10-33 micrograms/kg/min, i.v.),
WEB-2347 (1 mg/kg, p.o.) and
nicardipine (10 micrograms/kg, i.v.). Fifty per cent decrease in vessel temperature (T1/2), assessed by a thermic probe, averaged 15.1 +/- 1.2 (n = 11, p.o.) and 15.6 +/- 1.9 min (n = 8, i.v.) in the vehicle groups, and this was significantly prolonged by
aspirin (23.0 +/- 2.6 min),
ticlopidine at a dose of 100 mg/kg (24.6 +/- 2.5 min),
heparin (27.2 +/- 2.8 min) and
PPACK at a dose of 33 micrograms/kg (30.0 min). However,
WEB-2347 and
nicardipine were without effect. The effect of
aprosulate, a new class of polyanion with
anticoagulant activity, was further examined.
Aprosulate (1-30 mg/kg, i.v.) inhibited
thrombus formation in a dose-dependent manner. These results show that acute occlusive
thrombus can be readily and reproducibly formed in the rabbit femoral artery and suggest that this
thrombus formation depends on the activation of both platelets and blood coagulation. The merit of this model lies in its simplicity for evaluating the antithrombotic effects of antiplatelet and
anticoagulant agents and is therefore expected to be extensively used in the future.