GPIIb/IIIa antagonists are expected to have a beneficial effect on acute
cerebral infarction, however, the occurrence of
intracranial hemorrhage has not been as widely investigated. A rabbit focal thrombotic occlusion model of the middle cerebral artery was established by creating a photochemical reaction between green light and
Rose Bengal. Hemorrhagic transformation was common in the area of
cerebral infarction. Using this model, the effect of a GPIIb/IIIa antagonist,
ME3277 (low dose, (L); 0.15 mg/kg + 0.125 mg/kg x h, middle dose, (M); 0.3 mg/kg + 0.25 mg/kg x h and high dose, (H); 0.6 mg/kg + 0.5 mg/kg x h),
aspirin (20 mg/kg) and
sodium ozagrel (
thromboxane A2 synthase inhibitor, 1 mg/kg + 2 mg/ kg x h) were evaluated. Drugs were intravenously administrated 30 minutes after the photochemical reaction for 24 hours.
Aspirin inhibited the ex vivo platelet aggregation induced by
arachidonic acid and
collagen but not by
adenosine diphosphate (
ADP), while
sodium ozagrel only inhibited the
arachidonic acid-induced aggregation.
ME3277 dose-dependently inhibited the platelet aggregation induced by all the inducers (approximately 60% in L, 80% in M, and 90% in H). At 24 hours of middle cerebral artery (MCA) occlusion,
infarct volume was significantly reduced by
aspirin and each dose of
ME3277. These agents improved
neurologic deficits, with
ME3277 being more potent than
aspirin.
Sodium ozagrel did not alter the
infarct volume nor
neurologic deficits. No
drug was found to worsen
hemorrhage volume despite increasing bleeding time (2-3 fold) in the skin. In this model, the occluded artery was spontaneously recanalized and re-thrombosed frequently. One mechanism by which
antiplatelet agents reduced
infarct volume was inhibition of rethrombosis of the MCA. These results suggest that treatment with a GPIIb/IIIa antagonist is a useful intervention for acute
cerebral infarction prolonging dose bleeding time to 3 times the basal value.