Effect of Various Antiplatelet Agents on Acute Arterial Thrombosis in the Rat

 

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Summary

Electrical stimulation of the rat carotid artery causes a deep medial injury and the formation of a platelet-rich thrombus.

Occlusive thrombosis at sites of vessel wall injury was significantly reduced after the oral administration of clopidogrel, a potent analogue of ticlopidine, which showed dose-dependent inhibition of the thrombus formation (ED₅₀ = 1.0 ±0.2 mg/kg, p.o.). Accumulation of thrombotic material was also considerably reduced after the i. v. administration of SR 27417, a highly potent and selective platelet activating factor receptor antagonist (ED₅₀ = μg/kg, i.v.), nafagrel, a thromboxane A₂ synthetase inhibitor (ED₅₀ = 1.3 mg/kg, i.v.) and hirudin (ED₅₀ = 140 μg/ kg, i.v.). A high dose (20 mg/kg, i.v.) of the anti-adhesive tetrapeptide Arg-Gly-Asp-Ser (RGDS) showed only a slight effect on thrombus formation whereas aspirin was ineffective.

These results confirm that ADP and thromboxane A₂ play key roles in the initiation and progression of arterial thrombus formation and suggest that platelet activating factor may also modulate thrombosis in this experimental model.

• References

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