Anti-platelet effects of clopidogrel in rat middle cerebral artery thrombosis model.
We have developed a model whereby the middle cerebral artery (MCA) in an experimental animal can be occluded by photochemical reaction between rose bengal and green light which causes endothelial injury followed by platelet adhesion, aggregation and formation of a platelet and fibrin-rich thrombus at the site of photochemical reaction. Using this model, we investigated the effect of clopidogrel, an analogue of ticlopidine which is a potent inhibitor of adenosine 5'-diphosphate (ADP)-induced platelet aggregation. Oral clopidogrel (3-10mg/kg) inhibited ex-vivo platelet aggregation induced by ADP, thrombin or the thromboxane A2 mimetic, and U46619, when platelets had been primed with low concentration of phorbol myristate acetate. At these doses, clopidogrel significantly (P < 0.001) prolonged the time to produce thrombotic occlusion of the MCA and induced a significant (P < 0.001) reduction in the size of ischaemic cerebral damage examined 24 hours after photochemical reaction. The results suggest that ADP has a key role in the thrombotic occlusion of the MCA in this model. Clopidogrel may be beneficial in the prevention of arterial thrombosis.
Umemura
K
K
Department of Pharmacology, Hamamatsu University School of Medicine, Japan.
Ishihara
H
H
Nakashima
M
M
D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000077144:Clopidogrel; D002542:Intracranial Embolism and Thrombosis / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000378:metabolism; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology
D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D013917:Thrombin; D013988:Ticlopidine