ME3277, a GPIIb/IIIa antagonist reduces cerebral infarction without enhancing intracranial hemorrhage in photothrombotic occlusion of rabbit middle cerebral artery

Ken Ichi Kawano, Kazuyuki Fujishima, Yasuhiko Ikeda, Kazunao Kondo, Kazuo Umemura

研究成果: Article査読

23 被引用数 (Scopus)

抄録

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 · h, middle dose, (M); 0.3 mg/kg + 0.25 mg/kg · h and high dose, (H); 0.6 mg/kg + 0.5 mg/kg · h), aspirin (20 mg/kg) and sodium ozagrel (thromboxane A2 synthase inhibitor, 1 mg/kg + 2 mg/kg · 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.

本文言語English
ページ(範囲)988-997
ページ数10
ジャーナルJournal of Cerebral Blood Flow and Metabolism
20
6
DOI
出版ステータスPublished - 2000
外部発表はい

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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