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Titolo:
Superiority of platelet integrin GPIlb-IIIa receptor antagonist over aspirin in preventing cyclic flow reductions in the guinea pig middle cerebral artery
Autore:
Kawano, K; Ikeda, Y; Kondo, K; Umemura, K;
Indirizzi:
Hamamatsu Univ, Sch Med, Dept Pharmacol, Hamamatsu, Shizuoka 4313192, Japan Hamamatsu Univ Hamamatsu Shizuoka Japan 4313192 , Shizuoka 4313192, Japan
Titolo Testata:
EUROPEAN JOURNAL OF PHARMACOLOGY
fascicolo: 3, volume: 374, anno: 1999,
pagine: 377 - 385
SICI:
0014-2999(19990625)374:3<377:SOPIGR>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
THROMBOXANE A(2) FORMATION; PLASMINOGEN-ACTIVATOR; CORONARY ANGIOPLASTY; ANTIBODY FRAGMENT; FEMORAL-ARTERY; AGGREGATION; RAT; SHEAR; MODEL; OCCLUSION;
Keywords:
ME3277; aspirin; cyclic flow reductions; photochemical reaction; cerebral ischemia; platelet integrin GPIIb-IIIa receptor;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Kawano, K Hamamatsu Univ, Sch Med, Dept Pharmacol, Hamamatsu, Shizuoka 4313192, Japan Hamamatsu Univ Hamamatsu Shizuoka Japan 4313192 4313192, Japan
Citazione:
K. Kawano et al., "Superiority of platelet integrin GPIlb-IIIa receptor antagonist over aspirin in preventing cyclic flow reductions in the guinea pig middle cerebral artery", EUR J PHARM, 374(3), 1999, pp. 377-385

Abstract

We established a photothrombotic occlusion model in the guinea pig middle cerebral artery. In this model, the middle cerebral artery was recanalized within 10 to 20 mill after thrombotic occlusion. with subsequent cyclic flow reductions. Cyclic flow reductions in the middle cerebral artery are expected to manage cerebral infarction by modulating arterial patency. Therefore, we evaluated the effect of several antiplatelet agents on the frequency of cyclic flow reductions and subsequent cerebral infarction using this model. A platelet integrin GPIIb-IIIa receptor antagonist, ME3277 (sodium hydrogen [4-[(4,5,6,7-tetrahydrothieno[3,2 c]pyridin-2-yl) carbonylamino] acetyl-o-phenylene] dioxydiacetate. 0.3, 1 and 3 mg/kg i.v.) dose-dependently inhibited the ex vivo platelet aggregation induced by ADP (5 mu M) collagen (0.8 and 20 mu g/ml) and arachidonic acid (100 mu M). While the same doses of ME3277 reduced the frequency of the cyclic flow reductions and increased the total patency time of the middle cerebral artery, time to thrombotic occlusion was prolonged only at the highest dose, 3 mg/kg. ME3277 (0.3-3 mg/kg) significantly reduced the infarct volume and improved the neurological deficit at 24 h. In contrast, aspirin (30 mg/kg) did not affect these variables in spite of complete inhibition of platelet aggregation induced by arachidonic acid and collagen (0.8 mu g/ml). A thrombuxane A(2) synthetase inhibitor, sodium ozagrel, significantly increased the total patency time and reduced the infarct volume at 30 mg/kg. Inhibition of prostaglandin I-2 generation could explain the effectiveness of sodium ozagrel but not aspirin inthis model. These results suggest that platelet integrin GPIIb-IIIa receptor antagonists are more beneficial than aspirin for the treatment of cerebral thrombosis. (C) 1999 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/12/20 alle ore 05:05:58