EVALUATION OF A GPIIB IIIA ANTAGONIST YM337 IN A PRIMATE MODEL OF MIDDLE CEREBRAL-ARTERY THROMBOSIS/

We compared the antithrombotic effect of anti-GPIIb/IIIa antibody Fab fragment YM337 with that of a thromboxane A(2) synthetase inhibitor, s odium ozagrel. With the monkeys under halothane anesthesia, the right middle cerebral artery was observed via a transorbital approach withou t cutting the dura mater. Photoillumination (wavelength 510 nm) was ap plied to the middle cerebral artery, and then rose bengal (20 mg kg(-1 )) was administered intravenously. The experimental drugs were intrave nously injected 15 min before rose bengal injection and followed by co ntinuous infusion for 3 h after dye injection. The thrombotic occlusio n induced by this photochemical reaction in monkey middle cerebral art ery was reproducible. YM337 significantly prolonged the time to first occlusion and the total time of arterial patency during the 3-h observ ation period after dye injection. In contrast, sodium ozagrel had no s ignificant effect. YM337 but not sodium ozagrel significantly inhibite d ex vivo ADP-induced platelet aggregation. However, while sodium ozag rel significantly inhibited the thromboxane B-2 generation accompanyin g arachidonic acid-induced platelet aggregation, YM337 had no effect o n this variable. Neurological deficit in the YM337-treated animals was significantly milder than that in the control group. The area of infa rct in the YM337 treatment animals was smaller than that in the contro l group. The novel selective GPIIb/IIIa antagonist YM337 was effective in ameliorating the decrease in patency of the middle cerebral artery and reducing the area of cerebral infarction in monkeys. (C) 1998 Els evier Science B.V.