EFFECTS OF GP IIB IIIA RECEPTOR MONOCLONAL-ANTIBODY (7E3), HEPARIN, AND ASPIRIN IN AN EX-VIVO CANINE ARTERIOVENOUS SHUNT MODEL OF STENT THROMBOSIS/

Background Thrombosis is an important limitation of metallic coronary stents, especially in smaller Vessels in which shear rates are high. M onoclonal antibody to platelet glycoprotein IIb/IIIa receptor (7E3) ha s been shown to inhibit shear-induced platelet aggregation. In this st udy, we compared the effects of 7E3, heparin, and aspirin on stent thr ombosis in an ex vivo arteriovenous shunt model of high-shear blood fl ow. Methods and Results An ex vivo arteriovenous shunt was created in 10 anesthetized dogs. Control rough-surface slotted-tube nitinol stent s (n=72) expanded to 2 mm in diameter in a tubular perfusion chamber w ere interposed in the shunt and exposed to flowing arterial blood at a shear rate of 2100 s(-1) for 20 minutes. The animals were treated wit h intravenous murine 7E3 (Fab')(2) (0.2, 0.4, and 0.8 mg/kg), heparin (100 U/kg), or aspirin (10 mg/kg). Effects of the test agents on throm bus weight, platelet aggregation, platelet P-selectin expression, blee ding time, and activated clotting time (ACT) were quantified. 7E3 redu ced stent thrombosis by 95% (20+/-1 to 1+/-1 mg, P<.001) and platelet ag gregation by 94% (14+/-2 to 1+/-1 Ohm, P<.001) at the highest dose (0.8 mg/kg). 7E3 significantly prolonged bleeding time but had no effe ct on ACT and platelet P-selectin expression. Heparin prolonged ACT bu t had no significant effect on stent thrombosis or platelet aggregatio n. Aspirin, although it inhibited platelet aggregation by 65%, had no effect on stent thrombosis (19+/-2 Versus 20+/-1 mg in controls). Conc lusions 7E3 produced a dose-dependent inhibition of acute stent thromb osis under high-shear flow conditions. Stent thrombosis was resistant to heparin and aspirin. Thus, 7E3 may be an effective agent for preven ting stent thrombosis.