It is well recognized that thromboxane A2(TXA2) plays an important role in platelet reactivity. To determine the role of TXA2 in platelet-vessel wall (P-V) interaction, the effect of 1-benzylimidazole (1-BI), a specific inhibitor of thromboxane synthetase, and 13-azaprostanoic acid (APA), a TXA2 antagonist, on platelet thrombus formation was evaluated in vivo in NZW male rabbits using the autologous indium-111 (111In) labeled platelet technique. Rabbits were treated with intravenous 1-BI or APA or vehicles. After injection of autologous 111In-platelets, de-endothelialization of the abdominal aorta was created by a balloon catheter technique. At 3 hrs, blood samples were obtained and the animals were sacrificed. The aortae were removed and the injured and uninjured segments were dissected. Radioactivity counts and dry weight of the tissues and blood were determined. The vascular radioactivity counts were converted to platelet numbers by using a standard linear calibration curve. As small numbers of platelets adhered to normal vessel wall nonspecifically, this number was subtracted to obtain specific platelet accumulation at the injured sites. 1-BI at 10mg/kg reduced the specific platelet accumulation significantly (n=5, 12.3±S.D.I.5×106 pl/gm tissue; p<0.01) when compared with the controls (n=10, 33.0±5.1×106 pl/gm tissue). Platelet accumulation was further reduced by increasing the dosage to 30mg/kg. By contrast, APA injection (10mg/kg) had no significant effect. However, when APA was given by constant infusion at 250μg/kg/min 1 hr prior to injury, the APA-treated animals had an 80% reduction of platelet accumulation relative to controls. These findings indicate that TXA2 plays an important role in P-V interaction and specific inhibition of TXA2 appears to be efficacious in eliminating platelet thrombus formation.
SIN-1 reduces platelet adhesion and platelet thrombus formation in a porcine model of balloon angioplasty.