The reduction of platelet thrombi on damaged vessel wall by a thromboxane synthetase inhibitor in rabbits.

The role of thromboxane A2 (TXA2) in platelet-vessel wall interaction was investigated using 1-benzylimidazole (1-BI), a selective thromboxane synthetase inhibitor. 1-BI (0.9 mM) will reduce the aggregatory response of rabbit platelets to 0.2 mM arachidonate by 50% and their production of TXA2 by 84%. The effect of 1-BI on platelet thrombus formation was evaluated in vivo on New Zealand white male rabbits using the autologous indium-111 labeled platelet technique. After injection of autologous 111In-platelets, 10 cm of the abdominal aorta was de-endothelialized with a balloon catheter. Three hours later the animals were sacrificed and injured and uninjured segments of the aorta removed. The radioactivity and dry weight of the tissue were determined. The radioactivity/gm of tissue was greater for the injured tissue than for the uninjured tissue. 1-BI at 10 mg/kg reduced the specific platelet accumulation at the injured site (n = 5; 4.8 +/- 0.3 X 10(5) cpm/gm) compared to the controls (n = 10; 11.7 +/- 2.1 X 10(5) cpm/gm). Platelet accumulation on the injured tissue was further reduced by increasing the dosage to 30 mg/kg. Thirty minutes after 1-BI administration (30 mg/kg), platelets were less sensitive to arachidonate-induced aggregation (a 67% decrease) and TXA2 production was decreased 82%. Alterations in platelet sensitivity persisted for up to 3 hours. These findings indicate that TXA2 plays an important role in platelet-vessel wall interaction.