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Thromboxane A2 (TXA2) after vascular injury plays an important role in the process of restenosis. S-1452, a potent and selective TXA2 receptor antagonist, blocks the receptors of vascular smooth muscle cells (VSMC) as well as platelets. The purpose of this study was to determine whether S-1452 could reduce platelet deposition and intimal hyperplasia in vascular injury models. New Zealand White Rabbits (n = 41) were fed a 0.5% cholesterol diet. For the short-term study, eighteen rabbits after balloon injury of iliac artery were assigned to 3 groups; systemic administration of S-1452, single local administration of S-1452 using a local delivery balloon, and single local administration of saline solution. Platelet deposition in injured artery using 111In-labeled platelets was reduced by 50% in systemic administration and by 60% in local administration compared to saline infusion. For the long-term study, balloon injury of the iliac artery was performed 4 weeks after starting the 0.5% cholesterol diet. Twenty-three rabbits were classified into 4 groups; systemic administration of S-1452, oral placebo administration, single local administration of S-1452, and local administration of saline solution (control group). The platelet aggregation induced by U-46619 was significantly lower in the S-1452 group than in the control group. Systemic administration of S-1452 significantly reduced the intimal area (152 +/- 33 vs 735 +/- 135 microm2, p &lt; 0.001) and number of cells in the intima (513 +/- 57 vs 993 +/- 57, p &lt; 0.01) compared to controls. In contrast, a single local administration failed to reduce neointimal thickness. Systemic administration of S-1452 reduced intimal hyperplasia as well as platelet deposition in a rabbit injury model, but its single local administration inhibited only platelet deposition.

Effects of the Thromboxane A2 Receptor Antagonist on Platelet Deposition and Intimal Hyperplasia After Balloon Injury.