title: Effects of the thromboxane A2 receptor antagonist on platelet deposition and intimal hyperplasia after balloon injury.
abstract: 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 < 0.001) and number of cells in the intima (513 +/- 57 vs 993 +/- 57, p < 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.
authors.affiliation: Department of Cardiology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Yamagami
authors.forename: K
authors.initials: K
authors.lastname: Miyauchi
authors.forename: T
authors.initials: T
authors.lastname: Kimura
authors.forename: Y
authors.initials: Y
authors.lastname: Goh
authors.forename: H
authors.initials: H
authors.lastname: Daida
authors.forename: H
authors.initials: H
authors.lastname: Yamaguchi
mesh_terms: D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D006965:Hyperplasia; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D011897:Random Allocation; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology*
chemical_list: D001643:Bridged Bicyclo Compounds; D005229:Fatty Acids, Monounsaturated; D010975:Platelet Aggregation Inhibitors; D017482:Receptors, Thromboxane; C056566:S 145