Effects of the thromboxane A2 receptor antagonist on platelet deposition and intimal hyperplasia after balloon injury.
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.
Yamagami
S
S
Department of Cardiology, Juntendo University School of Medicine, Tokyo, Japan.
Miyauchi
K
K
Kimura
T
T
Goh
Y
Y
Daida
H
H
Yamaguchi
H
H
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*
D001643:Bridged Bicyclo Compounds; D005229:Fatty Acids, Monounsaturated; D010975:Platelet Aggregation Inhibitors; D017482:Receptors, Thromboxane; C056566:S 145