Yamagami S, Miyauchi K, Kimura T, Goh Y, Daida H, Yamaguchi H
Department of Cardiology, Juntendo University School of Medicine, Tokyo, Japan.
Jpn Heart J. 1999 Nov;40(6):791-802. doi: 10.1536/jhj.40.791.
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.
血管损伤后产生的血栓素A2（TXA2）在再狭窄过程中起重要作用。S - 1452是一种强效且选择性的TXA2受体拮抗剂，可阻断血管平滑肌细胞（VSMC）以及血小板的受体。本研究的目的是确定S - 1452是否能减少血管损伤模型中的血小板沉积和内膜增生。给41只新西兰白兔喂食0.5%胆固醇饮食。在短期研究中，18只髂动脉球囊损伤后的兔子被分为3组；S - 1452全身给药组、使用局部给药球囊单次局部给予S - 1452组和单次局部给予盐溶液组。与输注生理盐水相比，111铟标记血小板在损伤动脉中的沉积，在全身给药组减少了50%，在局部给药组减少了60%。在长期研究中，在开始0.5%胆固醇饮食4周后进行髂动脉球囊损伤。23只兔子被分为4组；S - 1452全身给药组、口服安慰剂组、单次局部给予S - 1452组和局部给予盐溶液组（对照组）。S - 1452组中由U - 46619诱导的血小板聚集明显低于对照组。与对照组相比，S - 1452全身给药显著减少了内膜面积（152±33对735±135平方微米，p<0.001）和内膜中的细胞数量（513±57对993±57，p<0.01）。相比之下，单次局部给药未能减少新生内膜厚度。在兔损伤模型中，S - 1452全身给药减少了内膜增生以及血小板沉积，但其单次局部给药仅抑制了血小板沉积。
