Effect of Beraprost Sodium on Neointimal hyperplasia after Sstent implantation : Experimental study in canine

目的：血管内支架是一种广泛接受的狭窄血管病变治疗方法。然而，急性血栓形成和晚期新生内膜形成仍然是一个问题。因此，我们测试的假设，短期管理的贝前列素钠（贝前列素），一个稳定的前列腺素12类似物与抗血小板聚集和抗增殖活性，将减少支架植入后的新生内膜增厚。材料和方法：在本研究的第一部分，Z-支架被放置在12只狗的髂静脉。6只犬输注贝前列素，另6只犬输注生理盐水作为对照组。从支架植入前30分钟开始，静脉注射生理盐水和贝前列素（0.35 μg/kg/min），持续5个半小时。在给药前和给药后，测量5 '-二磷酸腺苷（5μM）诱导的血小板聚集。在两组中，在支架植入后第3、7和14天各处死两只犬。普罗利夫 ...更多信息 用增殖细胞核抗原（PCNA）免疫组化染色定量血管平滑肌细胞（SMC）的脱落。在这项研究的第二部分，我们使用了另外10只狗。与第一部分相似，在右髂静脉中放置Z形支架，并输注贝前列素。三天后，另一个Z形支架被放置在对侧，盐水输注作为对照。在4周时，处死犬，在光学显微镜下使用内膜与中膜面积比测量新生内膜厚度。结果：所有血管在切取时均通畅。与对照组相比，治疗组的离体血小板聚集显著抑制约30%（p = 0.01）。支架术后7、14 d，治疗组SMC增殖活性明显低于未治疗组。我们观察到治疗侧和未治疗侧之间内膜与中膜面积比的显著差异（分别为1.30[-+]0.80和2.00[-+]1.23; p < 0.05）。结论：贝前列素短期给药可显著抑制血小板聚集和SMC增殖，并随后减少支架植入后新生内膜增厚。少

PURPOSE : Endovascular stents are a widely accepted treatment for stenotic vascular lesions. However, acute thrombosis and late neointimal formation remain a concern. Therefore, we tested the hypothesis that short-term administration of beraprost sodium (beraprost), a stable prostaglandin 12 analogue with antiplatelet-aggregatory and antiproliferative activities, would reduce neointimal thickening after stent implantation.MATERIALS AND METHODS : In the first part of this study, Z-stents were placed in the iliac veins of 12 dogs. Six dogs were infused with beraprost and the other 6 dogs were infused with saline as a control group. Both saline and beraprost (0.35 μg/kg/min) were administered intravenously for five and a half hours, beginning 30 minutes before stent implantation. Platelet aggregation induced by adenosine 5'-diphosphate (5μM) was measured before and after drug administration. In both groups, two dogs were killed on each of days 3, 7, and 14 after stent implantation. Prolif … More eration of vascular smooth muscle cells (SMCs) was quantified by immunohistochemical staining with proliferating cell nuclear antigen (PCNA). In the second part of this study, we used another 10 dogs. A Z-stent was placed in the right iliac vein with beraprost infusion similarly to the first part. Three days later, another Z-stent was placed contralaterally with saline infusion as a control. At 4 weeks, the dogs were sacrificed, and neointimal thickness was measured under light microscopy using the intima to media area ratio. The measurements were analyzed statistically.RESULTS : All the vessels were patent at the time of harvest. Ex vivo platelet aggregation was significantly suppressed in the treated group, by approximately 30% compared to the control group (p = 0.01). SMC proliferative activity was significantly lower in the treated group than in the untreated group 7 and 14 days after stenting. We observed a significant difference in the intima to media area ratio between the treated and untreated sides (1.30【minus-plus】0.80 versus 2.00【minus-plus】1.23, respectively ; p < 0.05).CONCLUSIONS : Short-term administration of beraprost significantly suppresses platelet aggregation and SMC proliferation, and subsequently reduces neointimal thickening after stent implantation. Less