| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
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
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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
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