Treatment of in-stent restenosis with beraprost sodium: An experimental study of short-and intermediate-term effects in dogs

The aim of the present study was to evaluate the inhibitory effects of the short-term administration of beraprost sodium, a stable prostaglandin I ₂ analogue, on neointimal thickening after stenting. To examine the immediate and short-term effects, Z-stents were placed in the iliac veins of 12 dogs, which were randomly assigned to either a beraprost-treated or control (saline) group. Beraprost (0.35 μg/kg per min) or saline (1.5 mL/min) was administered 30 min before stenting and was continued for 5 h thereafter. Platelet aggregation was measured before and after drug administration. At 3, 7 and 14 days after stenting, dogs were killed and immunohistochemical staining for proliferating cell nuclear antigen was used to quantify the proliferation of vascular smooth muscle cells (SMC). To evaluate intermediate-term effects, a Z-stent was placed in the right iliac vein in 10 dogs, followed by beraprost treatment. Three days later, a second Z-stent was placed contralaterally with saline infusion as a control. After 4 weeks, dogs were killed and neointimal thickness was measured under a light microscope to calculate the intima : media area ratio. Platelet aggregation was more significantly suppressed in the beraprost-treated than in the control group (P = 0.01). In addition, SMC proliferation was significantly lower in the beraprost-treated group 7 and 14 days after stenting (P < 0.05). Over the intermediate term, the intima : media area ratio was significantly lower in the beraprost-treated vein compared with control (P < 0.05). In conclusion, short-term beraprost treatment during stenting suppresses in situ platelet aggregation and SMC proliferation, thus reducing neointimal thickening.