Local Drug Delivery of ONO-4007 Inhibits Neointimal Hyperplasia in Dogs.

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ONO-4007 is a potent antineoplastic drug, which induces apoptosis in neoplastic cell. The aim of this study was whether facilitation of apoptosis in neointima after vascular injury could inhibit restenosis process by local ONO-4007 delivery. Methods : In eight dogs(13.2±2.2kg)bilateral femoral arteries were injured by three times 30 sec balloon inflation of PTCA catheter, which balloon size was 1.3〜1.5 times as large as the artery. In one side, ONO-4007(0.05mg or 0.5mg, n=4 in each group)was delivered by a microporous infusion catheter. In the other side saline was delivered as a control. Two or four weeks after balloon injury, the femoral arteries were resected and prepared for histological examination. Results : Total vassel area(VA)and medial area/VA did not differ between the groups. At four weeks, the intimal area/VA was significantly reduced in 0.5mg sites(2.75±1.06%)compared with the control sites(6.42±3.42%). Maximum neointimal thickness were significantly thinner in the treatment sites(0.05mg group, 65.5±64.4μm ; 0.5mg group, 50.5±21.7μm)than that in the control sites(128±104μm). At two weeks, Tunnel positive cells rate in the neointima were significantly increased in the treatment sites(71.4±14.1% vs 12.9±5.3%). Conclusion : These data indicate facilitation of apoptosis in the injured vassel by local ONO-4007 delivery inhibits neointimal hyperplasia in dog's femoral artery.