Inhibitory effect of prostaglandin E-1 on intimal thickening caused by poor runoff conditions in the canine autologous vein grafts

The efficacy of ONO-1608, a newly developed liposomal formulation of prosta glandin E-1 prodrug, was evaluated on intimal hyperplasia of experimental c anine autologous vein grafts under distal poor runoff conditions. The femor al vein was implanted into the femoral artery, preparing a distal poor runo ff canine model. After 4 weeks of preparing the poor runoff model. the femo ral vein was implanted into the femoral artery. They were then divided into two groups consisting of the control group and the ONO-1608 group. At 4 we eks. the grafts were harvested and intimal hyperplasia of the graft was mea sured with an ocular cytometer. Intimal cell proliferation was determined b y bromodeoxyuridine incorporation 2 weeks after surgery. In addition. the e ffect of ONO-1608 on the proliferation of platelet-derived growth factor (P DGF)-stimulated human aortic smooth muscle cells (HASMCs) in culture was al so investigated. At 4 weeks, the degree of intimal hyperplasia of the graft in the ONO-1608 group was significantly less than that of the control grou p. The bromodeoxyuridine labeling index 2 weeks after grafting was signific antly lower in the ONO-1608 group compared with that in the control group. In addition, ONO-1608 significantly inhibited the proliferation of PDGF-sti mulated HASMCs in culture. These results demonstrate the efficacy of ONO-16 08 in reducing the degree of intimal hyperplasia of canine autogenous vein grafts under poor runoff conditions. The mechanism of reducing the intimal hyperplasia may be that ONO-1608 inhibited PDGF-stimulated proliferation of the smooth muscle cell. These results suggest that the administration of O NO-1608 may be beneficial in patients who have undergone gone arterial reco nstruction.