External beam radiation attenuates venous neointimal hyperplasia in a pig model of arteriovenous polytetrafluoroethylene (PTFE) graft stenosis

Abstract

Purpose : Hemodialysis vascular access dysfunction is an enormous clinical problem that causes great morbidity and costs well over one billion dollars per annum. The vast majority of hemodialysis vascular access dysfunction occurs as a result of venous stenosis and thrombosis at the graft-vein anastomosis. At a cellular level, this venous stenosis is the result of venous neointimal hyperplasia (VNH). There are, unfortunately, no effective therapies for VNH. The purpose of this study was to assess the role of external radiation therapy in preventing VNH and venous stenosis. Methods and Materials : Seven-centimeter polytetrafluoroethylene loop grafts were placed bilaterally between the femoral artery and vein of 12 Yorkshire Cross pigs. One side was treated with a single 16-Gy dose of external beam radiation with a linear accelerator, while the contralateral side served as an internal control. Swine were killed after 28 days, and the grafts were carefully dissected out and removed. Neointimal hyperplasia and luminal stenosis were then assessed morphometrically at the graft-vessel anastomoses. Results : External beam radiation therapy significantly reduced the amount of luminal stenosis at the graft-vein anastomosis, with minimal local and systemic toxicity. Conclusions : External beam radiation therapy could be a useful and clinically relevant local treatment for venous stenosis in polytetrafluoroethylene dialysis grafts.