Abstract 554: Rabbit Arteriovenous Fistula Model and Identification of a Therapeutic Agent to Increase Fistula Patency

Abstract

An arteriovenous fistula (AVF) is a vein graft which is created to permit vascular access allowing haemodialysis to be performed in renal failure patients. AVF using native tissues is the preferred surgical option; however AVF are associated with failure rates as high as 50% at 6 months. Failure is principally due to vascular cell proliferation, leading to the development of neointima causing stenosis and impaired blood flow. The aims of this study were to 1) develop a rabbit model of AVF remodelling, 2) investigate the contribution of cannulation injury in AVF remodelling and 3) identify a potential therapeutic which could be delivered topically to reduce AVF stenosis. The proposed model was an AVF created between the femoral artery and vein of a New Zealand white rabbit. Briefly, the fistula was fashioned by creating a side to side anastomosis, followed by occlusion of the distal vein. Over phase I of the study (days 1-28) maturation of the vein was evident by the presence of a pulsatile flow in the venous branch of the AVF, as well as a significant increase in venous blood velocity from 55.2± 6.0cm/s at day 10 to 68.4± 3.1cm/s by day 28 (p<0.05). A degree of medial/adventitial thickening was also evident at this time point. Rabbits were assigned to 3 groups for phase II of the study (days 29-56). The control group received no intervention, the injury group received cannulation to the AVF every 48-72 hrs, and the injury plus diclofenac group received the same frequency of injury and topical diclofenac (1.16% of diclofenac diethylammonium) twice a day, 5 days a week. In the control group, vein wall width increased significantly from 10.5± 0.9μM in the counter lateral vein to 16.6± 1.6μM in the AVF (p<0.05). Cannulation injury caused vein wall thickness to significantly increase to 46.8± 5.7μM (p<0.05). With diclofenac treatment, vein wall width decreased significantly to 15.8± 1.8μM (p<0.05). These results show for the first time that cannulation injury significantly contributes to AVF remodelling in vivo . Topical treatment with diclofenac, which has anti-inflammatory as well as anti-proliferative properties, appears to reduce injury driven remodelling within AVF. Therefore, topical diclofenac could be used as a prophylactic treatment to reduce vascular stenosis in AVF.