Prevention of neointimal hyperplasia associated with modified stretch ePTFE hemodialysis grafts (Gore) in an experimental pre-clinical study in swine.

Objective Stenosis is the main cause of hemodialysis vascular graft failure, and it is primarily caused by neointimal hyperplasia (NH) development at the vein-graft anastomosis. Even though NH development factors are well known, their activation pathway still remains disputed and the real role of the mismatch compliance between the vein and the graft wall has not yet been resolved. The aim of this experimental study in swine was to verify the possibility of preventing the development of NH at vein-graft anastomosis using a modified commercially available longitudinal stretch ePTFE Gore graft (either standard or heparin-bonded) with an added hand-made ePTFE radial stretch cuff at one end to reduce the compliance between the graft and the vein wall. Methods. Twelve ePTFE stretch grafts (six modified and six unmodified) were surgically placed as artero-venous grafts between the carotid artery and the external jugular vein in six pigs. In each pig, one modified graft was placed on one side and one corresponding unmodified graft on the other side as a control. In four pigs, standard stretch ePTFE Gore grafts were used and, in two pigs, heparin-bonded stretch Gore grafts were used; 2 pigs were also treated with antiplatelet drugs. All the implanted grafts had a total length of 8 cm and a diameter of 6 mm. The modified graft was realised by cutting a short segment of the commercially available graft lengthwise which was then sewn crosswise (rotated 90°) with the same diameter as the original graft and was then added to it. Doppler ultrasound was used for monitoring the graft patency immediately, weekly and before sacrifice. At sacrifice (21-28 days after implantation), artery, vein and graft specimens were collected “en bloc” for histopathology. Results The modified grafts in the antiplatelet treated animals were able to completely prevent NH development on vein wall (100% in 2 subjects) which was also reduced in antiplatelet untreated animals (66,5, 96,4 and 100% in 3 subjects respectively). The modified standard stretch grafts and similarly modified heparin-bonded stretch grafts obtained the same good results in NH prevention. Conclusions Data provide evidence of the efficacy of modified stretch ePTFE grafts with an added radial stretch cuff for the prevention of NH in swine models and support the hypothesis of the pivotal role of mismatch compliance between the graft and the vein wall in NH development. Clinical Relevance If these results are confirmed in humans with a significantly improved graft patency, they would have a great effect on dialysis vascular access, especially in patients with unsuitable veins for fistula creation.