PEG-hirudin/iloprost Coating of Small Diameter ePTFE Grafts Effectively Prevents Pseudointima and Intimal Hyperplasia Development

Abstract

Small diameter PTFE grafts are prone to thrombosis and intimal hyperplasia development. Heparin graft coating has beneficial effects but also potential drawbacks. The purpose of this study was to evaluate the experimental efficacy of PEG-hirudin/iloprost coated small caliber PTFE grafts. Thirty-six femoro-popliteal ePTFE grafts (expanded polytetrafluoroethylene, diameter 4 mm) were inserted into 18 pigs. Grafts were randomised individually for each leg and grouped for 3 groups. Group I consisted of native ePTFE grafts, group II were grafts coated with a polylactide polymer (PLA) without drugs and group III grafts were coated with PLA containing a polyethylene glycol (PEG)-hirudin/iloprost combination. The follow-up period was 6 weeks. Patency rates were calculated and development of pseudointima inside the grafts was noted. Thickness of intimal hyperplasia at the distal anastomoses was measured using light microscopy. Patency rates for group I were 6/9 (67%), for group II 9/10 (90%) and 12/12 (100%) for group III. In groups I and II there was a significant reduction of blood flow proximal to the graft at graft harvest, to 29+/-12 and 28+/-20 ml/min respectively (both p<0.01 versus preoperative value), whilst in group III blood flow, 99+/-21 ml/min, remained at the preoperative level. Subtotal stenosis due to development of pseudointima was noted in each of the native and PLA coated grafts but not in group III grafts. Intimal hyperplasia at the distal anastomosis was lowest in group III. The PEG-hirudin/iloprost coating of ePTFE prostheses effectively reduced pseudointima and intimal hyperplasia development and led to superior graft patency.