Heparin-coated PTFE graft for aortoiliac bypass grafting inhibits intimal hyperplasia in baboons

Abstract

Purpose: Intimal hyperplasia and graft thrombosis represent the major causes of graft failure. Heparin has been shown to prolong graft patency and inhibit intimal hyperplasia in animal models. The purpose of the study was to evaluate the effect of a heparin-coated expanded polytetrafluoroethylene (ePTFE) graft in a baboon model of aortoiliac bypass graft placement. Methods: Six adult male baboons (mean weight: 9.3 kg) underwent bilateral aortoiliac bypass grafting with ePTFE grafts (4 mm internal diameter × 5 cm length). In each animal, a heparin-coated ePTFE graft was placed on one side while the contralateral aortoiliac artery received an uncoated graft that served as a control. Platelet counts and activated partial thromboplastin time measurements were performed weekly. The grafts were harvested at 4 weeks and were subjected to morphometric analysis. Cell proliferation was assessed with bromodeoxyuridine immunostaining. Results: All the harvested grafts were patent. No differences were found in platelet counts or activated partial thromboplastin time measurements taken before and after the bypass procedure. There was a significant reduction of neointimal area at both proximal (0.06 ± 0.05 mm2) and distal (0.13 ± 0.07 mm2) anastomoses in the heparin-coated grafts as compared with proximal (0.16 ± 0.07 mm2) and distal (0.33 ± 0.12 mm2) anastomoses in the untreated control grafts (P < 0.05). In addition, neointimal cell proliferation assayed by bromodeoxyuridine (BrdU) incorporation was reduced in both proximal (2.03 ± 0.81%) and distal (3.12 ± 0.14%) anastomoses of heparin-coated grafts compared with proximal (3.54 ± 1.23%) and distal (5.58 ±1.15%) anastomoses of untreated control grafts (P < 0.05). Conclusions: Heparin-coated ePTFE graft significantly reduces anastomotic intimal hyperplasia and cell proliferation without measurable side effects in a baboon model. This approach supports a useful strategy for improving prosthetic bypass graft patency.