Evaluation of platelet deposition and neointimal hyperplasia of heparin-coated small-caliber ePTFE grafts in a canine femoral artery bypass model 1

Abstract

Introduction Bypass graft failure due to acute thrombosis and intimal hyperplasia remains a major challenge in small-diameter vascular prosthetic graft reconstruction. Heparin has been shown to prevent thrombus formation and inhibit intimal antithrombotic in animal studies. In this study, we evaluated the effect of small-caliber heparin-coated expanded polytetrafluoroethylene (ePTFE) grafts on platelet deposition and intimal hyperplasia in a canine model of femoral artery bypass grafting. Methods Nine adult greyhound dogs underwent placement of bilateral femorofemoral artery bypass grafts with ePTFE grafts (4 mm diameter and 7 cm long). In each animal, a heparin-coated ePTFE graft was placed on one side while a noncoated graft was placed on the contralateral side which served as the control. Platelet deposition was measured by autologous 111indium-labeling and scintillation camera imaging analysis in 24 h. The graft patency was assessed at 4 weeks following the bypass. The effect of intimal hyperplasia was assessed with histological and morphometric analysis. Results Platelet deposition on the heparin-coated grafts at 24 h was significantly reduced by 72% as compared to controls ( P = 0.001). The patency rate was 44% in control grafts and 89% in heparin-coated grafts. There was a significant reduction of graft intimal hyperplasia at both proximal (0.38 ± 0.21 mm 2) and distal (0.19 ± 0.06 mm 2) anastomoses in the heparin-coated grafts as compared with proximal (1.01 ± 0.28 mm 2) and distal (0.42 ± 0.01 mm 2) anastomoses in the untreated control grafts, respectively ( P < 0.05). Heparin coating significantly reduced graft neointimal hyperplasia at patent graft anastomoses by 55–72% as compared to controls. Conclusions These data demonstrate that heparin coating of ePTFE significantly reduced early platelet deposition and inhibited anastomotic neointimal hyperplasia. Moreover, small-caliber heparin-coated ePTFE graft significantly increased graft patency in a canine femoral artery bypass model. This may represent a promising treatment strategy for improving the clinical performance of small-caliber prosthetic vascular grafts.