Low shear stress promotes intimal hyperplasia thickening

This study was designed to evaluate the biological effects of differences in wall shear stress levels on anastomotic neointimal hyperplasia rate in end-to-side polytetrafluoroethylene (PTFE) grafts. Twenty 4-7 mm tapered PTFE grafts were inserted in the femoral and carotid arteries in five mongrel dogs to create a range of wall shear stress conditions. Because shear stress is inversely proportional to the diameter to the third power, shear stress will be 5.3 times greater at the 4 mm end than at the 7 mm end of the graft. The grafts were harvested after 16 weeks using a pressure perfusion technique. Wall thickness of anastomotic neointimal hyperplasia and mid-graft pseudointima was measured by computer image analysis of histologic sections. At the time of implantation, the mean shear stress was 18 dynes/cm² at the smaller 4 mm end versus 3.4 dynes/cm² at the 7 mm end of the tapered grafts (P < 0.0001). Flow was significantly higher for the carotid grafts over the femoral grafts, thus four different levels of shear stresses could be differentiated (P < 0.001). At the time of harvest, 17 of 20 grafts were patent. Intimal thickening was significantly skewed to the PTFE side at each anastamosis. The graft neointimal thickness was consistently greater at the 7 mm end, compared to the 4 mm end of these grafts (mean = 0.29 mm vs 0.18 mm, P < 0.05), and was also significantly greater for all femoral grafts when compared to the carotid grafts (0.29 mm vs 0.19 mm, P < 0.001). The amount of intimal thickening could be statistically related to the inverse of the local mean shear rate yielding a correlation coefficient of 0.96. The thickness of anastomotic neointima or mid-graft pseudointima did not differ significantly when comparing the direction of graft taper. This data shows that in vivo anastomotic neointimal thickness was a direct function of low wall shear stress present with larger diameter anastamoses for a variety of flow conditions and graft orientations.