Increased blood flow inhibits neointimal hyperplasia in endothelialized vascular grafts

Abstract

Intimal hyperplasia is a primary cause of failure after vascular reconstruction and may be affected by blood flow. We have studied the effects of increased blood flow on intimal hyperplasia in porous polytetrafluoroethylene grafts implanted in baboons. These grafts develop an endothelial lining by 2 weeks and neointimal thickening due to proliferation of underlying smooth muscle cells by 1 month. Creation of a distal arteriovenous fistula increased flow (from 230±35 to 785±101 ml/min, p<0.001) and mean shear (from 26±4 to 78±10 dynes/cm2, p<0.001) without causing a drop in pressure across the grafts. Fistula flow did not alter the pattern of endothelial coverage but did cause a marked reduction in the cross-sectional area of the neointima (from 2.60±0.52 to 0.42±0.07 mm2 at 3 months, p<0.01). Detailed morphometric analysis revealed an equivalent percentage decrease in smooth muscle cells and matrix content, suggesting that the primary effect of increased flow was to reduce smooth muscle cell number without affecting the amount of matrix produced by individual cells. The neointima remained sensitive to changes in flow at late times; ligation of the fistula after 2 months resulted in a rapid increase in neointimal thickness (from 0.60±0.03 mm2 after 2 months of fistula flow to 3.88±0.55 mm2 1 month after ligation of fistula, p<0.01). These results support the hypothesis that changes in blood flow affect the structure of diseased as well as normal vessels.