A novel vein graft model: adaptation to differential flow environments

Abstract

Accelerated intimal hyperplasia in response to altered flow environment is critical to the process of vein bypass graft failure. Lack of a reproducible animal model for dissecting the mechanisms of vein graft (VG) remodeling has limited progress toward solving this clinically significant problem. Combining a cuffed anastomotic technique with other surgical manipulations, we developed a well-defined, more robust method for studying hemodynamic factors in VG arterialization. VG with fistula placement, complete occlusion, or partial distal branch ligation (DBL) was performed in the carotid artery of 56 rabbits. Extensive hemodynamic and physiological analyses were performed to define the hemodynamic forces and histological adaptations of the wall at 1–28 days. Anastomotic time averaged 12 min, with 100% patency of bilateral grafts and unilateral grafts plus no adjunct or delayed fistula. Bilateral VG-DBL resulted in an immediate disparity in wall shear (0.8 ± 0.1 vs. 12.4 ± 1.1 dyn/cm2, ligated vs. contralateral graft). Grafts exposed to low shear stress responded primarily through enhanced intimal thickening (231 ± 35 vs. 36 ± 18 μm, low vs. high shear). High-shear-stress grafts adapted through enhanced outward remodeling, with a 24% increase in lumen diameter at 28 days (3.0 ± 0.1 vs. 3.7 ± 0.2 mm, low vs. high shear). We have taken advantage of the cuffed anastomotic technique and combined it with a bilateral VG-DBL model to dissect the impact of hemodynamic forces on VG arterialization. This novel model offers a robust, clinically relevant, statistically powerful small animal model for evaluation of high- and low-shear-regulated VG remodeling.