Differential response of arteries and vein grafts to blood flow reduction

Abstract

Purpose: This study was undertaken to evaluate the effect of blood flow on the dimensions and cellular composition of normal arteries and freshly placed vein grafts (VG).Methods: Bilateral jugular vein interposition grafts were placed in the common carotid arteries of 12 New Zealand white rabbits, and blood flow was reduced on one side by external carotid artery ligation. Shear stress, tangential stress, vessel dimensions, and smooth muscle cell (SMC) proliferation of reduced-flow arteries and VG were compared with these measures in contralateral controls (CON).Results: A sustained reduction in blood flow was documented at 4 weeks (13 ± 4 ml/min reduced-flow vs 21 ± 4 ml/min CON; p < 0.05). Reduced-flow carotid arteries had a smaller lumen radius and greater medial thickness compared with normal-flow arteries, but there was no difference in medial cross-sectional area or medial SMC volume and no differences in any intimal measurements. These changes resulted in normalization of shear stress (15.2 ± 4.6 dynes/cm2 reduced-flow vs 13.6 ± 2.5 dynes/cm2 CON; p = NS). All VG underwent a marked postimplantation hyperplasia in intima and media, but the major effect of flow reduction on VG dimensions occurred in the intima. Intimal thickness in reduced-flow VG was 60% greater than that in control VG (57 ± 12 μm vs 35 ± 5 μm; p = 0.05), and intimal area was 70% greater than that in controls (0.83 ± 0.24 μm2 vs 0.48 ± 0.08 μm2; p > 0.05). Smaller differences were found in medial thickness (74 ± 4 μm reduced-flow vs 63 ± 4 μm CON; p = 0.02) and medial area (1.03 ± 0.36 μm2 reduced-flow vs 0.84 ± 0.22 μm2 CON; p = 0.05). Intimal SMC volume in reduced-flow VG was 37% greater than that in control VG (p = 0.07). Tangential stress in VG equaled that in ipsilateral arteries, whereas shear stress in VG remained much lower than that in arteries.Conclusions: In this model, arteries and VG responded to flow reduction by wall thickening, but the mechanism differed. Arteries underwent medial remodeling, lumen caliber reduction, and shear stress normalization, whereas VG responded by an upward modulation of the proliferative response that follows graft placement. These data support a primary role for tangential stress and a secondary role for shear stress in determination of VG dimensions.