Arterial Remodeling in the Rabbit: Structural Changes in Response to Chronic Hindlimb Ischemia

Abstract

Background The structure of arteries changes in response to changes in flow. Most studies of flow-induced arterial remodeling either focus on the microcirculation, employ nonphysiologic flow models (AV fistula), or use acute measurements of flow. We used a chronic, conscious rabbit model of remodeling of the internal iliac artery (IIA) after external iliac (EIA) ligation to study the interaction of flow and structural changes in a large conduit artery collateral. Methods Thirty-four adult male NZW rabbits underwent distal right EIA ligation or sham operation. Animals had aortography at 0, 1, 2, 4, or 8 weeks, were killed, and perfusion fixed, and the IIAs were excised. Luminal diameter (LD) and medial thickness (MT) and medial smooth muscle nuclear number (NN) were measured in the IIA by computer digital image analysis. Transit time flow probes were placed on the common iliac artery (CIA) of 28 additional rabbits 1 week before EIA ligation. Flow data were measured daily. Data (mean ± SEM) were analyzed by ANOVA (*P Results Right IIA LD increased more than 20% at 2 weeks and more than 40% at 8 weeks. Right IIA MT increased in a bimodal fashion at 1 and 4 to 8 weeks. Right IIA wall area increased progressively from 20% at 1 week to 80% at 8 weeks (P P Conclusion This model of modestly increased collateral flow demonstrates arterial remodeling with increased arterial diameter, luminal area, wall thickness, and nuclear number. These structural changes are first seen at 1 to 2 weeks and are complete at 8 weeks. Because the early increase in medial thickness is not associated with an increase in cell nuclei, early remodeling may involve changes in extracellular matrix. Late remodeling may involve smooth muscle proliferation. The temporal discordance between structural change and shear normalization suggests that factors other than shear normalization may either initiate or perpetuate the arterial remodeling in this model.