Remodeling and suppression of intimal hyperplasia of vascular grafts with a distal arteriovenous fistula in a rat model

Abstract

Purpose: The purpose of this study was to evaluate the effects of a distal arteriovenous fistula (dAVF) on the morphologic changes occurring in arterial bypass grafts by the use of a novel experimental model. Methods: Aortofemoral bypass grafts with or without dAVFs were constructed in 36 Sprague-Dawley rats with a microsurgical technique. The bypass graft material consisted of deendothelialized autogenous tail artery (length, 25 mm; inside diameter, 0.5 mm). In 18 rats, dAVFs were constructed at the distal anastomosis. After 6 weeks, flow rates and shear stress were determined, and grafts were then harvested. Luminal, intimal, and medial cross-sectional areas were measured with computer imaging. Desmin, α–smooth muscle actin, and von Willebrand factor (vWF) were identified with immunohistochemistry. Endothelialization was evaluated with SEM. Results: All bypass grafts remained patent at the time of graft harvest. Grafts with dAVFs showed increased flow rates (11.5 ± 0.6 mL/min) compared with grafts without dAVFs (2.1 ± 0.3 mL/min; P <.01). Shear stress was also increased in the dAVF group (340.9 ± 23.4 dyne/cm2 vs 113.7 ± 12.5 dyne/cm2; P <.01), with a corresponding suppression of intimal hyperplasia (0.059 ± 0.011 mm2 for dAVF grafts vs 0.225 ± 0.009 mm2 for non-dAVF grafts; P <.01). Staining for vWF was found in both the reendothelialized flow surface and the neointimal extracellular matrix. Remodeling of the grafts was characterized by a 50% increased luminal area, 70% decreased intimal area, and a 25% decreased medial area when a dAVF was constructed. Conclusion: A small animal experimental model of an arterial bypass graft can enable the evaluation of a variety of factors that influence graft patency. Increased blood flow velocity and shear stress induced by a dAVF are associated with a decrease in intimal and medial areas, which may reflect changes in cell proliferation, apoptosis, migration, or matrix deposition. Deposition of vWF was also found both in the endothelium and throughout the hyperplastic intima. These findings suggest that the hemodynamic and morphologic changes associated with dAVF may potentiate graft patency and function. (J Vasc Surg 2001;34:701-6.)