Investigation of the mechanical and biochemical stimuli of physiological and pathological remodeling in porcine saphenous veins ex vivo

Bypass grafting remains one of the most common surgical interventions for the treatment of cardiovascular disease. Despite its poorer patency rate relative to arteries such as the internal mammary, the saphenous vein continues to be among the most commonly used conduits in bypass grafting. The work presented in this thesis aims to improve our understanding of vein graft failure, by specifically focusing on both the mechanical and biochemical factors that contribute to the physiological and pathological remodeling of veins. To achieve this goal, an ex vivo perfusion system capable of subjecting excised porcine saphenous veins to a variety of mechanical and biochemical, physiological, hemodynamic environments was developed. Mechanical environment. Saphenous veins cultured for one week in the ex vivo perfusion system remodeled structurally and geometrically in response to specific mechanical stimuli through a combination of cellular proliferation, extracellular matrix deposition, and reorganization of vein wall constituents. Specifically, pressure regulated vein medial area, independent of pulsatility, and shear stress modulated the extent of intimal hyperplasia. However, veins subjected to a mechanical environment that mimicked their native, in vivo environment, underwent pathological remodeling, including the development of intimal hyperplasia and eutrophic remodeling. Biochemical environment. Saphenous veins cultured for one week in the ex vivo perfusion system under venous conditions without serum, in the presence of nitric oxide, or with lower oxygen tension demonstrated less luminal narrowing, both through a reduction in the extent of intimal hyperplasia and eutrophic remodeling, the two primary means by which vein grafts narrow and fail in vivo. Mechanical properties. Changes in vein mechanical properties, specifically reductions in compliance, effected through alterations in the ex vivo mechanical or biochemical environment were due more to changes in vein geometry and not changes in the intrinsic properties of the vein wall. Oxidative stress. Trends in gene expression of the antioxidant genes glutathione peroxidase and heme oxygenase suggest that arterial levels of oxygen tension subject cultured veins to oxidative stress. Both the mechanical and biochemical environment seemingly regulate the expression of these genes