Atherosclerotic cardiovascular disease, the common pathophysiologic process leading to arterial occlusive disease and end organ ischemia, kills more people worldwide annually in developed countries than any other disease. The treatment of atherosclerotic cardiac disease and other end organ ischemia involves surgical revascularization, which has been shown to provide significant survival benefit. The durability of this benefit has been limited by bypass graft occlusion, which is associated with adverse clinical outcomes. The limited patency of currently used bypass grafts has led to the development of various strategies to limit neointimal hyperplasia, which is the primary lesion leading to bypass graft occlusion. In this application, we propose to utilize a novel intraluminal drug delivery system to infuse antiproliferative and angiogenic factors following the bypass of small- and medium-sized arteries. Using this model, we expect to prevent neointimal hyperplasia formation and improve long-term graft patency. Rapamycin and vascular endothelial growth factor (VEGF) are 2 agents that will be studied in this system. Both have been studied in other models of cardiovascular revascularization and been shown to inhibit neointimal hyperplasia formation. Successful development of a conduit and minipump system that delivers these agents locally will have immediate clinical implications and potential to improve clinical outcomes for the thousands of patients requiring surgical revascularization in this country.
