Date of Award
Spring 2004
Document Type
Dissertation - Restricted
Degree Name
Doctor of Philosophy (PhD)
Department
Biomedical Engineering
First Advisor
Olson, Lars E.
Second Advisor
Audi, Said H.
Third Advisor
Hettrick, Douglas A.
Abstract
Cardiovascular disease is a leading cause of mortality in the United States and throughout the World. Many patients undergo catheter-based procedures to treat this pathology and 80% of such procedures involve stent implantation. As a result, over one million stents are deployed annually to restore blood flow distal to vascular stenoses. Unfortunately, approximately 30% of patients experience persistent vascular narrowing of the stented region within six-months. This phenomenon is termed restenosis and is primarily due to neointimal hyperplasia. Interestingly, rates of restenosis after stent implantation vary with stent design and stent geometry has been identified as an important predictor of neointimal hyperplasia. Vascular geometry is known to influence local wall shear stress distributions in various regions of the body as branching in the carotid arteries and the curvature of the coronary arteries threaten the preferential flow environment of intravascular cells and correlate with sites of neointimal hyperplasia. Importantly, stent deployment also causes appreciable vascular damage and removal of endothelial cells during implantation exposing the subendothelial matrix and injured smooth muscle cells to shear stress caused by flowing blood. Recent data indicates that spatial distributions of shear stress mediate the rate and location of smooth muscle cell migration and proliferation after vascular injury. Collectively, these data suggest that the geometry of an implanted stent and native vessel may influence distributions of wall shear stress within the stented segment of a vessel and may spatially correlate with regions neointimal hyperplasia. Therefore, this investigation tested the hypothesis that alterations in local distributions of wall shear stress unique to the geometry of the stented portion of a vessel correlate with sites of neointimal hyperplasia. Identifying perturbations in vascular geometry and wall shear stress after stent placement may help delineate mechanisms associated with neointimal hyperplasia, stimulate the development of new stent designs and novel drug coatings, enhance overall stent performance, and ultimately contribute to a lower rate of restenosis.