Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2003. / Includes bibliographical references (leaves 164-169). / Hemodynamics has long been identified as a major factor in the determination and localization of atherosclerotic lesions. While the precise mechanism by which different hemodynamic factors act is not yet clear, the fact that they correlate highly with atherogenesis suggests that local disturbances in flow through blood vessels can promote arterial disease. These issues have become increasingly acute as physicians seek to alter the pathological arterial anatomy with bypass grafting or endovascular manipulations such as angioplasty or stenting. We proposed that local vascular interventions might cause previously unforeseen effects elsewhere in the arterial tree. As an example of these interactions, manipulation of one branch of a bifurcation might adversely affect the contralateral branch of the bifurcation. The goal of this work was to study the distant impact of local flow alterations, as well as to classify and evaluate the different parameters that determine their severity. Dynamic flow models of the arterial system were developed that allowed for the continuous alteration of model geometry in a controlled fashion to simulate the healthy and diseased states as well as the entire range in between. Moreover, these models permit simulation of different strategies of clinical intervention. Flow through the models was investigated using both qualitative and quantitative tools. Boundary layer separation and vascular resistance in one location of the arterial tree varied with geometrical alterations in another. In-vivo models were developed that allowed investigation of the effect of side branch occlusion or dilation on the acute and chronic outcome of main branch stenting in a bifurcation. Chronic side branch occlusions were protective of main branch stenting as reflected by a reduction in in-stent neo-intimal hyperplasia. / (cont.) This protective influence was mediated by an acute modulation of monocyte adhesion and accumulation on the lateral wall of the main branch, correlating with the location of flow disturbance demonstrated by the flow models. Chronic main branch vascular remodeling plays a major role in achieving this beneficial effect. The results of this study could have important implications for the diagnosis, treatment and long-term follow-up of the large number of patients who suffer from complex arterial diseases and undergo vascular interventions. In clinical manipulation of one arterial site one may well need to consider the hemodynamic impact on vascular segments at a distance. / by Yoram Richter. / Ph.D.
| Identifer | oai:union.ndltd.org:MIT/oai:dspace.mit.edu:1721.1/29944 |
| Date | January 2003 |
| Creators | Richter, Yoram, 1971- |
| Contributors | Elazer R. Edelman., Harvard University--MIT Division of Health Sciences and Technology., Harvard University--MIT Division of Health Sciences and Technology. |
| Publisher | Massachusetts Institute of Technology |
| Source Sets | M.I.T. Theses and Dissertation |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | 174 leaves, 11458555 bytes, 11480281 bytes, application/pdf, application/pdf, application/pdf |
| Rights | M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission., http://dspace.mit.edu/handle/1721.1/7582 |
Page generated in 0.0018 seconds