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Dissertation
Impact of nitric oxide in the regulation of blood flow in the microcirculation: a computational analysis
Doctor of Philosophy (Ph.D.), Drexel University
01 Mar 2015
DOI:
https://doi.org/10.17918/etd-6356
Abstract
Nitric oxide (NO) is historically known as a vasodilator. A clear role for NO in metabolic autoregulation within the microcirculation and its relationship to both blood flow and local O2 concentrations has yet to have been established. As NO production from endothelial cells is limited under hypoxic conditions, increased vascular tone and a subsequent decrease in vascular diameter develop. This decrease in vascular diameter is expected to trigger a decrease in the amount of O2 transported to the surrounding tissue. In terms of the local flow mediated response, this decrease in vessel diameter will also lead to an increase in hydraulic resistance, which should theoretically lead to a decrease in blood flow through the vasculature (and thereby reducing O2 transport to the tissue). Experimental studies have shown that at bifurcations an unequal distribution of red blood cells will flow into the larger of the two daughter vessels, in a fashion not proportional to the bulk fluid distribution in the two daughter branches(1). Therefore, in relation to NO, a decrease in vessel diameter will lead to a decrease in red blood cell flux to the hypoxic tissue. This decrease in red blood cells could be beneficial in terms of CNO by reducing the presence of NO scavangers, thereby increasing CNO in and around the vessel wall and promoting vessel dilation. Yet, this increase in blood flow will also immediately allow for a greater influx of red blood cells into the region and lead to a greater scavenging of NO. Theoretically this would lead to a decrease in vessel diameter, and make this means of autoregulatory control unstable. It is the desire of this work to explore a role of NO in the autoregulatory control of arteriole diameter and subsequent blood flow to connected vessels. Ideally a pathway is sought, which would allow for a steady increase in CNO around a resistive vessel until relationship stable equilibrium between the vasculature and its surrounding tissue is resumed To define the role of NO in the metabolic signaling leading to the autoregulation of local blood transport, this study computationally examines the relationship between NO and O2 within a vascular network. Specifically, this work explores if a decrease in local PO2 can lead to an increase in local CNO around the arteriole wall. In addition, this thesis models the relationship between CNO and changes in the vessel diameter to determine their influence on the resultant distribution of blood. Finally, this work examines the pathway most commonly associated with NO production; the shear mediated NO production by endothelial cells. A fuller understanding of the mechanisms of NO production and its relationship to blood transport within the vasculature is expected to provide insight into the metabolic auto-regulatory system and future potential therapeutic avenues for metabolic dysfunction.
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Details
- Title
- Impact of nitric oxide in the regulation of blood flow in the microcirculation
- Creators
- Patrick L. Kirby - DU
- Contributors
- Dov Jaron (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems (1997-2026); Drexel University
- Other Identifier
- 6356; 991014632825604721