Theoretical Models for Blood Flow Regulation in Heterogeneous Microvascular Networks

Persistent Link:
http://hdl.handle.net/10150/293413
Title:
Theoretical Models for Blood Flow Regulation in Heterogeneous Microvascular Networks
Author:
Fry, Brendan
Issue Date:
2013
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Proper distribution of blood flow in the microcirculation is necessary to match changing oxygen demands in various tissues. How this coordination of perfusion and consumption occurs in heterogeneous microvascular networks remains incompletely understood. Theoretical models are powerful tools that can help bridge this knowledge gap by simulating a range of conditions difficult to obtain experimentally. Here, an algorithm is first developed to estimate blood flow rates in large microvascular networks. Then, a theoretical model is presented for metabolic blood flow regulation in a realistic heterogeneous network structure, derived from experimental results from hamster cremaster muscle in control and dilated states. The model is based on modulation of arteriolar diameters according to the length-tension characteristics of vascular smooth muscle. Responses of smooth muscle cell tone to myogenic, shear-dependent, and metabolic stimuli are included. Blood flow is simulated including unequal hematocrit partition at diverging vessel bifurcations. Convective and diffusive oxygen transport in the network is simulated, and oxygen-dependent metabolic signals are assumed to be conducted upstream from distal vessels to arterioles. Simulations are carried out over a range of tissue oxygen demand. With increasing demand, arterioles dilate, blood flow increases, and the numbers of flowing arterioles and capillaries, as defined by red-blood-cell flux above a small threshold value, increase. Unequal hematocrit partition at diverging bifurcations contributes to capillary recruitment and enhances tissue oxygenation. The results imply that microvessel recruitment can occur as a consequence of local control of arteriolar tone. The effectiveness of red-blood-cell-dependent and independent mechanisms for the metabolic response of local blood flow regulation is examined over a range of tissue oxygen demands. Model results suggest that although a red-blood-cell-independent mechanism is most effective in increasing flow and preventing hypoxia, the addition of a red-blood-cell-dependent mechanism leads to a higher median tissue oxygen level, indicating distinct roles for the two mechanisms. In summary, flow rates in large microvessel networks can be estimated with the proposed algorithm, and the theoretical model for flow regulation predicts a mechanism for capillary recruitment, as well as roles for red-blood-cell-dependent and independent mechanisms in the metabolic regulation of blood flow in heterogeneous microvascular networks.
Type:
text; Electronic Dissertation
Keywords:
capillary recruitment; flow estimation; microcirculation; oxygen transport; theoretical model; Applied Mathematics; blood flow
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Applied Mathematics
Degree Grantor:
University of Arizona
Advisor:
Secomb, Timothy

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleTheoretical Models for Blood Flow Regulation in Heterogeneous Microvascular Networksen_US
dc.creatorFry, Brendanen_US
dc.contributor.authorFry, Brendanen_US
dc.date.issued2013-
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractProper distribution of blood flow in the microcirculation is necessary to match changing oxygen demands in various tissues. How this coordination of perfusion and consumption occurs in heterogeneous microvascular networks remains incompletely understood. Theoretical models are powerful tools that can help bridge this knowledge gap by simulating a range of conditions difficult to obtain experimentally. Here, an algorithm is first developed to estimate blood flow rates in large microvascular networks. Then, a theoretical model is presented for metabolic blood flow regulation in a realistic heterogeneous network structure, derived from experimental results from hamster cremaster muscle in control and dilated states. The model is based on modulation of arteriolar diameters according to the length-tension characteristics of vascular smooth muscle. Responses of smooth muscle cell tone to myogenic, shear-dependent, and metabolic stimuli are included. Blood flow is simulated including unequal hematocrit partition at diverging vessel bifurcations. Convective and diffusive oxygen transport in the network is simulated, and oxygen-dependent metabolic signals are assumed to be conducted upstream from distal vessels to arterioles. Simulations are carried out over a range of tissue oxygen demand. With increasing demand, arterioles dilate, blood flow increases, and the numbers of flowing arterioles and capillaries, as defined by red-blood-cell flux above a small threshold value, increase. Unequal hematocrit partition at diverging bifurcations contributes to capillary recruitment and enhances tissue oxygenation. The results imply that microvessel recruitment can occur as a consequence of local control of arteriolar tone. The effectiveness of red-blood-cell-dependent and independent mechanisms for the metabolic response of local blood flow regulation is examined over a range of tissue oxygen demands. Model results suggest that although a red-blood-cell-independent mechanism is most effective in increasing flow and preventing hypoxia, the addition of a red-blood-cell-dependent mechanism leads to a higher median tissue oxygen level, indicating distinct roles for the two mechanisms. In summary, flow rates in large microvessel networks can be estimated with the proposed algorithm, and the theoretical model for flow regulation predicts a mechanism for capillary recruitment, as well as roles for red-blood-cell-dependent and independent mechanisms in the metabolic regulation of blood flow in heterogeneous microvascular networks.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjectcapillary recruitmenten_US
dc.subjectflow estimationen_US
dc.subjectmicrocirculationen_US
dc.subjectoxygen transporten_US
dc.subjecttheoretical modelen_US
dc.subjectApplied Mathematicsen_US
dc.subjectblood flowen_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplineApplied Mathematicsen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorSecomb, Timothyen_US
dc.contributor.committeememberTabor, Michaelen_US
dc.contributor.committeememberWatkins, Josephen_US
dc.contributor.committeememberBrio, Moyseyen_US
dc.contributor.committeememberSecomb, Timothyen_US
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