Multi-Scale Model Analysis of O<sub>2</sub> Transport and Metabolism: Effects of Hypoxia and Exercise

Multi-Scale Model Analysis of O<sub>2</sub> Transport and Metabolism: Effects of Hypoxia and Exercise

Bibliographic Details
Main Author: Zhou, Haiying
Language:English
Published: Case Western Reserve University School of Graduate Studies / OhioLINK 2010
Subjects:
Biomedical Research
oxygen utilization
oxygen transport
mathematical modeling
muscle oxygenation
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=case1254502393
id ndltd-OhioLink-oai-etd.ohiolink.edu-case1254502393
record_format oai_dc
collection NDLTD
language English
sources NDLTD
topic Biomedical Research
oxygen utilization
oxygen transport
mathematical modeling
muscle oxygenation
spellingShingle Biomedical Research
oxygen utilization
oxygen transport
mathematical modeling
muscle oxygenation
Zhou, Haiying
Multi-Scale Model Analysis of O<sub>2</sub> Transport and Metabolism: Effects of Hypoxia and Exercise
author Zhou, Haiying
author_facet Zhou, Haiying
author_sort Zhou, Haiying
title Multi-Scale Model Analysis of O<sub>2</sub> Transport and Metabolism: Effects of Hypoxia and Exercise
title_short Multi-Scale Model Analysis of O<sub>2</sub> Transport and Metabolism: Effects of Hypoxia and Exercise
title_full Multi-Scale Model Analysis of O<sub>2</sub> Transport and Metabolism: Effects of Hypoxia and Exercise
title_fullStr Multi-Scale Model Analysis of O<sub>2</sub> Transport and Metabolism: Effects of Hypoxia and Exercise
title_full_unstemmed Multi-Scale Model Analysis of O<sub>2</sub> Transport and Metabolism: Effects of Hypoxia and Exercise
title_sort multi-scale model analysis of o<sub>2</sub> transport and metabolism: effects of hypoxia and exercise
publisher Case Western Reserve University School of Graduate Studies / OhioLINK
publishDate 2010
url http://rave.ohiolink.edu/etdc/view?acc_num=case1254502393
work_keys_str_mv AT zhouhaiying multiscalemodelanalysisofosub2subtransportandmetabolismeffectsofhypoxiaandexercise
_version_ 1719421672585428992
spelling ndltd-OhioLink-oai-etd.ohiolink.edu-case12545023932021-08-03T05:33:16Z Multi-Scale Model Analysis of O<sub>2</sub> Transport and Metabolism: Effects of Hypoxia and Exercise Zhou, Haiying Biomedical Research oxygen utilization oxygen transport mathematical modeling muscle oxygenation <p>To maintain O<sub>2</sub> and ATP homeostasis, cardio-respiratory system variables including ventilation and blood flow and muscle tissue O<sub>2</sub> consumption are regulated in response to increased energy demand and/or alteration in oxygen supply. In human or animal experimental studies, direct measurements of those control mechanisms are not feasible. To evaluate these mechanisms and physiological processes linking pulmonary to cellular respiration, a “systems bioengineering” approach was applied. This included experimental studies with non-invasive measurements of human subjects and computational models to quantify the relative significance of various factors controlling respiration. The experimental measurements were obtained at two levels: (a) whole body (by indirect calorimetry, bioempedence cardiography); and (b) muscle tissue (by near-infrared spectroscopy).</p><p>A multi-organ systems model of O<sub>2</sub> and CO<sub>2</sub> transport was developed to analyze the control of ventilation and blood flow during hypoxia by comparison with experimental data. Among the aspects of the control processes that this model assessed were possible mechanisms responsible for hypoxic ventilatory decline (HVD). Under isocapnic hypoxia, simulations indicate that HVD can be entirely described by central ventilatory depression and an increase in brain blood flow has no effect on HVD.</p><p>The measurements of pulmonary O<sub>2</sub> uptake (VO<sub>2p</sub>) and muscle oxygenation (ΔHbMbO<sub>2</sub>) were combined with a multi-scale computational model of oxygen transport and muscle cellular metabolism. This model incorporates mechanisms of O2 transport from the airway opening to working muscle, as well as the phosphogenic and oxidative pathways of ATP synthesis in tissue cells. Based on experimental data from healthy subjects, the model simulated responses to a step increase in work rate. The simulations show that VO<sub>2p</sub> and muscle O<sub>2</sub> utilization UO2m have similar characteristic mean response times even though a transit delay exists between tissue cell and the lungs.</p><p>In response to a step increase in work rate, the dynamics of muscle oxygenation (ΔHbMbO<sub>2</sub>) measured by NIRS differs from oxygenation of venous blood (S<sub>v</sub>O<sub>2</sub>). To distinguish oxygenated hemoglobin (Hb) and myoglobin (Mb) concentrations from the NIRS signal, a mathematical model of muscle O2 transport and utilization was developed and validated by comparison to experimental data. Simulations of this model, which incorporated changes in muscle microvascular composition during exercise, indicated that Hb and Mb contributions to the NIRS signal are of comparable magnitude. During exercise, the changes in oxygenated Hb and Mb are responsible for different patterns of ΔHbMbO<sub>2</sub> and S<sub>v</sub>O<sub>2</sub> dynamics.</p><p>The measurements of VO<sub>2p</sub> and ΔHbMbO<sub>2</sub> were also used to evaluate the muscle adaptations to endurance training. The multi-scale model was combined with the changes in muscle microvascular composition to simulate VO<sub>2p</sub> and ΔHbMbO2 responses to a step increase in work rate. By comparing simulated outputs with experimental data before and after training, optimal estimates of model parameters were obtained that characterize muscle adaptation. These parameter values indicate that training increased the maximal flux rate of oxidative phosphorylation (Vmax) by 53% but did not change significantly the physiological factors related to permeability-surface area (PS<sub>m</sub>).</p> 2010 English text Case Western Reserve University School of Graduate Studies / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=case1254502393 http://rave.ohiolink.edu/etdc/view?acc_num=case1254502393 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.

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