Master of Engineering Science
In skeletal muscle (SM), the microcirculation distributes blood flow to capillary networks to meet local oxygen (O2) demand. Experiments using intra-vital video microscopy (IVVM) have quantified blood flow and O2 supply in capillary networks, and using an O2 exchange chamber have measured local changes in blood flow believed due to O2-dependent regulation. However, IVVM is unable to simultaneously measure capillary O2 supply and SM O2 content, implying the need for theoretical models to understand how flow regulation and SM oxygenation interact. In this thesis, a novel blood-tissue O2 transport model using continuously distributed capillaries was developed to study SM O2 transport and flow regulation affected by an O2 chamber. The steady-state effects of the chamber on capillary and SM O2 were quantified for ranges of physiological and experimental parameters, and our simplified dynamic regulation model was shown to support current understanding of the local O2-dependent blood flow response in SM.
Summary for Lay Audience
The microcirculation is a component of the cardiovascular system encompassing the smallest blood vessels in the body. Amongst these, capillaries though on a microscopic length scale, are responsible for the large task of carrying oxygen from your arteries through blood and delivering oxygen to ensure the surrounding tissue can perform its metabolism. This metabolism, in tissue such as skeletal muscle (SM), has been shown to have a large range depending on the activity level needed. Experiments using a microscope technique called intra-vital video microscopy (IVVM), are capable of analyzing SM microcirculation, while still attached to an organism's physiology. IVVM experiments have revealed SM microcirculation is capable of changing its blood flow to match the metabolism demand of the surrounding SM at several levels of activity. IVVM, is capable of measuring blood speed, and the oxygen concentration within capillaries. However, IVVM is unable to measure how much oxygen leaves through capillary walls, and into the surrounding tissues. Without a strong method to understand the balance between tissue and capillary oxygen, explaining the phenomenon of how the microcirculation can vary its flow under a variety of activity levels is not possible. Thus, in the last hundred years, mathematical models have been developed to relate capillary blood flow and oxygen concentration that many techniques (including IVVM) can obtain, and return tissue oxygen concentrations. As IVVM has become capable of simulating larger networks of SM and capillaries, many of these models, are becoming impractical to use. Therefore, there is a need for an oxygen transport model, which can calculate tissue oxygen levels at the length scale of modern IVVM experiments, and also is capable of explaining regulation observations seen in IVVM. In this thesis, a new oxygen transport model representing capillaries as a smooth distribution rather than traditionally used discrete cylinders, was developed to study SM oxygen transport and blood flow regulation. Effects of oxygen chambers used in IVVM experiments to stimulate muscle were simulated, and a second model to simulate microcirculatory regulation reproduced trends seen in IVVM experiments. These models can be used to investigate SM and its oxygen regulation further.
Afas, Keith C., "A two-layer continuous-capillary oxygen transport model: Development and application to blood flow regulation in resting skeletal muscle." (2022). Electronic Thesis and Dissertation Repository. 8721.
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