Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Master of Science

Program

Medical Biophysics

Supervisor

Goldman, Daniel

2nd Supervisor

Ellis, Christopher G.

Abstract

Background: Skeletal muscle (SM), with its precise O2 supply-demand matching, is ideal for studying microvascular (MV) function, which is crucial in cardiovascular physiology and disease. Our goal is to gain understanding of SM microcirculation using recent capillary network module (CM) data from rat in a computational model.

Methods: We construct a 4-CM network, with single-vessel equivalents for each CM, three arterioles, and two venules. A two-phase (plasma/RBCs) steady-state model is used to calculate blood flow. An iterative boundary pressure finding method is developed to match flow in CMs.

Results: We validate our flow and pressure models vs. experimental data, and show how inflow hematocrit affects resistance and RBC distribution. We show that venular pressure regulation is needed to control individual CM RBC flow.

Discussion: Our computational model sheds new light on flow and regulation in interconnected CMs, and supports future studies using more CMs or time-dependent flow and regulation.

Summary for Lay Audience

The microcirculation comprises blood vessels less than 300mm in diameter and is responsible for local delivery of oxygen to tissue cells through the movement of red blood cells (RBCs). Oxygen delivery is important for our overall cardiovascular health and its impairment predicts diseases across all organs. This study investigates the flow of blood and RBCs through networks of capillaries, the smallest blood vessels in the body, based on data from experiments in rat skeletal muscle. Our aim is to improve understanding of blood flow and its regulation in multiple interconnected capillary networks through the application of computational models to experimental data. Computational modeling is an important tool in studying the microcirculation because once a basic model is developed it can be used to study a range of normal and unhealthy conditions without requiring extensive and lengthy new experiments.

In the present work, a computational model of capillary network geometry, blood flow, and pressure is developed and used to simulate how the flow of blood and RBCs changes under different conditions, and to compare the results from the computer model to data gathered from experiments. We find that our model gives good agreement with experimental measurements for blood flow and pressure drops in capillary networks. In addition, our model predicts how RBC distribution to interconnected capillary networks changes as the hematocrit (RBC concentration) entering the system varies. Lastly, our model shows that proper regulation of RBC supply to individual capillary networks requires regulation of not only the microvessels supplying RBCs to the networks (arterioles), but also the microvessels draining the networks (venules). The computational model developed in this work will form the basis for future studies using a larger number of capillary networks, to better represent actual muscle microcirculation, and including time-dependent effects to better represent the dynamic processes of blood flow and its regulation.

Creative Commons License

Creative Commons Attribution-Noncommercial 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 License.

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