Dependence of Whole Blood Rheology on Oxygen Tension in Sickle Cell DIsease
2018-02
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Dependence of Whole Blood Rheology on Oxygen Tension in Sickle Cell DIsease
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2018-02
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In sickle cell disease, oxygen tension plays a major role in dictating the mechanical function of single red blood cells. As oxygen tension decreases, cellular stiffness increases, to the point where the flow of whole blood can come to a compete occlusion. Unfortunately, there are also many unknowns in sickle cell disease, which is clinically expressed by the severe lack of approved treatment options for the disease. To solve many of these issues, we aim to expand our understanding of sickle cell disease by diving into the fundamental mechanisms by which the whole blood rheology becomes impaired in response to oxygen tension. Here, we use an in vitro disease model of sickle cell rheology, built within a microfluidic platform, to simulate whole blood flow within the microvasculature. We first report on the relationship between whole blood rheology and oxygen tension in sickle cell disease under steady state conditions and map out the specific oxygen tension where rheological impairment of blood flow begins. We then report on this measurement in both sickle cell trait (the heterozygous carrier state of sickle cell disease) as well as transfusion therapy in sickle cell disease, where we find and report on the rheological differences compared to native sickle cell disease. Next, we modify our microfluidic disease model to investigate the temporal and spatial dynamics of sickle cell disease by creating a microvascular capillary tree design couple to physiologically relevant oxygen tension gradients. Finally, we revisit the specific response of whole blood rheology as a function of oxygen tension by mapping out the velocity gradients and velocity profiles of blood flow, where we find characteristic differences in velocity profile shapes relative to oxygen.
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University of Minnesota Ph.D. dissertation. February 2018. Major: Biomedical Engineering. Advisor: David Wood. 1 computer file (PDF); xii, 154 pages.
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Lu, Xinran. (2018). Dependence of Whole Blood Rheology on Oxygen Tension in Sickle Cell DIsease. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/213131.
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