Browsing by Subject "Oxygen transport"

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    Blood flow regulation and oxygen transport in a heterogeneous model of the mouse retina
    (Elsevier, 2020-11) Fry, Brendan C.; Harris, Alon; Siesky, Brent; Arciero, Julia; Mathematical Sciences, School of Science
    Elevated intraocular pressure is the primary risk factor for glaucoma, yet vascular health and ocular hemodynamics have also been established as important risk factors for the disease. The precise physiological mechanisms and processes by which flow impairment and reduced tissue oxygenation relate to retinal ganglion cell death are not fully known. Mathematical modeling has emerged as a useful tool to help decipher the role of hemodynamic alterations in glaucoma. Several previous models of the retinal microvasculature and tissue have investigated the individual impact of spatial heterogeneity, flow regulation, and oxygen transport on the system. This study combines all three of these components into a heterogeneous mathematical model of retinal arterioles that includes oxygen transport and acute flow regulation in response to changes in pressure, shear stress, and oxygen demand. The metabolic signal (Si) is implemented as a wall-derived signal that reflects the oxygen deficit along the network, and three cases of conduction are considered: no conduction, a constant signal, and a flow-weighted signal. The model shows that the heterogeneity of the downstream signal serves to regulate flow better than a constant conducted response. In fact, the increases in average tissue PO2 due to a flow-weighted signal are often more significant than if the entire level of signal is increased. Such theoretical work supports the importance of the non-uniform structure of the retinal vasculature when assessing the capability and/or dysfunction of blood flow regulation in the retinal microcirculation.
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    Metabolic Signaling in a Theoretical Model of the Human Retinal Microcirculation
    (MDPI, 2021) Arciero, Julia; Fry, Brendan; Albright, Amanda; Mattingly, Grace; Scanlon, Hannah; Abernathy, Mandy; Siesky, Brent; Verticchio Vercellin, Alice; Harris, Alon; Mathematical Sciences, School of Science
    Impaired blood flow and oxygenation contribute to many ocular pathologies, including glaucoma. Here, a mathematical model is presented that combines an image-based heterogeneous representation of retinal arterioles with a compartmental description of capillaries and venules. The arteriolar model of the human retina is extrapolated from a previous mouse model based on confocal microscopy images. Every terminal arteriole is connected in series to compartments for capillaries and venules, yielding a hybrid model for predicting blood flow and oxygenation throughout the retinal microcirculation. A metabolic wall signal is calculated in each vessel according to blood and tissue oxygen levels. As expected, a higher average metabolic signal is generated in pathways with a lower average oxygen level. The model also predicts a wide range of metabolic signals dependent on oxygen levels and specific network location. For example, for high oxygen demand, a threefold range in metabolic signal is predicted despite nearly identical PO2 levels. This whole-network approach, including a spatially nonuniform structure, is needed to describe the metabolic status of the retina. This model provides the geometric and hemodynamic framework necessary to predict ocular blood flow regulation and will ultimately facilitate early detection and treatment of ischemic and metabolic disorders of the eye.
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    Modeling cerebrovascular responses to assess the impact of the collateral circulation following middle cerebral artery occlusion
    (Wiley, 2024) Zhao, Erin; Barber, Jared; Mathew-Steiner, Shomita S.; Khanna, Savita; Sen, Chandan K.; Arciero, Julia; Mathematical Sciences, School of Science
    Objective: An improved understanding of the role of the leptomeningeal collateral circulation in blood flow compensation following middle cerebral artery (MCA) occlusion can contribute to more effective treatment development for ischemic stroke. The present study introduces a model of the cerebral circulation to predict cerebral blood flow and tissue oxygenation following MCA occlusion. Methods: The model incorporates flow regulation mechanisms based on changes in pressure, shear stress, and metabolic demand. Oxygen saturation in cerebral vessels and tissue is calculated using a Krogh cylinder model. The model is used to assess the effects of changes in oxygen demand and arterial pressure on cerebral blood flow and oxygenation after MCA occlusion. Results: An increase from five to 11 leptomeningeal collateral vessels was shown to increase the oxygen saturation in the region distal to the occlusion by nearly 100%. Post-occlusion, the model also predicted a loss of autoregulation and a decrease in flow to the ischemic territory as oxygen demand was increased; these results were consistent with data from experiments that induced cerebral ischemia. Conclusions: This study highlights the importance of leptomeningeal collaterals following MCA occlusion and reinforces the idea that lower oxygen demand and higher arterial pressure improve conditions of flow and oxygenation.