Browsing by Subject "Blood flow"

Now showing 1 - 7 of 7
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    GPR68 Senses Flow and Is Essential for Vascular Physiology
    (Elsevier, 2018-04-19) Xu, Jie; Mathur, Jayanti; Vessières, Emilie; Hammack, Scott; Nonomura, Keiko; Favre, Julie; Grimaud, Linda; Petrus, Matt; Francisco, Allain; Li, Jingyuan; Lee, Van; Xiang, Fu-Li; Mainquist, James K.; Cahalan, Stuart M.; Orth, Anthony P.; Walker, John R.; Ma, Shang; Lukacs, Viktor; Bordone, Laura; Bandell, Michael; Laffitte, Bryan; Xu, Yan; Chien, Shu; Henrion, Daniel; Patapoutian, Ardem; Obstetrics and Gynecology, School of Medicine
    Mechanotransduction plays a crucial role in vascular biology. One example of this is the local regulation of vascular resistance via flow-mediated dilation (FMD). Impairment of this process is a hallmark of endothelial dysfunction and a precursor to a wide array of vascular diseases, such as hypertension and atherosclerosis. Yet the molecules responsible for sensing flow (shear stress) within endothelial cells remain largely unknown. We designed a 384-well screening system that applies shear stress on cultured cells. We identified a mechanosensitive cell line that exhibits shear stress-activated calcium transients, screened a focused RNAi library, and identified GPR68 as necessary and sufficient for shear stress responses. GPR68 is expressed in endothelial cells of small-diameter (resistance) arteries. Importantly, Gpr68-deficient mice display markedly impaired acute FMD and chronic flow-mediated outward remodeling in mesenteric arterioles. Therefore, GPR68 is an essential flow sensor in arteriolar endothelium and is a critical signaling component in cardiovascular pathophysiology.
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    In Vivo Visualization and Quantification of Rat Laryngeal Blood Supply After Hydration Challenge
    (Wiley, 2024) Duan, Chenwei; Anderson, Jennifer L.; Schepers, Luke E.; Damen, Frederick W.; Cox, Abigail; Goergen, Craig J.; Sivasankar, Preeti M.; Surgery, School of Medicine
    Objectives: Systemic dehydration decreases total body blood volume; however, hemodynamic alterations at the level of local organs, such as the larynx, remain unclear. Here we sought to quantify superior thyroid artery (STA) blood flow after dehydration and rehydration using in vivo magnetic resonance angiography (MRA) and ultrasound imaging in a rat model. Methods: Male Sprague-Dawley rats (N = 17) were included in this prospective, repeated measures design. Rats first underwent MRA to determine baseline STA cross-sectional area, followed by high-frequency in vivo ultrasound imaging to measure STA blood velocity at baseline. Next, rats were systemically dehydrated (water withholding), followed by rehydration (water ad-lib). Ultrasound imaging was repeated immediately after dehydration and following rehydration. The STA blood velocity and STA cross-sectional area were used to compute STA blood flow. Three rats served as temporal controls for ultrasound imaging. To determine if the challenges to hydration status affected the STA cross-sectional area, four rats underwent only MRA at baseline, dehydration, and rehydration. Results: Systemic dehydration resulted in 10.5% average body weight loss. Rehydration resulted in average body weight gain of 10.9%. Statistically significant reductions were observed in STA mean blood flow rate after dehydration. Rehydration reversed these changes to pre-dehydration levels. No significant differences were observed in STA cross-sectional area with dehydration or rehydration. Conclusion: Systemic dehydration decreased blood flow in the superior thyroid artery. Rehydration restored blood flow in the STA. Change in hydration status did not alter the STA cross-sectional area. These preliminary findings demonstrate the feasibility of using ultrasound and MRA to quantify hemodynamic changes and visualize laryngeal blood vessels.
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    Mathematical modeling approaches in the study of glaucoma disparities among people of African and European descents
    (American Scientific, 2013) Guidoboni, Giovanna; Harris, Alon; Arciero, Julia C.; Siesky, Brent A.; Amireskandari, Annahita; Gerber, Austin L.; Huck, Andrew H.; Kim, Nathaniel J.; Cassani, Simone; Carichino, Lucia; Mathematical Sciences, School of Science
    Open angle glaucoma (OAG) is a severe ocular disease characterized by progressive and irreversible vision loss. While elevated intraocular pressure (IOP) is a well-established risk factor for OAG, the progression of OAG in many cases, despite IOP treatment, suggests that other risk factors must play significant roles in the development of the disease. For example, various structural properties of the eye, ocular blood flow properties, and systemic conditions have been identified as risk factors for OAG. Ethnicity has also been indicated as a relevant factor that affects the incidence and prevalence of OAG; in fact, OAG is the leading cause of blindness among people of African descent. Numerous clinical studies have been designed to examine the possible correlation and causation between OAG and these factors; however, these studies are met with the challenge of isolating the individual role of multiple interconnected factors. Over the last decade, various mathematical modeling approaches have been implemented in combination with clinical studies in order to provide a mechanical and hemodynamical description of the eye in relation to the entire human body and to assess the contribution of single risk factors to the development of OAG. This review provides a summary of the clinical evidence of ocular structural differences, ocular vascular differences and systemic vascular differences among people of African and European descent, describes the mathematical approaches that have been proposed to study ocular mechanics and hemodynamics while discussing how they could be used to investigate the relevance to OAG of racial disparities, and outlines possible new directions of research.
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    Metabolic blood flow regulation in a hybrid model of the human retinal microcirculation
    (Elsevier, 2023) Albright, Amanda; Fry, Brendan C.; Verticchio, Alice; Siesky, Brent; Harris, Alon; Arciero, Julia; Mathematical Sciences, School of Science
    The retinal vascular network supplies perfusion to vital visual structures, including retinal ganglion cells responsible for vision. Impairments in retinal blood flow and oxygenation are involved in the progression of many ocular diseases, including glaucoma. In this study, an established theoretical hybrid model of a retinal microvascular network is extended to include the effects of local blood flow regulation on oxygenation. A heterogeneous representation of the arterioles based on confocal microscopy images is combined with a compartmental description of the downstream capillaries and venules. A Green’s function method is used to simulate oxygen transport in the arterioles, and a Krogh cylinder model is applied to the capillary and venular compartments. Acute blood flow regulation is simulated in response to changes in pressure, shear stress, and metabolism. Model results predict that both increased intraocular pressure and impairment of blood flow regulation can cause decreased tissue oxygenation, indicating that both mechanisms represent factors that could lead to impaired oxygenation characteristic of ocular disease. Results also indicate that the metabolic response mechanism reduces the fraction of poorly oxygenated tissue but that the pressure- and shear stress-dependent response mechanisms may hinder the vascular response to changes in oxygenation. Importantly, the heterogeneity of the vascular network demonstrates that traditionally reported average values of tissue oxygen levels hide significant localized defects in tissue oxygenation that may be involved in disease processes, including glaucoma. Ultimately, the model framework presented in this study will facilitate future comparisons to sectorial-specific clinical data to better assess the role of impaired blood flow regulation in ocular disease.
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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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    Role of Voltage-Dependent K+ and Ca2+ Channels in Coronary Electromechanical Coupling: Effects of Metabolic Syndrome
    (2012-10-19) Berwick, Zachary C.; Tune, Johnathan D.; Basile, David P.; Mather, Kieren J.; Obukhov, Alexander G.; Sturek, Michael Stephen
    Regulation of coronary blood flow is a highly dynamic process that maintains the delicate balance between oxygen delivery and metabolism in order to preserve cardiac function. Evidence to date support the finding that Kv and Cav1.2 channels are critical end-effectors in modulating vasomotor tone and blood flow. Yet the role for these channels in the coronary circulation in addition to their interdependent relationship remains largely unknown. Importantly, there is a growing body of evidence that suggests obesity and its pathologic components, i.e. metabolic syndrome (MetS), may alter coronary ion channel function. Accordingly, the overall goal of this investigation was to examine the contribution coronary Kv and Cav1.2 channels to the control of coronary blood flow in response to various physiologic conditions. Findings from this study also evaluated the potential for interaction between these channels, i.e. electromechanical coupling, and the impact obesity/MetS has on this mechanism. Using a highly integrative experimental approach, results from this investigation indicate Kv and Cav1.2 channels significantly contribute to the control of coronary blood flow in response to alterations in coronary perfusion pressure, cardiac ischemia, and during increases in myocardial metabolism. In addition, we have identified that impaired functional expression and electromechanical coupling of Kv and Cav1.2 channels represents a critical mechanism underlying coronary dysfunction in the metabolic syndrome. Thus, findings from this investigation provide novel mechanistic insight into the patho-physiologic regulation of Kv and Cav1.2 channels and significantly improve our understanding of obesity-related cardiovascular disease.
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    Tissue oxidative metabolism can increase the difference between local temperature and arterial blood temperature by up to 1.3oC: Implications for brain, brown adipose tissue, and muscle physiology
    (Taylor & Francis, 2018-04-04) Zaretsky, Dmitry V.; Romanovsky, Andrej A.; Zaretskaia, Maria V.; Molkov, Yaroslav I.; Emergency Medicine, School of Medicine
    Tissue temperature increases, when oxidative metabolism is boosted. The source of nutrients and oxygen for this metabolism is the blood. The blood also cools down the tissue, and this is the only cooling mechanism, when direct dissipation of heat from the tissue to the environment is insignificant, e.g., in the brain. While this concept is relatively simple, it has not been described quantitatively. The purpose of the present work was to answer two questions: 1) to what extent can oxidative metabolism make the organ tissue warmer than the body core, and, 2) how quickly are changes in the local metabolism reflected in the temperature of the tissue? Our theoretical analysis demonstrates that, at equilibrium, given that heat exchange with the organ is provided by the blood, the temperature difference between the organ tissue and the arterial blood is proportional to the arteriovenous difference in oxygen content, does not depend on the blood flow, and cannot exceed 1.3oC. Unlike the equilibrium temperature difference, the rate of change of the local temperature, with respect to time, does depend on the blood flow. In organs with high perfusion rates, such as the brain and muscles, temperature changes occur on a time scale of a few minutes. In organs with low perfusion rates, such changes may have characteristic time constants of tens or hundreds of minutes. Our analysis explains, why arterial blood temperature is the main determinant of the temperature of tissues with limited heat exchange, such as the brain.