Browsing by Subject "Blood flow"
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Item Adenosine and blood flow regulatory mechanisms in hippocampal ischemia(Texas Tech University, 2002-05) Gervitz, Leon MAccording to the National Institutes of Health (NIH), stroke affects more than 700,000 people annually, making it the third leading cause of death and the most common cause of adult disability in the United States. The success of medical intervention after a stroke depends on its being started soon after the insult. Defined as an acute neurological disorder caused by disturbances of the cerebral blood supply, stroke can rapidly lead to the development of ischemic brain tissue that is comprised of a nonviable, necrotic core surrounded by a penumbral region. Although functionally depressed, the penumbral region remains metabolically intact making it potentially salvageable during the post-ischemic therapeutic window. As such, it is considered a promising target for acute therapeutic intervention. The limited success of current early interventions, however, argues for a greater understanding of the regulatory mechanisms governing the physiology of the ischemic brain. Of particular interest are the regulatory mechanisms governing neuronal function and blood flow within the ischemic hippocampus. An integral part of the limbic system that is involved in the processing of short-term memory, the hippocampus is a bilateral structure that is exquisitely sensitive to hypoxia and/or ischemia. It is well established that an early response to cerebral hypoxic and/or ischemic conditions is a reversible inhibition of evoked synaptic potentials. The suppression of synaptic function is thought to serve as a neuroprotective mechanism to reduce energy expenditure during metabolic stress, i.e. hypoxia/ischemia. There is substantial evidence in in vitro preparations that the initial reversible loss of synaptic activity during exposure to hypoxia or ischemic-like conditions in the hippocampus is due to the release of endogenous adenosine acting at neuronal Ai receptors. Such roles for adenosine in in vivo preparations, however, have not been as convincingly demonstrated. Using a rat model of unilateral common carotid artery occlusion coupled with hypoxia, this dissertation examines the regulatory mechanisms of hippocampal blood flow and the contribution of adenosine to the early hypoxic/ischemic inhibition of synaptic transmission in an in vivo model of ischemic penumbra, and additionally examines the role of adenosine in the initiation of a post-ischemic, anti-apoptotic signal transduction pathway, Akt/Protein Kinase B. Animals were placed in a stereotaxic apparatus and evoked excitatory postsynaptic potentials (fEPSPs) were recorded from CAl of the rat hippocampus. Additionally, body temperature, systemic blood pressure, arterial blood gases, and hippocampal blood flow using laser Doppler flowmetry were monitored during experiments. Akt/PKB activation was examined using Western blot analysis. We demonstrate for the first time in an in vivo preparation, that A1 receptor activation plays a central role in the early hypoxic-ischemic depression of the evoked hippocampal synaptic potentials. Moreover, we demonstrate that while hypoxia is a potent stimulus for the adenosine-mediated depression of the synaptic potentials in vitro, reduced hippocampal tissue p02 alone does not appear to be sufficient to induce an adenosine-mediated depression of synaptic transmission in vivo. There must be, it seems, an accompanying reduction in local hippocampal blood flow. Moreover, the adenosine A1- mediated depression of synaptic depression occurs in proportion to reductions in local cerebral blood flow over a wide range of flows typical of penumbra. We also demonstrated that A] receptor activation leads to the activation of the neurotrophic/anti-apoptotic protein kinase Akt/Protein Kinase B (PKB). This result suggest that Akt/PKB activation may play a heretofore unappreciated role in adenosine A1-mediated signal transduction and, therefore, in adenosine A 1-mediated neuroprotection. We conclude from this work that adenosine acts as both an endogenous mediator and a sensitive indicator of penumbral conditions throughout the range of penumbral blood flows, and is an important mediator of the cellular response to survivable levels of ischemia.Item Association between reduced limb perfusion and muscle spasticity in persons with spinal cord injury(2010-12) Parmar, Yesha Jayantilal; Griffin, Lisa; Tanaka, HirofumiIndividuals with spinal cord injury (SCI) demonstrate reduced limb blood flow and muscle spasticity. It is plausible that the accumulation of metabolites, resulting from reduced perfusion, could exacerbate spasticity via activation of fusimotor neurons by Group III and IV afferents. PURPOSE: To determine the association between peripheral blood flow and muscle spasticity in persons with SCI. METHODS: A total of 16 individuals with SCI were classified into high (N=6), low (N=5), and no (N=5) spasticity groups according to their spasticity levels indicated by the modified Ashworth scale scores. Blood flow was measured in femoral and brachial arteries using duplex Doppler ultrasound and was normalized to limb lean mass obtained with dual energy X-ray absorptiometry. RESULTS: There were no significant group differences in age (30.5±4.15, 38.48±4.61, 32.6±4.89 years), time post SCI (8.5±4.2, 12.6±4.74, 6.8±1.66 years), American SCI Association motor scores (39.2±7.78, 59±12.34, 53.4±1.08), or sensory scores (96±22.1, 144.4±13.97, 130±13.8). Femoral artery blood flow, adjusted for limb lean mass, was significantly different (p=0.002) across the three leg spasticity groups (high 76.03±6.44, low 95.12±15.49, no 142.53±10.86 ml/min/kg).Total leg muscle spasticity scores were significantly and negatively correlated with femoral artery blood flow (r=-0.60, p=0.014). There was no significant difference in brachial artery blood flow between the three groups, indicating that the reduction in blood flow was confined to injured limbs and not due to systemic cardiovascular disorder. CONCLUSION: Among SCI patients, whole-leg blood flow is progressively lower in individuals with greater spasticity scores. These results suggest that a reduction in lower limb perfusion, among other factors, plays a significant role in the pathogenesis leading to muscle spasticity after SCI.Item Computer simulation of blood flow in microvessels and numerical experiments on a cell-free layer(2007-05) Jee, Sol Keun, 1979-; Moser, Robert deLanceySimulating blood flow in microvessels is a major challenge because of the numerous blood cells suspended in the blood. Furthermore, red blood cells (RBCs), which constitute 45% of the total blood volume, are highly deformable. RBCs deformation and RBC-RBC interactions determine the complex rheology of the blood. In this research, we simulate the blood flow in periodic two dimensional channels and conduct numerical experiments on the cell-free layer which appears near the wall. We use the boundary integral method and the smooth particle mesh Ewald method to represent the blood flow, and cells are modeled as deformable capsules. In the numerical experiments, we examine four possible mechanisms that may contribute to the cell-free layer: RBC deformation, RBC aggregation, configuration constraint, and the lubrication mechanism. Our simulations correctly represent hemodynamic phenomena such as the blunt velocity profile and the Fåhræus effect. We observed that more deformable RBCs migrate more away from the wall, and, consequently, the thickness of the cell-free layer increases. However, RBC aggregation increased the cell-free layer thickness by only 5%. In the experiment on the configuration constraint, no cell-free "layer" was detected when we removed cells which intersected an artificial constraint in the microvessel. In the last experiment on the lubrication mechanism, the cell-free layer disappeared at a no-shear stress boundary, and the hematocrit profile was similar to that in the constraint test. Therefore, this research clearly shows that the cell-free layer is generated by the lateral migration of deformable RBCs due to the lubrication mechanism.Item Novel optical techniques for imaging oxygen and other hemodynamic parameters during physiological events(2010-12) Ponticorvo, Adrien; Dunn, Andrew Kenneth, 1970-; Jones, Theresa; Ress, David; Rylander, Grady; Tunnell, JamesThis dissertation presents the development and use of a novel optical imaging system capable of monitoring changes in blood flow, oxygenated hemoglobin, deoxygenated hemoglobin, and absolute pO₂ in the brain. There are several imaging modalities capable of monitoring these parameters separately. Laser speckle contrast imaging (LSCI) and multi-spectral reflectance imaging (MSRI) have been used to monitor relative blood flow and hemoglobin changes respectively. Phosphorescence quenching, while not typically used for imaging, is capable of noninvasive measurements of pO₂. Combining these three techniques has led to the development of an imaging system that could ultimately lead to a better understanding of brain physiology. By combining techniques such as LSCI and MSRI, it becomes possible to estimate the cerebral metabolic rate of oxygen (CMRO₂), an important indicator of neuronal function. It is equally important to understand absolute pO₂ levels so that oxygen metabolism can be examined in context. Integrating phosphorescence quenching and a spatial light modulator into the imaging system allowed absolute pO₂ to be simultaneously measured in distinct regions. This new combined system was used to investigate pathophysiological conditions such as cortical spreading depression (CSD) and ischemia. The observed hemodynamic changes associated with these events were largely dictated by baseline oxygen levels and varied significantly in different regions. This finding highlighted the importance of having a system capable of monitoring hemodynamic changes and absolute pO₂ simultaneously while maintaining enough spatial resolution to distinguish the changes in different regions. It was found that animals with low baseline pO₂ were unable to deliver enough oxygen to the brain during events like CSD because of the high metabolic demand. In order for this technique to become more prevalent among researchers, it is essential to make it cost effective and simple to use. This was accomplished by replacing the expensive excitation sources with cheaper light emitting diodes (LEDs) and redesigning the software interface so that it was easier to control the entire device. The final system shows the potential to become a key tool for researchers studying the role of absolute pO₂ and other hemodynamic parameters during pathophysiological conditions such as CSD and ischemia.Item Regulation of adrenal blood flow: Response to hemorrhagic hypotension(Texas Tech University, 1980-05) Houck, Peter CushmanNot availableItem Thermal study of vulnerable atherosclerotic plaque(2009-05-15) Kim, TaehongAtherosclerotic plaques with high probability of rupture show the presence of a hot spot due to the accumulation of inflammatory cells. This study utilizes two and three dimensional (2-D and 3-D) arterial geometries containing an atherosclerotic plaque experiencing different levels of inflammation and uses models of heat transfer analysis to determine the temperature distribution in the plaque region. The 2-D studies consider three different vessel geometries: a stenotic straight artery, a bending artery and an arterial bifurcation which model a human aorta, a coronary artery and a carotid bifurcation, respectively. The 3-D model considers a stenotic straight artery using realistic and simplified geometries. Three different blood flow cases are considered: steady-state, transient state and blood flow reduction. In the 3-D model, thermal stress produced by local inflammation is estimated to determine the effect of inflammation over plaque stability. For fluid flow and heat transfer analysis, Navier-Stokes equations and energy equation are solved; for structural analysis, the governing equations are expressed in terms of equilibrium equation, constitutive equation, and compatibility condition, which are are solved using the multi-physics software COMSOL 3.3 (COMSOL, Inc.). Our results indicate that the best location to measure plaque temperature in the presence of blood flow is recommended between the middle and the far edge of the plaque. The blood flow reduction leads to a non-uniform temperature increase ranged from 0.1 to 0.25 oC in the plaque/lumen interface. In 3-D realistic model, the multiple measuring points must be considered to decrease the potential error in temperature measurement even within 1 or 2 mm at centerline region of plaque. The most highly thermal stressed regions with the value of 1.45 Pa are observed at the corners of lipid core and the plaque/lumen interface. The mathematical model developed provides a tool to analyze the factors affecting heat transfer at the plaque surface. The results may contribute to the understanding of the relationship between plaque temperature and the likelihood of rupture, and also provide a tool to better understand arterial wall temperature measurements obtained with novel catheters.