Browsing by Subject "cerebral blood flow"
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Item Cerebral Blood Flow Regulation in Intermittent Hypoxia(2009-05-01) Eubank, Wendy L.; Raven, Peter B.Item Effects of Sex Steroids on Stroke(2004-02-01) Yang, Shaohua; Simpkins, James W.Yang, Shaohua, Effects of Sex Steroids on Stroke. Doctor of Philosophy (Biomedical Science), February 2004, pp210, 5 tables, 27 illustrations, 64 titles. Estrogens and androgens are recognized as major sex steroids for females and males, respectively. However, it is clear that estrogens as well as androgens are more than gender hormones. Our data indicated that female steroids, such as 17β-estradiol (E2), exert neuroprotective effects on stroke, while male steroids, like testosterone, exert deleterious effects on stroke. The neuroprotective effects of estrogens have been very well demonstrated both in vitro as well as in vivo. Our studies indicated that neuroprotective effects of E2 are exerted both ischemic and hemorrhagic stroke. In our subarachnoid hemorrhage (SAH) model, E2 reduced secondary ischemic damage and mortality consequent to SAH. These effects were not associated with the change of the clot volume in SAH. The neuroprotective effects of estrogens were not only seen in the pre-treatment paradigms. E2 exerted neuroprotective effects even when administered after ischemia, with a therapeutic window of about 3 hours in a permanent focal cerebral ischemia model. This effect of estradiol was associated with no immediate change on blood flow, but with a delayed increasing in cerebral blood flow (CBF). Further our studies indicated that a non-estrogen receptor (ER)-binding analogue possessed both neuroprotective and vasoactive effects, which suggests that both the neuroprotective and vasoactive effects of estrogens are receptor-independent. This molecule also offers the possibility of clinical application for stroke without the side effects of estrogens. We used immunochemistry, immunoblot and mass spectrometry to demonstrate that ERβ is localized to mitochondria. Our data established this ERβ localization in a variety of cell types, suggesting that ERβ is not a nuclear receptor, which was thought to mediate the genomic function of estrogens. In contrast to estrogens, testosterone increased neuronal toxicity and exacerbated cerebral ischemia-reperfusion injury. These results suggest that sex differences in outcome after stroke may result from both the protective effects of estrogens and the damaging effects of testosterone. Further, our study indicated that stress induced testosterone reduction contributes to cerebral ischemia tolerance against ischemia reperfusion injury, providing the first in vivo evidences for a neuroendocrine mechanism for the cerebral preconditioning in males.Item Hemodynamic Oscillations: Physiological Consequences and Therapeutic Potential(2022-05) Anderson, Garen K.; Rickards, Caroline A.; Goulopoulou, Styliani; Romero, Steven A.; Cunningham, J. ThomasHemorrhage, or massive blood loss, continues to be a leading cause of preventable death. Therapeutic approaches that protect vital organ function are needed to improve outcomes from hemorrhage. In this dissertation, I explored the use of hemodynamic oscillations below the respiratory frequency (i.e., oscillations in arterial pressure and cerebral blood flow) as a novel technique for protecting tissue oxygenation during hemorrhage. In the first study of this dissertation, I hypothesized that hemodynamic oscillations would contribute to improved tolerance to central hypovolemia simulating hemorrhage. In further assessing the role of arterial blood gases on the physiological responses to forcing hemodynamic oscillations during a simulated hemorrhage, I hypothesized that forcing hemodynamic oscillations during simulated hemorrhage would protect tissue oxygenation during conditions of hypoxia and isocapnia, and improve cerebral blood flow. I also hypothesized that this protection would occur equally for both females and males. To address these hypotheses, I conducted five independent studies using lower body negative pressure as a method of simulating hemorrhage in healthy, conscious humans: in one study I utilized a maximal step-wise LBNP protocol to assess endogenous hemodynamic oscillations and tolerance to simulated hemorrhage, and in the remaining 4 studies, I utilized oscillatory and non-oscillatory LBNP to assess the potential therapeutic utility of forcing hemodynamic oscillations during simulated hemorrhage. The major findings from these investigations were: 1) greater amplitude of low frequency oscillations in arterial pressure are associated with greater LBNP tolerance, but the relative time to peak oscillatory power was not dependent on tolerance; 2) forced hemodynamic oscillations protect cerebral tissue oxygenation without protecting cerebral blood flow during the combined stress of simulated hemorrhage and hypobaric hypoxia; 3) isocapnia with simulated hemorrhage prevents the reduction in cerebral blood flow and tissue oxygenation, and forced hemodynamic oscillations during this stress protects stroke volume and arterial pressure; 4) females exhibit protected muscle tissue oxygenation to simulated hemorrhage, and the reduction in muscle tissue oxygenation in males can be attenuated with forced hemodynamic oscillations; and 5) forced hemodynamic oscillations at high altitude are greater in amplitude and result in similar protection of cerebral tissue oxygenation as low altitude conditions. These findings contribute to the growing body of literature highlighting the potential utility of oscillatory hemodynamics for therapeutic application.Item Influence of the Carotid Baroreflex on Cerebral Blood Flow During Seated Upright Rest(2007-07-01) Eubank, Wendy L.; Peter B. Raven; Robert Mallet; James CaffreyEubank, Wendy L., Influence of Carotid Baroreflex on Cerebral Blood Flow During Seated Upright Rest. Master of Science (Integrative Physiology), July, 2007, 25 pp., 1 table, 4 illustrations, 34 references. This study tested the hypothesis that sympathetic activation via the carotid baroreflex directly influences cerebral vasomotion during seated upright test. This study also examined the effects of pulsatile neck pressure (NP) and neck suction (NS) during seated upright rest in healthy human subjects. Changes in mean arterial pressure (MAP) and mean middle cerebral arterial velocity (MCA V mean), were measured. The power spectral density (PSD) of MAP of 0.1Hz increased during pulsatile NP and NS. The PSD of MCA V mean at 0.1Hz was much greater during NP than that of NS. There were no significant differences between end-tidal CO2 between each condition. These findings suggest that cerebral vasoconstriction during NP was a result of the autoregulatory response to the NP mediated pulsatile changes in arterial pressure and the NP induced sympathetically mediated vasoconstriction.Item Pulsatile Perfusion Therapy: A Novel Approach for Improving Cerebral Blood Flow and Oxygenation Under Simulated Hemorrhagic Stress(2018-05) Anderson, Garen K.; Rickards, Caroline A.; Goulopoulou, Styliani; Mallet, Robert T.; Jones, Harlan P.Introduction: Tolerance to both actual and simulated hemorrhage varies between individuals. Low frequency (~0.1 Hz) oscillations in mean arterial pressure (MAP) and brain blood flow (indexed via middle cerebral artery velocity, MCAv), may play a role in tolerance to reduced central blood volume; subjects with high tolerance to simulated hemorrhage induced via application of lower body negative pressure (LBNP) exhibit greater low frequency power in MAP and MCAv compared to low tolerant subjects. The mechanism for this association has not been explored. We hypothesized that inducing low frequency oscillations in arterial pressure and cerebral blood flow would attenuate reductions in cerebral blood flow and oxygenation during simulated hemorrhage. Methods: 14 subjects (11M/3F) were exposed to oscillatory (0.1 Hz, 0.05 Hz) and non-oscillatory (0 Hz) LBNP profiles with an average chamber pressure of -60 mmHg. Each profile was separated by a 5-min recovery. Measurements included arterial pressure and stroke volume via finger photoplethysmography, MCAv via transcranial Doppler ultrasound, and cerebral oxygenation of the frontal lobe (ScO2) via near infrared spectroscopy. Results: No differences were observed between profiles for reductions in MAP (P=0.60) and MCAv (P=0.90). The reduction in ScO2, however, was attenuated (P=0.04) during the oscillatory profiles compared to the 0 Hz profile. A similar attenuation was observed in stroke volume (P [less than] 0.001). Importantly, tolerance was higher during the oscillatory profiles (P=0.03). Discussion: In partial support of our hypothesis, cerebral oxygenation was protected during the oscillatory profiles. While MCAv was similar between conditions, the oscillatory pattern of cerebral blood flow may elicit a shear-stress induced vasodilation, so assessment of velocity may mask an increase in flow. Importantly, more subjects were able to tolerate the oscillatory profiles compared to the static 0 Hz profile, despite similar arterial pressure responses. These findings emphasize the potential importance of hemodynamic oscillations in maintaining perfusion and oxygenation of cerebral tissue during hemorrhagic stress.Item The Role of Cerebral Oxygenation and Perfusion on Tolerance to Central Hypovolemia(2016-12-01) Kay, Victoria L.; Caroline A. Rickards; Robert T. Mallet; Michael L. SmithTolerance to central hypovolemia, including hemorrhage, is highly variable between individuals. The role of cerebral oxygenation and regional cerebral perfusion on tolerance to central hypovolemia has not been explored. Protection of posterior cerebral perfusion may be an important factor in tolerance, as the posterior circulation supplies blood to the autonomic and respiratory control centers in the brain stem. Additionally, despite the reduction in cerebral oxygen delivery with central hypovolemia via decreased flow, the role of compensatory increases in oxygen extraction and subsequent cerebral tissue oxygenation on tolerance have not been identified. The oscillatory pattern of cerebral blood flow has recently been identified as a contributing factor to improving tolerance to central hypovolemia, and may be more important than the protection of absolute flow. This finding was demonstrated when comparing high vs. low tolerant individuals, and in subjects who exhibited increased tolerance to central hypovolemia while breathing against inspiratory resistance. We hypothesized that healthy human subjects with naturally high tolerance to central hypovolemia, and subjects breathing against inspiratory resistance under hypovolemic stress would exhibit 1) protection of cerebral oxygen saturation (ScO2); 2) prolonged preservation of cerebral blood flow in the posterior versus anterior cerebral circulation, and; 3) higher LF oscillations in cerebral blood flow. The major findings from these investigations are: 1) subjects with high tolerance to central hypovolemia exhibited protection of ScO2 and velocity in the posterior cerebral circulation; 2) LF oscillations did not play a role in the protection of ScO2; 3) resistance breathing improved tolerance to central hypovolemia, but not via protection of ScO2 or velocity in either the anterior or posterior cerebral circulation, and; 4) resistance breathing was associated with increased high frequency oscillatory power in arterial pressure, anterior and posterior cerebral blood velocity, and ScO2. We conclude that individuals with naturally high tolerance to central hypovolemia exhibit protection of cerebral tissue oxygenation and prolonged preservation of perfusion within the posterior cerebral circulation, but not in the anterior circulation, thus delaying the onset of presyncope. Improved tolerance to central hypovolemia via resistance breathing was not related to these mechanisms, but may have been associated with increased depth of breathing, subsequently decreasing intracranial pressure and increasing cerebral perfusion pressure.