Browsing by Subject "Cerebrovascular Circulation"
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Item Characterization of Arterial Pressure and Cerebral Blood Flow Responses To Repeated Thigh Cuff Inflation In Three Experimental Models (Humans, Pigs, Rats)(2022-05) Bhuiyan, Nasrul A.; Rickards, Caroline A.; Tune, Johnathan D.; Cunningham, J. ThomasIn a human model of simulated blood loss, oscillatory patterns of arterial pressure and blood flow, or "pulsatile perfusion", can protect cerebral and peripheral tissue oxygenation, and prolong tolerance to this stress. In this pilot study, we characterize the hemodynamic responses to pulsatile perfusion therapy induced via repeated thigh cuff inflations in humans at rest, and in pig and rat models of actual blood loss. In 2 human participants, 0.1 Hz (10-second cycle) thigh cuff oscillations induced robust 0.1 Hz oscillations in arterial pressure and cerebral blood flow. In the two animal models, all subjects underwent a baseline period, hemorrhage of 55% of total blood volume, then a 30-min period with or without thigh cuff oscillations (0.1 Hz for pigs, and 0.5 Hz for rats). Decreases in mean arterial pressure (MAP) and carotid artery blood flow were observed in response to hemorrhage (P≤0.002) in both pigs and rats. At the end of the PPT period, however, no differences were observed between the oscillation or no oscillation groups for absolute MAP (rats, P=0.44; pigs, P=0.90) or common carotid artery (CCA) peak blood flow (rats, P=0.92; pigs, P=0.93). When examining the frequency power spectrums, there was not a robust increase in 0.5 Hz oscillations for MAP (P=0.23) or CCA flow (P=0.82), but 0.1 Hz oscillations were detected in CCA flow for pigs (P=0.09). While in the human model, large increases in oscillatory power were observed for both arterial pressure and cerebral blood flow, the responses in the two animal models were inconclusive due to high inter-individual variability. These findings indicate the need for further studies and refinement of the thigh cuff approach in the animal models to reliably induce hemodynamic oscillations.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 Hemodynamic Responses to Oscillatory Thigh Cuff Inflations(2023-05) McIntyre, Benjamin J.; Rickards, Caroline A.; Tune, Johnathan D.; Farmer, GeorgeExperimental generation of 0.1 Hz oscillations (~10-s cycle) in arterial pressure and cerebral blood flow (CBF) increases tolerance to simulated hemorrhage, and protects cerebral tissue oxygenation. In this study we evaluated a clinically applicable method of inducing 0.1 Hz oscillations in arterial pressure and CBF via repeated thigh cuff inflations. We also characterized the effect of common carotid artery (CCA) stiffness on the magnitude of cerebral blood flow oscillations, and evaluated the effects of intermittent thigh cuff inflation on several markers of cardiac function. We hypothesized that: 1) the amplitude of arterial pressure and CBF oscillations at 0.1 Hz would increase in response to repeated thigh cuff inflations at 0.1 Hz, 2) the magnitude of 0.1 Hz CBF oscillations would be positively correlated to the stiffness of the CCA, and 3) measurements of cardiac function would increase in response to thigh cuff induced oscillations of arterial pressure at 0.1 Hz. Thirteen healthy human participants were tested (6 male, 7 female; 27.1 ± 4.3 y). In response to 10-min of intermittent thigh cuff inflations at 0.1 Hz, the amplitude of 0.1 Hz oscillations increased for mean arterial pressure (MAP; 24.4 ± 20.1 mmHg2 vs. 932.0 ± 758.1 mmHg2; P<0.01) and middle cerebral artery velocity (MCAv; 17.5 ± 13.8 (cm/s)2 vs. 325.5 ± 279.9 (cm/s)2; P<0.01). There was also a large increase in MAP-MCAv coherence at 0.1 Hz (0.60 ± 0.24 a.u. vs. 0.90 ± 0.11 a.u.; P<0.01) during the oscillatory period compared to baseline. There was a moderate positive relationship between CCA stiffness and amplitude of MCAv power at 0.1 Hz during intermittent thigh cuff inflations (r=0.68, P=0.01), but not at rest (r=-0.08, P=0.80). When compared to baseline, no changes were observed during the oscillatory period for heart rate (P=0.47), stroke volume (P=0.87), cardiac output (P=0.55), MAP (P=0.20), or dP/dTmax (P=0.61). Future studies directly examining sympathetic nerve activity are needed to better elucidate the effects of induced 0.1 Hz hemodynamic oscillations on neural regulation of the cardiovascular system. In conclusion, we have shown that intermittent thigh cuff inflations can be used to increase hemodynamic variability at a target frequency, and therefore could be a therapy for treating tissue hypoperfusion following severe blood loss injuries.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 Slow Recovery of Cerebral Perfusion During Hypotension in Elderly Humans(2021-05) Abdali, Kulsum; Shi, Xiangrong; Hodge, Lisa M.; Mallet, Robert T.Purpose: The study sought to test the hypothesis that the function of maintaining cerebral perfusion is diminished in elderly adults due to compromised cerebral autoregulation (CA) and cardiovascular systemic mechanisms with aging. Methods: Thirteen healthy elderly (67.5±1.1 yr) and 13 young (25.8±1.0 yr) adults signed a consent form and passed a physical exam to be enrolled in the study, which was approved by the IRB at UNTHSC. Heart rate (HR), mean arterial pressure (MAP), and cerebral blood flow velocity of the middle cerebral artery (VMCA) were continuously measured during systemic hypotension induced by a rapid cuff deflation after 3-min supra-systolic occlusion with bilateral thigh cuffs. This hypotension elicited a transient decrease in VMCA i.e. ΔVMCA and a reflexive increase in HR i.e. ΔHR. Duration and rate of the recovery response from the nadir of MAP and VMCA were compared between the groups. Results: Rapid cuff deflation after 3-min supra-systolic occlusion to the legs significantly decreased MAP (ΔMAP) in both the elderly (-14.1±1.1 mmHg) and young (-16.5±1.2 mmHg) groups which were not significantly different. This hypotension elicited similar significant hypoperfusion to the brain as indicated by ΔVMCA in the elderly (-7.9±0.9 cm/s) and young (-9.5±1.0 cm/s) groups. However, the time elapsed from deflation to the nadir of MAP and VMCA (T0) and recovery time (Tr) of these variables from the nadir to return to baseline were significantly prolonged in the elderly subjects. The rates of relative changes in HR (%ΔHR/s, elderly vs young groups: 1.42±0.20 vs 4.02±0.42 %/s), MAP (%ΔMAP/sec, elderly vs young groups: 0.93±0.11 vs 1.93±0.20 %/s) and VMCA (%ΔVMCA/sec, elderly vs young groups: 1.72±0.02 vs 2.97±0.40 %/s) during recovery were diminished in elderly vs. young adults. Overall TR-ΔVMCA was significantly explained by the rates of %ΔHR, %ΔMAP, and %ΔVMCA. However, the TR-ΔVMCA/vasomotor-factor slope (-3.0±0.9) was steeper (P=0.046) than the TR-ΔVMCA/cardiac-factor slope (-1.1±0.4). The TR-ΔVMCA/CA-factor slope (-2.3±0.5) was greater (P=0.055) than the TR-ΔVMCA/cardiac-factor slope; but it did not differ from the TR-ΔVMCA/vasomotor-factor slope. Discussion: Maintenance of MAP was regulated by vasomotion and HR factors; whereas regulation of VMCA seemed to be affected by intrinsic and systemic mechanisms. Both T0 and TR were remarkably shorter for VMCA than MAP, suggesting the presence of cerebral autoregulation, which evoked an early rebound of VMCA from its nadir before MAP reached the nadir and explained a quick recovery of VMCA before MAP completed its restoration. Nonetheless, both T0 and TR were significantly longer in the elderly subjects. In addition to the response rate of VMCA, relative change rates of both MAP and HR were significantly diminished with aging, which explained a prolonged recovery of cerebral perfusion during hypotension.Item The Interaction Between Arterial Stiffness, Amplitude of Cerebral Blood Flow Oscillations, and Cerebral Tissue Oxygenation(2024-05) Hudson, Lindsey M.; Rickards, Caroline A.; Tune, Johnathan D.; Dick, Gregory M.Inducing 0.1 Hz (10-s cycle) oscillations in cerebral blood flow attenuates the reduction in cerebral tissue oxygenation during simulated hemorrhage in humans. Our laboratory has developed a potential therapeutic technique called pulsatile perfusion therapy (PPT) which induces 0.1 Hz oscillations in cerebral blood flow. It is unknown, however, how stiffness of the arteries influences the magnitude of cerebral blood flow oscillations, and/or the protection of cerebral tissue oxygenation. When 0.1 Hz oscillations are induced during simulated hemorrhage, we hypothesized that: 1) arterial stiffness of the internal carotid artery (ICA) and common carotid artery (CCA) would increase from rest; 2) the amplitude of 0.1 Hz oscillations in cerebral blood flow would be higher in individuals with stiffer arteries, and; 3) the reduction in cerebral tissue oxygenation would be smaller with higher amplitude of cerebral blood flow oscillations. Two studies using two different techniques of PPT were performed to investigate these hypotheses. Study 1: In a retrospective analysis, 8 healthy human participants (age: 30.1±7.6 y) underwent a 10-min hypovolemic oscillatory lower body negative pressure (OLBNP) protocol, where chamber pressure oscillated every 5-s between -30 mmHg and -90 mmHg (i.e., 0.1 Hz). ICA β-stiffness index was calculated from measurements of ICA diameter (via ultrasound imaging), and arterial pressure (via finger photoplethysmography). Middle cerebral artery velocity (MCAv) was measured using transcranial doppler ultrasound, and cerebral tissue oxygenation (ScO2) was measured with near infrared spectroscopy. Fast Fourier transformation was used to quantify oscillations in mean MCAv at ~0.1 Hz. While mean MCAv 0.1 Hz oscillations increased from baseline to OLBNP (N=8, 34.0±33.9 (cm/s)2 vs. 104.7±58.1 (cm/s)2, p=0.01), ICA β stiffness did not increase (N=5, 6.1±0.7 au vs. 8.2±2.7 au, p=0.21). There was no relationship between baseline ICA β-stiffness and the percent change in mean MCAv 0.1 Hz oscillations (N=5; r=0.44, p=0.46). ScO2 decreased from baseline to OLBNP (N=8, 66.5±2.9 % vs. 64.8±2.9 %, p=0.03), but there was also no relationship between the percent change in mean MCAv 0.1 Hz oscillations and the decrease in ScO2 (r=0.28, p=0.50). Study 2: In a prospective pilot study, 3 participants underwent a 10-min LBNP protocol to a chamber pressure of -60 mmHg, and hemodynamic oscillations were simultaneously induced with bilateral thigh cuffs inflating for 5-s to 230 mmHg then deflating for 5-s in a 10-s cycle (i.e., 0.1 Hz). β-stiffness index of the CCA was measured. In this pilot study, insufficient data were collected to perform statistics for each of the three aims, so descriptive results are presented. Adequate ultrasound measurements were made for assessment of CCA β- stiffness in two participants; in the control condition, CCA β-stiffness was 6.7 ± 2.4 au during baseline and increased to 7.4 ± 1.1 au during LBNP (N=2). With PPT, CCA β-stiffness was 6.6 ± 1.6 au during baseline and increased to 7.8 ± 2.2 au during LBNP (N=2). The amplitude of MCAv 0.1 Hz oscillations increased from 7.9 (cm/s)2 at baseline of the control condition to 179.8 (cm/s)2 (i.e., a ~23-fold increase) during LBNP. The amplitude of MCAv 0.1 Hz oscillations increased from 25.8 (cm/s)2 during baseline of PPT to 210.2 (cm/s)2 (~8-fold increase) during LBNP (N=1). ScO2 decreased from 75.0% to 71.3% during LBNP in the control condition, and from 73.4% to 71.6% in the PPT condition (N=1). Based on the results of Study 1, 0.1 Hz OLBNP does not increase ICA stiffness, and there is no relationship between ICA stiffness, amplitude of induced 0.1 Hz cerebral blood flow oscillations, and the reduction in cerebral tissue oxygenation during simulated hemorrhage. However, as this analysis was performed retrospectively, and arterial stiffness was not initially an outcome measure, there were limited data available for analysis. For Study 2, we were successfully able to induce 0.1 Hz oscillations in cerebral blood flow by combining LBNP with bilateral thigh cuff inflations. However, insufficient data were available to make definitive conclusions about the role of PPT on CCA β-stiffness, 0.1 Hz oscillations in cerebral blood flow, or the relationship in 0.1 Hz oscillations in cerebral blood flow and protection of cerebral tissue oxygenation. This study is currently ongoing, and additional data will provide further insight into these relationships.