Browsing by Author "Anderson, Garen"
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Item A Comparison of Protocols for Simulating Hemorrhage in Humans: Step vs. Ramp Lower Body Negative Pressure(2019-03-05) Kay, Victoria; Anderson, Garen; Sprick, Justin; Rickards, Caroline; Rosenberg, AlexanderLower body negative pressure (LBNP) elicits central hypovolemia, and has been used to characterize the cardiovascular and cerebrovascular responses to simulated hemorrhage in humans. LBNP protocols traditionally employ a progressive stepwise reduction in pressure that is maintained for specific time periods. More recently, however, continuous ramp LBNP protocols have been utilized to simulate the continuous nature of most bleeding injuries. Purpose: The aim of this study was to compare tolerance and hemodynamic responses between a step LBNP protocol and a continuous ramp LBNP protocol until the onset of presyncope. Methods: Healthy human subjects (N=20; 8F, 12M) participated in two LBNP protocols to presyncope: 1) Step Protocol, where chamber pressure decreased every 5-min to -15, -30, -45, -60, -70, -80, -90 and -100 mmHg, and, 2) Ramp Protocol, where chamber pressure decreased 3 mmHg/min. Heart rate (HR), mean arterial pressure (MAP), stroke volume (SV), middle and posterior cerebral artery velocity (MCAv and PCAv), muscle and cerebral oxygen saturation (SmO2 and ScO2), and end-tidal CO2 (etCO2) were measured continuously. Time to presyncope, the cumulative stress index (CSI; summation of chamber pressure*time at each pressure), and hemodynamic responses were compared between the two protocols. Results: Time to presyncope (Step: 1611.8 ± 80.5 s vs. Ramp: 1675.4 ± 68.3 s; P=0.17), and the ensuing magnitude of central hypovolemia (%Δ SV, Step: -54.3 ± 2.5 % vs. Ramp: -51.9 ± 2.7 %; P=0.31) were similar between protocols, despite a higher CSI for the step protocol (Step: 946.5 ± 98.4 mmHg*min vs. Ramp: 836.7 ± 81.6 mmHg*min; P=0.06). While there were no differences at presyncope between protocols for the maximum change in HR, MCAv, or SmO2 (P≥0.21), the reduction in MAP was slightly less (Step: -17.1 ± 1.8 % vs. Ramp: -20.0 ± 1.4 %; P=0.02) and the reductions in PCAv, ScO2,and etCO2 (P≤0.08) were slightly greater for the step protocol compared to the ramp protocol. Conclusion: These results suggest that step and continuous ramp LBNP protocols elicit relatively similar tolerance times, reductions in central blood volume, and subsequent reflex hemodynamic responses, despite a greater cumulative stress in young healthy adults.Item Evaluating the Role of Arterial Stiffness on Amplitude of Cerebral Blood Flow Oscillations(2024-03-21) Lal, Kevin; Davis, Austin; Anderson, Garen; Bhuiyan, Nasrul; Rickards, CarolineBackground: Changing the pattern of cerebral blood flow by forcing oscillations in arterial pressure and blood flow at 0.1 Hz (10-second cycle) can limit reductions in cerebral tissue oxygenation during a condition of reduced cerebral perfusion. This method of inducing 0.1 Hz hemodynamic oscillations is called Pulsatile Perfusion Therapy (PPT). Sympathetic activation can increase the amplitude of 0.1 Hz hemodynamic oscillations, and acutely increase arterial stiffness. The impact of increasing carotid arterial stiffness on the magnitude of 0.1 Hz cerebral blood flow oscillations has not been examined. We hypothesize that the with application of 0.1 Hz PPT during a condition of cerebral hypoperfusion, 1) the subsequent increase in sympathetic activity will acutely increase carotid arterial stiffness, and; 2) greater carotid artery stiffness will result in a higher amplitude of oscillations in cerebral blood flow. Methods: 10 healthy participants (8 males, 2 females) were exposed to 10-min of oscillatory lower body negative pressure (OLBNP) at 0.1 Hz, which induced both a state of cerebral hypoperfusion, and 0.1 Hz hemodynamic oscillations. Middle cerebral artery velocity (MCAv), internal carotid artery (ICA) diameter, and beat-to-beat arterial pressure were measured. ICA stiffness was determined using the beta-stiffness index, incorporating ICA diameter and arterial pressure measurements. The amplitude of 0.1 Hz MCAv oscillations was assessed via fast Fourier transformation. Results: While OLBNP increased MCAv 0.1 Hz oscillations (36.1 ± 24.2 cm/s2 vs. 812.4 ± 668.0 cm/s2; P=0.01), ICA beta stiffness was not different between the baseline and OLBNP conditions (12.3 ± 4.9 au vs. 13.2 ± 5.7 au; P=0.56). There was no relationship between ICA stiffness and the amplitude of MCAv oscillations during OLBNP (r=0.17, P=0.68). Conclusions: Contrary to our hypothesis, ICA stiffness did not increase during 0.1 Hz OLBNP, and there was no correlation between ICA stiffness and the magnitude of MCAv oscillations induced at 0.1 Hz. These data suggest that ICA stiffness may not determine the magnitude of induced oscillations in cerebral blood flow. Future studies will examine these effects in older adults to determine the potential beneficial application of PPT for the treatment of low cerebral perfusion conditions (e.g., Alzheimer’s disease, stroke).Item Interactions Between Carotid Arterial Stiffness, Amplitude of Cerebral Blood Flow Oscillations, and Cerebral Tissue Oxygenation During Simulated Hemorrhage in Humans(2024-03-21) Hudson, Lindsey; Davis, Austin; Anderson, Garen; Rosenberg, Alexander; McKeefer, Haley; Bird, Jordan; Pentz, Brandon; Byman, Britta; Jendzjowsky, Nicholas; Wilson, Richard; Day, Trevor; Rickards, CarolineIntroduction: Inducing 0.1 Hz (10-s cycle) oscillations in cerebral blood flow attenuates the reduction in cerebral tissue oxygenation during simulated hemorrhage in humans. It is unknown, however, how stiffness of the cerebral feed 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 hypothesize that: 1) arterial stiffness of the internal carotid artery (ICA) will increase from rest; 2) the amplitude of 0.1 Hz oscillations in cerebral blood flow will be higher in individuals with stiffer arteries, and; 3) the reduction in cerebral tissue oxygenation will be smaller with higher amplitude of cerebral blood flow oscillations. Methods: 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 beta 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. Results: While Mean MCAv 0.1 Hz oscillations increased from baseline to OLBNP (N=8, 34.0±33.9 (cm/s)2vs. 104.7±58.1(cm/s)2, p=0.01), ICA beta 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 beta 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). Conclusions: Based on these data, 0.1 Hz OLBNP does not affect 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 was limited data available for analysis. This limitation will be addressed in a project currently in progress in our laboratory.Item Oxidative Stress During Simulated Hemorrhage Elicited by Lower Body Negative Pressure(2018-03-14) Kay, Victoria; Anderson, Garen; Sprick, Justin; Rickards, Caroline; Park, FloraPurpose: Hemorrhage is a leading cause of potentially preventable death in both civilian and military trauma settings. Hemorrhage also elicits an oxidative stress response as a direct result of losing blood volume, or as an indirect response to ischemia-reperfusion injury. Lower body negative pressure (LBNP) is a well validated, non-invasive, and reproducible approach to simulate hemorrhage by inducing central hypovolemia in healthy conscious humans. The oxidative stress response to simulated hemorrhage via LBNP has not been quantified. We hypothesized that systemic markers of oxidative stress would increase with application of LBNP. Methods: 15 healthy human subjects (11M, 4F; 27 ± 1 y) were recruited for a step-wise LBNP exposure to presyncope (systolic blood pressuresymptoms). After baseline, LBNP pressure progressively decreased every 5 minutes to -15, -30, -45, -60, -70, -80, -90, and -100 mmHg. Arterial pressure and stroke volume were measured continuously via finger photoplethysmography, and venous blood samples were collected at baseline and during the LBNP profile. Plasma samples were analyzed for F2-isoprostanes, a global marker of oxidative stress, via gas chromatography/mass spectrometry. Results: The magnitude of central hypovolemia, indexed by the % change in stroke volume, ranged from a 27% to 74%. LBNP induced a -12.6 ± 2.6 % decrease in MAP (%Δ MAP) from baseline (P Conclusion: Simulated hemorrhage elicited by step-wise LBNP to presyncope elicited an increase in a global marker of oxidative stress. These findings have important implications in the study of hemorrhage and potential application of targeted interventions. Funding Source: US Army Medical Research and Materiel Command (W81XWH-11-2-0137) & Owens Foundation Grant. Analysis of eicosanoids (F2-isoprostanes) were performed in the Vanderbilt University Eicosanoid Core Laboratory.Item Peak Analysis of Cerebral Blood Velocity Responses to Forced Low Frequency Oscillations during Simulated Hemorrhagic Stress in Humans(2019-03-05) Anderson, Garen; Rosenburg, Alexander; Park, Flora; Sprick, Justin; Rickards, Caroline; Barnes, Haley J.Peak Analysis of Cerebral Blood Velocity Responses to Forced Low Frequency Oscillations during Simulated Hemorrhagic Stress in Humans Haley J. Barnes, B.S., Garen K. Anderson, M.S., Alexander J. Rosenberg, Ph.D., Flora S. Park, M.S., Justin D. Sprick, Ph.D., Caroline A. Rickards, Ph.D Purpose: Tolerance to blood loss injuries (actual and simulated) varies across individuals. Higher amplitude of low frequency oscillations (10-s cycle; ~0.1 Hz) in brain blood flow and arterial pressure have been associated with higher tolerance to simulated hypovolemic episodes using lower body negative pressure (LBNP). We have previously demonstrated that forcing oscillations in cerebral blood flow and arterial pressure at 0.1 Hz and 0.05 Hz with oscillatory LBNP (OLBNP) protects cerebral oxygenation during central hypovolemia. However, there was no protection of mean cerebral blood flow (indexed via mean middle cerebral artery velocity, MCAv) with these oscillatory conditions. We hypothesize that the peak mean MCAv will be higher in the 0.05 Hz and 0.1 Hz OLBNP conditions compared to the 0 Hz condition, which may account for the protection of cerebral tissue oxygenation. Methods: Fourteen healthy human subjects (3 female/11 male) were randomly exposed to 10-min of non-oscillatory (0 Hz) and oscillatory (0.05 Hz and 0.1 Hz) LBNP conditions with an average LBNP chamber pressure of -60 mmHg. Measurements included MCAv via transcranial Doppler ultrasound, frontal lobe cerebral oxygenation (ScO2) via near infrared spectroscopy, and stroke volume and arterial pressure via finger photoplethysmography. Peak analysis was performed in 10-s and 5-s windows for the 0.05 Hz and 0.1 Hz profiles, respectively. Peak responses to the three LBNP conditions were compared using a linear mixed model for repeated measures with Tukey post hoc tests. Results: As previously reported, tolerance to the two OLBNP conditions was higher compared to the 0 Hz condition (P ≤ 0.09 for both vs. 0 Hz). In partial support of our hypothesis, when compared to the 0 Hz profile, the peak MCAv was higher with 0.05 Hz OLBNP (51.0±4.2 cm/s vs. 46.3±3.4 cm/s; P = 0.004) but not with the 0.1 Hz profile (49.0±3.9 cm/s; P = 0.11 vs. 0 Hz). Conclusions: The higher peak MCAv during the 0.05 Hz OLBNP profile may contribute to the attenuated decrease in cerebral oxygenation. These findings demonstrate the potential contribution of oscillatory peaks in cerebral blood flow to the protection of cerebral oxygenation and increased tolerance to simulated hemorrhage.Item Sex Differences in the Oxidative Stress and Inflammation Response During and After Simulated Hemorrhage in Humans(2020) Rosenberg, Alexander; Luu, My-Loan; Anderson, Garen; Rickards, Caroline; Barnes, Haley J.Introduction: Hemorrhage (i.e., massive blood loss) induces an oxidative stress and inflammatory response that can persist even following hemostasis and resuscitation. In this study, we hypothesized that young males would elicit a greater oxidative stress and inflammatory response compared to young females, both during and after simulated hemorrhage. Methods: Healthy human subjects (10F; 10M) participated in a presyncopal lower body negative pressure (LBNP) protocol (simulating hemorrhage). Stroke volume was estimated as a marker of central hypovolemia (indexed to body surface area). Venous blood samples were collected at baseline, at the onset of presyncope, and 60-min into recovery ("resuscitation"). Oxidative stress and inflammation responses were assessed via measurement of circulating F2-Isoprostanes (F2-IsoP) and interleukin (IL)-6 and IL-10. Results: LBNP tolerance time was similar between male and female subjects (Males, 1592±124 s vs. Females, 1437±113 s; P=0.37), and stroke volume index decreased by a similar magnitude at presyncope (Males, -50.2±6.3% vs. Females, -49.4±3.2%; P=0.87). There was no effect of time or sex on the %Δ [F2-IsoP] during or after LBNP (P≥0.12). However, male subjects exhibited a greater increase in both the %Δ [IL-6] and %Δ [IL-10] compared to female subjects at the 60-min recovery time point (IL-6: Males, 101.4±138.9% vs. Females, 12.3±34.0%; P=0.06. IL-10: Males, 71.1±133.3% vs. Females, -2.2±11.8%; P=0.06). Conclusion: These data suggest there may be a sex difference in the inflammatory response to blood loss and subsequent fluid resuscitation.Item Visit-to-Visit Reproducibility of Cerebral Vascular Reactivity to CO2 in Healthy Young Humans(2020) Anderson, Garen; Rickards, Caroline; Rosenberg, Alexander; Barnes, Haley; Hua, VincentPartial pressure of arterial CO2 (PaCO2) is an important regulator of cerebral blood flow. The magnitude of change in cerebral blood flow per unit change in PaCO2 represents the cerebral vascular responsiveness to a CO2 stimulus, and is used as an index of cerebrovascular health. Accordingly, it is important to assess the reproducibility of this technique for clinical diagnoses. Purpose: To assess visit-to-visit reproducibility of a cerebral vascular reactivity to CO2 test in healthy young humans. Methods: Healthy adults (n=6, 25±2 y) performed a 5-min cerebral vascular reactivity to CO2 protocol (+5 mmHg end-tidal CO2 (etCO2) above eucapnic baseline) on two separate visits (7-234 days between visits). EtCO2 and middle cerebral artery velocity (MCAv) were measured continuously. Coefficient of variation (CV) was calculated for cerebral vascular reactivity to CO2 ((%Δ MCAv)/Δ etCO2), etCO2, and mean MCAv responses between the two visits. Results: While the CO2 stimulus between visits was similar (Visit 1: 5.3±0.2 mmHg vs. Visit 2: 5.1±0.3 mmHg, p=0.54) with a CV of 2.8%, there was a difference in the MCAv response to this stimulus (Visit 1: +15±1 cm/s vs. Visit 2: +12±2 cm/s, p=0.09; CV=19%). This resulted in a large variation in cerebral vascular reactivity to CO2 between visits (Visit 1: 4.6±0.3 %/mmHg vs. Visit 2: 3.6±0.5 %/mmHg, p=0.06; CV=18%). Conclusion: These findings suggest that despite a similar magnitude of change in the CO2 stimulus, physiological variations in cerebral vascular reactivity to CO2 occur in young healthy adults between two experimental visits.Item White Mountain Expedition 2019: The Impact of Sustained Hypoxia on Cerebral Blood Flow Responses and Tolerance to Simulated Hemorrhage(2020) Anderson, Garen; Rickards, Caroline; Barnes, Haley; Bird, Jordan; Pentz, Brandon; Byman, Britta; Jendzjowsky, Nicholas; Wilson, Richard; Day, Trevor; Rosenberg, AlexanderTrauma-induced hemorrhage can occur at high altitude (HA) from a variety of causes, including battlefield injuries, motor vehicle/air accidents, and major falls. Based on the known compensatory increases in cerebral blood flow that occur with exposure to hypoxia, we hypothesized that tolerance to simulated hemorrhage (via application of lower body negative pressure, LBNP) at HA would be similar compared to low altitude (LA) due to increased cerebral blood flow and oxygen delivery, and the subsequent preservation of cerebral tissue oxygenation. Healthy human subjects (N=8; 4F/4M) participated in LBNP protocols to presyncope at LA (1045 m) and at HA (3800 m) following 4-5 days of acclimatization. Arterial pressure, heart rate, stroke volume, internal carotid artery (ICA) blood flow, and cerebral oxygen saturation were measured continuously. Time to presyncope was similar between conditions (LA: 1276±108s vs. HA: 1208±108s; P=0.58). Similar responses to LBNP were observed at LA and HA in mean arterial pressure (LA: -16±2% vs. HA: -16±2%; P=0.85), stroke volume (LA: -57±5% vs. HA: -60±5%; P=0.39), and heart rate (LA: +69±12% vs. HA: +65±8%; P=0.71). ICA blood flow was higher at HA vs. LA (P=0.01), and decreased with LBNP under both conditions (P≤0.005), with no effect of altitude on cerebral oxygen saturation (P=0.73). These findings suggest that hypoxia with ascent to 3800 m does not affect tolerance to simulated hemorrhage in young healthy adults, which may be due to 1) similar cardiovascular reflex responses, and/or 2) compensatory increases in cerebral blood flow and subsequent preservation of cerebral tissue oxygenation.