Browsing by Author "Anderson, Garen K."
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Item Are Spontaneous Low Frequency Oscillations in Arterial Pressure and Cerebral Blood Flow Associated with the Protection of Cerebral Tissue Oxygenation during Simulated Hemorrhage?(2019-03-05) Rosenberg, Alexander; Kay, Victoria; Sprick, Justin; Rickards, Caroline; Anderson, Garen K.Introduction: Prior studies have independently demonstrated that subjects with higher tolerance to simulated hemorrhage elicited by lower body negative pressure (LBNP) exhibit maintenance of cerebral tissue oxygenation, and higher amplitude in spontaneously generated low frequency (~0.1 Hz) oscillations in arterial pressure and cerebral blood flow. We hypothesized that these two independent observations are related, wherein subjects with higher tolerance to LBNP would exhibit increased low frequency power in arterial pressure and cerebral blood flow, which may contribute to the protection of cerebral tissue oxygenation. Methods: Healthy male (n=19, 25±1 y) and female (n=13, 28±1 y) subjects participated in a stepwise LBNP protocol to pre-syncope. Mean arterial pressure (MAP), middle cerebral artery velocity (MCAv), cerebral tissue oxygen saturation (ScO2), and end tidal CO2 (etCO2) were measured continuously. Subjects were classified as high tolerant if they completed the -60 mmHg step of LBNP. Low frequency oscillations in MAP and MCAv were assessed in the 0.04-0.15 Hz range. Both time and frequency domain data were analyzed using a linear mixed model analysis of variance with Tukey post hoc tests. Comparisons were made at baseline across LBNP stages (-15, -30, -45, and -60 mmHg). Results: Of the 32 subjects tested, 20 were classified as high tolerant and 12 as low tolerant. No differences were observed between high and low tolerant subjects in MAP (P=0.28), low frequency power of MAP (P=0.13), or low frequency power of MCAv (P=0.24) during LBNP. However, high tolerant subjects exhibited greater protection against reductions in ScO2 (P2(P Conclusion: Contrary to our hypothesis, low frequency oscillations in MAP and MCAv did not account for the observed protection in ScO2 for high tolerant subjects. Rather, maintenance of oxygen delivery (indexed via MCAv) appeared to account for the protection in cerebral oxygenation in this cohort of young, healthy subjects.Item Characterization of arterial pressure and carotid blood flow responses to pulsatile perfusion therapy in a rat model of hemorrhage(2022) Bhuiyan, Nasrul; Farmer, George; Anderson, Garen K.; Davis, Kenneth; Cunningham, Joseph; Rickards, CarolineIntroduction: In 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 investigate whether pulsatile perfusion therapy can protect arterial pressure and cerebral blood flow in a rat model of actual blood loss. We hypothesized that pulsatile perfusion therapy (PPT), applied via repeated thigh cuff inflations, would attenuate the reduction in arterial pressure and cerebral blood flow following hemorrhage. Methods: Sprague Dawley rats underwent the following protocols: hemorrhage alone (control: N=4; 2 male, 2 female), or hemorrhage plus PPT (N=3; 1 male, 2 female). PPT was applied via rapid 1 s inflations and deflations of a thigh cuff (0.5 Hz). A catheter was inserted in the femoral artery for continuous measurement of arterial pressure, and a perivascular flow probe was placed around the common carotid artery (CCA) for measurement of blood flow. Following instrumentation, each animal completed a baseline period (15 min), followed by a ~55% hemorrhage (25 min), PPT or control (30 min), and a recovery period (155 min or until death). Results: Decreases in mean arterial pressure (MAP) and CCA blood flow were observed in response to hemorrhage (P≤0.002). At the end of the PPT period, no differences were observed between the PPT and control groups for MAP (PPT: 46.7±27.3 mmHg vs. control: 30.2±13.5 mmHg; P=0.44) or CCA peak blood flow (PPT: 2.7±1.5 ml/min vs. control: 1.9±1.3 ml/min; P=0.92). Similarly, no differences were observed in the relative change from baseline to the end of the PPT period for MAP (PPT: -45±38% vs. control: -55±14%; P=0.65) or CCA peak blood flow (PPT: -65±21% vs. control: -66±12%; P=0.70). Conclusion: These results suggest that following a 55% hemorrhage in rats, PPT did not protect arterial pressure or carotid blood flow. However, the sample size was low in this pilot study, resulting in high variability in the observed responses. Accordingly, additional experiments are needed with an increased sample size to accurately determine the potential beneficial effects of PPT following hemorrhage.Item Effects of Sustained Hypobaric Hypoxia on Amplitude of Forced Hemodynamic Oscillations During Central Hypovolemia(2022) Anderson, Garen K.; Rosenberg, Alexander; McKeefer, Haley; Bird, Jordan D.; Pentz, Brandon; Byman, Britta; Jendzjowsky, Nicholas; Wilson, Richard; Day, Trevor; Rickards, CarolineIntroduction: Forcing oscillations in arterial pressure and cerebral blood flow at 0.1 Hz during simulated hemorrhage protects cerebral oxygenation at both low and high altitude. Arterial pressure oscillations at 0.1 Hz are endogenously driven by rhythmic fluctuations in sympathetic nerve activity. As hypobaric hypoxia increases basal sympathetic activity, we hypothesize that the amplitude of forced oscillations in arterial pressure and cerebral blood flow during simulated hemorrhage will be greater at high altitude compared to low altitude. Methods: 8 healthy human participants (4 M, 24.7 ± 4.1 y; 4 F, 34.3 ± 8.3 y) underwent a hypovolemic oscillatory lower body negative pressure (OLBNP) protocol, where chamber pressure reduced to -60 mmHg then oscillated every 5-s between -30 mmHg and -90 mmHg over 10-min (0.1 Hz). This protocol was performed at both low altitude (LA; Calgary, Alberta, Canada; 1045 m) and high altitude (HA; White Mountain, California, USA; 3800 m). Mean arterial pressure (MAP), mean middle cerebral artery velocity (MCAv), and cerebral tissue oxygenation (ScO2) were recorded continuously. Frequency analysis (via continuous wavelet transform) was used to quantify oscillations in MAP and mean MCAv at ~0.1 Hz. Data were analyzed with linear mixed-models and paired t-tests. All data are represented as mean ± SD. Results: Baseline amplitude of oscillations were similar between HA and LA for MAP (1.9 ± 0.6 mmHg vs. 1.2 ± 0.5 mmHg; P = 0.47) and mean MCAv (0.9 ± 0.4 cm/s vs. 1.1 ± 0.3 cm/s; P = 0.91). Oscillatory amplitudes increased with 0.1 Hz OLBNP and altitude for MAP (ANOVA main effect, OLBNP: P < 0.001, Altitude: P = 0.007) and mean MCAv (ANOVA main effect, OLBNP: P = 0.002, Altitude: P = 0.008). Amplitude of oscillations during OLBNP were greater at HA for both MAP (4.0 ± 2.1 mmHg vs. 2.6 ± 1.4 mmHg, P = 0.05) and mean MCAv (2.4 ± 1.1 cm/s vs. 0.9 ± 0.4 cm/s; P = 0.01). The relative (%Δ) decrease in ScO2 was not different between HA and LA (-0.63 ± 0.92 % vs. -2.56 ± 2.61 %, P = 0.11). Conclusions: Oscillatory amplitudes at 0.1 Hz in both MAP and mean MCAv increased during OLBNP at high altitude. This effect may be due, in part, to the sympathoexcitatory stimulus of hypobaric hypoxia, and does not alter the protection of cerebral tissue oxygenation in this environment.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 Impact of Sleep Quality on Cardiovascular Responses to Simulated Hemorrhage in Humans(2021) Hua, Vincent; Barnes, Haley J.; Rosenberg, Alexander; Anderson, Garen K.; Luu, My-Loan; Rickards, CarolinePoor sleep quality may limit cardiovascular responsiveness to physiological stress. We hypothesized that subjects with poor sleep quality would be less tolerant to simulated hemorrhage, which would be associated with lower arterial pressure and cerebral blood flow, and higher heart rates compared to subjects with good sleep quality. Hemorrhage was simulated in 20 human subjects with lower body negative pressure (LBNP). Sleep quality was classified as POOR in 5 subjects (Global Pittsburgh Sleep Quality Index (PSQI) score ≥5), and GOOD in 15 subjects (Global PSQI score < 5). Markers of cardiovascular function were measured continuously throughout the LBNP protocol. Sleep quality had no effect on LBNP tolerance (POOR: 1453±223 s vs. GOOD: 1535±88 s; P=0.34), and there were no differences in the magnitude of central hypovolemia at presyncope (%Δ stroke volume, POOR: -53±8 % vs. GOOD: -49±4 %; P=0.32). However, there were differences in the magnitude of hypotension (%Δ mean arterial pressure, POOR: -18±3 % vs. GOOD: -22±2 %; P=0.08), cerebral blood flow reduction (%Δ MCAv, POOR: -19±6 % vs. GOOD: -28±2 %; P=0.03), and reflex tachycardia (% Δ heart rate, POOR: 103±30 % vs. GOOD: 72±9 %; P=0.09). There was a moderate association between sleep quality and the magnitude of MCAv reduction at presyncope (r=0.53; P=0.02). Sleep quality did not affect tolerance to simulated hemorrhage in healthy human subjects. While there were differences in hemodynamic responses, this may be related to premature termination of the protocol due to early onset of subjective presyncopal symptoms.Item Investigating the Use of Resistance Breathing for the Detection of Acute Hypovolemia(2021) Rusy, Ryan; Anderson, Garen K.; Kay, Victoria; Rickards, CarolineIntroduction: Standard vital signs (e.g., heart rate and blood pressure) lack sensitivity and specificity to detect blood volume status following hemorrhage. Inspiratory resistance breathing has therapeutic potential to increase blood pressure and cardiac output following blood loss. We hypothesize that resistance breathing will elicit greater increases in absolute and breath-to-breath amplitude of stroke volume and arterial pressure under hypovolemic vs. normovolemic conditions. Methods: Data were retrospectively analyzed from 23 healthy human subjects aged 18-45 years. Subjects underwent lower body negative pressure (LBNP) protocols to simulate hemorrhage with and without resistance breathing. Continuous mean arterial pressure (MAP) and stroke volume were measured via finger photoplethysmography. Comparisons of absolute and changes in the breath-to-breath amplitude of MAP and stroke volume were made under 4 conditions: 1) normovolemia; 2) normovolemia + resistance breathing; 3) hypovolemia, and; 4) hypovolemia + resistance breathing. Results: Preliminary findings show an average change in MAP of -3.1% in response to resistance breathing during normovolemia, and +8.2% during hypovolemia. MAP amplitude during normovolemia decreased by -1.5% and increased by 22.4% during hypovolemia. Stroke volume maximum increased by 3.8% during normovolemia and 20.0% during hypovolemia, while stroke volume amplitude during normovolemia increased by 52.4% % and 19.0% during hypovolemia. Conclusions: These data indicate that there may be differences in the hemodynamic response to resistance breathing that could aid in the diagnosis of acute hypovolemia.Item Peaks and Valleys - Oscillatory cerebral blood flow at high altitude(2021) Anderson, Garen K.; Rosenberg, Alexander; Barnes, Haley J.; Bird, Jordan D.; Pentz, Brandon; Byman, Britta; Jendzjowsky, Nicholas; Wilson, Richard; Day, Trevor; Rickards, CarolineAn oscillatory pattern in cerebral blood flow (at ~0.1 Hz) protects cerebral tissue oxygen saturation (ScO2) under conditions of cerebral hypoperfusion. In this study, we hypothesized that inducing oscillations in cerebral blood flow at 0.1 Hz would protect cerebral blood flow and ScO2 during exposure to combined simulated hemorrhage and sustained hypobaric hypoxia. Eight healthy human subjects (4 M:4 F, 30.1 ± 7.6 y) participated in two lower body negative pressure (LBNP) experiments (simulating hemorrhage) at high altitude (3800 m): 1) 0 Hz control condition (CTRL) and 2) 0.1 Hz oscillatory LBNP (OLBNP) condition. Measurements included internal carotid artery (ICA) blood flow via duplex Doppler ultrasound, middle cerebral artery velocity (MCAv) via transcranial Doppler ultrasound, and ScO2 via near-infrared spectroscopy. Mean MCAv waveforms were fast Fourier transformed to verify oscillations were generated at ~0.1 Hz. Low frequency power (0.07-0.15 Hz) in mean MCAv increased during OLBNP vs. CTRL (P = 0.05). OLBNP did not protect ICA flow (OLBNP: -32.5±12.2 Δ%; CTRL: -20.2±24.3 Δ%; P = 0.18) or mean MCAv (OLBNP: -26.5±13.8 Δ%; CTRL: -17.7±15.7 Δ%; P = 0.58), but ScO2 was protected (OLBNP: -0.89±0.61 Δ%; CTRL: -3.99±2.2 Δ%; P = 0.007). These results support our hypothesis that inducing oscillatory blood flow leads to protection of cerebral tissue oxygenation, despite no differences in ICA blood flow or mean MCAv. Overall, these data suggest that therapies using oscillatory perfusion may help preserve cerebral tissue oxygen saturation under conditions of reduced oxygen delivery.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 Responses of cerebral blood flow and tissue oxygenation to low frequency oscillations during simulated hemorrhagic stress in humans(2018-03-14) Park, Flora; Sprick, Justin; Rickards, Caroline; Anderson, Garen K.Introduction: Tolerance to both actual and simulated hemorrhage varies between individuals. Low frequency (LF; ~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 LF power in MAP and MCAv compared to low tolerant subjects. The mechanism for this association has not been explored. We hypothesized that inducing LF oscillations would attenuate reductions in cerebral blood flow and oxygenation during simulated hemorrhage. Methods: 11 subjects (9M/2F) were exposed to two LBNP profiles with an average chamber pressure of -60 mmHg: 1) 0 Hz - chamber pressure remained at -60 mmHg for 9-min, or 2) 0.1 Hz - chamber pressure oscillated between -30 mmHg and -90 mmHg at a frequency of 0.1 Hz for 9-min. Profiles were 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. Hemodynamic data was analyzed using a paired t-test. Tolerance was assessed with a Fischer’s exact test. Results: No differences were observed between profiles for MAP (0 Hz, 79.8±2.5 mmHg vs. 0.1 Hz, 80.0±1.9 mmHg; P=0.93) and MCAv (0 Hz, 42.4±3.3 cm/s vs. 0.1 Hz, 43.5±3.7 cm/s P=0.43). The reduction in ScO2 was attenuated (P=0.05) during the 0.1 Hz profile (-4.1±1.2 %) compared to the 0 Hz profile (-6.1±1.1 %). A similar attenuation was observed in stroke volume (0 Hz, -42.6±2.5 % vs. 0.1 Hz, -30.6±2.5 %; P Discussion:In partial support of our hypothesis, cerebral oxygenation was protected during the 0.1 Hz OLBNP profile. 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 0.1 Hz profile 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 Sex Differences in the Oxidative Stress and Inflammation Response During and After Simulated Hemorrhage in Humans(2021) Barnes, Haley J.; Rosenberg, Alexander; Anderson, Garen K.; Luu, My-Loan; Rickards, CarolineIntroduction: 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"). The oxidative stress and inflammation response 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 White Mountain Expedition 2019: Peaks and Valleys - Oscillatory cerebral blood flow at high altitude(2020) Rickards, Caroline; Barnes, Haley; Rosenberg, Alexander; Bird, Jordan; Pentz, Brandon; Byman, Britta; Jendzjowsky, Nicholas; Wilson, Richard; Day, Trevor; Anderson, Garen K.An oscillatory pattern in cerebral blood flow (at ~0.1 Hz) protects cerebral tissue oxygen saturation (ScO2) under conditions of cerebral hypoperfusion. In this study, we hypothesized that inducing oscillations in cerebral blood flow at 0.1 Hz would protect cerebral blood flow and ScO2 during exposure to combined simulated hemorrhage and sustained hypobaric hypoxia. Eight healthy human subjects (4 M, 24.7 ± 4.1 y; 4 F, 34.3 ± 8.3 y) participated in two lower body negative pressure (LBNP) experiments (simulating hemorrhage) at high altitude (3800 m): 1) 0 Hz control condition (CTRL) and 2) 0.1 Hz oscillatory LBNP (OLBNP) condition. Measurements included internal carotid artery (ICA) blood flow via duplex Doppler ultrasound, middle cerebral artery velocity (MCAv) via transcranial Doppler ultrasound, and ScO2 via near-infrared spectroscopy. Mean MCAv waveforms were fast Fourier transformed to verify oscillations were generated at ~0.1 Hz. Low frequency power (0.07-0.15 Hz) in mean MCAv increased during OLBNP vs. CTRL (P = 0.02). OLBNP did not protect ICA flow (OLBNP: -32.5±4.5 Δ%; CTRL: -19.9±8.9 Δ%; P = 0.18) or mean MCAv (OLBNP: -18.5±3.4 Δ%; CTRL: -15.3±5.4 Δ%; P = 0.58), but ScO2 was protected (OLBNP: -0.67±1.0 Δ%; CTRL: -4.07±2.0 Δ%; P = 0.004). These results support our hypothesis that inducing oscillatory blood flow leads to protection of cerebral tissue oxygenation, despite no differences in ICA blood flow or mean MCAv. Overall, these data suggest that therapies using oscillatory perfusion may help preserve cerebral tissue oxygen saturation under conditions of reduced oxygen delivery.Item White Mountain Expedition 2019: The Impact of Sustained Hypoxia on Cerebral Blood Flow Responses and Tolerance to Simulated Hemorrhage(2021) Rosenberg, Alexander; Anderson, Garen K.; Barnes, Haley J.; Bird, Jordan D.; Pentz, Brandon; Byman, Britta; Jendzjowsky, Nicholas; Wilson, Richard; Day, Trevor; Rickards, CarolineTrauma-induced hemorrhage can occur at high altitude (HA) from a variety of causes, including battlefield injuries, vehicle/air accidents, and major falls. As the partial pressure of oxygen decreases with ascent to altitude, compensatory increases in cerebral blood flow (CBF) and oxygen delivery occur to preserve cerebral tissue oxygenation (ScO2). Accordingly, we hypothesized that tolerance to simulated hemorrhage (via lower body negative pressure, LBNP) following sustained exposure to HA would be similar compared to low altitude (LA) due to compensatory increases in CBF and oxygen delivery, and the subsequent preservation of ScO2. Healthy adults (N=8;4F/4M) participated in LBNP protocols to presyncope at LA (1045m) and at HA (3800m) following 5-7 days of acclimatization. Arterial pressure, heart rate (HR), stroke volume (SV), internal carotid artery blood flow (ICA BF), and ScO2 were measured continuously. Time to presyncope was similar between conditions (LA:1276±304s vs. HA:1208±306s;P=0.58). Similar maximal responses to LBNP were observed at LA and HA in mean arterial pressure (LA:-16±6% vs. HA:-16±6%;P=0.85), SV (LA:-57±14% vs. HA:-60±13%;P=0.39), and HR (LA:+69±33% vs. HA:+65±23%;P=0.71). ICA BF was elevated at baseline at HA vs. LA (P=0.04) and decreased with LBNP under both conditions (P< 0.0001). There was no effect of altitude (P=0.59) on ScO2, which decreased with LBNP under both conditions (P=0.09). Sustained exposure to hypoxia at an altitude of 3800m does not affect tolerance to simulated hemorrhage in adults, which may be due to 1) similar cardiovascular reflex responses, and 2) compensatory increases in CBF and subsequent preservation of ScO2.