Oscillatory Lower Body Negative Pressure Research Articles

Interactions Between Carotid Arterial Stiffness, Amplitude of Cerebral Blood Flow Oscillations, and Cerebral Tissue Oxygenation During Simulated Hemorrhage in Humans

Introduction: 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)2 vs. 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. American Heart Association Grant in Aid. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Directional sensitivity of the cerebral pressure-flow relationship during forced oscillations induced by oscillatory lower body negative pressure

A directional sensitivity of the cerebral pressure-flow relationship has been described using repeated squat-stands. Oscillatory lower body negative pressure (OLBNP) is a reproducible method to characterize dynamic cerebral autoregulation (dCA). It could represent a safer method to examine the directional sensitivity of the cerebral pressure-flow relationship within clinical populations and/or during pharmaceutical administration. Therefore, examining the cerebral pressure-flow directional sensitivity during an OLBNP-induced cyclic physiological stress is crucial. We calculated changes in middle cerebral artery mean blood velocity (MCAv) per alterations to mean arterial pressure (MAP) to compute ratios adjusted for time intervals (ΔMCAvT/ΔMAPT) with respect to the minimum-to-maximum MCAv and MAP, for each OLBNP transition (0 to −90 Torr), during 0.05 Hz and 0.10 Hz OLBNP. We then compared averaged ΔMCAvT/ΔMAPT during OLBNP-induced MAP increases (INC) (ΔMCAvT/ Δ MAP T INC ) and decreases (DEC) (ΔMCAvT/ Δ MAP T DEC ). Nineteen healthy participants [9 females; 30 ± 6 years] were included. There were no differences in ΔMCAvT/ΔMAPT between INC and DEC at 0.05 Hz. ΔMCAvT/ Δ MAP T INC (1.06 ± 0.35 vs. 1.33 ± 0.60 cm⋅s−1/mmHg; p = 0.0076) was lower than ΔMCAvT/ Δ MAP T DEC at 0.10 Hz. These results support OLBNP as a model to evaluate the directional sensitivity of the cerebral pressure-flow relationship.

Effect of oscillatory lower body negative pressure and isometric handgrip exercise on cardioautonomic tone of healthy individuals

Objectives: The influence of the autonomic nervous system on the heart can be quantified by assessing changes in the heart rate variability (HRV) during orthostatic challenge and exercise. However, the combination of oscillatory lower body negative pressure (oLBNP) and isometric handgrip exercise (IHE) on HRV has not been previously investigated. Therefore, the present study aimed to assess the effects of (oLBNP) at sympathetic (0.1 Hz) and parasympathetic (0.25 Hz) frequencies and IHE at 30% of maximum voluntary contraction (MVC) on HRV in normal healthy individuals. Materials and Methods: We conducted a cross-sectional study on 18 healthy male subjects. Beat-to-beat blood pressure, lead-II electrocardiogram, and oLBNP chamber pressure were recorded continuously during oLBNP at 0.1 and 0.25 Hz for 3 min each and IHE at 30% of MVC (for 4 min) along with oLBNP at 0.1 or 0.25 Hz (oLBNP was added in last 3 min) each followed by HRV analysis. Results: The oLBNP at 0.25 Hz reduced the root mean square of successive inter-beat (RR) interval differences significantly as compared to baseline values and came to normal during the recovery phase (P = 0.008). The absolute power of the high-frequency band (HF power), Poincaré plot standard deviation perpendicular to the line of identity (SD1), and percentage of successive RR intervals that differ by more than 50 ms (pNN50) were also reduced significantly during oLBNP at 0.25 Hz and when IHE at 30% of MVC (IHE) was added to oLBNP at 0.25 Hz as compared to baseline (P < 0.05). Conclusion: oLBNP and IHE could be used as a non-invasive haemodynamic stressor to assess the neurocardiac axis and its mechanism of action during orthostatic stresses.

Validity and reliability of deriving the autoregulatory plateau through projection pursuit regression from driven methods.

To compare the construct validity and between-day reliability of projection pursuit regression (PPR) from oscillatory lower body negative pressure (OLBNP) and squat-stand maneuvers (SSMs). Nineteen participants completed 5 min of OLBNP and SSMs at driven frequencies of 0.05 and 0.10 Hz across two visits. Autoregulatory plateaus were derived at both point-estimates and across the cardiac cycle. Between-day reliability was assessed with intraclass correlation coefficients (ICCs), Bland-Altman plots with 95% limits of agreement (LOA), coefficient of variation (CoV), and smallest real differences. Construct validity between OLBNP-SSMs were quantified with Bland-Altman plots and Cohen's d. The expected autoregulatory curve with positive rising and negative falling slopes were present in only ~23% of the data. The between-day reliability for the ICCs were poor-to-good with the CoV estimates ranging from ~50% to 70%. The 95% LOA were very wide with an average spread of ~450% for OLBNP and ~350% for SSMs. Plateaus were larger from SSMs compared to OLBNPs (moderate-to-large effect sizes). The cerebral pressure-flow relationship is a complex regulatory process, and the "black-box" nature of this system can make it challenging to quantify. The current data reveals PPR analysis does not always elicit a clear-cut central plateau with distinctive rising/falling slopes.

Hemodynamic responses to oscillatory thigh cuff inflations

Background. In the clinical setting, individuals have varying tolerance to hypovolemia induced by blood loss. Experimental generation of 0.1 Hz oscillations (~10-s cycle) in arterial pressure and cerebral blood flow via oscillatory lower body negative pressure (OLBNP) increases tolerance to this simulated hemorrhage, and protects cerebral tissue oxygenation. However, use of OLBNP as a method of inducing hemodynamic oscillations in the clinical setting is limited as: 1) it is a large and cumbersome technique, and; 2) it induces central hypovolemia, which would only worsen the magnitude of hemorrhage. In this study we evaluated a more clinically applicable method of inducing 0.1 Hz oscillations in arterial pressure and cerebral blood flow, using intermittent inflation of bilateral thigh cuffs. We hypothesized that the amplitude of arterial pressure and cerebral blood flow oscillations at 0.1 Hz would increase in response to repeated thigh cuff inflations at 0.1 Hz when compared with a baseline control condition. Methods. Ten healthy human subjects were tested (6 male, 4 female; 26.8 ± 4.1 y). Middle cerebral artery velocity (MCAv) was measured via transcranial doppler ultrasound, arterial pressure was measured via finger photoplethysmography, and end tidal CO2 (etCO2) was measured via capnography. Following a 10-min baseline period, intermittent thigh cuff inflations at 0.1 Hz and 230 mmHg (5-s inflation, 5-s deflation) were performed for 10-min (“oscillations”). 0.1 Hz oscillatory amplitude of mean arterial pressure and mean MCAv were quantified using Fast Fourier transformation during the last 5-min of baseline and the oscillatory period, and compared via two-tailed paired t-tests. Results. The amplitude of 0.1 Hz oscillations increased during the oscillatory period vs. baseline for mean arterial pressure (baseline: 1.7 ± 1.0 mmHg2 vs. oscillations: 9.0 ± 6.2 mmHg2; P = 0.004) and mean MCAv (baseline: 1.1 ± 0.6 (cm/s)2 vs. oscillations: 3.4 ± 3.1 (cm/s)2; P = 0.04). Absolute mean arterial pressure was similar between baseline and the oscillatory period (baseline: 97.2 ± 8.1 mmHg vs. oscillations: 99.1 ± 15.0 mmHg; P = 0.54), but absolute mean MCAv was lower during the oscillatory period (baseline: 61.7 ± 14.6 cm/s vs. oscillations: 53.2 ± 13.1 cm/s; P = 0.02). This reduction in mean MCAv was most likely due to hypocapnia (indexed by etCO2) induced by pacing the breathing of all subjects at ≥10 breaths/min (baseline: 33.2 ± 4.8 mmHg vs. oscillations 27.2 ± 4.5 mmHg; P = 0.005). Conclusions. Intermittent thigh cuff inflations at 0.1 Hz induced 0.1 Hz oscillations in both arterial pressure and cerebral blood flow when compared to baseline. These findings indicate that intermittent thigh cuff inflations could be developed as a method to induce pulsatile perfusion as a potential new therapy for individuals experiencing major blood loss. American Heart Association (Transformational Project Award) #19TPA34910073 and UNTHSC Physiology and Anatomy Seed Grant 2021 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

An orthostatic load of 1/4G and 1/3G differentially activates vascular and cardiac components of cardiopulmonary reflexes

Introduction – Orthostatic load of varying degree affects cardiopulmonary reflexes and baroreflex. Cardiopulmonary reflexes initiate even before the baroreflex activation in response to volume changes in body caused by changed G load. The cardiopulmonary reflex has two effector components i.e., Heart and Vasculature. Lower body negative pressure (LBNP) is a non-invasive tool used to study the physiological effects of varying G loads. Aim & Objective - The study was designed to explore the varying orthostatic load triggering cardiopulmonary reflexes. Material & Methods - 33 healthy human volunteers were recruited. Continuous heart rate and blood pressure – Systolic, diastolic and mean blood pressure (measured as the area under curve of the pulse waveform) were recorded. Orthostatic load of 1/4G and 1/3G were chosen in order to prevent fall in blood pressure and baroreflex activation. The measurements were taken in supine resting state (0 mmHg), at -10 mmHg (1/4 G) and -15 mmHg (1/3G). Heart rate variability was calculated from the Lead II ECG with the help of Labchart Pro 8 ® software. Peripheral vascular resistance (PVR) was estimated indirectly from arterial pressure waveform. Statistical analysis was performed using Graphpad Prism. Results – At 1/4G of orthostatic load (-10 mmHg of oscillatory LBNP) activation of vascular component (PVR) of cardiopulmonary reflex was found with no changes in the cardiac component (HRV). At 1/3G of orthostatic load (-15 mmHg of oscillatory LBNP), there were activation of the cardiac component (LF:HRV, LF/HF:HRV) associated with further increase in the vascular component (PVR). Conclusion – Data suggests that 1/3G and 1/4G orthostatic load applied using LBNP despite no change in blood pressure, causes differential activation of vasculature and cardiac effector components of cardiopulmonary reflexes No funding received for carrying out the study This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Vasoconstriction during non-hypotensive hypovolemia is not associated with activation of baroreflex: A causality-based approach.

Non-hypotensive hypovolemia simulated with oscillatory lower body negative pressure in the range of -10 to -20 mmHg is associated with vasoconstriction {increase in total peripheral vascular resistance (TPVR)}. Due to the mechanical stiffening of vessels, there is a disjuncture of mechano-neural coupling at the level of arterial baroreceptors which has not been investigated. The study was designed to quantify both the cardiac and vascular arms of the baroreflex using an approach based on Wiener-Granger causality (WGC) - partial directed coherence (PDC). Thirty-three healthy human volunteers were recruited and continuous heart rate and blood pressure {systolic (SBP), diastolic (DBP), and mean (MBP)} were recorded. The measurements were taken in resting state, at -10 mmHg (level 1) and -15 mmHg (level 2). Spectral causality - PDC was estimated from the MVAR model in the low-frequency band using the GMAC MatLab toolbox. PDC from SBP and MBP to RR interval and TPVR was calculated.The PDC from MBP to RR interval showed no significant change at -10 mmHg and -15 mmHg. No significant change in PDC from MBP to TPVR at -10 mmHg and -15 mmHg was observed. Similar results were obtained for PDC estimation using SBP as input. However, a significant increase in TPVR from baseline at both levels of oscillatory LBNP (p-value <0.001). No statistically significant change in PDC from blood pressure to RR interval and blood pressure to TPVR implies that vasoconstriction is not associated with activation of the arterial baroreflex in ≤-15 mmHg LBNP. Thereby, indicating the role of cardiopulmonary reflexes during the low level of LBNP simulated non-hypotensive hypovolemia.

Cerebral blood flow response to cardiorespiratory oscillations in healthy humans

Dynamic cerebral autoregulation (CA) characterizes the cerebral blood flow (CBF) response to abrupt changes in arterial blood pressure (ABP). CA operates at frequencies below 0.15Hz. ABP regulation and probably CA are modified by autonomic nervous activity. We investigated the CBF response and CA dynamics to mild increase in sympathetic activity. Twelve healthy volunteers underwent oscillatory lower body negative pressure (oLBNP), which induced respiratory-related ABP oscillations at an average of 0.22Hz. We recorded blood velocity in the internal carotid artery (ICA) by Doppler ultrasound and ABP. We quantified variability and peak wavelet power of ABP and ICA blood velocity by wavelet analysis at low frequency (LF, 0.05-0.15Hz) and Mayer waves (0.08-0.12Hz), respectively. CA was quantified by calculation of the wavelet synchronization gamma index for the pair ABP-ICA blood velocity in the LF and Mayer wave band. oLBNP increased ABP peak wavelet power at the Mayer wave frequency. At the Mayer wave, ABP peak wavelet power increased by >70% from rest to oLBNP (p<0.05), while ICA blood flow velocity peak wavelet power was unchanged, and gamma index increased (from 0.49 to 0.69, p<0.05). At LF, variability in both ABP and ICA blood velocity and gamma index were unchanged from rest to oLBNP. Despite an increased gamma index at Mayer wave, ICA blood flow variability was unchanged during increased ABP variability. The increased synchronization during oLBNP did not cause less stable CBF or less active CA. Sympathetic activation seems to improve the mechanisms of CA.

Assessment of baroreflex sensitivity during isometric handgrip exercise and oscillatory lower body negative pressure

ObjectivesBaroreflex sensitivity (BRS) is an estimate of autonomic control of cardiovascular system via the baroreflex arc. It has been suggested that exercise pressure reflex and muscle metaboreflex override baroreflex during exercise to decrease baroreflex gain, which facilitates the simultaneous rise in blood pressure (BP) and heart rate during the exercise. This study investigated the effects of isometric handgrip exercise (IHE) on baroreflex gain and frequency dependence of baroreflex sensitivity while fluctuations in arterial BP were generated. MethodsThirteen healthy men performed IHE at 20% and 30% of their maximum voluntary contraction (MVC), while oscillatory lower body negative pressure (OLBNP) of 40 mmHg was applied in 0.1 and 0.25 Hz frequencies. ResultsCompared to the OLBNP at 0.25 Hz frequency alone, the baroreflex gain for diastolic BP (DBP) was significantly reduced with the addition of IHE at 20% and 30% of MVC in the high frequency band. At rest (without IHE and OLBNP) the baroreflex gain was significantly more in the high frequency band for DBP, but the baroreflex gain for DBP was not significantly different when IHE + OLBNP were applied at 20% and 30% of MVC in both frequencies. ConclusionsThe significant reduction of DBP baroreflex gain with the addition of graded IHE might indicate that exercise pressure reflex and muscle metaboreflex override baroreflex during exercise to decrease baroreflex gain at a high frequency band (0.25 Hz). The frequency-dependent phenomenon of BRS was altered when IHE and OLBNP were applied, meaning that the frequency dependence of BRS was nullified during IHE.

Effects of Sustained Hypobaric Hypoxia on Amplitude of Forced Hemodynamic Oscillations During Central Hypovolemia

IntroductionForcing 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.Methods8 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.ResultsBaseline 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 &lt; 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 mmHgvs. 2.6 ± 1.4 mmHg, P = 0.05) and mean MCAv (2.4 ± 1.1 cm/svs. 0.9 ± 0.4 cm/s; P = 0.01). The relative (%∆) decrease in ScO2 was not different between HA and LA (‐0.63 ± 0.92 % vs. ‐2.56 ± 2.61 %, P = 0.11).ConclusionsOscillatory 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.

Neurohormonal responses to oscillatory lower body negative pressure in healthy subjects

Lower body negative pressure (LBNP) has been employed in multiple countermeasure protocols against post spaceflight orthostatic hypotension. However, protocols utilizing oscillatory LBNP (oLBNP) have not been explored in this regard. oLBNP has shown promise in few studies to have good tolerance in conditions of hypovolemic stress and since the negative suction is only phasic, the extravascular fluid shifts associated with negative suction are also hypothesized to be less. Our study addressed the paucity of information on oLBNP by investigating the cardiovascular and neurohormonal effects of oLBNP of −15 and −45 mm Hg in 40 healthy adult males (mean age = 29.6 ± 4.7 years, BMI = 25.1 ± 3.6 kg/m2). After supine rest of 10 min (baseline), oLBNP was applied at −15 mm Hg and −45 mm Hg for 10 min each with a gap of 10 min. Blood sample for neurohormonal analysis was collected at the end of baseline and after each oLBNP exposure. Blood pressure, heart rate, respiratory rate and end tidal CO2 (EtCO2) were recorded for the entire duration. Serum angiotensin II (ATII), antidiuretic hormone (ADH) and atrial natriuretic peptide (ANP) were analyzed using ELISA. On comparison with the baseline [SBP: 114 ± 2.38, MBP: 75.8 ± 2.16 mm Hg] there was a significant fall in SBP on application of −15 mm Hg as well as −45 mm Hg oLBNP[-15 oLBNP: 107.4 ± 2.34 mm Hg; −45 oLBNP: 105.3 ± 2.28 mm Hg], while there was no significant difference observed in the DBP. There was a significant increase in the heart rate at both −15 [77.29(72.75–85.65) BPM] and −45 mm Hg [81.29 (73.93–86.09) BPM] oLBNP as compared to the baseline [70.41(64.32–79.80) BPM]. No significant difference in the serum ATII, ADH and ANP after 10 min of application of −15 or −45 mm Hg oLBNP as compared to baseline was observed. In conclusion, oLBNP induced legward pooling of blood causes a fall in the blood pressure which initiates the neural reflex mechanisms, most important being the baroreflex and the cardiopulmonary reflex. However, since there was no significant difference in the serum ATII, ADH and ANP from baseline, this suggests that 10 min oLBNP up to −45 mm Hg results in recruitment of cardiovascular neural reflex response but it does not evoke neurohormonal responses which mediate long term volume changes.

Effects of Transient Cerebral Hypoperfusion on Human Auditory Brainstem Responses

Adequate cerebral blood flow perfusion is crucial to maintaining brain function. The auditory brainstem response (ABR) has been demonstrated to be the most powerful diagnostic tool for assessing auditory function. This study aimed to determine the ABR under transient cerebral hypoperfusion caused by using oscillatory lower body negative pressure (OLBNP). As chronic cerebral hypoperfusion has been associated with the prolongation of the latency of ABR waves, we hypothesized that the fluctuation of cerebral blood flow perfusion also affects this latency. As prior data showing that cerebral autoregulation is not effectively engaged when pressure fluctuations are shorter than 30 sec periods (i.e., higher than 0.03 Hz), we used the sinusoidal pattern of an 18 sec period (0.056 Hz) of 0 ~ - 40 mmHg OLBNP to induce transient cerebral hypoperfusion. Here, we measured ABR and cerebral blood flow velocity (MCAv) during 12 min of control and 12 min of OLBNP (40 cycle of 18-sec periods) in 15 subjects (3 of whom were excluded from the analysis due to an insufficient number of data for ABR). Periodical changes in cerebrovascular variables were aligned relative to each 18 sec of OLBNP cycle onset and were subdivided into three phases (phase-1: 0 ~ 6 sec, phase-2: 6 ~ 12 sec, and phase-3: 12 ~ 18 sec of OLBNP onset). For the ABR analysis, a total of 6800 individual sweeps were recorded for 12 min in the control and OLBNP conditions, and the recorded sweeps in the OLBNP condition were subdivided into three phases. We observed that OLBNP caused cyclic fluctuations of MCAv. One-way repeated-measures analysis of variance (ANOVA) and the post-hoc comparison revealed that MCAv decreased significantly in phases-1 and -2 compared to the control and phase-3 (F(3, 33) = 16.54, p < 0.001). As for the ABR data, ANOVA and the post-hoc comparison revealed that the latency of wave V of ABR at phase-2 was delayed compared to phase-1 (F(3, 33) = 3.70, p < 0.05). Moreover, the results showed that the inter-individual difference in the variance over the phase conditions of the latency of wave V was significantly related to that of cerebral blood flow (r = 0.641, p < 0.05). Our data demonstrate that the fluctuation of cerebral blood flow perfusion could lead to the prolongation of the latency of ABR waves. This suggests that the transient cerebral hypoperfusion induced by an acute orthostatic blood shift to the lower body could impair auditory function.

White Mountain Expedition 2019: Peaks and Valleys ‐ Oscillatory cerebral blood flow at high altitude

IntroductionCerebral tissue oxygenation can be impaired by decreases in oxygen delivery as a result of reduced cerebral blood flow, and environmental conditions such as ascent to high altitude. Recent evidence suggests that an oscillatory pattern in cerebral blood flow (at ~0.1 Hz) may protect cerebral oxygenation 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 cerebral tissue oxygen saturation during exposure to combined simulated hemorrhage and sustained hypobaric hypoxia (ascent and partial acclimatization to high altitude).Methods8 healthy human subjects (4 M, 24.7 ± 4.1 y; 4 F, 34.3 ± 8.3 y) participated in two experiments at high altitude (White Mountain, California, USA; altitude, 3800 m): 1) a control condition (CTRL) where lower body negative pressure (LBNP) was used to induce central hypovolemia by reducing chamber pressure to −60 mmHg for 10‐min, and 2) oscillatory LBNP (OLBNP) where chamber pressure was reduced to −60 mmHg, then oscillated every 5‐s between −30 mmHg and −90 mmHg for 10‐min (0.1 Hz). Measurements included internal carotid artery (ICA) blood flow via duplex Doppler ultrasound, middle cerebral artery velocity (MCAv) via transcranial Doppler ultrasound, and cerebral tissue oxygen saturation via near‐infrared spectroscopy. Frequency analysis (via fast Fourier transform) was performed to verify that oscillations in mean MCAv were generated at ~0.1 Hz. Data were analyzed with a linear mixed‐model. All data are represented as mean ± SE.ResultsLow 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 cerebral tissue oxygenation was protected (OLBNP: −0.67 ± 1.0 Δ%; CTRL: −4.07 ± 2.0 Δ%; P = 0.004).ConclusionsThese 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.Support or Funding InformationAHA 17GRNT33671110

Cardiac Baroreflex Sensitivity during Mild Hypercapnia Following Acute Beetroot Juice Consumption

IntroductionPatients with obstructive sleep apnea often exhibit augmented arterial carbon dioxide tension (CO2) and autonomic dysfunction, which result in increased sympathetic activity and reduced baroreflex sensitivity. Beetroot juice (BRJ) is a popular nutraceutical that decreases resting sympathetic nerve activity and improves vascular function. However, the effects of acute BRJ consumption on cardiac baroreflex sensitivity (cBRS) in healthy individuals with elevated arterial CO2 is unknown.PurposeWe tested the hypothesis that acute BRJ consumption will decrease cBRS during mild hypercapnia.MethodsThirteen healthy adults (age: 26±4 years; 5 females) participated in two oscillatory lower body negative pressure (OLBNP) protocols while breathing a mild hypercapnic gas (3% CO2; 21% O2; 76% N2) during one study visit. OLBNP protocols were completed before (PRE) and 3 hours after consuming 500 mL of beetroot juice (BRJ). After a 5 min resting baseline (BL), the OLBNP protocols consisted of alternating 30 s intervals between −70 mmHg and 0 mmHg for a total of 5 min. Blood pressure (finger photoplethysmography), heart rate (HR; ECG), and end‐tidal CO2 tension (PETCO2; capnography) were continuously recorded and mean values across the −70 mmHg and 0 mmHg intervals during OLBNP were calculated. The sequence method (WinCPRS) was used to calculate cBRS from the obtained beat‐to‐beat blood pressure and R‐R interval data at PRE and BRJ throughout the 5 min BL and 5 min of OLBNP. cBRS was represented by Up‐cBRS and Down‐cBRS sequences and overall cBRS gain.ResultsAt BL, there were no differences in HR (PRE: 65±9 vs BRJ: 66±9 bpm; P=0.69), systolic blood pressure (SBP; PRE: 132±10 vs BRJ: 130±10 mmHg; P=0.17), diastolic blood pressure (DBP; PRE: 74±8 vs BRJ: 72±5 mmHg; P=0.14) and PETCO2 (PRE: 49±4 vs BRJ: 49±4 mmHg; P=0.45). At BL, mean arterial pressure (MAP) was lower with BRJ (96±8 vs 93±7 mmHg; P=0.01). At BL, there were no differences in Up‐BRS (PRE: 27±16 vs BRJ: 26±14 ms/mmHg; P=0.93), Down‐BRS (PRE: 22±11 vs BRJ: 20±9 ms/mmHg; P=0.65), or cBRS Gain (PRE: 17±8 vs BRJ: 19±8 ms/mmHg; P=0.18). During 0 mmHg of OLBNP, there were no differences in HR (PRE: 62±8 vs BRJ: 63±9 bpm; P=0.38), MAP (PRE: 98±7 vs BRJ: 97±6 mmHg; P=0.73), SBP (PRE: 133±7 vs BRJ: 133±10 mmHg; P=0.79), DBP (PRE 73±9 vs BRJ 74±5 mmHg; P=0.48), and PETCO2 (PRE 48±3 vs BRJ 48±4 mmHg; P=0.86). During −70 mmHg of OLBNP, there were no differences in DBP (PRE: 71±12 vs BRJ: 72±9 mmHg; P=0.48) or PETCO2 (PRE: 46±3 vs BRJ: 46±4 mmHg; P=0.86). During −70 mmHg of OLBNP with BRJ, HR was higher (77±10 vs 81±13 bpm; P&lt;0.01), MAP was lower (90±10 vs 88±10 mmHg; P=0.01), and SBP was lower (123±13 vs 120±16 mmHg; P=0.01). During OLBNP, there were no differences in Up‐BRS (PRE: 15±8 vs BRJ: 16±8 ms/mmHg; P=0.94), Down‐BRS (PRE: 14±7 ms/mmHg vs BRJ: 13±5 ms/mmHg; P=0.65), or cBRS Gain (PRE 13±6 vs BRJ 11±6 ms/mmHg P=0.18).ConclusionsDespite slight reductions in MAP following a single bolus of BRJ, there was no difference in cBRS in healthy participants while breathing a hypercapnic gas during an orthostatic challenge. Further research is warranted to determine the effects of chronic BRJ consumption on cBRS.

The Influence of Acute Beetroot Juice Consumption on Cerebral Autoregulation during Orthostatic Stress

Beetroot juice (BRJ) supplementation improves cerebrovascular function during exercise. Breathing a mild hypercapnic gas transiently reduces cerebral autoregulation in healthy participants. However, it is unknown if acute BRJ consumption improves cerebral autoregulation while breathing a mild hypercapniac gas.PurposeWe tested the hypothesis that acute BRJ consumption improves cerebral autoregulation while breathing a mild hypercapnic gas during oscillatory lower body negative pressure (LBNP).MethodsEight healthy participants (age: 27±5 y, 3 F) completed a 5 min baseline (BL) followed by 6 min of LBNP intervals (30s at −70 mmHg, 30s at 0 mmHg) while breathing a mild hypercapnic gas (3% CO2, 21% O2, 76% N2). LBNP was performed pre (PRE) and 3 hours after consuming 500 mL of BRJ (BRJ). Mean arterial pressure (MAP), heart rate (HR), end‐tidal carbon dioxide tension (PETCO2), and middle cerebral artery blood velocity (MCAv) were continuously recorded. Cerebral vascular conductance (CVC) was calculated as MCAv divided by MAP. The magnitude of change in MAP, HR, PETCO2, MCAv, and CVC due to LBNP were calculated from the mean change from BL (Δ) obtained during each interval throughout the LBNP protocols. Cerebral autoregulation (i.e., gain and phase) was assessed throughout the LBNP protocols using Fourier transformation and is reported for BL and as the change from BL (Δ). Values are reported as Δ mean±SD.ResultsThere were no differences between conditions at BL for MAP (PRE: 99±8 vs. BRJ: 95±7 mmHg; P=0.10), HR (PRE: 65±9 vs. BRJ: 65±10 bpm; P=0.40), PETCO2 (PRE: 48±3 vs. BRJ: 49±3 mmHg; P=0.30), CVC (PRE: 0.86±0.18 vs. BRJ: 0.83±0.13 cm/s/mmHg; P=0.16) gain (PRE: 0.96±0.29 vs. BRJ: 0.93±0.22 cm/s/mmHg; P=0.31), or phase (PRE: 7±5 vs. BRJ: 10±6°; P=0.19). At BL, MCAv was lower with BRJ (PRE: 84±14 vs. BRJ: 79±11 cm/s; P&lt;0.01). The ΔMAP during −70 mmHg did not differ with BRJ (PRE: −8±5 vs. BRJ: −6±6 mmHg; P=0.51). The ΔMAP did not differ from BL during 0 mmHg PRE (P=0.44) but the ΔMAP was greater during 0 mmHg with BRJ (PRE: 1±3 vs. BRJ: 4±2 mmHg; P=0.03). The ΔHR was greater during −70 mmHg with BRJ (PRE: 13±10 vs. BRJ: 16±11 bpm; P=0.05) but the ΔHR during 0 mmHg did not differ with BRJ (PRE: −5±4 vs. BRJ: −3±3 bpm; P=0.29). The ΔPETCO2 did not differ between PRE and BRJ during −70 mmHg (PRE: −3±1 vs. BRJ: −3±2 mmHg; P=0.91) or 0 mmHg (PRE: −1±1 vs. BRJ: −1±2 mmHg; P=0.91). ΔMCAv did not differ from BL or between PRE and BRJ during −70 mmHg (PRE: −5±18 vs. BRJ: −4±16 cm/s; P=0.76) and 0 mmHg (PRE: −2±14 vs. BRJ: −1±13 cm/s; P=0.76). The ΔCVC did not differ with BRJ during −70 mmHg (PRE: −0.01±0.11 vs. BRJ: −0.03±0.08 cm/s/mmHg; P=0.20) but was greater with BRJ during 0 mmHg (PRE: −0.07±0.05 vs. BRJ: −0.11±0.08 cm/s/mmHg; P=0.02). During LBNP, there were no differences between conditions for Δgain (PRE: −0.03±0.18 vs. BRJ −0.05±0.10 cm/s/mmHg; P=0.41) or Δphase (PRE: −1±5 vs. BRJ: −3±8.2°; P=0.34).ConclusionsThese preliminary data indicate that acute BRJ does not alter cerebral autoregulation during an orthostatic stressor while healthy participants breathed a mild hypercapnic gas. Further investigations are warranted to determine if chornic BRJ ingestion affects cerebral autoregulation.

Responses of cerebral blood flow and tissue oxygenation to low frequency oscillations during simulated hemorrhagic stress in humans

IntroductionHemorrhage is a leading cause of death from traumatic injury in both the military and civilian populations. Use of lower body negative pressure (LBNP) as a model of hemorrhage in humans has revealed that there is a spectrum of tolerance to this stress. Recent evidence from our laboratory suggests that low frequency (LF; ~0.1 Hz) oscillations in mean arterial pressure (MAP) and middle cerebral artery velocity (MCAv) play a role in this tolerance; high tolerant subjects exhibit greater LF power in MAP and MCAv when compared to low tolerant subjects. We hypothesize that exogenously inducing LF oscillations via oscillatory LBNP (OLBNP) will attenuate reductions in cerebral blood flow and oxygenation during simulated hemorrhagic stress.Methods11 young, healthy subjects (9M/2F) were exposed to two LBNP profiles with an average chamber pressure of −60 mmHg in a randomized and counterbalanced design: 1) static LBNP (0 Hz) and, 2) oscillatory LBNP (0.1 Hz). During both profiles, chamber pressure was gradually reduced to −60 mmHg over 1‐min after which pressure remained at −60 mmHg (0 Hz) for 9‐min or oscillated between −30 mmHg and −90 mmHg (0.1 Hz) for 9‐min. Profiles were separated by a 5‐min recovery. Physiological measurements included arterial pressure and stroke volume via finger photoplethysmography, MCAv via transcranial Doppler ultrasound, and regional 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.ResultsNo 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 the stroke volume response (0 Hz, −42.6±2.5 % vs. 0.1 Hz, −30.6±2.5 %; P&lt;0.001). Importantly, 8/11 subjects completed the 0.1 Hz profile compared with just 5/11 subjects for the 0 Hz profile (P=0.048).DiscussionIn partial support of our hypothesis, cerebral oxygenation was protected during the 0.1 Hz OLBNP profile. While MCAv was similar between conditions, we propose that the oscillatory pattern of cerebral blood flow may elicit a shear‐stress induced vasodilation, so assessment of velocity may be masking an increase in flow. This possibility is further supported by the finding that stroke volume was also protected during the 0.1 Hz profile, which may reflect an increase in venous return during the upstroke period of the OLBNP profile. 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 a hemorrhagic stress.Support or Funding InformationUNTHSC ICMD Junior Faculty Seed GrantThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Oscillatory lower body negative pressure impairs working memory task-related functional hyperemia in healthy volunteers.

Neurovascular coupling (NVC) describes the link between an increase in task-related neural activity and increased cerebral blood flow denoted "functional hyperemia." We previously showed induced cerebral blood flow oscillations suppressed functional hyperemia; conversely functional hyperemia also suppressed cerebral blood flow oscillations. We used lower body negative pressure (OLBNP) oscillations to force oscillations in middle cerebral artery cerebral blood flow velocity (CBFv). Here, we used N-back testing, an intellectual memory challenge as a neural activation task, to test the hypothesis that OLBNP-induced oscillatory cerebral blood flow can reduce functional hyperemia and NVC produced by a working memory task and can interfere with working memory. We used OLBNP (-30 mmHg) at 0.03, 0.05, and 0.10 Hz and measured spectral power of CBFv at all frequencies. Neither OLBNP nor N-back, alone or combined, affected hemodynamic parameters. 2-Back power and OLBNP individually were compared with 2-back power during OLBNP. 2-Back alone produced a narrow band increase in oscillatory arterial pressure (OAP) and oscillatory cerebral blood flow power centered at 0.0083 Hz. Functional hyperemia in response to 2-back was reduced to near baseline and 2-back memory performance was decreased by 0.03-, 0.05-, and 0.10-Hz OLBNP. OLBNP alone produced increased oscillatory power at frequencies of oscillation not suppressed by added 2-back. However, 2-back preceding OLBNP suppressed OLBNP power. OLBNP-driven oscillatory CBFv blunts NVC and memory performance, while memory task reciprocally interfered with forced CBFv oscillations. This shows that induced cerebral blood flow oscillations suppress functional hyperemia and functional hyperemia suppresses cerebral blood flow oscillations.NEW & NOTEWORTHY We show that induced cerebral blood flow oscillations suppress functional hyperemia produced by a working memory task as well as memory task performance. We conclude that oscillatory cerebral blood flow produces causal reductions of memory task neurovascular coupling and memory task performance. Reductions of functional hyperemia are constrained by autoregulation.

Oscillatory lower body negative pressure impairs task related functional hyperemia in healthy volunteers

Neurovascular coupling refers to the link between an increase in neural activity in response to a task and an increase in cerebral blood flow denoted "functional hyperemia." Recent work on postural tachycardia syndrome indicated that increased oscillatory cerebral blood flow velocity (CBFv) was associated with reduced functional hyperemia. We hypothesized that a reduction in functional hyperemia could be causally produced in healthy volunteers by using oscillations in lower body negative pressure (OLBNP) to force oscillations in CBFv. CBFv was measured by transcranial Doppler ultrasound of the left middle cerebral artery. We used passive arm flexion applied during eight periodic 60-s flexion/60-s relaxation epochs to produce 120-s periodic changes in functional hyperemia (at 0.0083 Hz). We used -30 mmHg of OLBNP at 0.03, 0.05, and 0.10 Hz, the range for cerebral autoregulation, and measured spectral power of CBFv at all frequencies. Arm flexion power performed without OLBNP was compared with arm flexion power during OLBNP. OLBNP power performed in isolation was compared with power during OLBNP plus arm flexion. Cerebral flow velocity oscillations at 0.05 Hz reduced and at 0.10 Hz eliminated functional hyperemia, while 0.03 Hz did not reach significance. In contrast, arm flexion reduced OLBNP-induced oscillatory power at all frequencies. The interactions between OLBNP-driven CBFv oscillations and arm flexion-driven CBFv oscillations are reciprocal. Thus induced cerebral blood flow oscillations suppress functional hyperemia, and functional hyperemia suppresses cerebral blood flow oscillations. We conclude that oscillatory cerebral blood flow produces a causal reduction of functional hyperemia.

Relationship between blood pressure and cerebral blood flow during supine cycling: influence of aging.

The cerebral pressure-flow relationship can be quantified as a high-pass filter, where slow oscillations are buffered (<0.20 Hz) and faster oscillations are passed through relatively unimpeded. During moderate intensity exercise, previous studies have reported paradoxical transfer function analysis (TFA) findings (altered phase or intact gain). This study aimed to determine whether these previous findings accurately represent this relationship. Both younger (20-30 yr; n = 10) and older (62-72 yr; n = 9) adults were examined. To enhance the signal-to-noise ratio, large oscillations in blood pressure (via oscillatory lower body negative pressure; OLBNP) were induced during steady-state moderate intensity supine exercise (∼45-50% of heart rate reserve). Beat-to-beat blood pressure, cerebral blood velocity, and end-tidal Pco2 were monitored. Very low frequency (0.02-0.07 Hz) and low frequency (0.07-0.20 Hz) range spontaneous data were quantified. Driven OLBNP point estimates were sampled at 0.05 and 0.10 Hz. The OLBNP maneuvers augmented coherence to >0.97 at 0.05 Hz and >0.98 at 0.10 Hz in both age groups. The OLBNP protocol conclusively revealed the cerebrovascular system functions as a high-pass filter during exercise throughout aging. It was also discovered that the older adults had elevations (+71%) in normalized gain (+0.46 ± 0.36%/%: 0.05 Hz) and reductions (-34%) in phase (-0.24 ± 0.22 radian: 0.10 Hz). There were also age-related phase differences between resting and exercise conditions. It is speculated that these age-related changes in the TFA metrics are mediated by alterations in vasoactive factors, sympathetic tone, or the mechanical buffering of the compliance vessels.

Non-Linear Characterisation of Cerebral Pressure-Flow Dynamics in Humans.

Cerebral metabolism is critically dependent on the regulation of cerebral blood flow (CBF), so it would be expected that vascular mechanisms that play a critical role in CBF regulation would be tightly conserved across individuals. However, the relationships between blood pressure (BP) and cerebral blood velocity fluctuations exhibit inter-individual variations consistent with heterogeneity in the integrity of CBF regulating systems. Here we sought to determine the nature and consistency of dynamic cerebral autoregulation (dCA) during the application of oscillatory lower body negative pressure (OLBNP). In 18 volunteers we recorded BP and middle cerebral artery blood flow velocity (MCAv) and examined the relationships between BP and MCAv fluctuations during 0.03, 0.05 and 0.07Hz OLBNP. dCA was characterised using project pursuit regression (PPR) and locally weighted scatterplot smoother (LOWESS) plots. Additionally, we proposed a piecewise regression method to statistically determine the presence of a dCA curve, which was defined as the presence of a restricted autoregulatory plateau shouldered by pressure-passive regions. Results show that LOWESS has similar explanatory power to that of PPR. However, we observed heterogeneous patterns of dynamic BP-MCAv relations with few individuals demonstrating clear evidence of a dCA central plateau. Thus, although BP explains a significant proportion of variance, dCA does not manifest as any single characteristic BP-MCAv function.