Cerebral Blood Flow Oscillations 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.

A Method to Assess Granger Causality, Isolation and Autonomy in the Time and Frequency Domains: Theory and Application to Cerebrovascular Variability.

Concepts of Granger causality (GC) and Granger autonomy (GA) are central to assess the dynamics of coupled physiologic processes. While causality measures have been already proposed and applied in time and frequency domains, measures quantifying self-dependencies are still limited to the time-domain formulation and lack of clear spectral representation. We embed into the linear parametric framework for computing GC from a driver X to a target process Y a measure of Granger Isolation (GI) quantifying the part of the dynamics of Y not originating from X, and a new spectral measure of GA assessing frequency-specific patterns of self-dependencies in Y. The measures are illustrated in theoretical simulations and applied to time series of arterial pressure and cerebral blood flow obtained in syncope subjects and healthy controls. Simulations show that GI is complementary to GC but not trivially related to it, while GA reflects the regularity of the internal dynamics of the target process. In the application to cerebrovascular interactions, spectral GA quantified the physiological response to postural stress of slow cerebral blood flow oscillations, while spectral GC and GI detected an altered response to orthostasis in syncope subjects, likely related to impaired cerebral autoregulation. The new spectral measures of GI and GA are useful complements to GC for the analysis of interacting oscillatory processes, and detect pathophysiological responses to postural stress which cannot be traced in the time domain. The thorough assessment of causality, isolation and autonomy opens new perspectives for the analysis of coupled processes in both physiological and clinical investigations.

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.

Dynamic cerebral autoregulation measured by diffuse correlation spectroscopy

Dynamic cerebral autoregulation (dCA) can be derived from spontaneous oscillations in arterial blood pressure (ABP) and cerebral blood flow (CBF). Transcranial Doppler (TCD) measures CBF-velocity and is commonly used to assess dCA. Diffuse correlation spectroscopy (DCS) is a promising optical technique for non-invasive CBF monitoring, so here we aimed to validate DCS as a tool for quantifying dCA. In 33 healthy adults and 17 acute ischemic stroke patients, resting-state hemodynamic were monitored simultaneously with high-speed (20 Hz) DCS and TCD. dCA parameters were calcaulated by a transfer function analysis using a Fourier decomposition of ABP and CBF (or CBF-velocity). Strong correlation was found between DCS and TCD measured gain (magnitude of regulation) in healthy volunteers (r = 0.73, p < 0.001) and stroke patients (r = 0.76, p = 0.003). DCS-gain retained strong test-retest reliability in both groups (ICC 0.87 and 0.82, respectively). DCS and TCD-derived phase (latency of regulation) did not significantly correlate in healthy volunteers (r = 0.12, p = 0.50) but moderately correlated in stroke patients (r = 0.65, p = 0.006). DCS-derived phase was reproducible in both groups (ICC 0.88 and 0.90, respectively). High-frequency DCS is a promising non-invasive bedside technique that can be leveraged to quantify dCA from resting-state data, but the discrepancy between TCD and DCS-derived phase requires further investigation.

Low frequency cerebral arterial and venous flow oscillations in healthy neonates measured by NeoDoppler.

A cerebroprotective effect of low frequency oscillations (LFO) in cerebral blood flow (CBF) has been suggested in adults, but its significance in neonates is not known. This observational study evaluates normal arterial and venous cerebral blood flow in healthy neonates using NeoDoppler, a novel Doppler ultrasound system which can measure cerebral hemodynamics continuously. Ultrasound Doppler data was collected for 2 h on the first and second day of life in 36 healthy term born neonates. LFO (0.04-0.15 Hz) were extracted from the velocity curve by a bandpass filter. An angle independent LFO index was calculated as the coefficient of variation of the filtered curve. Separate analyses were done for arterial and venous signals, and results were related to postnatal age and behavioral state (asleep or awake). The paper describes normal physiologic variations of arterial and venous cerebral hemodynamics. Mean (SD) arterial and venous LFO indices (%) were 6.52 (2.55) and 3.91 (2.54) on day one, and 5.60 (1.86) and 3.32 (2.03) on day two. After adjusting for possible confounding factors, the arterial LFO index was estimated to decrease by 0.92 percent points per postnatal day (p < 0.001). The venous LFO index did not change significantly with postnatal age (p = 0.539). Arterial and venous LFO were not notably influenced by behavioral state. The results indicate that arterial LFO decrease during the first 2 days of life in healthy neonates. This decrease most likely represents normal physiological changes related to the transitional period. A similar decrease for venous LFO was not found.

Physiological Mechanisms and Significance of Intracranial B Waves.

ObjectiveRecently published studies have described slow spontaneous cerebral blood flow (CBF) and cerebrospinal fluid (CSF) oscillations measured by magnetic resonance imaging (MRI) as potential drivers of brain glymphatic flow, with a similar frequency as intracranial B-waves. Aiming to establish the relationship between these waveforms, we performed additional analysis of frequency and waveform parameters, of our previously published transcranial Doppler (TCD) and intracranial pressure (ICP) recordings of intracranial B waves, to compare to published MRI frequency measurements of CBF and CSF slow oscillations.Patients and MethodsWe analyzed digital recordings of B waves in 29 patients with head injury, including middle cerebral artery (MCA) flow velocity (FV), ICP, end tidal CO2, and arterial blood pressure (ABP). A subset of these recordings demonstrated high B wave activity and was further analyzed for parameters including frequency, interaction, and waveform distribution curve features. These measures were compared to published similar measurements of spontaneous CBF and CSF fluctuations evaluated using MRI.ResultsIn patients with at least 10% amplitude B wave activity, the MCA blood flow velocity oscillations comprising the B waves, had a maximum amplitude at 0.0245 Hz, and time derivative a maximum amplitude at 0.035 Hz. The frequency range of the B waves was between 0.6–2.3 cycles per min (0.011-0.038 Hz), which is in the same range as MRI measured CBF slow oscillations, reported in human volunteers. Waveform asymmetry in MCA velocity and ICP cycles during B waves, was also similar to published MRI measured CBF slow oscillations. Cross-correlation analysis showed equivalent time derivatives of FV vs. ICP in B waves, compared to MRI measured CBF slow oscillations vs. CSF flow fluctuations.ConclusionsThe TCD and ICP recordings of intracranial B waves show a similar frequency range as CBF and CSF flow oscillations measured using MRI, and share other unique morphological wave features. These findings strongly suggest a common physiological mechanism underlying the two classes of phenomena. The slow blood flow and volume oscillations causing intracranial B waves appear to be part of a cascade that may provide a significant driving force for compartmentalized CSF movement and facilitate glymphatic flow.

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.

CBF oscillations induced by trigeminal nerve stimulation protect the pericontusional penumbra in traumatic brain injury complicated by hemorrhagic shock

Traumatic peri-contusional penumbra represents crucial targets for therapeutic interventions after traumatic brain injury (TBI). Current resuscitative approaches may not adequately alleviate impaired cerebral microcirculation and, hence, compromise oxygen delivery to peri-contusional areas. Low-frequency oscillations in cerebral blood flow (CBF) may improve cerebral oxygenation in the setting of oxygen deprivation. However, no method has been reported to induce controllable oscillations in CBF and it hasn’t been applied as a therapeutic strategy. Electrical stimulation of the trigeminal nerve (TNS) plays a pivotal role in modulating cerebrovascular tone and cerebral perfusion. We hypothesized that TNS can modulate CBF at the targeted frequency band via the trigemino-cerebrovascular network, and TNS-induced CBF oscillations would improve cerebral oxygenation in peri-contusional areas. In a rat model of TBI complicated by hemorrhagic shock, TNS-induced CBF oscillations conferred significant preservation of peri-contusional tissues leading to reduced lesion volume, attenuated hypoxic injury and neuroinflammation, increased eNOS expression, improved neurological recovery and better 10-day survival rate, despite not significantly increasing CBF as compared with those in immediate and delayed resuscitation animals. Our findings indicate that low-frequency CBF oscillations enhance cerebral oxygenation in peri-contusional areas, and play a more significant protective role than improvements in non-oscillatory cerebral perfusion or volume expansion alone.

Astrocytes regulate ultra-slow arteriole oscillations via stretch-mediated TRPV4-COX-1 feedback.

Very-low-frequency oscillations in microvascular diameter cause fluctuations in oxygen delivery that are important for fueling the brain and for functional imaging. However, little is known about how the brain regulates ongoing oscillations in cerebral blood flow. In mouse and rat cortical brain slice arterioles, we find that selectively enhancing tone is sufficient to recruit a TRPV4-mediated Ca2+ elevation in adjacent astrocyte endfeet. This endfoot Ca2+ signal triggers COX-1-mediated "feedback vasodilators" that limit the extent of evoked vasoconstriction, as well as constrain fictive vasomotion in slices. Astrocyte-Ptgs1 knockdown invivo increases the power of arteriole oscillations across a broad range of very low frequencies (0.01-0.3Hz), including ultra-slow vasomotion (∼0.1Hz). Conversely, clamping astrocyte Ca2+invivo reduces the power of vasomotion. These data demonstrate bidirectional communication between arterioles and astrocyte endfeet to regulate oscillatory microvasculature activity.

Peaks and valleys: oscillatory cerebral blood flow at high altitude protects cerebral tissue oxygenation

Introduction. Oscillatory patterns in arterial pressure and blood flow (at ∼0.1 Hz) may protect tissue oxygenation during conditions of reduced cerebral perfusion and/or hypoxia. We hypothesized that inducing oscillations in arterial pressure and cerebral blood flow at 0.1 Hz would protect cerebral blood flow and cerebral tissue oxygen saturation during exposure to a combination of simulated hemorrhage and sustained hypobaric hypoxia. Methods. Eight healthy human subjects (4 male, 4 female; 30.1 ± 7.6 year) participated in two experiments at high altitude (White Mountain, California, USA; altitude, 3800 m) following rapid ascent and 5–7 d of acclimatization: (1) static lower body negative pressure (LBNP, control condition) was used to induce central hypovolemia by reducing chamber pressure to −60 mmHg for 10 min (0 Hz), and; (2) oscillatory LBNP 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 arterial pressure, internal carotid artery (ICA) blood flow, middle cerebral artery velocity (MCAv), and cerebral tissue oxygen saturation (ScO2). Results. Forced 0.1 Hz oscillations in mean arterial pressure and mean MCAv were accompanied by a protection of ScO2 (0.1 Hz: −0.67% ± 1.0%; 0 Hz: −4.07% ± 2.0%; P = 0.01). However, the 0.1 Hz profile did not protect against reductions in ICA blood flow (0.1 Hz: −32.5% ± 4.5%; 0 Hz: −19.9% ± 8.9%; P = 0.24) or mean MCAv (0.1 Hz: −18.5% ± 3.4%; 0 Hz: −15.3% ± 5.4%; P = 0.16). Conclusions. Induced oscillatory arterial pressure and cerebral blood flow led to protection of ScO2 during combined simulated hemorrhage and sustained hypoxia. This protection was not associated with the preservation of cerebral blood flow suggesting preservation of ScO2 may be due to mechanisms occurring within the microvasculature.

Time‐Frequency Analysis of Hemodynamics Oscillations during Presyncopal Lower Body Negative Pressure (LBNP)

Introduction Greater low frequency (LF) oscillations (~0.1 Hz) in mean arterial pressure (MAP) and cerebral blood flow (indexed by middle cerebral artery velocity; MCAv) have been associated with higher tolerance to central hypovolemia. As the fast Fourier transform approach was used in these prior studies, measuring exact timing of oscillatory amplitude was not possible. In the present study, the continuous wavelet transform was used for time localization and measurement of the magnitude of LF oscillations during application of lower body negative pressure (LBNP) to presyncope to reduce cerebral perfusion. We hypothesized that the magnitude of LF oscillations in MAP and MCAv would be higher in subjects with greater tolerance to this stress. We also hypothesized that the time of instantaneous maximum magnitude of LF oscillations would be further from baseline for high tolerant subjects. Methods 31 healthy human subjects (14 F: 17 M; 25.1 ± 3.0 y) underwent a stepwise LBNP protocol to presyncope. Subjects were classified as high tolerant (HT) if they completed the -60 mmHg stage of LBNP, and low tolerant (LT) if they did not. Continuous beat-to-beat MAP and mean MCAv were recorded. The continuous wavelet transform was used to extract magnitude of oscillations within the LF range (0.07-0.15 Hz) over time for both MAP and mean MCAv. The instantaneous maximum magnitude of LF oscillations was then extracted. Pearson's correlation was calculated for instantaneous LF magnitude of MAP and mean MCAv versus presyncopal time. A t-test was then used to compare magnitude and relative time of LF oscillations between HT and LT subjects. Results The maximum magnitude of MAP LF oscillations was positively correlated with presyncopal time (R = 0.39, P = 0.03). The maximum magnitude of MCAv LF oscillations, however, was not correlated with presyncopal time (R = -0.03, P = 0.86). When assessing HT and LT subjects, no differences were observed for maximum magnitude of LF oscillations in MAP (HT 4.3 ± 1.0, LT 3.7 ± 1.2, P=0.15) or MCAv (HT 3.1 ± 0.9, LT 3.1 ± 0.7, P=0.91). Time to maximum magnitude of LF oscillations was greater in high tolerant subjects for both MAP (HT 1384.5 ± 329.6 s, LT 798.6 ± 416.8 s, P<0.01) and MCAv (HT 1064.3 ± 431.6 s, LT 662.4 ± 380.1 s, P=0.01). When expressing the time of maximum amplitude as a percent of presyncopal time, the average time in all subjects for MAP was 73.6 ± 22.0 % and 59.6 ± 26.1 % for MCAv, and there were no differences between tolerance groups in either MAP (HT 79.5 ± 14.0 %, LT 67.4 ± 27.3 %, P=0.14) or MCAv (HT 61.8 ± 24.8 %, LT 57.3 ± 28.1 %, P=0.64). Conclusions Using wavelet analysis, only the maximum magnitude of MAP LF oscillations was modestly correlated to presyncopal time. Contrary to previous measures using fast Fourier transform, there was no difference in instantaneous maximum magnitude of oscillations in MAP and mean MCAv between high and low tolerant subjects indicating that both groups could mount similar responses. Interestingly, the relative timing of maximum magnitude of oscillations in MAP and MCAv was no different between tolerance groups.

Diffuse optical assessment of cerebral-autoregulation in older adults stratified by cerebrovascular risk.

Diagnosis of cerebrovascular disease (CVD) at early stages is essential for preventing sequential complications. CVD is often associated with abnormal cerebral microvasculature, which may impact cerebral-autoregulation (CA). A novel hybrid near-infrared diffuse optical instrument and a finger plethysmograph were used to simultaneously detect low-frequency oscillations (LFOs) of cerebral blood flow (CBF), oxy-hemoglobin concentration ([HbO2 ]), deoxy-hemoglobin concentration ([Hb]) and mean arterial pressure (MAP) in older adults before, during and after 70° head-up-tilting (HUT). The participants with valid data were divided based on Framingham risk score (FRS, 1-30 points) into low-risk (FRS ≤15, n = 13) and high-risk (FRS >15, n = 11) groups for developing CVD. The LFO gains were determined by transfer function analyses with MAP as the input, and CBF, [HbO2 ] and [Hb] as the outputs (CA ∝ 1/Gain). At resting-baseline, LFO gains in the high-risk group were relatively lower compared to the low-risk group. The lower baseline gains in the high-risk group may attribute to compensatory mechanisms to maintain stronger steady-state CAs. However, HUT resulted in smaller gain reductions in the high-risk group compared to the low-risk group, suggesting weaker dynamic CAs. LFO gains are potentially valuable biomarkers for early detection of CVD based on associations with CAs.

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

Acute Brain Injury Is Associated With Prolonged Suppression of Cerebral Blood Flow Oscillations

Abstract INTRODUCTION Low-frequency oscillations (LFOs, &lt; 0.1 Hz) in cerebral blood flow (CBF) reflect changes in the coordinated activity of neuronal assemblies. Synchronized LFOs across multiple brain regions can be identified using magnetic resonance imaging to reveal functionally connected networks; however, how LFOs are altered by brain injury is largely unknown. METHODS We quantified changes in LFO magnitude over time in brain-injured patients where CBF was recorded continuously using invasive thermal diffusion flowmetry. Intracranial pressure (ICP), brain tissue oxygen (PbO2), and arterial blood pressure (ABP) were recorded concurrently in all patients. For each epoch of uninterrupted CBF data, the power spectral density within the 0.05 to 0.1 Hz frequency band was calculated. Periods of LFO suppression were defined as occurring when equal to 10% of the total power across all frequencies occurred in the 0.05 to 1 Hz frequency band. Average values of CBF, ICP, PbO2, and ABP were compared between suppressed and nonsuppressed epochs across all patients. RESULTS Twenty-five patients were included in this retrospective observational study. LFO suppression was associated with a lower average CBF (11.3 mL/100 g/min suppressed vs 31.6 mL/100 g/min unsuppressed, P &lt; .0001) and lower average PbO2 (21.6 mm Hg suppressed vs 31.0 mm Hg unsuppressed, P &lt; .0001). In a subset of patients, LFO suppression was associated with intracranial hypertension (ICP 25-60 mm Hg). Patients that regained consciousness and were discharged to acute rehab had a lower median fraction of time spent in the suppressed state (0.03 rehab vs 0.67 death/nursing home, P = .053). CONCLUSION Brain injury is associated with the suppression of low-frequency CBF fluctuations. LFO suppression is associated with periods of physiological distress and may provide a sensitive marker of disrupted brain function. The degree of LFO suppression may have a prognostic significance, and the re-emergence of LFOs after a period of suppression may provide a marker of return of consciousness after coma.

Dynamic Estimation of Cerebral Blood Flow Using Blood Pressure Signal in sleep Apnea Patients.

Monitoring apnea-induced cerebral blood flow (CBF) oscillations is of importance for assessing apnea patient brain health. Blood pressure (BP) oscillations during apnea can induce oscillations in CBF. Preliminary results of testing an Auto Regressive Moving Average model relating nocturnal CBP oscillations to nocturnal BP variations in 8 obstructive sleep apnea subjects (3 F, 55±8 yrs., BMI 34.2±7.85 kg/m2) showed that largest mean and standard deviation of the CBF estimation errors was 4.49±7.57 cm/s and maximum root mean squared of the errors was 8.80 cm/s. Hence, reasonable accuracy in estimating CBF from BP during sleep apnea events was observed.

Dynamic Estimation of Cerebral Blood Flow Using Photoplethysmography Signal during Simulated Apnea.

Monitoring apnea-induced cerebral blood flow oscillations is of importance for assessing apnea patient brain health. Using an autoregressive moving average model, peak and trough values of cerebral blood flow were estimated from a concurrently recorded forehead photoplethysmography signal. Preliminary testing of the method in 7 subjects (4 F, 32±4 yrs., BMI 24.57±3.87 kg/m2) using a breath hold paradigm for simulating apnea shows that maximum mean and standard deviation of the prediction error is -1.10±8.49 cm/s and the maximum root mean squared of the error is 8.92 cm/s.

Are Spontaneous Low Frequency Oscillations in Arterial Pressure and Cerebral Blood Flow Associated with the Protection of Cerebral Tissue Oxygenation during Simulated Hemorrhage?

IntroductionPrior 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.MethodsHealthy 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).ResultsOf 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 (P&lt;0.01), MCAv (P&lt;0.01), and etCO2 (P&lt;0.01) compared to low tolerant subjects during LBNP.ConclusionContrary 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.Support or Funding InformationFunding for this study was provided by the U.S. Army MRMC Combat Casualty Care Research Program Grant # W81XWH‐11‐2‐0137, and a contract with Pendar Medical LLC. The content is solely the responsibility of the authors and does not necessarily represent the official views the US Department of Defense.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

RGB camera-based imaging of cerebral tissue oxygen saturation, hemoglobin concentration, and hemodynamic spontaneous low-frequency oscillations in rat brain following induction of cortical spreading depression.

To evaluate cerebral hemodynamics and spontaneous low-frequency oscillations (SLFOs) of cerebral blood flow in rat brain, we investigated an imaging method using a digital RGB camera. In this method, the RGB values were converted into tristimulus values in the CIE (Commission Internationale de l'Eclairage) XYZ color space, which is compatible with the common RGB working spaces. Monte Carlo simulation for light transport in tissue was then used to specify the relationship among the tristimulus XYZ values and the concentrations of oxygenated hemoglobin (CHbO), deoxygenated hemoglobin (CHbR), and total hemoglobin (CHbT) and cerebral tissue oxygen saturation (StO2). Applying the fast Fourier transform to each pixel of the sequential images of CHbT along the timeline, SLFOs of cerebral blood volume were visualized as a spatial map of power spectral density (PSD) at specific frequencies related to vasomotion. To confirm the feasibility of this method, we performed in vivo experiments using exposed rat brain during a cortical spreading depression (CSD) evoked by topical application of KCl. Cerebral hemodynamic responses to CSD such as initial hypoperfusion, profound hyperemia, and post-CSD oligemia and hypoxemia were successfully visualized with this method. At the transition to the hyperemia phase from hypoperfusion, CHbO and StO2 were significantly increased, which implied vasodilatation in arterioles and increased cerebral blood volume in response to CSD. In the wake of the hyperemic phase, CHbO and CHbT were significantly reduced to 25 ± 12% and 3.5 ± 1% of baseline, respectively, suggesting long-lasting vasoconstriction after CSD. In this persistent oligemia, StO2 significantly dropped to at most 23 ± 12% of the level before CSD, indicating long-lasting hypoxemia. The PSD value of SLFOs in CHbT for arteriole regions during CSD was significantly reduced to 28 ± 20% of baseline with respect to the pre-CSD level, which was correlated with the reduction in StO2. The results showed the possibility of RGB camera-based diffuse reflectance spectroscopy imaging for evaluating cerebral hemodynamics and SLFOs under normal and pathologic conditions.

The physiology of blood loss and shock: New insights from a human laboratory model of hemorrhage.

The ability to quickly diagnose hemorrhagic shock is critical for favorable patient outcomes. Therefore, it is important to understand the time course and involvement of the various physiological mechanisms that are active during volume loss and that have the ability to stave off hemodynamic collapse. This review provides new insights about the physiology that underlies blood loss and shock in humans through the development of a simulated model of hemorrhage using lower body negative pressure. In this review, we present controlled experimental results through utilization of the lower body negative pressure human hemorrhage model that provide novel insights on the integration of physiological mechanisms critical to the compensation for volume loss. We provide data obtained from more than 250 human experiments to classify human subjects into two distinct groups: those who have a high tolerance and can compensate well for reduced central blood volume (e.g. hemorrhage) and those with low tolerance with poor capacity to compensate.We include the conceptual introduction of arterial pressure and cerebral blood flow oscillations, reflex-mediated autonomic and neuroendocrine responses, and respiration that function to protect adequate tissue oxygenation through adjustments in cardiac output and peripheral vascular resistance. Finally, unique time course data are presented that describe mechanistic events associated with the rapid onset of hemodynamic failure (i.e. decompensatory shock). Impact Statement Hemorrhage is the leading cause of death in both civilian and military trauma. The work submitted in this review is important because it advances the understanding of mechanisms that contribute to the total integrated physiological compensations for inadequate tissue oxygenation (i.e. shock) that arise from hemorrhage. Unlike an animal model, we introduce the utilization of lower body negative pressure as a noninvasive model that allows for the study of progressive reductions in central blood volume similar to those reported during actual hemorrhage in conscious humans to the onset of hemodynamic decompensation (i.e. early phase of decompensatory shock), and is repeatable in the same subject. Understanding the fundamental underlying physiology of human hemorrhage helps to test paradigms of critical care medicine, and identify and develop novel clinical practices and technologies for advanced diagnostics and therapeutics in patients with life-threatening blood loss.

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.