Arterial Blood Pressure Oscillations Research Articles

Dynamic cerebral autoregulation quantification with spontaneous arterial blood pressure oscillations: Is transfer function analysis our best option?

Dynamic cerebral autoregulation quantification with spontaneous arterial blood pressure oscillations: Is transfer function analysis our best option?

Conductivity reactivity index for monitoring of cerebrovascular autoregulation in early cerebral ischemic rabbits

BackgroundCerebrovascular autoregulation (CVAR) is the mechanism that maintains constant cerebral blood flow by adjusting the caliber of the cerebral vessels. It is important to have an effective, contactless way to monitor and assess CVAR in patients with ischemia.MethodsThe adjustment of cerebral blood flow leads to changes in the conductivity of the whole brain. Here, whole-brain conductivity measured by the magnetic induction phase shift method is a valuable alternative to cerebral blood volume for non-contact assessment of CVAR. Therefore, we proposed the correlation coefficient between spontaneous slow oscillations in arterial blood pressure and the corresponding magnetic induction phase shift as a novel index called the conductivity reactivity index (CRx). In comparison with the intracranial pressure reactivity index (PRx), the feasibility of the conductivity reactivity index to assess CVAR in the early phase of cerebral ischemia has been preliminarily confirmed in animal experiments.ResultsThere was a significant difference in the CRx between the cerebral ischemia group and the control group (p = 0.002). At the same time, there was a significant negative correlation between the CRx and the PRx (r = − 0.642, p = 0.002) after 40 min after ischemia. The Bland–Altman consistency analysis showed that the two indices were linearly related, with a minimal difference and high consistency in the early ischemic period. The sensitivity and specificity of CRx for cerebral ischemia identification were 75% and 20%, respectively, and the area under the ROC curve of CRx was 0.835 (SE = 0.084).ConclusionThe animal experimental results preliminarily demonstrated that the CRx can be used to monitor CVAR and identify CVAR injury in early ischemic conditions. The CRx has the potential to be used for contactless, global, bedside, and real-time assessment of CVAR of patients with ischemic stroke.

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.

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.

Association between temporal patterns of baroreflex sensitivity after traumatic brain injury and prognosis: a preliminary study

IntroductionTraumatic brain injury (TBI) may lead to an increase in intracranial pressure (ICP) as well as impairment of cerebral vascular reactivity and the autonomic nervous system. This study aimed to investigate individual patterns of changes in baroreflex sensitivity (BRS) along with the assessment of pressure reactivity index (PRx) and ICP after TBI.Materials and methodsTwenty-nine TBI patients with continuous arterial blood pressure (ABP) and ICP monitoring were included. BRS was calculated using the sequential cross-correlation method. PRx was estimated using slow-wave oscillations of ABP and ICP. Outcome was assessed using the Glasgow Outcome Scale.ResultsPooled data analysis of the lower breakpoint during the week that followed TBI revealed that BRS reached a minimum about 2 days after TBI. In patients with good outcome, there was a significant increase in BRS during the 7 days following TBI: rp = 0.21; p = 0.008 and the temporal changes in BRS showed either a “U-shaped” pattern or a gradual increase over time. The BRS value after 1.5 days was found to be a significant predictor of mortality (cut-off BRS = 1.8 ms/mm Hg; AUC = 0.83). In patients with poor outcome, ICP and PRx increased while BRS remained low.ConclusionsWe found an association between temporal patterns of BRS and prognosis in the early days following TBI. Further research in a larger cohort of patients is needed to confirm the weight of these preliminary observations for prediction of prognosis in TBI patients.

Coherent Spontaneous Hemodynamics in the Human Brain

<italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Goal:</i> This work investigates the presence of cerebral hemodynamics (namely Oxy (O) and Deoxy (D) hemoglobin concentrations) that are coherent with spontaneous oscillations in Arterial Blood Pressure (ABP) in 78 healthy subjects during a driving simulation task. <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Methods:</i> Spatially resolved O and D were measured on the prefrontal cortex with multi-channel near-infrared spectroscopy (NIRS). Wavelet coherence and phasor analysis were performed between O and ABP, and between D and ABP to evaluate the amplitude ratio, phase difference, and duration of significant coherence. <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Results</i> : In the low-frequency range, oscillations at 0.1 Hz featured significant coherence for the longest time fraction (∼10%-30%). At this frequency, the amplitude ratio and phase difference showed a greater variance across subjects than over cortical locations, and no significant difference between driving tasks and baseline. <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Conclusions</i> : Measuring low-frequency cerebral hemodynamics that are coherent with systemic ABP holds promise for non-invasive assessment of cerebral perfusion and autoregulation at the cerebral microvascular level.

Inducing oscillations in positive end-expiratory pressure improves assessment of cerebrovascular pressure reactivity in patients with traumatic brain injury.

The cerebral pressure reactivity index (PRx), through intracranial pressure (ICP) measurements, informs clinicians about the cerebral autoregulation (CA) status in adult-sedated patients with traumatic brain injury (TBI). Using PRx in clinical practice is currently limited by variability over shorter monitoring periods. We applied an innovative method to reduce the PRx variability by ventilator-induced slow (1/min) positive end-expiratory pressure (PEEP) oscillations. We hypothesized that, as seen in a previous animal model, the PRx variability would be reduced by inducing slow arterial blood pressure (ABP) and ICP oscillations without other clinically relevant physiological changes. Patients with TBI were ventilated with a static PEEP for 30 min (PRx period) followed by a 30-min period of slow [1/min (0.0167 Hz)] +5 cmH2O PEEP oscillations (induced (iPRx period). Ten patients with TBI were included. No clinical monitoring was discontinued and no additional interventions were required during the iPRx period. The PRx variability [measured as the standard deviation (SD) of PRx] decreased significantly during the iPRx period from 0.25 (0.22-0.30) to 0.14 (0.09-0.17) (P = 0.006). There was a power increase around the induced frequency (1/min) for both ABP and ICP (P = 0.002). In conclusion, 1/min PEEP-induced oscillations reduced the PRx variability in patients with TBI with ICP levels <22 mmHg. No other clinically relevant physiological changes were observed. Reduced PRx variability might improve CA-guided perfusion management by reducing the time to find "optimal" perfusion pressure targets. Larger studies with prolonged periods of PEEP-induced oscillations are required to take it to routine use.NEW & NOTEWORTHY Cerebral autoregulation assessment requires sufficient slow arterial blood pressure (ABP) waves. However, spontaneous ABP waves may be insufficient for reliable cerebral autoregulation estimations. Therefore, we applied a ventilator "sigh-function" to generate positive end-expiratory pressure oscillations that induce slow ABP waves. This method demonstrated a reduced variability of the pressure reactivity index, commonly used as continuous cerebral autoregulation measure in a traumatic brain injury population.

Relationship Between Baroreflex and Cerebral Autoregulation in Patients With Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage.

Introduction: Common consequences following aneurysmal subarachnoid hemorrhage (aSAH) are cerebral vasospasm (CV), impaired cerebral autoregulation (CA), and disturbance in the autonomic nervous system, as indicated by lower baroreflex sensitivity (BRS). The compensatory interaction between BRS and CA has been shown in healthy volunteers and stable pathological conditions such as carotid atherosclerosis. The aim of this study was to investigate whether the inverse correlation between BRS and CA would be lost in patients after aSAH during vasospasm. A secondary objective was to analyze the time-trend of BRS after aSAH.Materials and Methods: Retrospective analysis of prospectively collected data was performed at the Neuro-Critical Care Unit of Addenbrooke's Hospital (Cambridge, UK) between June 2010 and January 2012. The cerebral blood flow velocity (CBFV) was measured in the middle cerebral artery using transcranial Doppler ultrasonography (TCD). The arterial blood pressure (ABP) was monitored invasively through an arterial line. CA was quantified by the correlation coefficient (Mxa) between slow oscillations in ABP and CBFV. BRS was calculated using the sequential cross-correlation method using the ABP signal.Results: A total of 73 patients with aSAH were included. The age [median (lower-upper quartile)] was 58 (50–67). WFNS scale was 2 (1–4) and the modified Fisher scale was 3 (1–3). In the total group, 31 patients (42%) had a CV and 42 (58%) had no CV. ABP and CBFV were higher in patients with CV during vasospasm compared to patients without CV (p = 0.001 and p < 0.001). There was no significant correlation between Mxa and BRS in patients with CV, neither during nor before vasospasm. In patients without CV, a significant, although moderate correlation was found between BRS and Mxa (rS = 0.31; p = 0.040), with higher BRS being associated with worse CA. Multiple linear regression analysis showed a significant worsening of BRS after aSAH in patients with CV (Rp = −0.42; p < 0.001).Conclusions: Inverse compensatory correlation between BRS and CA was lost in patients who developed CV after aSAH, both before and during vasospasm. The impact of these findings on the prognosis of aSAH should be investigated in larger studies.

Characterization of Mayer-wave oscillations in functional near-infrared spectroscopy using a physiologically informed model of the neural power spectra.

.Significance: Mayer waves are spontaneous oscillations in arterial blood pressure that can mask cortical hemodynamic responses associated with neural activity of interest.Aim: We aim to characterize the properties of oscillations in the functional near-infrared spectroscopy (fNIRS) signal generated by Mayer waves in a large sample of fNIRS recordings. Further, we aim to determine the impact of short-channel correction for the attenuation of these unwanted signal components.Approach: Mayer-wave oscillation parameters were extracted from 310 fNIRS measurements using the fitting oscillations and one-over-f method to compute normative values. The effect of short-channel correction on Mayer-wave oscillation power was quantified on 222 measurements. The practical benefit of the short-channel correction approach for reducing Mayer waves and improving response detection was also evaluated on a subgroup of 17 fNIRS measurements collected during a passive auditory speech detection experiment.Results: Mayer-wave oscillations had a mean frequency of 0.108 Hz, bandwidth of 0.04 Hz, and power of . The distribution of oscillation signal power was positively skewed, with some measurements containing large Mayer waves. Short-channel correction significantly reduced the amplitude of these undesired signals; greater attenuation was observed for measurements containing larger Mayer-wave oscillations.Conclusions: A robust method for quantifying Mayer-wave oscillations in the fNIRS signal spectrum was presented and used to provide normative parameterization. Short-channel correction is recommended as an approach for attenuating Mayer waves, particularly in participants with large oscillations.

Noninvasive Optical Measurements of Dynamic Cerebral Autoregulation by Inducing Oscillatory Cerebral Hemodynamics.

Objective: Cerebral autoregulation limits the variability of cerebral blood flow (CBF) in the presence of systemic arterial blood pressure (ABP) changes. Monitoring cerebral autoregulation is important in the Neurocritical Care Unit (NCCU) to assess cerebral health. Here, our goal is to identify optimal frequency-domain near-infrared spectroscopy (FD-NIRS) parameters and apply a hemodynamic model of coherent hemodynamics spectroscopy (CHS) to assess cerebral autoregulation in healthy adult subjects and NCCU patients.Methods: In five healthy subjects and three NCCU patients, ABP oscillations at a frequency around 0.065 Hz were induced by cyclic inflation-deflation of pneumatic thigh cuffs. Transfer function analysis based on wavelet transform was performed to measure dynamic relationships between ABP and oscillations in oxy- (O), deoxy- (D), and total- (T) hemoglobin concentrations measured with different FD-NIRS methods. In healthy subjects, we also obtained the dynamic CBF-ABP relationship by using FD-NIRS measurements and the CHS model. In healthy subjects, an interval of hypercapnia was performed to induce cerebral autoregulation impairment. In NCCU patients, the optical measurements of autoregulation were linked to individual clinical diagnoses.Results: In healthy subjects, hypercapnia leads to a more negative phase difference of both O and D oscillations vs. ABP oscillations, which are consistent across different FD-NIRS methods and are highly correlated with a more negative phase difference CBF vs. ABP. In the NCCU, a less negative phase difference of D vs. ABP was observed in one patient as compared to two others, indicating a better autoregulation in that patient.Conclusions: Non-invasive optical measurements of induced phase difference between D and ABP show the strongest sensitivity to cerebral autoregulation. The results from healthy subjects also show that the CHS model, in combination with FD-NIRS, can be applied to measure the CBF-ABP dynamics for a better direct measurement of cerebral autoregulation.

The Influence of Carbon Dioxide on Cerebral Autoregulation During Sevoflurane-based Anesthesia in Patients With Type 2 Diabetes.

Cerebral autoregulation (CA) continuously adjusts cerebrovascular resistance to maintain cerebral blood flow (CBF) constant despite changes in blood pressure. Also, CBF is proportional to changes in arterial carbon dioxide (CO 2 ) (cerebrovascular CO 2 reactivity). Hypercapnia elicits cerebral vasodilation that attenuates CA efficacy, while hypocapnia produces cerebral vasoconstriction that enhances CA efficacy. In this study, we quantified the influence of sevoflurane anesthesia on CO 2 reactivity and the CA-CO 2 relationship. We studied patients with type 2 diabetes mellitus (DM), prone to cerebrovascular disease, and compared them to control subjects. In 33 patients (19 DM, 14 control), end-tidal CO 2 , blood pressure, and CBF velocity were monitored awake and during sevoflurane-based anesthesia. CA, calculated with transfer function analysis assessing phase lead (degrees) between low-frequency oscillations in CBF velocity and mean arterial blood pressure, was quantified during hypocapnia, normocapnia, and hypercapnia. In both control and DM patients, awake CO 2 reactivity was smaller (2.8%/mm Hg CO 2 ) than during sevoflurane anesthesia (3.9%/mm Hg; P <0.005). Hyperventilation increased CA efficacy more (3 deg./mm Hg CO 2 ) in controls than in DM patients (1.8 deg./mm Hg CO 2 ; P <0.001) in both awake and sevoflurane-anesthetized states. The CA-CO 2 relationship is impaired in awake patients with type 2 DM. Sevoflurane-based anesthesia does not further impair this relationship. In patients with DM, hypocapnia induces cerebral vasoconstriction, but CA efficacy does not improve as observed in healthy subjects.

Similar Effects of an Orexin Receptor Antagonistand Benzodiazepine Receptor Agonist on Cerebral Blood Flow Regulation

Orexin receptor antagonists have a different sleep-inducing mechanism from common hypnotic benzodiazepinereceptor agonists. Thus, orexin receptor antagonists may affect cerebral circulation differently, although theireffects have rarely been investigated. In this study, the effects of an orexin receptor antagonist on cerebral bloodflow regulation were compared with those of a benzodiazepine, including dynamic cerebral autoregulation. Fifteenhealthy males received suvorexant (1 tablet, 20 mg), an orexin receptor antagonist, and brotizolam (1 tablet, 0.25mg), a benzodiazepine receptor agonist, in a randomized order at least 7 days apart. Before and 1.5 h after drugadministration, arterial blood pressure and cerebral blood flow velocity were measured by transcranial Doppler ina supine position. Dynamic cerebral autoregulation was evaluated by transfer function analysis between mean arterial blood pressure variability and mean cerebral blood flow velocity variability. The steady-state mean cerebralblood flow velocity decreased significantly with both suvorexant and brotizolam (significant main effect of time,P = 0.003) and was associated with unchanged steady-state mean arterial blood pressure. Moreover, transfer function gain in the low- and high-frequency ranges were decreased significantly by both suvorexant and brotizolam(significant main effect of time, P < 0.001), suggesting a decrease in the magnitude of transfer from arterial bloodpressure oscillations to cerebral blood flow fluctuations. These changes were not significantly different betweensuvorexant and brotizolam (no significant interaction effect). The present results indicate that suvorexant andbrotizolam, two different types of hypnotic drug, have similar effects on cerebral blood flow regulation, includingpossible improvements in dynamic cerebral autoregulation with decreased steady-state cerebral blood flow.

Impact Of 6-month Exercise Training On Cerebrovascular Function In Persons With Spinal Cord Injury

Persons with spinal cord injury (SCI) have a four-fold greater risk for cerebrovascular disease, suggesting that they cannot maintain steady cerebral perfusion. While disruption in autonomic control after SCI may impact cerebral vascular function, chronic physical deconditioning may also play a substantial role. If so, full-body aerobic exercise may improve cerebrovascular function in persons with SCI. PURPOSE: To assess the impact of injury and habitual, whole-body functional electric stimulation (FES)-assisted aerobic exercise training on cerebrovascular function in persons with SCI. METHODS: Baseline hemodynamic (heart rate, blood pressure, CO2) and cerebral blood flow (CBF) responses to oscillations in arterial blood pressure via low-resistance breathing (i.e. autoregulation) and progressive increases in arterial CO2 via rebreathing (i.e. vasoreactivity) were measured in 16 able-bodied controls and 30 participants with SCI (n= 15 cervical and n = 15 thoracic). Nineteen participants with SCI (n= 9 cervical and n = 10 thoracic) completed 6-months of a FES-assisted rowing exercise training program. Changes in autoregulatory function, vasoreactivity, and VO2max were compared before and after aerobic exercise training via linear mixed effect model. RESULTS: Individuals with higher level SCI had slightly lower hemodynamic variables in comparison to able-bodied and those with lower level SCI and able-bodied. Greater VO2max was related to increased vasoreactivity (R2=0.45, p<0.01) at baseline. Overall, VO2max increased significantly after training (p<0.01). Vasoreactivity also tended to increase with training, but the change was not statistically significant due to high variability. Given this, we assessed the relation between the change in VO2max and vasoreactivity in exercise “responders,” defined as those with >10% change in VO2max; n=8. In responders, an increase in VO2max was strongly associated with an increase in vasoreactivity (R2=0.72, p<.01) regardless of the level of SCI. CONCLUSION: Cerebral vasoreactivity is impaired in individuals with SCI. This impairment is primarily due to physical deconditioning, and can be improved by habitual aerobic exercise.

Characterization of Blood Pressure and Heart Rate Oscillations of POTS Patients via Uniform Phase Empirical Mode Decomposition.

Postural Orthostatic Tachycardia Syndrome (POTS) is associated with the onset of tachycardia upon postural change. The current diagnosis involves the measurement of heart rate (HR) and blood pressure (BP) during head-up tilt (HUT) or active standing test. A positive diagnosis is made if HR changes with more than 30bpm (40bpm in patients aged 12-19 years), ignoring all of the BP and most of the HR signals. This study examines 0.1Hz oscillations in systolic arterial blood pressure (SBP) and HR signals providing additional metrics characterizing the dynamics of the baroreflex. We analyze data from 28 control subjects and 28 POTS patients who underwent HUT. We extract beat-to-beat HR and SBP during a 10 min interval including 5 minutes of baseline and 5 minutes of HUT. We employ Uniform Phase Empirical Mode Decomposition (UPEMD) to extract 0.1Hz stationary modes from both signals and use random forest machine learning and k-means clustering to analyze the outcomes. Results show that the amplitude of the 0.1Hz oscillations is higher in POTS patients and that the phase response between the two signals is shorter (p < 0.005). POTS is associated with an increase in the amplitude of SBP and HR 0.1Hz oscillation and shortening of the phase between the two signals. The 0.1Hz phase response and oscillation amplitude metrics provide new markers that can improve POTS diagnostic augmenting the existing diagnosis protocol only analyzing the change in HR.

Phase dual-slopes in frequency-domain near-infrared spectroscopy for enhanced sensitivity to brain tissue: First applications to human subjects.

We present a first in vivo application of phase dual-slopes (DSϕ), measured with frequency-domain near-infrared spectroscopy on four healthy human subjects, to demonstrate their enhanced sensitivity to cerebral hemodynamics. During arterial blood pressure oscillations elicited at a frequency of 0.1 Hz, we compare three different ways to analyze either intensity (I) or phase (ϕ) data collected on the subject's forehead at multiple source-detector distances: Single-distance, single-slope and DS. Theoretical calculations based on diffusion theory show that the method with the deepest maximal sensitivity (at about 11 mm) is DSϕ. The in vivo results indicate a qualitative difference of phase data (especially DSϕ) and intensity data (especially single-distance intensity [SDI]), which we assign to stronger contributions from scalp hemodynamics to SDI and from cortical hemodynamics to DSϕ. Our findings suggest that scalp hemodynamic oscillations may be dominated by blood volume dynamics, whereas cortical hemodynamics may be dominated by blood flow velocity dynamics.

Lifelong high‐altitude hypoxia induces arterial baroreflex adaptations: new insights and future directions

Lifelong high‐altitude hypoxia induces arterial baroreflex adaptations: new insights and future directions

Cerebral Autoregulation Fails to Maintain Cerebral Blood Flow During Arterial Blood Pressure Oscillations at Respiratory Frequency

IntroductionCerebral autoregulation (CA) maintains cerebral blood flow (CBF) despite changes in arterial blood pressure (ABP). However, CA has been shown to be frequency‐dependent: Slow‐frequency ABP oscillations are buffered, while rapid changes in ABP may be transmitted to the cerebral circulation. This may be clinically relevant, as mechanical ventilation during hypovolemia can induce oscillations in ABP. Our objective was to investigate whether CBF is maintained when ABP oscillates at respiratory frequency.MethodsIn eight healthy subjects (3 males), median age 21 yrs (range 19–29), rapid cyclical variations in ABP were generated by oscillatory lower body negative pressure (LBNPosc). The LBNP was changed from 0 to −30 mmHg within 0.5 s, oscillating at the individual subject's respiratory frequency, which was maintained by metronome breathing. Start of inspiration coincided with onset of LBNP, while chamber pressure was normalized during expiration. Beat‐by‐beat blood velocity in the right internal carotid artery (ICA) was measured by Doppler ultrasound (5 MHz, Vingmed SD‐100, GE). ICA beat volume (ICA BV) was calculated using right internal carotid artery diameter measured at normovolemia by B‐mode ultrasound. Non‐invasive finger ABP was recorded continuously from the right middle finger (Finometer), providing beat‐to‐beat mean arterial pressure (MAP) and estimated beat‐to‐beat cardiac stroke volume (SV). Heart rate (HR, ECG), respiratory frequency (respiration belt), and end□tidal CO2 (ETCO2, capnography) were also recorded. The study was approved by the regional ethics committee and conformed to the Declaration of Helsinki. MAP variability (MAPV) and ICA beat volume variability (ICA BVV) were calculated by spectral analysis. Results are medians and 95% confidence intervals calculated by Hodges‐Lehmann's estimates. Wilcoxon signed rank sum test for paired samples was used to test differences between conditions. P&lt;0.05 was considered significant.Preliminary resultsMAPV increased significantly from 1.18 mmHg2 (0.55; 1.59) at baseline to 4.81 mmHg2 (2.8; 7.4) during LBNPosc (p=0.01). Median MAP barely decreased [baseline: 70 mmHg (62; 83), LBNPosc: 68 mmHg (58; 82), p=0.02], while SV, HR, and ETCO2 remained unchanged. Median ICA BV decreased by 10% (−19.7; −2.1) from baseline [6.7 ml (5.3; 8.2)] to LBNPosc [6 ml (4.8; 6.9), p=0.04]. ICA BVV was not significantly changed [from 0.07 ml2 (0.04; 0.18) to 0.14 ml2 (0.05; 0.29)], however coherence between MAPV and ICA BVV was high [0.6 (0.43; 0.76)] at LBNPosc, and significantly increased from baseline [0.32 (0.2; 0.56), p=0.01].ConclusionsOscillatory LBNP at respiratory frequency increased MAPV markedly, while the change in MAP was very small. ICA BV decreased by 10% during oscillations in MAP. Coherence between MAPV and ICA BVV was high during LBNPosc. Thus, the buffering capacity of the CA may be outpaced during rapid variations in ABP, resulting in CBF not being maintained. This might have clinical implications for cerebral perfusion in hypovolemic patients undergoing mechanical ventilation.Support or Funding InformationRCN and UiOThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Slow sinusoidal tilt movements demonstrate the contribution to orthostatic tolerance of cerebrospinal fluid movement to and from the spinal dural space.

Standing up elicits a host of cardiovascular changes which all affect the cerebral circulation. Lowered mean arterial blood pressure (ABP) at brain level, change in the cerebral venous outflow path, lowered end‐tidal PCO 2 (PETCO 2), and intracranial pressure (ICP) modify cerebral blood flow (CBF). The question we undertook to answer is whether gravity‐induced blood pressure (BP) changes are compensated in CBF with the same dynamics as are spontaneous or induced ABP changes in a stable position. Twenty‐two healthy subjects (18/4 m/f, 40 ± 8 years) were subjected to 30° and 70° head‐up tilt (HUT) and sinusoidal tilts (SinTilt, 0°↨60° around 30° at 2.5–10 tilts/min). Additionally, at those three tilt levels, they performed paced breathing at 6–15 breaths/min to induce larger than spontaneous cardiovascular oscillations. We measured continuous finger BP and cerebral blood flow velocity (CBFv) in the middle cerebral artery by transcranial Doppler to compute transfer functions (TFs) from ABP‐ to CBFv oscillations. SinTilt induces the largest ABP oscillations at brain level with CBFv gains strikingly lower than for paced breathing or spontaneous variations. This would imply better autoregulation for dynamic gravitational changes. We demonstrate in a mathematical model that this difference is explained by ICP changes due to movement of cerebrospinal fluid (CSF) into and out of the spinal dural sack. Dynamic cerebrovascular autoregulation seems insensitive to how BP oscillations originate if the effect of ICP is factored in. CSF‐movement in‐and‐out of the spinal dural space contributes importantly to orthostatic tolerance by its effect on cerebral perfusion pressure.

The role of l-type calcium channels in the mediation of fast oscillation of arterial blood pressure and renal blood flow in rats

The investigation of dynamic characteristics of blood pressure and renal blood flow provides detailed information about the fast regulatory mechanisms involved in arterial blood pressure (ABP) and renal blood flow (RBF) autoregulation. The aim of our study was to investigate the role of L-type Ca2+ channels in the mediation of fast oscillations of arterial blood pressure and renal blood flow in rats by means of spectral analysis. The experiments were performed on anesthetized male Wistar rats (n=7) at the age of 12-14 weeks. The ABP was measured directly in femoral artery; RBF was registered by perivascular ultrasonic Doppler probe (Transonic system) in control and experimental period. The spectrograms from APB and RBF were derived in Lab View 3.11 software. In experimental period the selective L-type Ca2+ channel blocker amlodipine besylate (AML) in dose 200 mkg.kg-1 bolus followed by 50 mkg.kg-1.h infusions was applied. Our results by using a spectral method of analysis of ABP and RBF confirmed involvement of L-type Ca2+ channels in the mediation of dynamic nature of myogenic vascular response. The L-type Ca2+ channels in different specific manner participate in the regulation of renal blood flow and arterial blood pressure.

Differentiating compensatory mechanisms associated with low tolerance to central hypovolemia in women.

Women generally display lower tolerance to acute central hypovolemia than men. The measurement of compensatory reserve (CRM) is a novel metric that provides information about the sum total of all mechanisms that together work to compensate for the relative blood volume deficit. Hemodynamic decompensation occurs with depletion of the CRM (i.e., 0% CRM). In the present study, we hypothesized that the lower tolerance to progressive central hypovolemia reported in women can be explained by a faster reduction rate in CRM compared with men rather than sex differences in absolute integrated compensatory responses. Continuous, noninvasive measures of CRM were collected from 208 healthy volunteers (107 men and 85 women) who underwent progressive stepwise central hypovolemia induced by lower body negative pressure to the point of presyncope. Comparisons revealed shorter ( P < 0.01) times in female participants compared with male participants to reach 30% and 0% CRM. Similarly, the lower body negative pressure level, represented by the cumulative stress index, was less at 30% and 0% CRM in women compared with men ( P < 0.01). Changes in hemodynamic responses and frequency-domain data (oscillations in cerebral blood flow velocity and mean arterial blood pressure) were similar between men and women at 0% CRM ( P > 0.05). We conclude that compensatory responses to central hypovolemia in women were similar to men but were depleted at a faster rate compared with men. The earlier depletion of the compensatory reserve in women appears to be influenced by failure to maintain adequate cerebral oxygen delivery. NEW & NOTEWORTHY We compared hemodynamic and metabolic responses in men and women to experimentally controlled reductions in central blood volume at physiologically equivalent levels of compensatory reserve. We corroborated previous findings that females have lower tolerance to central hypovolemia than males but demonstrated for the first time that compensatory responses are similar. Our findings suggest lower tolerance to central hypovolemia in women results from reaching critical cerebral delivery of oxygen faster than men.