Middle Cerebral Artery Mean Velocity Research Articles

Effects of a high-sugar mixed-meal on cerebral hemodynamics in young versus middle-aged adults

High-sugar mixed-meal consumption increases both glucose and insulin and elicits mixed vascular effects, with impairments in peripheral microvascular but improved conduit artery function. It is underexplored 1) if a high-sugar mixed-meal elicits vascular segment-specific effects within cerebrovasculature and 2) whether these responses are altered in middle-aged adults with cardiovascular disease (CVD) risk factors. This study sought to test the hypotheses that a high-sugar mixed-meal would elicit differential effects within the middle cerebral artery (MCA) versus downstream hemodynamics, and that changes in cerebral hemodynamics would be blunted among at-risk middle-aged adults compared to young adults. 21 young, healthy adults (24±6 years; 23.7±3.0 kg/m2) and 20 middle-aged adults (55±5 years; 28.2±5.2 kg/m2) with CVD risk factors (hypertension, obesity, or dyslipidemia) consumed a high-sugar mixed-meal consisting of 930 kcals (35.5 g fat, 129 g carbohydrates, 100.5 g sugar, 14 g protein). Vascular measures were taken prior to meal consumption and 30- and 60-min post-meal. MCA pulsatility index (PI), resistance index (RI), mean velocity, and conductance were assessed via transcranial Doppler. Mean arterial pressure (MAP) and common carotid artery diameter were assessed via automated oscillometric cuff and ultrasound, respectively. MCA PI and RI were taken as proxy measures of downstream vascular tone, while MCA mean velocity and conductance, and carotid artery diameter were taken as measures of larger artery cerebrovascular hemodynamics. MCA PI and RI were unchanged in middle-aged adults but increased at 30- (PI+Δ0.13±0.13 au; RI+Δ0.05±0.05 au) and 60-min (PI+Δ0.10 ±0.11 au; RI+Δ0.04±0.05 au) compared to baseline in young adults (p<0.05). MCA conductance increased at 30-min (+Δ0.04±0.08 cm/s per mmHg, p<0.05), carotid diameter increased at 60-min (+Δ0.13±0.20 mm, p<0.05), and MAP tended (p=0.07-0.09) to decrease at 30- (-Δ2.01±5.7 mmHg) and 60-min (-Δ2.26±6.54 mmHg) compared to baseline in both groups. MCA mean velocity was not significantly different across timepoints in both groups. These data suggest a high-sugar mixed-meal may transiently dilate larger cerebral arteries in both young and middle-aged adults but elicit vasoconstriction downstream of the MCA in young adults only. As such, our data suggest that 1) cerebrovascular response to a high-sugar mixed-meal may be vascular segment-specific, and 2) age and risk-factor burden may alter the sensitivity of vasculature downstream of the MCA to a high-sugar mixed-meal. Further research is needed to dissect mechanisms underlying the complex cerebrovascular response to a high-sugar mixed-meal in young versus middle-aged adults with CVD risk factors. 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.

Associations Between Grip Strength and Cerebral Hemodynamics in Young and Middle-Aged Adults

Aerobic fitness and aerobic exercise are widely accepted as having protective effects on cognitive function and brain health, with less understood regarding muscular fitness and resistance exercise. Strength is beneficially associated with cognitive function, but the mechanisms underlying this relationship remain understudied and may relate to cerebral hemodynamics. The purpose of this study was to examine the associations between strength and cerebrovascular hemodynamics in young and middle-aged men and women. It was hypothesized that greater strength would be associated with better cerebral hemodynamics (greater mean blood velocity, lower pulsatility, greater pulsatile damping). Ninety-two generally healthy adults between 18-64 years old (36±16 yrs; BMI 25.9±4.0 kg/m2; n=39 women) underwent a hand grip strength assessment and resting cerebrovascular measures. Grip strength was measured via dynamometer and recorded as the highest value of 3 attempts. Middle cerebral artery (MCA) mean velocity and pulsatility index (PI) were measured via transcranial Doppler. Pulsatile damping was calculated as the ratio between the common carotid artery and MCA PI. Mean arterial pressure was assessed via an oscillometric blood pressure cuff. No significant associations were observed between relative grip strength and MCA mean velocity (r=-0.15), MCA PI (r=0.05), or MAP (r=0.07) after adjusting for age. Greater relative grip strength, however, was associated with greater pulsatile damping after adjusting for age (r=0.21; p<0.05). This relationship appeared to be driven by weak associations within each sex (men, r=0.10; women, r=0.02) that were not statistically significant on their own. Our preliminary results suggest there are no strong relations between grip strength and cerebral hemodynamics among generally healthy young and middle-aged adults after accounting for the effects of age and sex. Future studies should examine sex-specific associations with a larger sample, consider disease states related to cerebrovascular health, and include more comprehensive assessments of muscular strength and performance (e.g., power). 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.

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.

Effects of Perceived Social Stress on Cerebrovascular Hemodynamics in Young and Middle-Aged Adults

Depression is associated with altered cerebrovascular hemodynamics, including lower cerebral blood flow, higher cerebral pulsatility, and greater arterial stiffness. There is evidence that perceived stress may contribute to depressive symptomology, but it is unknown if stress may directly impact cerebrovascular hemodynamics. The purpose of this investigation was to examine associations among middle cerebral artery (MCA) hemodynamics, arterial stiffness, and perceived stress in young and middle-aged adults. It was hypothesized that individuals with higher reported social stress would have lower MCA mean velocity and higher MCA pulsatility and arterial stiffness. Methods: 168 adults (range 18-64 years; 40 ± 16 years; BMI 26.6 ± 4.6 kg/m2; n=88 females) underwent resting cerebrovascular measures and completed the self-reported perceived stress scale (PSS-10). Brachial blood pressure and carotid pulse pressure were assessed via oscillometric cuff and tonometry, respectively. Arterial stiffness was assessed as carotid-femoral pulse wave velocity (cfPWV) via tonometry and MCA mean velocity and pulsatility index were assessed via Transcranial Doppler. Results: The sample contained 4 adults with high (PSS score ≥27; mean, 28 ± 1), 38 adults with moderate (PSS score 14-26; mean, 17 ± 2), and 126 adults with low stress (PSS score <13; mean, 8 ± 3). Self-reported perceived stress was not significantly linearly associated with MCA mean velocity (r=-0.10), MCA Pulsatility Index (r=-0.08), or arterial stiffness (r=0.05). A secondary analysis comparing adults with moderate/high stress (n=42) to adults with low stress (n=126) revealed a significantly lower MCA mean velocity among moderate/high stress adults (p<0.05), however this difference was attenuated and no longer statistically significant after covarying for age. Conclusions: This data suggests that perceived stress 1) is not associated with altered cerebrovascular hemodynamics or arterial stiffness in our sample of generally healthy young and middle-aged adults, and 2) may not play a major role in altering cerebrovascular hemodynamics in the context of stress-related disorders (e.g., depression), however future research is required to directly test this hypothesis. Iowa State University College of Human Sciences Faculty Seed Grant. 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.

Feasibility and preliminary efficacy of a theory-informed resistance exercise training single-arm intervention for major depression

Many adults with major depressive disorder (MDD) do not receive effective treatment. The potential benefits of resistance exercise training (RET) are understudied and may be mechanistically related to cerebral blood flow changes. PurposeTo assess feasibility, acceptability, and preliminary efficacy of a 16-week, theory-informed RET trial for the treatment of MDD and explore changes in cerebral blood flow. MethodsTen adults with DSM-5-diagnosed MDD were enrolled in a single-arm, 16-week, twice-weekly, whole-body RET intervention, consistent with US and WHO Physical Activity resistance exercise guidelines. To build intrinsic motivation and develop exercise-preparatory habits, motivators and commitment were discussed weekly. Screening, enrollment, and intervention attendance and compliance rates documented feasibility. At baseline and weeks 8, 16, and 26, current MDD diagnosis, clinician-rated, and self-reported symptom severity were evaluated along with cerebral blood flow which was assessed as middle cerebral artery (MCA) mean blood velocity, conductance, and pulsatility. ResultsNine participants completed the intervention. Strong feasibility and acceptability (98 % adherence, 93 % compliance, and 90 % retention) were found. MDD remission was reached by 8/9 participants at week 16 and persisted through week 26. There were large decreases in clinician-rated and self-reported symptoms at each assessment (Hedges’ g = 0.84–2.13). There were small-to-moderate increases in MCA velocity (g = 0.32–0.57) and conductance (g = 0.20–0.76) across time, with minimal changes in pulsatility (all g < 0.21). ConclusionsPreliminary results suggest RET for MDD treatment is feasible and plausibly efficacious, finding large antidepressant effects. A sufficiently powered randomized controlled trial to assess RET’s efficacy for treating MDD via potential cerebrovascular mechanisms is warranted.

Hyperemia in head injury: can transcranial doppler help to personalize therapies for intracranial hypertension?

An increase in cerebral blood flow is frequent after traumatic brain injury (TBI) and can lead to brain swelling and refractory intracranial hypertension. We hypothesized that Transcranial EcoDoppler (TCD) monitoring could be useful to detect the cause of intracranial hypertension in these patients. Our main objective was to investigate if the increase of velocity in the middle cerebral artery (MCA) on TCD could be associated with intracranial hypertension. We retrospectively studied TBI patients consecutively monitored with TCD. Hyperemia was defined as MCA mean velocity higher than 80 cm/s. Intracranial hypertension was considered when hyperosmolar therapy, hyperventilation, or deep sedation was used. We found hyperemia in 40 patients out of 118 (33.9%). On average, it started at day 2.1 ± 0.9 from admission and significantly increased (MCA velocity at day 1: 74 ± 25 cm/s vs. 109 ± 36 cm/s at day 4; p < 0.001). Intracranial hypertension was significantly associated with hyperemia, occurring in 92.5% of hyperemic and 51.3% of non-hyperemic patients (p < 0.001). Moreover, we found that hyperemia preceded severe intracranial hypertension (p < 0.0001). In a logistic regression model, hyperemia was the only variable significantly correlated with intracranial hypertension (OR 10.64; p < 0.001). Hyperemia was frequent in our population of TBI patients and preceded intracranial hypertension. TCD monitoring, if performed on a daily regular basis, can be a useful method to detect this phenomenon and to guide the therapy. It could be a tool for a cause-oriented therapy of intracranial hypertension.

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.

Carotid arterial stiffness and cerebral blood flow variability in individuals with mild cognitive impairment

Background: It is unclear whether cerebral blood flow variability is a sign of impaired vascular function or an adaptation to chronic cerebral hypoperfusion in individuals with cognitive dysfunction. Elevated arterial stiffness increases transmission of pulsatile pressure to the brain, but the relationship between arterial stiffness, the magnitude of cerebral blood flow variability, and cognitive dysfunction is unknown. In this pilot study, we hypothesized that carotid artery stiffness would be higher in individuals with mild cognitive impairment (MCI) compared with individuals with normal cognition (NC), resulting in higher cerebral blood flow variability. Methods: In individuals with MCI (N=5) or NC (N=7), R-wave to common carotid artery (CCA) pulse wave velocity (PWV) was assessed as an index of arterial stiffness (via tonometry). CCA velocity (CCAv) and middle cerebral artery velocity (MCAv) were measured via transcranial Doppler ultrasound, with concurrent measurements of mean arterial pressure (MAP) via finger photoplethysmography. The amplitude of MAP, CCAv, and MCAv oscillations in the low frequency range (LF; 0.07-0.15 Hz) were assessed via fast Fourier transformation, and normalized to total power (0.04-0.4 Hz) for each participant to account for high inter-individual variability. Relationships between R-wave-carotid PWV and LF variability in CCAv and MCAv were assessed via correlational analyses. Results: There were no between-group differences for R-wave-carotid PWV (MCI: 0.91±0.16 m/s vs. NC: 0.87±0.07 m/s; P=0.70), mean CCAv (MCI: 31.8±8.8 cm/s vs. NC: 29.7±2.0 cm/s; P=0.54), mean MCAv (MCI: 50.9±6.5 cm/s vs. NC: 47.9±12.7 cm/s; P=0.63), or MAP (MCI: 102.1±10.2 mmHg vs. 104.7±13.8 mmHg; P=0.73). While there was also no difference between groups for nLF power of CCAv (MCI: 0.28±0.03 au vs. NC: 0.33±0.10 au; P=0.41), nLF power for MCAv was lower in the MCI group (MCI: 0.26±0.07 au vs. 0.43±0.12; P=0.02). Overall, there was a strong positive correlation between R-wave-carotid PWV and CCAv nLF power (R=0.81, P=0.005), but a weaker relationship for MCAv nLF power (R=0.56, P=0.09). While sub-group correlational analyses are limited based on the small sample sizes, relationships between R-wave-carotid PWV and CCAv nLF power were high for both MCI (R=0.98, P=0.02) and NC (R=0.79, P=0.06) groups, but were lower for MCAv nLF power (MCI: R=-0.12, P=0.88; NC: R=0.69, P=0.13). Conclusion: Contrary to our hypothesis, there were no differences in R-wave-carotid PWV between groups, and blood flow variability was either similar between groups (for CCAv), or lower in the MCI group (for MCAv). Overall, there was a strong positive relationship between R-wave-carotid PWV and blood flow variability in the CCA, which was also observed in sub-analysis of the MCI and NC groups. Future investigations with a larger sample size are needed to definitively determine the role of arterial stiffness on cerebral blood flow variability with cognitive dysfunction. R56AG068630, NIH National Institute for Aging (NIA), “Hemodynamic Mechanisms Linking Aortic Arch Stiffness with Brain Insult in Older Adults” 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.

Influence of sex and presence of cardiovascular risk factors on relations between cardiorespiratory fitness and cerebrovascular hemodynamics.

Cerebral hemodynamics and pulsatility are important mechanisms of cerebrovascular and brain health. Cardiorespiratory fitness may improve cerebrovascular pulsatility in healthy females, but not in males. Whether cardiovascular disease (CVD) risk factors modify sex-specific associations of fitness with cerebral hemodynamics and vascular contributors to cerebral hemodynamics is unknown. We assessed V̇o2peak and cerebrovascular hemodynamics in 157 adults without (42 ± 13 yr, BMI 24.5 ± 2.7 kg/m2), and 66 adults with modifiable CVD risk factors (54 ± 8 yr, BMI 29.9 ± 4.0 kg/m2). Intracranial [middle cerebral artery (MCA) pulsatility index (PI), mean velocity, conductance, and pulsatile damping] and extracranial hemodynamics [carotid artery wave transmission/reflection, PI, pulse wave velocity (PWV)-β, and carotid-femoral PWV] were assessed via transcranial Doppler/ultrasound and tonometry. Cardiorespiratory fitness was assessed via V̇o2peak during an incremental exercise test. Multiple regression was used to assess contributions of V̇o2peak to cerebrovascular outcomes after adjustment for relevant covariates. V̇o2peak was inversely associated with MCA PI among females (β = -0.39, P = 0.01) but not males (β = -0.16, P = 0.25) without CVD risk factors. V̇o2peak was positively associated with MCA PI among females (β = 0.44, P = 0.01) and not associated in males with CVD risk factors (β = -0.06, P = 0.079). V̇o2peak was beneficially associated with vascular contributors to cerebral hemodynamics but had sex-specific associations with carotid stiffness and pulse pressure in females without CVD risk factors only. These results suggest that sex-specific associations between fitness and cerebral pulsatility among females without CVD risk factors may relate to the differential effects of fitness on carotid stiffness and pulse pressure. In addition, the presence of modifiable CVD risk factors may influence the protective relations of fitness on cerebrovascular hemodynamics.NEW & NOTEWORTHY We identify beneficial associations between cardiorespiratory fitness and lower carotid stiffness and pulse pressure as potential mechanisms underlying sex-specific associations of fitness and cerebral pulsatility in females without modifiable risk factors. Greater fitness is beneficially associated with conductance, pulsatile damping, and forward wave energy among adults without risk factors; however, associations are attenuated among adults with modifiable risk factors. These data suggest sex and risk factors may alter cerebrovascular sensitivity to cardiorespiratory fitness.

Exploration of cerebral hemodynamic pathways through which large artery function affects neurovascular coupling in young women.

BackgroundThe interactions between large artery function and neurovascular coupling (NVC) are emerging as important contributors to cognitive health. Women are disproportionally affected by Alzheimer's disease and related dementia later in life. Understanding large artery correlates of NVC in young women may help with preservation of cognitive health with advancing age.PurposeTo explore the association between large artery function, NVC and cognitive performance in young women.MethodsVascular measurements were made in 61 women (21 ± 4 yrs) at rest and during a cognitive challenge (Stroop task). Transcranial Doppler was used to measure left middle cerebral artery (MCA) maximum velocity (Vmax), mean velocity (Vmean), and pulsatility index (PI). NVC was determined as MCA blood velocity reactivity to the Stroop task. Large artery function was determined using carotid-femoral pulse wave velocity (cfPWV) as a proxy measure of aortic stiffness and carotid ultrasound-derived measures of compliance and reactivity (diameter change to the Stroop task). Cognitive function was assessed separately using a computerized neurocognitive battery that included appraisal of response speed, executive function, information processing efficiency, memory, attention/concentration, and impulsivity.ResultsMCA Vmax reactivity was positively associated with executive function (β = 0.26, 95% CI 0.01–0.10); MCA Vmean reactivity was negatively associated with response speed (β = −0.33, 95% CI −0.19 to −0.02) and positively with memory score (β = 0.28, 95% CI 0.01–0.19). MCA PI reactivity was negatively associated with attention performance (β = −0.29, 95% CI −14.9 to −1.0). Path analyses identified significant paths (p < 0.05) between carotid compliance and carotid diameter reactivity to select domains of cognitive function through MCA reactivity.ConclusionsNVC was associated with cognitive function in young women. Carotid artery function assessed as carotid compliance and carotid reactivity may contribute to optimal NVC in young women through increased blood flow delivery and reduced blood flow pulsatility.

Brain Oxygen–Directed Management of Aneurysmal Subarachnoid Hemorrhage. Temporal Patterns of Cerebral Ischemia During Acute Brain Attack, Early Brain Injury, and Territorial Sonographic Vasospasm

Neurocritical management of aneurysmal subarachnoid hemorrhage focuses on delayed cerebral ischemia (DCI) after aneurysm repair. This study conceptualizes the pathophysiology of cerebral ischemia and its management using a brain oxygen-directed protocol (intracranial pressure [ICP] control, eubaric hyperoxia, hemodynamic therapy, arterial vasodilation, and neuroprotection) in patients with subarachnoid hemorrhage, undergoing aneurysm clipping (n = 40). The brain oxygen-directed protocol reduced Lbo2 (Pbto2 [partial pressure of brain tissue oxygen] <20 mm Hg) from 67% to 15% during acute brain attack (<24 hours of ictus), by increasing Pbto2 from 11.31 ± 9.34 to 27.85 ± 6.76 (P < 0.0001) and then to 29.09 ± 17.88 within 72 hours. Day-after-bleed, Fio2 change, ICP, hemoglobin, and oxygen saturation were predictors for Pbto2 during early brain injury. Transcranial Doppler ultrasonography velocities (>20 cm/second) increased at day 2. During DCI caused by territorial sonographic vasospasm (TSV), middle cerebral artery mean velocity (Vm) increased from 45.00 ± 15.12 to 80.37 ± 38.33/second by day 4 with concomitant Pbto2 reduction from 29.09 ± 17.88 to 22.66 ± 8.19. Peak TSV (days 7-12) coincided with decline in Pbto2. Nicardipine mitigated Lbo2 during peak TSV, in contrast to nimodipine, with survival benefit (P < 0.01). Intravenous and cisternal nicardipine combination had survival benefit (Cramer Φ = 0.43 and 0.327; G2 = 28.32; P < 0.001). This study identifies 4 zones of Lbo2 during survival benefit (Cramer Φ = 0.43 and 0.3) TSV, uncompensated; global cerebral ischemia, compensated, and normal Pbto2. Admission Glasgow Coma Scale score (not increased ICP) was predictive of low Pbto2 (β = 0.812, R2 = 0.661, F1,30 = 58.41; P < 0.0001) during early brain injury. Coma was the only credible predictor for mortality (odds ratio, 7.33/>4.8∗; χ2 = 7.556; confidence interval, 1.70-31.54; P < 0.01) followed by basilar aneurysm, poor grade, high ICP and Lbo2 during TSV. Global cerebral ischemia occurs immediately after the ictus, persisting in 30% of patients despite the high therapeutic intensity level, superimposed by DCI during TSV. We propose implications for clinical practice and patient management to minimize cerebral ischemia.

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.

Utility of quantitative magnetic resonance angiography and non-invasive optimal vessel analysis for identification of complications and long-term hemodynamic changes in post-pipeline embolization patients.

Quantitative magnetic resonance angiography and non-invasive optimal vessel analysis serve as powerful tools to collect and analyze hemodynamic data from pipeline embolization patients. At our institution, patients receive post-embolization quantitative magnetic resonance angiography within 24 h of treatment and within 6 months for follow-up to evaluate pipeline patency. Here, we aim to elucidate the long-term hemodynamic changes following pipeline embolization device placement and report two cases in which in-stent stenosis was detected. Medical records of patients who underwent pipeline embolization device placement for an internal carotid artery aneurysm between 2017 and 2019 were reviewed. Patients who received post-procedure NOVA and follow-up NOVA were included in the study (n = 32). Location and size of aneurysm, number of pipeline embolization device deployed, and complications were collected along with the non-invasive optimal vessel analysis report (flow volume rate (ml/min), mean, systolic, and diastolic flow velocities (cm/s), and vessel diameter (mm)). Internal carotid artery vessel flow rate was measured proximal to the pipeline embolization device. Derivations of hemodynamic parameters (pulsatility index, Lindegaard ratio, and wall shear stress) were calculated. The middle cerebral artery mean and diastolic flow velocities were significantly lower on the follow-up NOVA compared to the post-procedure NOVA. Moreover, follow-up NOVA demonstrated lower middle cerebral artery wall shear stress on the side with flow diversion compared to the post-procedure NOVA. In-stent stenosis, requiring intervention, was detected in two patients on follow-up NOVA. One patient had a successful balloon angioplasty of the stented internal carotid artery that resolved her stenosis. However, the second patient developed progressive stenosis and expired despite intervention. Long-term hemodynamic adaptations post-pipeline embolization device demonstrate decreased wall shear stress and decreased mean and diastolic flow velocities in the distal middle cerebral artery, which suggest decreasing velocity of blood flow with endothelialization of the device. Furthermore, follow-up NOVA is a useful tool for detecting potential flow-related complications such as in-stent stenosis.

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.

Dose Escalation and Safety of Capsaicin for Cerebral Perfusion Augmentation: A Pilot Study.

Sphenopalatine ganglion (SPG) electrical stimulation has been studied in the setting of acute ischemic stroke to enhance collateral flow. Capsaicin poses an alternative to chemically stimulate the sphenopalatine ganglion. Therefore, the objective of this study was to determine the safety and effect of increasing doses of capsaicin upon serial transcranial Doppler markers of cerebral blood flow. We performed serial transcranial Doppler testing in 30 healthy volunteers divided into 5 equal groups. Capsaicin doses ranged from 33 to 165 μMol. We recorded peak systolic and end-diastolic velocities in the middle cerebral artery, arterial pressure, and perceived pungency in 5-minute intervals up to 20 minutes. We then calculated the mean velocity, the pulsatility index, and the cerebral blood flow index. The participants’ median age was 21 years (range, 5 years); all reported consumption of capsaicin in their diets. After and during the study, none reported side effects. Perceived pungency peaked at 5 minutes, and by the 20-minute mark, none perceived any pungency. All the tested doses produced the same pattern, consisting of augmentation of the middle cerebral artery mean velocity with the pulsatility index’s diminution. The effects peaked between the 5- and the 10-minute measurements and then returned to basal levels except for the 66-μMol doses, which produced a sustained effect. We found no correlation between perceived pungency and dose, but the middle cerebral artery mean velocity was strongly correlated with the dose administered. This study provides evidence supporting the safety and tolerability of oral capsaicin in a population of healthy volunteers. Capsaicin appears to produce effects similar to those of sphenopalatine ganglion electrical stimulation. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04545892.

Transcranial Dopplers Revisited: Development of Novel Markers for Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage.

BackgroundCerebral vasospasm has been monitored by conventional angiography or transcranial Doppler (TCD). While angiography is the most accurate and reliable method for detection, TCDs are a noninvasive alternative to monitor onset and resolution of vasospasm. We aim to determine whether alternative TCD parameters rather than Lindegaard ratio lead to an improved method to diagnose and potentially prevent cerebral vasospasm.MethodsA total of 103 consecutive patients with subarachnoid hemorrhage (SAH) were retrospectively reviewed and TCD studies were performed during the first 14 days post-bleed or longer if indicated. Multivariate logistic regression models were developed using significant univariate characteristics. Receiver operating characteristic (ROC) curves evaluated the mean middle cerebral artery (MCA), peak systolic MCA (PSV MCA), and end diastolic MCA (EDV MCA) velocities as well as ratios when compared to the ipsilateral extracranial internal carotid artery (ICA). The area under the curve was calculated to compare accuracy for symptomatic vasospasm.ResultsThirteen patients (12.6%) were observed to develop cerebral vasospasm. Aneurysm location (p = 0.51), Hunt and Hess grade (p = 0.44), Fischer grade (p = 0.87), comorbidities, age (p = 0.67), or gender (p = 0.41) did not appear to have any effect in predicting the presence of vasospasm. ROC curves demonstrated that MCA EDV appeared to be slightly better compared to MCA velocity in predicting symptomatic vasospasm. PSV MCA/extracranial ICA and the EDV MCA/extracranial ICA ratios appeared to be an improvement to the Lindegaard ratio in the prediction of symptomatic vasospasm.ConclusionThe utility of peak systolic and end diastolic velocities, instead of the classically referenced mean velocities and Lindegaard ratio, may improve diagnostic sensitivity of cerebral vasospasm after subarachnoid hemorrhage.

Which repetitive transcranial magnetic stimulation modality affects vasomotor reactivity in healthy subjects and how long does it last?

Objectives The aim of our study was to evaluate the effects of low and high-frequency repetitive transcranial magnetic stimulation (rTMS) on hypoxia-induced changes in bilateral cerebrovascular reserve up to 24 h in the same individuals. Methods Right-handed ten healthy male individuals participated in the study. All participants had neither drug therapy nor a concomitant disease and none of them had a variation in the circle of Willis, intracranial stenosis, arteriovenous malformation, or aneurysm which may have an impact on transcranial doppler ultrasound (TCD) examination and transcranial magnetic stimulation (TMS) recording. Results There was a statistically significant difference in the breath‐holding index (BHI) between before and after 0, 15, 30 min after 1 Hz repetitive stimulation (p < 0.05). When applying 5 Hz repetitive stimulation there was no difference before and after BHI values (p > 0.05). There were no differences in bilateral, ipsilateral, or contralateral middle cerebral artery (MCA) mean cerebral blood flow velocity (CBFV) after low or high-frequency rTMS application (p > 0.05). Conclusion The main result of the study was that low-frequency rTMS reduced vasomotor reactivity (VMR) for the very first 30 min and then this effect disappears. And the high-frequency rTMS did not affect VMR at all. Significance The effect of rTMS on VMR may continue up to 30 min but then return to the baseline and can be used safely.

The influence of age and sex on cerebrovascular reactivity and ventilatory response to hypercapnia in children and adults.

What is the central question of this study? In this study, we investigated intracranial cerebrovascular and ventilatory reactivity to 6% CO2 in children and adults and explored dynamic ventilatory and cerebrovascular onset responses. What is the main finding and its importance? We showed that cerebrovascular reactivity was similar in children and adults, but the intracranial blood velocity onset response was markedly attenuated in children. Sex differences were apparent, with greater increases in intracranial blood velocity in females and lower ventilatory reactivity in adult females. Our study confirms the importance of investigating dynamic onset responses when assessing the influence of development on cerebrovascular regulation. The purpose of this study was to compare the integrated intracranial cerebrovascular reactivity (CVR) and hypercapnic ventilatory response between children and adults and to explore the dynamic response of the middle cerebral artery mean velocity (MCAV ). Children (n=20; 9.9±0.7years of age) and adults (n=21; 24.4±2.0years of age) completed assessment of CVR over 240s using a fixed fraction of inspired CO2 (0.06). Baseline MCAV was higher in the adult females compared with the males (P≤0.05). The MCAV was greater in female children compared with male children (P≤0.05) and in female adults compared with male adults (P≤0.05) with hypercapnia. Relative CVR was similar in children and adults (3.71±1.06 versus 4.12±1.32%mmHg-1 ; P=0.098), with absolute CVR being higher in adult females than males (3.27±0.86 versus 2.53±0.70cms-1 mmHg-1 ; P≤0.001). Likewise, the hypercapnic ventilatory response did not differ between the children and adults (1.89±1.00 versus 1.77±1.34lmin-1 mmHg-1 ; P=0.597), but was lower in adult females than males (1.815±0.37 versus 2.33±1.66lmin-1 mmHg-1 ; P≤0.05). The heart rate response to hypercapnia was greater in children than in adults (P=0.001). A monoexponential regression model was used to characterize the dynamic onset, consisting of a delay term, amplitude and time constant (τ). The results revealed that MCAV τ was faster in adults than in children (34±18versus 74±28s; P=0.001). Our study provides new insight into the impact of age and sex on CVR and the dynamic response of the MCAV to hypercapnia.

Carotid Plaque Strain Indices Were Correlated With Cognitive Performance in a Cohort With Advanced Atherosclerosis, and Traditional Doppler Measures Showed no Association.

Traditional Doppler measures have been used to predict cognitive performance in patients with carotid atherosclerosis. Novel measures, such as carotid plaque strain indices (CPSIs), have shown associations with cognitive performance. We hypothesized that lower mean middle cerebral artery (MCA) velocities, higher bulb-internal carotid artery (ICA) velocities, the MCA pulsatility index (PI), and CPSIs would be associated with poorer cognitive performance in individuals with advanced atherosclerosis. Neurocognitive testing, carotid ultrasound imaging, transcranial Doppler imaging, and carotid strain imaging were performed on 40 patients scheduled for carotid endarterectomy. Kendall tau correlations were used to examine relationships between cognitive tests and the surgical-side maximum peak systolic velocity (PSV; from the bulb, proximal, mid, or distal ICA), mean MCA velocity and PI, and maximum CPSIs (axial, lateral, and shear strain indices used to characterize plaque deformations with arterial pulsation). Cognitive measures included age-adjusted indices of verbal fluency, verbal and visual learning/memory, psychomotor speed, auditory attention/working memory, visuospatial construction, and mental flexibility. Participants had a median age of 71.0 (interquartile range, 9.75) years; 26 were male (65%), and 14 were female (35%). Traditional Doppler parameters, PSV, mean MCA velocity, and MCA PI did not predict cognitive performance (all P > .05). Maximum CPSIs were significantly associated with cognitive performance (P < .05). Traditional velocity measurements of the maximum bulb-ICA PSV, mean MCA velocity, and PI were not associated with cognitive performance in patients with advanced atherosclerotic disease; however, maximum CPSIs were associated with cognitive performance. These findings suggest that cognition may be associated with unstable plaque rather than blood flow.

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