Middle Cerebral Artery Velocity Research Articles

Intensive antihypertensive treatment does not lower cerebral blood flow or cause orthostatic hypotension in frail older adults

AbstractThis study aimed to examine the effects of intensive antihypertensive treatment (AHT), i.e., systolic blood pressure target ≤ 140 mmHg, on cerebral blood flow, cerebral autoregulation, and orthostatic hypotension, in a representative population of frail older adults. Fourteen frail hypertensive patients (six females; age 80.3 ± 5.2 years; Clinical Frailty Scale 4–7; unattended SBP ≥ 150 mmHg) underwent measurements before and after a median 7-week AHT targeting SBP ≤ 140 mmHg. Transcranial Doppler measurements of middle cerebral artery velocity (MCAv), reflecting changes in cerebral blood flow (CBF), were combined with finger plethysmography recordings of continuous BP. Transfer function analysis assessed cerebral autoregulation (CA). ANCOVA analysed AHT-induced changes in CBF and CA and evaluated non-inferiority of the relative change in CBF (margin: -10%; covariates: pre-AHT values and AHT-induced relative mean BP change). McNemar-tests analysed whether the prevalence of OH and initial OH, assessed by sit/supine-to-stand challenges, increased with AHT. Unattended mean arterial pressure decreased by 15 mmHg following AHT. Ten (71%) participants had good quality TCD assessments. Non-inferiority was confirmed for the relative change in MCAv (95%CI: -2.7, 30.4). CA remained normal following AHT (P > 0.05), and the prevalence of OH and initial OH did not increase (P ≥ 0.655). We found that AHT in frail, older patients does not reduce CBF, impair autoregulation, or increase (initial) OH prevalence. These observations may open doors for more intensive AHT targets upon individualized evaluation and monitoring of hypertensive frail patients.Clinical Trial Registration: This study is registered at ClinicalTrials.gov (NCT05529147; September 1, 2022) and EudraCT (2022-001283-10; June 28, 2022).

REDUCED AEROBIC FITNESS IS ASSOCIATED WITH IMPAIRED CEREBROVASCULAR FUNCTION IN INDIVIDUALS WITH ATRIAL FIBRILLATION

INTRODUCTION & AIMS Lower aerobic fitness (V̇O2peak) is associated with higher risk of cerebrovascular disease. However, the relationship between V̇O2peak and cerebrovascular function and cerebral blood velocity at rest and during exercise has not been investigated in adults with atrial fibrillation (AF). We aimed to compare resting and exercise cerebral blood velocity responses and cerebrovascular function in individuals with AF to healthy controls. METHODS Eight inactive adults either with AF or healthy age-matched controls (AF: n=4, 64±6 years, 50% female; control: n=4, 66±4 years, 75% female) completed a maximal graded exercise test to measure V̇O2peak. Transcranial Doppler was used to measure bilateral middle cerebral artery velocity (MCAv). Vascular function was assessed by measuring MCAv increases and time to peak following a 30s hypercapnia stimulus (9% CO2, 21% O2, and balanced nitrogen), and MCAv during aerobic exercise (3-minute stages at 40%, 60% and 80% V̇O2peak). Blood pressure, heart rate and end-tidal gases were collected alongside MCAv. RESULTS Compared to controls, individuals with AF (both P<0.01) had higher BMI (AF: 31.8±2.0 kg/m2; control: 27.3±0.6 kg/m2), lower V̇O2peak (AF: 19.9±2.5 mL/kg/min; control: 33.7±5.8 mL/kg/min), and similar blood pressure. Resting right and left MCAv was higher in the AF group (R: 66.6±34.0 cm/s; L: 44.2±10.1 cm/s) compared to the control (R: 36.1±6.7 cm/s; L: 34.9±8.7 cm/s); this was not significant (P=0.121 and 0.258). Right MCAv was higher than left MCAv in individuals with AF but this was not significant (P=0.247). Hypercapnia and exercise induced MCAv and time to peak were similar between groups (P>0.05). CONCLUSION Lower V̇O2peak may be associated with increased resting MCAv in individuals with AF. Furthermore, there may be regional disparities in MCAv in individuals with AF. Future studies with larger sample sizes investigating potential mechanisms and volumetric cerebrovascular changes (e.g., vessel diameter, arterial stiffness) in AF are warranted.

1 Sex Differences in Middle Cerebral Artery Velocity in Patients with Persistent Post-Concussion Convergence Insufficiency (PPCS-CI)

OBJECTIVES/GOALS: The objective of this study is to investigate the neurophysiological mechanism of vision therapy in male and female adolescents with persistent post-concussion convergence insufficiency (PPCS-CI). This study may improve diagnostics and inform more effective personalized point of care treatment strategies to remediate symptoms. METHODS/STUDY POPULATION: Participants (ages 11-25) were diagnosed with PPCS by a physician, CI was diagnosed by an optometrist and OBVAT was performed by certified therapists. Patients with PPCS-CI were randomly assigned to a therapy type (immediate therapy or natural recovery). Hemodynamic measures were examined in patients with PPCS-CI at baseline (1-3 months post-concussion), and post OBVAT to evaluate recovery outcomes. Non-invasive techniques were used to measure middle cerebral artery velocity (MCAv), blood pressure, heart rate, and end-tidal CO2 at rest and during objective symmetrical convergence step eye movements. Functional magnetic resonance imaging (fMRI) was acquired during convergence step eye movement experiments contrasted to sustained fixation and resting state data collection. RESULTS/ANTICIPATED RESULTS: To investigate the neural mechanism of OBVAT, eye movements, fMRI and physiological measures were collected in 8 patients with PPCS-CI (4 men and 4 women). Results show an 10% decrease in the MCA during 4-degree symmetrical convergent eye movement responses in males post-OBVAT and a 19% increase in MCA during convergent eye movement responses in females. Furthermore, there was a group level activation of the frontal eye fields, which improves post-OBVAT. The beta weights in the left frontal eye fields show a trending decrease in male patients post-OBVAT and trending increase in females. Males had a decrease in MCAv post OBVAT (baseline 83.6 ± 7.5 cm/sec & 75.7 ± 12.5 cm/sec post-OBVAT), while females show a significant increase post-OBVAT (baseline 53.77 ± 5.2 cm/sec & post-OBVAT 65.13 cm/sec ± 12.5). DISCUSSION/SIGNIFICANCE: This initial pilot demonstrates there may be different underlying pathophysiological outcomes associated with a concussion dependent on sex. This work may have direct implications on treatment strategies for male and female adolescent patients with PPCS-CI.

The effect of esketamine combined with propofol-induced general anesthesia on cerebral blood flow velocity: a randomized clinical trial

BackgroundEsketamine is increasingly used in clinical anesthesia. The effect of esketamine on the blood flow velocity of the middle cerebral artery has a clinical guiding effect. To investigate the effect of esketamine combined with propofol-induced general anesthesia for endotracheal intubation on the blood flow velocity of middle cerebral artery and hemodynamics during the induction period.MethodsThe randomized clinical trial included 80 patients aged 20-65 years who would undergo non-intracranial elective surgery under general anesthesia in our hospital from May 2022 to May 2023. The participants were divided into two groups based on anesthesia drugs: sufentanil 0.5μg/kg (group C) or 1.5mg/kg esketamine (group E). The primary outcome was variation value in average cerebral blood velocity. The secondary outcomes included cerebral blood flow velocities (CBFV), blood pressure (BP) and heart rate (HR) at four different time points: before induction of general anesthesia (T0), 1 min after the induction drug injected (T1), before endotracheal intubation (T2), and 1min after endotracheal intubation (T3). The occurrence of hypotension, hypertension, tearing and choking during induction was also documented.ResultsThe variation of average CBFV from time T0 to T2(ΔVm1) and the variation from time T3 to T0 (ΔVm2) were not obviously different. The median consumption of intraoperative sufentanil in group C was obviously lower than that in group E. At T1, the mean HR of group E was significantly higher than that of group C. At T2 and T3, the BP and HR of group E were obviously higher than that of group C. At T2, the CBFV in the group E were obviously higher than those in the group C. The incidence of hypotension was significantly reduced in the group E compared with the group C. There were no differences in the other outcomes.ConclusionsThe induction of esketamine combined with propofol does not increase the blood flow velocity of middle cerebral artery. Esketamine is advantageous in maintaining hemodynamic stability during induction. Furthermore, the administration of esketamine did not result in an increased incidence of adverse effects.Trial Registration15/06/2023 clinicaltrials.gov ChiCTR2300072518 https://www.chictr.org.cn/bin/project/edit?pid=176675.

Correlation Between Fetal Umbilical Artery and Middle Cerebral Artery Doppler Indices in Preeclamptic and Normotensive Pregnancies

Objective: To assess the correlation between fetal umbilical artery (UA) and middle cerebral artery (MCA) Doppler indices in a cohort of preeclamptic and normotensive pregnancies. Materials and Methods: This cross-sectional analytical study recruited 70 pregnant women (28–40 weeks of gestation) using a non-probability convenient technique. The study included 33 patients with preeclampsia and 37 normotensive participants. Results: In the normotensive group, a significant ( P = .00) strong correlation ( r = 0.72) was observed between UA velocity, systolic/diastolic (S/D) ratio, and pulsatility index (PI), and MCA velocity; a significant ( P = .00) correlation ( r = 0.56) between UA, S/D ratio, and the MCA resistive index (RI); a significant ( P = .00) moderate correlation ( r = 0.66) between S/D ratio, UA velocity, and MCA velocity; a significant ( P = .00) negative correlation ( r = −0.50) between UA velocity, RI, and MCA PI; a significant ( P = .01) negative correlation ( r = −0.44) between UA velocity, RI, and MCA S/D ratio. In contrast, in the preeclamptic group, we observed a substantial ( P = .01) moderate correlation ( r = 0.43) between UA, PI, and MCA velocity; a significant ( P = .04) correlation ( r = 0.368) between UA, RI, and MCA PI; a significant ( P = .05) moderate correlation ( r = 0.35) between UA, PI, and MCA RI; a significant ( P = .00) strong correlation ( r = 0.83) between UA S/D ratio UA and MCA velocity. Conclusion: This study suggests potential diagnostic value in Doppler measurements for assessing preeclampsia-related vascular changes. However, caution is warranted owing to a split sample and limited statistical power, necessitating further research for validation.

Predictive Value of Quantitative Electroencephalogram Combined with Transcranial Doppler Ultrasound in Delayed Cerebral Ischemia after Subarachnoid Hemorrhage

ObjectiveTo explore the predictive value of transcranial Doppler ultrasound (TCD) combined with quantitative electroencephalogram (QEEG) in delayed cerebral ischemia (DCI) caused by aneurysmal subarachnoid hemorrhage (aSAH). MethodsThe subjects were 105 patients with aSAH from June 2020 to December 2022. Patients were divided into DCI group (n=34) and non-DCI group (n=71) according to the presence of DCI 14d after onset. Further comparison was conducted on the baseline data as well as the parameters of QEEG and TCD within 24h after admission. Multivariate logistic analysis was performed to investigate risk factors related to DCI within 14 days of admission in aSAH patients. ResultsThere were significant differences in the comparison of the proportion of Hunt-Hess grading, relative δ power (RDP), relative α power (RAP), relative α/β power ratio (ADR), as well as peak systolic velocity (Vs), mean blood flow velocity (MBFV) and pulsatility index (PI) of middle cerebral artery between the two groups (P<0.05). Furthermore, Logistic regression analysis revealed that ADR [OR=1.668, 95%CI (1.369, 4.345)] and MBFV of middle cerebral artery [OR=3.279, 95%CI (2.332, 6.720)] were risk factors for the occurrence of DCI in aSAH patients (P<0.05). In addition, evaluation of the predictive value revealed that combined use of the two indicators showed the highest predictive value (AUC: 0.959, 95%CI: 0.896∼0.993). ConclusionPatients with aSAH complicated by DCI have relatively higher MBFV of middle cerebral artery and ADR. Combined use of the two indicators can provide reference for early prediction of DCI in aSAH patients.

Effects of butylphthalide on cerebral vascular circulation, coagulation function, and neurological function in patients with acute severe ischemic stroke following intravenous thrombolysis: a preliminary study

Objective To analyze the effects of Butylphthalide on cerebral vascular circulation, coagulation function, and neurological function in patients with acute severe ischemic stroke following intravenous thrombolysis. Methods Clinical efficacy, cerebral vascular circulation indicators [anterior cerebral artery (ACA), middle cerebral artery (MCA), vertebral artery (VA) blood flow velocity], coagulation function indicators [prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB)], neurological function indicators [Activities of Daily Living (ADL) score. Results The total effective rate of treatment in the control group was 76.47%, while in the observation group, it was 96.08%, with the observation group showing a significantly higher total effective rate than the control group (p < 0.05). Before treatment, there was no significant difference in ACA, MCA, and VA blood flow velocity between the two groups (p > 0.05). However, after treatment, the ACA, MCA, and VA blood flow velocity in the observation group were significantly higher than those in the control group (p < 0.05). Before treatment, there was no significant difference in PT, APTT, TT, and FIB levels between the two groups (p > 0.05). Conclusion In patients with acute severe ischemic stroke undergoing intravenous thrombolysis, the addition of Butylphthalide to the treatment regimen yields favorable clinical outcomes. Compared to Alteplase alone, the addition of Butylphthalide further improves cerebral vascular circulation and coagulation function, promoting the recovery and reconstruction of neurological function in patients. Importantly, the addition of Butylphthalide does not increase the risk of adverse reactions, making it a safe and ideal option for clinical application.

Standing middle cerebral artery velocity predicts cognitive function and gait speed in older adults with cognitive impairment, and is impacted by sex differences

Upright posture challenges the cerebrovascular system, leading to changes in middle cerebral artery velocity (MCAv) dynamics which are less evident at supine rest. Chronic alterations in MCAv have been linked to hypoperfusion states and the effect that this may have on cognition remains unclear. This study aimed to determine if MCAv and oscillatory metrics of MCAv (ex. pulsatility index, PI) during upright posture are i) associated with cognitive function and gait speed (GS) to a greater extent than during supine rest, and ii) are different between sexes.Beat-by-beat MCAv (transcranial Doppler ultrasound) and mean arterial pressure (MAP, plethysmography) were averaged for 30-seconds during supine-rest through a transition to standing for 53 participants (73±6yrs, 17 females). While controlling for age, multiple linear regressions predicting MoCA scores and GS from age, supine MCAv metrics, and standing MCAv metrics, were completed. Simple linear regressions predicting Montreal Cognitive Assessment (MoCA) score and GS from MCAv metrics were performed separately for females and males. Significance was set to p<0.05.Lower standing diastolic MCAv was a significant (p = 0.017) predictor of lower MoCA scores in participants with mild cognitive impairment, and this relationship only remained significant for males. Lower standing PI was associated with slower GS (p = 0.027, r=-0.306) in both sexes. Our results indicate a relationship between blunted MCAv and altered oscillatory flow profiles during standing, with lower MoCA scores and GS. These relationships were not observed in the supine position, indicating a unique relationship between standing measures of MCAv with cognitive and physical functions.

Cerebral Hemodynamics and Vagally Mediated HRV Associated with High- and Low-frequency Yoga Breathing: An Exploratory, Randomized, Crossover Study

Abstract Background: Volitionally modifying respiration leads to changes in middle cerebral arterial (MCA) blood flow. The effect of changes in breath rate on MCA blood flow has not been reported. Aims and Objectives: To determine the effect of slow (bumblebee yoga breathing) and fast (high frequency yoga breathing) yoga breathing techniques on MCA blood flow and vagally mediated heart rate variability. Materials and Methods: Thirty participants (mean age ± standard deviation, 27.3 ± 4.2 years) were assessed on 2 separate days practicing either high frequency yoga breathing (HFYB, breath frequency 54.2/min) or slow frequency bumblebee yoga breathing (BBYB, breath frequency 3.8/min) in random order to determine the effects of changes in breath frequency on MCA hemodynamics. Assessments included transcranial Doppler sonography, vagally mediated heart rate variability (VmHRV), and respiration. Results: Both HFYB and BBYB (i) reduced MCA flow velocities, i.e., peak systolic, end diastolic, and mean flow velocities, and (ii) increased MCA pulsatility indices. There was an increase in VmHRV during BBYB based on increased power in high frequency (HF) and low frequency (LF). LF reflects VmHRV for slow breath frequencies. In BBYB the average breath rate was 3.8 breaths/min. In contrast, VmHRV decreased during HFYB (based on reduced HF power; repeated measures analysis of variance, P &lt; 0.05, all cases). Conclusion: Hence, irrespective of the differences in breath frequency, both HFYB and BBYB appear to reduce MCA flow velocities and increase the resistance to blood flow bilaterally, although the VmHRV changed in opposite directions. MCA velocity and pulsatility changes are speculated to be associated with low global neural activity during yoga breathing.

The Music Within: A Doppler Harmonic Pattern Report in Non-Subarachnoid Hemorrhage Related Cerebral Vasospasm

A 40-year-old male presented an episode of severe thunderclap headache with right hemiparesis. Imaging revealed severe stenosis in the left middle cerebral artery, associated with increased mean velocities detected by Transcranial Doppler Ultrasound (TCD). Notably, a distinctive "tin whistle" sound, known as a doppler harmonic effect, near the highest velocity point was observed during the examination. Extensive workup was performed, including CSF analysis and laboratory investigations, and the diagnosis of Reversible Cerebral Vasoconstriction Syndrome (RCVS) was established. Treatment involving medication and daily monitoring led to a decline in the left MCA's velocity, enabling the patient's discharge with no recurrent headaches or neurological deficits. Notably, a follow-up MRI exhibited the disappearance of the left MCA stenosis. This report discusses the rare occurrence of "musical murmurs" in cerebrovascular diseases, underscoring the potential for early diagnosis using techniques like TCD in emergency settings, particularly in conditions like RCVs.

The influence of maturation and sex on intracranial blood velocities during exercise in children.

Cerebral blood velocity (CBv) increases in response to moderate exercise in humans, but the magnitude of change is smaller in children compared with postpubertal adolescents and adults. Whether sex differences exist in the anterior or posterior CBv response to exercise across pubertal development remains to be determined. We assessed middle cerebral artery (MCAv) and posterior cerebral artery (PCAv) blood velocity via transcranial Doppler in 38 prepubertal (18 males) and 48 postpubertal (23 males) with cerebrovascular and cardiorespiratory measures compared at baseline and ventilatory threshold. At baseline, MCAv was higher in both sexes pre- versus postpuberty. Females demonstrated a greater MCAv (P < 0.001) than their male counterparts (prepubertal females; 78 ± 11 cm·s-1 vs. prepubertal males; 72 ± 8 cm·s-1, and postpubertal females; 68 ± 10 cm·s-1 vs. postpubertal males; 62 ± 7 cm·s-1). During exercise, MCAv remained higher in postpubertal females versus males (81 ± 15 cm·s-1 vs. 73 ± 11 cm·s-1), but there were no differences in prepuberty. The relative increase in PCAv was greater in post- versus prepubertal females (51 ± 9 cm·s-1 vs. 45 ± 11 cm·s-1; P = 0.032) but was similar in males and females. Our findings suggest that biological sex alters anterior cerebral blood velocities at rest in both pre- and postpubertal youth, but the response to submaximal exercise is only influenced by sex postpuberty.NEW & NOTEWORTHY Cerebral blood velocity (CBv) in the anterior circulation was higher in females compared with males irrespective of maturational stage, but not in the posterior circulation. In response to exercise, females demonstrated a greater CBv compared with males, especially post-peak height velocity (post-PHV) where the CBv response to exercise was more pronounced. Our findings suggest that both CBv at rest and in response to acute submaximal exercise are altered by biological sex in a maturity-dependent manner.

Comparison of diffuse correlation spectroscopy analytical models for measuring cerebral blood flow in adults.

Although multilayer analytical models have been proposed to enhance brain sensitivity of diffuse correlation spectroscopy (DCS) measurements of cerebral blood flow, the traditional homogeneous model remains dominant in clinical applications. Rigorous in vivo comparison of these analytical models is lacking. We compare the performance of different analytical models to estimate a cerebral blood flow index (CBFi) with DCS in adults. Resting-state data were obtained on a cohort of 20 adult patients with subarachnoid hemorrhage. Data at 1 and 2.5cm source-detector separations were analyzed with the homogenous, two-layer, and three-layer models to estimate scalp blood flow index and CBFi. The performance of each model was quantified via fitting convergence, fit stability, brain-to-scalp flow ratio (BSR), and correlation with transcranial Doppler ultrasound (TCD) measurements of cerebral blood flow velocity in the middle cerebral artery (MCA). The homogeneous model has the highest pass rate (100%), lowest coefficient of variation (CV) at rest (median [IQR] at 1Hz of 0.18 [0.13, 0.22]), and most significant correlation with MCA blood flow velocities (, ) compared with both the two- and three-layer models. The multilayer model pass rate was significantly correlated with extracerebral layer thicknesses. Discarding datasets with non-physiological BSRs increased the correlation between DCS measured CBFi and TCD measured MCA velocities for all models. We found that the homogeneous model has the highest pass rate, lowest CV at rest, and most significant correlation with MCA blood flow velocities. Results from the multilayer models should be taken with caution because they suffer from lower pass rates and higher coefficients of variation at rest and can converge to non-physiological values for CBFi. Future work is needed to validate these models in vivo, and novel approaches are merited to improve the performance of the multimodel models.

Exposure to passive heat and cold stress differentially modulates cerebrovascular-CO2 responsiveness.

Heat and cold stress influence cerebral blood flow (CBF) regulatory factors (e.g., arterial CO2 partial pressure). However, it is unclear whether the CBF response to a CO2 stimulus (i.e., cerebrovascular-CO2 responsiveness) is maintained under different thermal conditions. This study aimed to compare cerebrovascular-CO2 responsiveness between normothermia, passive heat, and cold stress conditions. Sixteen participants (8 females; 25 ± 7 yr) completed two experimental sessions (randomized) comprising normothermic and either passive heat or cold stress conditions. Middle and posterior cerebral artery velocity (MCAv, PCAv) were measured during rest, hypercapnia (5% CO2 inhalation), and hypocapnia (voluntary hyperventilation to an end-tidal CO2 of 30 mmHg). The linear slope of the cerebral blood velocity (CBv) response to changing end-tidal CO2 was calculated to measure cerebrovascular-CO2 responsiveness, and cerebrovascular conductance (CVC) was used to examine responsiveness independent of blood pressure. CBv-CVC-CO2 responsiveness to hypocapnia was greater during heat stress compared with cold stress (MCA: +0.05 ± 0.08 cm/s/mmHg/mmHg, P = 0.04; PCA: +0.02 ± 0.02 cm/s/mmHg/mmHg, P = 0.002). CBv-CO2 responsiveness to hypercapnia decreased during heat stress (MCA: -0.67 ± 0.89 cm/s/mmHg, P = 0.02; PCA: -0.64 ± 0.62 cm/s/mmHg; P = 0.01) and increased during cold stress (MCA: +0.98 ± 1.33 cm/s/mmHg, P = 0.03; PCA: +1.00 ± 0.82 cm/s/mmHg; P = 0.01) compared with normothermia. However, CBv-CVC-CO2 responsiveness to hypercapnia was not different between thermal conditions (P > 0.08). Overall, passive heat, but not cold, stress challenges the maintenance of cerebral perfusion. A greater cerebrovascular responsiveness to hypocapnia during heat stress likely reduces an already impaired cerebrovascular reserve capacity and may contribute to adverse events (e.g., syncope).NEW & NOTEWORTHY This study demonstrates that thermoregulatory-driven perfusion pressure changes, from either cold or heat stress, impact cerebrovascular responsiveness to hypercapnia. Compared with cold stress, heat stress poses a greater challenge to the maintenance of cerebral perfusion during hypocapnia, challenging cerebrovascular reserve capacity while increasing cerebrovascular-CO2 responsiveness. This likely exacerbates cerebral hypoperfusion during heat stress since hyperthermia-induced hyperventilation results in hypocapnia. No regional differences in middle and posterior cerebral artery responsiveness were found with thermal stress.

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.

Cerebral Vasomotor Reactivity Testing in the Middle Cerebral Artery Using Transcranial Doppler to Assess Brain Dysregulation in Long-haul COVID Patients

Introduction: COVID-19 has wide-ranging physiological effects, with many patients complaining of persistent asthenia following recovery from the acute phase of the infection. The frequent term for this is “Long-Haul COVID.” While we have tools to measure effects on general physiology in human subjects, a metric for cerebral dysregulation is lacking. Cerebral blood flow is closely regulated in a healthy young person. Cerebral vasomotor reactivity (CVR) was used as a tool to assess this dysregulation. Methods: A transcranial Doppler (TCD) study for CVR was performed under the influence of Carbogen gas. A questionnaire collected prior to the procedure provided additional details on subjects’ demographics and COVID history. Cases and controls were recruited using the self-reported questionnaire. Statistics involved assessing the reproducibility of the test, as well as discovering differences between cases and control groups. Results: Cerebral vasomotor reactivity was assessed in 26 subjects (10 cases and 16 controls). Mean flow velocity in the left middle cerebral artery was analyzed at baseline, at peak Carbogen gas exposure, and in the hypercapnic phase. The reproducibility of the test was established within the longitudinal repeated measures data. The case and control groups were insignificant in difference at the base level but significant when controlled for confounders. Cerebral vasomotor reactivity was found to increase by 3.8 units in cases compared to controls. Confounders like body mass index, gender, and age were found significantly different between cases and controls. The number of COVID episodes and symptom severity was significant for CVR. Conclusion: This simple TCD bedside test was found to be effective in assessing CVR among all the subjects and was homogenous in its effect irrespective of baseline subject differences. As a preliminary test, the test showed differences among cases and control groups. The sample for the test lacked sufficient power and observations. A bigger sample size and a subsequent longitudinal follow-up may help better understand the use of CVR to screen high-risk populations for cerebrovascular anomalies.

Abstract 14917: The Influence of Coronary Artery Disease on Cerebrovascular Reactivity and Cognitive Function

Introduction: Patients with coronary artery disease (CAD) are at increased risk of cognitive decline. A proposed mechanism is cerebral hypoperfusion related to vascular dysfunction and impaired cerebral blood flow regulation Hypothesis: Patients with CAD will have lower cerebrovascular function than age- and sex-matched controls, assessed as reactivity to a vasodilatory carbon dioxide (CO 2 ) stimulus. Methods: Adults 40-70years old with CAD were recruited on enrollment to a cardiac rehabilitation program following a cardiac event or hospitalization. Age and sex-matched adults without known disease or cardiovascular risk factors were recruited as healthy controls. Cognitive function was assessed by the Fluid Composite of the NIH Cognition Toolbox. Following a familiarization visit, participants underwent a stepped CO 2 protocol (room air, 2% CO 2 , 4% CO 2 , 6% CO 2 ) while continuously measuring middle cerebral artery velocity (MCAv) using transcranial doppler ultrasound, mean arterial pressure (MAP), ventilation (VE), and end-tidal CO 2 . Cerebrovascular conductance (CVCi) was calculated as MCAv/MAP. Cerebrovascular reactivity was calculated as the linear regression slope of CVCi against the change in end-tidal CO 2 . The reactivity of MAP and VE (or chemosensitivity) were also calculated. Results: 19 patients with CAD and 10 healthy controls were recruited ( Table 1 ). Compared with controls, patients with CAD had a 2-fold lower cerebrovascular reactivity (p=0.003), higher MAP reactivity (p&lt;0.05), and a trend towards higher chemosensitivity (p&lt;0.1) ( Table 2 ). There were no group differences in resting CVCi or cognition ( Table 2 ). After adjustment for age and sex, lower cerebrovascular reactivity was associated with lower peak oxygen uptake, diabetes, and smoking history ( Table 3 ). Conclusions: Compared with healthy controls, we report that patients with CAD have significantly lower cerebrovascular function, with no differences in cognitive function.

Influence of sex on the reliability of cerebral blood velocity regulation during lower body negative pressure and supine cycling with considerations of the menstrual cycle

Objective. To evaluate sex differences in the reliability of absolute and relative cerebral blood velocity (CBv) during concurrent supine cycling with lower body negative pressure (LBNP). Approach. A total of 19 participants (11 females; aged 20–33 years) completed five testing sessions, occurring on 7 d intervals. Visit 1 was a maximal-ramp-cycle test to ascertain peak CBv wattage. During visits 2–5, supine cycling protocol occurred at individualized peak CBv wattages with progressive decreases in LBNP from 0 to −20, −40, −60, −70, and −80 Torr. Menstrual cycle day was self-reported via the Rhinessa Women’s Questionnaire. Transcranial Doppler ultrasound insonated bilateral middle cerebral artery velocity (MCAv). Two-way ANOVA assessed potential day- and sex-differences at each LBNP stage. Reliability was determined using intraclass correlation coefficients (ICC) and coefficient of variation (CoV). Main results. For all physiological measures, no main-effects were present for day- or interaction-terms (p > 0.067; negligible-to-small effect sizes), while sex differences were noted for MCAv, blood pressure, and heart rate (p < 0.046). Across visits, males and females displayed excellent and good-to-excellent levels of reliability for MCAv metrics, respectively (ICC range: 0.745–0.999; CoV range: 0.33%–9.90%). Significance. During the current investigation, both relative and absolute CBv demonstrated high reliability in both male and female participants during a supine LBNP cycling protocol. An exploratory analysis revealed increased variance was found in female participants dependent on contraceptive use. Despite this, results indicate future LBNP studies may include females at any menstrual cycle stage.

Acute hypoxia impairs posterior cerebral bioenergetics and memory in man.

Hypoxia has the potential to impair cognitive function; however, it is still uncertain which cognitive domains are adversely affected. We examined the effects of acute hypoxia (∼7h) on central executive (Go/No-Go) and non-executive (memory) tasks and the extent to which impairment was potentially related to regional cerebral blood flow and oxygen delivery (CDO2 ). Twelve male participants performed cognitive tasks following 0, 2, 4 and 6h of passive exposure to both normoxia and hypoxia (12% O2 ), in a randomized block cross-over single-blinded design. Middle cerebral artery (MCA) and posterior cerebral artery (PCA) blood velocities and corresponding CDO2 were determined using bilateral transcranial Doppler ultrasound. In hypoxia, MCA DO2 was reduced during the Go/No-Go task (P=0.010 vs. normoxia, main effect), and PCA DO2 was attenuated during memorization (P=0.005 vs. normoxia) and recall components (P=0.002 vs. normoxia) in the memory task. The accuracy of the memory task was also impaired in hypoxia (P=0.049 vs. normoxia). In contrast, hypoxia failed to alter reaction time (P=0.19 vs. normoxia) or accuracy (P=0.20 vs. normoxia) during the Go/No-Go task, indicating that selective attention and response inhibition were preserved. Hypoxia did not affect cerebral blood flow or corresponding CDO2 responses to cognitive activity (P>0.05 vs. normoxia). Collectively, these findings highlight the differential sensitivity of cognitive domains, with memory being selectively vulnerable in hypoxia. NEW FINDINGS: What is the central question of this study? We sought to examine the effects of acute hypoxia on central executive (selective attention and response inhibition) and non-executive (memory) performance and the extent to which impairments are potentially related to reductions in regional cerebral blood flow and oxygen delivery. What is the main finding and its importance? Memory was impaired in acute hypoxia, and this was accompanied by a selective reduction in posterior cerebral artery oxygen delivery. In contrast, selective attention and response inhibition remained well preserved. These findings suggest that memory is selectively vulnerable to hypoxia.

The effect of oscillatory hemodynamics on the cardiovascular responses to simulated hemorrhage during isocapnia.

During cerebral hypoperfusion induced by lower body negative pressure (LBNP), cerebral tissue oxygenation is protected with oscillatory arterial pressure and cerebral blood flow at low frequencies (0.1 Hz and 0.05 Hz), despite no protection of cerebral blood flow or oxygen delivery. However, hypocapnia induced by LBNP contributes to cerebral blood flow reductions, and may mask potential protective effects of hemodynamic oscillations on cerebral blood flow. We hypothesized that under isocapnic conditions, forced oscillations of arterial pressure and blood flow at 0.1 Hz and 0.05 Hz would attenuate reductions in extra- and intracranial blood flow during simulated hemorrhage using LBNP. Eleven human participants underwent three LBNP profiles: a nonoscillatory condition (0 Hz) and two oscillatory conditions (0.1 Hz and 0.05 Hz). End-tidal (et) CO2 and etO2 were clamped at baseline values using dynamic end-tidal forcing. Cerebral tissue oxygenation (ScO2), internal carotid artery (ICA) blood flow, and middle cerebral artery velocity (MCAv) were measured. With clamped etCO2, neither ICA blood flow (ANOVA P = 0.93) nor MCAv (ANOVA P = 0.36) decreased with LBNP, and these responses did not differ between the three profiles (ICA blood flow: 0 Hz: 2.2 ± 5.4%, 0.1 Hz: -0.4 ± 6.6%, 0.05 Hz: 0.2 ± 4.8%; P = 0.56; MCAv: 0 Hz: -2.3 ± 7.8%, 0.1 Hz: -1.3 ± 6.1%, 0.05 Hz: -3.1 ± 5.0%; P = 0.87). Similarly, ScO2 did not decrease with LBNP (ANOVA P = 0.21) nor differ between the three profiles (0 Hz: -2.6 ± 3.3%, 0.1 Hz: -1.6 ± 1.5%, 0.05 Hz: -0.2 ± 2.8%; P = 0.13). Contrary to our hypothesis, cerebral blood flow and tissue oxygenation were protected during LBNP with isocapnia, regardless of whether hemodynamic oscillations were induced.NEW & NOTEWORTHY We examined the role of forcing oscillations in arterial pressure and blood flow at 0.1 Hz and 0.05 Hz on extra- and intracranial blood flow and cerebral tissue oxygenation during simulated hemorrhage (using lower body negative pressure, LBNP) under isocapnic conditions. Contrary to our hypothesis, both cerebral blood flow and cerebral tissue oxygenation were completely protected during simulated hemorrhage with isocapnia, regardless of whether oscillations in arterial pressure and cerebral blood flow were induced. These findings highlight the protective effect of preventing hypocapnia on cerebral blood flow under simulated hemorrhage conditions.

Frailty is associated with worse executive function and higher cerebral blood velocity in cognitively healthy older adults: a cross-sectional study.

Frailty is characterized by an increased vulnerability to adverse health events. Executive function impairment is an early sign of progression towards cognitive impairments. Whether frailty is associated with executive function and the associated mechanisms are unclear. We test the hypothesis that higher frailty is associated with worse executive function (Trail Making Test) and if aerobic fitness, prefrontal cortex oxygenation (ΔO2Hb), or middle-cerebral artery velocity (MCAv) impact this association. Forty-one (38 females) cognitively health older adults (70.1 ± 6.3 years) completed a Trail task and 6-min walk test. Prefrontal cortex oxygenation was measured during the Trail task (via functional near-infrared spectroscopy) and MCAv in a sub-sample (n=26, via transcranial Doppler). A 35-item frailty index was used. Frailty was independently, non-linearly related to trail B performance (Frailty2: β=1927 [95% CI: 321-3533], p= 0.02), with the model explaining 22% of the variance of trail B time (p= 0.02). Aerobic fitness was an independent predictor of trail B (β=-0.05 [95% CI: -0.10-0.004], p= 0.04), but age and ΔO2Hb were not (both, p> 0.78). Frailty was positively associated with the difference between trails B and A (β=105 [95% CI: 24-186], p= 0.01). Frailty was also associated with a higher peak MCAv (ρ =0.40, p= 0.04), but lower ΔO2Hb-peakMCAv ratio (ρ= -0.44, p= 0.02). Higher frailty levels are associated to worse Trail times after controlling for age, aerobic fitness, and prefrontal oxygenation. High frailty level may disproportionately predispose older adults to challenges performing executive function tasks that may manifest early as a compensatory higher MCAv despite worse executive function, and indicate a greater risk of progressing to cognitive impairment.