Cerebrovascular Response Research Articles

Cerebrovascular reactivity and response times describe recent ischemic symptomatology in patients with moyamoya

Abstract Moyamoya is a non-atherosclerotic intracranial steno-occlusive condition that places patients at high risk for ischemic stroke. Randomized trials of surgical revascularization demonstrating efficacy in ischemic moyamoya have not been performed, and as such, biomarkers of parenchymal hemodynamic impairment are needed to assist with triage and evaluate post-surgical response. In this prospective study, we test the hypothesis that parenchymal cerebrovascular reactivity (CVR) metrics in response to a fixed-inspired 5% carbon dioxide challenge correlate with recent focal ischemic symptoms. Hypercapnic reactivity blood oxygenation level-dependent (BOLD) MRI (echo time=35ms; spatial resolution=3.5x3.5x3.5mm) and catheter angiography assessments of cortical reserve capacity and vascular patency, respectively, in moyamoya disease and syndromic participants (n=73) were performed in sequence. Cerebrovascular reactivity uncorrected for response time (CVRRAW) was quantified, and time regression analyses were applied to quantify maximum cerebrovascular reactivity (CVRMAX) and cerebrovascular reactivity response time (CVRDELAY). Symptomatology was categorized by a stroke neurologist by hemisphere: symptomatic (lateralizing ischemic symptoms < 6 months) or asymptomatic (no ischemic symptom history). Values are presented as median [interquartile range]; logistic regression assessed the association of cerebrovascular reactivity metrics with symptoms, controlling for age and sex. A total of 109 hemispheres, including 39 symptomatic and 70 asymptomatic hemispheres, met inclusion criteria. Symptomatic hemispheres displayed reduced CVRRAW (p<0.01) (symptomatic=0.45 [0.28-0.70] z-statistic/ΔEtCO2 vs. asymptomatic=0.67 [0.44-0.98] z-statistic/ΔEtCO2), lengthened CVRDELAY (p<0.001) (symptomatic=47.6 [37.7-57.0] seconds vs. asymptomatic=37.7 [30.4-46.4] seconds), and reduced CVRMAX (p=0.037) (symptomatic=1.31 [0.99-1.94] z-statistic/ΔEtCO2 vs. asymptomatic=1.64 [1.29-2.12] z-statistic/ΔEtCO2). CVRDELAY (p<0.001) was found to be significantly related to age in asymptomatic hemispheres (0.33-unit increase/year). Of assessed measures, the receiver operating characteristic curves suggest that CVRDELAY is associated most closely with recent ischemic symptoms (p<0.001). Findings support that cerebrovascular reactivity metrics are uniquely altered in hemispheres with recent ischemic symptoms, further motivating their utilization as biomarkers of ischemic symptomatology and potential treatment efficacy in moyamoya disease and syndrome.

Regional heterogeneity of cerebral blood flow immediately after the onset of ventricular pacing in anesthetized rats.

Selective distribution of cerebral blood flow (CBF) to vital brain regions likely occurs during rapid severe hypotension caused by tachyarrhythmia, but has not yet been demonstrated. In this study, we aimed to test the hypothesis that CBF is differentially preserved between brain regions depending on the degree of hypotension. In anesthetized rats, CBF was measured in the motor cortex (MC), medial prefrontal cortex, amygdala, thalamus, dorsal hypothalamus, hippocampus, ventral tegmental area, dorsolateral periaqueductal gray (dlPAG), and parabrachial nucleus (PB) by using laser-Doppler flowmetry. Ventricular pacing was performed for 30 s at 550-800 beats/min. The cerebrovascular CO2 response time and reactivity were evaluated during 5% CO2 exposure. During 1-4 s of ventricular pacing, mean arterial pressure (MAP) rapidly decreased, with minor changes in central venous and intracranial pressures. CBF was relatively well maintained in brain regions other than the MC (Ps ≤ 0.012) when moderate hypotension occurred (-34 mmHg ≤ ΔMAP ≤ -15 mmHg), whereas severe hypotension (-54 mmHg ≤ ΔMAP ≤ -35 mmHg) induced selective CBF distribution to regions other than the MC, thalamus, and dlPAG. The cerebrovascular CO2 response time/reactivity was rapid or high in the thalamus, dlPAG, and PB, which almost completely differed from the brain regions in which CBF was relatively maintained during pacing-induced severe hypotension. These results suggest that regional heterogeneity of CBF arises depending on the degree of tachyarrhythmia-induced hypotension. Clarifying the mechanisms and functions of CBF maintenance would be beneficial to syncope and cerebral ischemia management in patients with arrhythmia.

The relationships between age, sex and exercise intensity on cerebral artery haemodynamics during isometric handgrip exercise.

Age and sex may alter the cerebral blood flow (CBF) responses to acute isometric exercise, via associated elevations in mean arterial pressure (MAP) and sympathetic activation. Our aim was to determine the relationships between age, sex and exercise intensity on cerebrovascular responses to isometric handgrip exercise. In 78 healthy adults (18-80 years, N=42 female), cerebrovascular responses were assessed during two minute isometric exercise bouts at three intensities (15, 30, 45% maximal voluntary contraction). Intracranial responses of the middle cerebral artery (MCA) and posterior cerebral artery (PCA) velocity (v) were measured using transcranial Doppler ultrasound. Extracranial responses of the internal carotid artery (ICA) and vertebral artery (VA) were assessed using Duplex ultrasound. Cardiopulmonary haemodynamic and neural parameters were measured throughout, including muscle sympathetic nerve activity, end-tidal carbon dioxide, and MAP. There were significant positive relationships between exercise intensity and the cerebral responses of the MCAv (P<0.001) and PCAv (P=0.005). There were no effects of intensity on ICA and VA responses (P>0.05), despite intensity-dependent increases in MAP (P<0.001). The increased MCAv response to exercise was blunted with advancing age (P=0.01) with no influence of sex (P=0.86). The present study provides data on age, sex and intensity specific relationships with intracranial and extracranial cerebrovascular responses to isometric exercise. Despite similar ICA, VA, and PCA responses, MCAv responses were attenuated with advancing age during handgrip exercise with no sex dependent influence. Further, intracranial responses were intensity dependent, whereas extracranial blood flow, shear-stress and velocity responses were similarly increased at all intensities during handgrip exercise.

From red blood cells to blue brains: a spectrum of hypoxic cerebrovascular responses painted in broad strokes.

From red blood cells to blue brains: a spectrum of hypoxic cerebrovascular responses painted in broad strokes.

Alterations of cerebrovascular reactivity following pediatric mild traumatic brain injury are independent of neurodevelopmental changes.

Cerebrovascular dysfunction following mild traumatic brain injury (mTBI) is understudied relative to other microstructural injuries, especially during neurodevelopment. The blood-oxygen level dependent response was used to investigate cerebrovascular reactivity (CVR) in response to hypercapnia following pediatric mTBI (pmTBI; ages 8-18 years), as well as pseudocontinuous arterial spin labeling to measure cerebral blood flow (CBF). Data were collected ∼1-week (N = 107) and 4 months (N = 73) post-injury. Sex- and age-matched healthy controls (HC) underwent identical examinations at comparable time points (N = 110 and N = 91). Subtle clinical and cognitive deficits existed at ∼1 week that resolved for some, but not all domains at 4 months post-injury. At both visits, pmTBI showed an increased maximal fit between end-tidal CO2 regressor and the cerebrovascular response across multiple regions (primarily fronto-temporal), as well as increased latency to maximal fit in independent regions (primarily posterior). Hypoperfusion was also noted within the bilateral cerebellum. A biphasic relationship existed between CVR amplitude and age (i.e., positive until 14.5 years, negative thereafter) in both gray and white matter, but these neurodevelopment effects did not moderate injury effects. CVR metrics were not associated with post-concussive symptoms or cognitive deficits. In conclusion, cerebrovascular dysfunction may persist for up to four months following pmTBI.

Effects of sodium bicarbonate ingestion on ventilatory and cerebrovascular responses in resting heated humans.

Hyperthermia stimulates ventilation in humans. This hyperthermia-induced hyperventilation may be mediated by the activation of peripheral chemoreceptors implicated in the regulation of respiration in reaction to various chemical stimuli, including reductions in arterial pH. Here, we investigated the hypothesis that during passive heating at rest, the increases in arterial pH achieved with sodium bicarbonate ingestion, which could attenuate peripheral chemoreceptors activity, mitigate hyperthermia-induced hyperventilation. We also assessed that the effect of sodium bicarbonate ingestion on cerebral blood flow responses, which are associated with hyperthermia-induced hyperventilation. Twelve healthy men ingested a sodium bicarbonate (0.3 g/kg body weight) or sodium chloride (0.208 g/kg). One hundred minutes after the ingestion, the participants were passively heated using hot-water immersion (42°C) combined with a water-perfused suit. Increases in esophageal temperature (an index of core temperature) and minute ventilation (VE) during the heating were similar in the two trials. Moreover, when VE is expressed as a function of esophageal temperature, there were no between-trial differences in the core temperature threshold for hyperventilation (37.9 ± 0.3 vs. 38.0 ± 0.4°C, P = 0.338), and sensitivity of hyperthermia-induced hyperventilation as assessed by the slope of the core temperature-VE relation (13.7 ± 14.9 vs. 15.8 ± 15.6 L/min/°C, P = 0.748). Furthermore, middle cerebral artery mean blood velocity (an index of cerebral blood flow) decreased similarly with heating duration in both trials. These results suggest that sodium bicarbonate ingestion does not mitigate hyperthermia-induced hyperventilation and the reductions in cerebral blood flow index in resting heated humans.

Cerebral hypoperfusion exacerbates vascular dysfunction after traumatic brain injury

Traumatic brain injuries are extremely common, and although most patients recover from their injuries many TBI patients suffer prolonged symptoms and remain at a higher risk for developing cardiovascular disease and neurodegeneration. Moreover, it remains challenging to identify predictors of poor long-term outcomes. Here, we tested the hypothesis that preexisting cerebrovascular impairment exacerbates metabolic and vascular dysfunction and leads to worse outcomes after TBI. Male mice underwent a mild surgical reduction in cerebral blood flow using a model of bilateral carotid artery stenosis (BCAS) wherein steel microcoils were implanted around the carotid arteries. Then, 30 days post coil implantation, mice underwent TBI or sham surgery. Gene expression profiles, cerebral blood flow, metabolic function, oxidative damage, vascular health and angiogenesis were assessed. Single nuclei RNA sequencing of endothelial cells isolated from mice after TBI showed differential gene expression profiles after TBI and BCAS, that were further altered when mice underwent both challenges. TBI but not BCAS increased mitochondrial oxidative metabolism. Both BCAS and TBI decreased cerebrovascular responses to repeated whisker stimulation. BCAS induced oxidative damage and inflammation in the vasculature as well as loss of vascular density, and reduced the numbers of angiogenic tip cells. Finally, intravascular protein accumulation was increased among mice that experienced both BCAS and TBI. Overall, our findings reveal that a prior vascular impairment significantly alters the profile of vascular health and function of the cerebrovasculature, and when combined with TBI may result in worsened outcomes.

Updates in inspiratory muscle training for older adults: A systematic review

Systematic reviews support the benefits of inspiratory muscle training (IMT) for exercise performance. Recently, many health benefits from IMT have been reported in older adults. Therefore, this work reviewed the literature focusing on IMT effects beyond physical performance in older adults, such as cardiorespiratory, metabolic, and postural balance outcomes. Searches were conducted with the following terms: ("respiratory muscle training" OR "inspiratory muscle training") OR ("inspiratory muscle strength training") AND ("elderly" OR "older" OR "aging" OR "aging"), and using the databases: MEDLINE (PubMed), SCOPUS and EUROPE PMC. Of the 356 articles found, 13 matched the inclusion criteria after screening. Based on reviewed studies, four to eight weeks of IMT (Mostly from 50 % up to 75 % of MIP, 7 days/week) improve cardiac autonomic control at rest and post-exercise, cerebrovascular response to orthostatic stress, static and dynamic balance, blood pressure control, endothelial function, and oxidative stress in older adults. The benefits of IMT in cardiac autonomic and vascular functions are reversed after training cessation. It thus appears that IMT promotes broad physiological gains for the older population. It is necessary to carry out more randomized clinical trials on the subject to confirm the findings of this research.

The effects of habitual resistance exercise training on cerebrovascular responses to lower body dynamic resistance exercise: A cross-sectional study.

Dynamic resistance exercise (RE) produces sinusoidal fluctuations in blood pressure with simultaneous fluctuations in middle cerebral artery blood velocity (MCAv). Some evidence indicates that RE may alter cerebrovascular function. This study aimed to examine the effects of habitual RE training on the within-RE cerebrovascular responses. RE-trained (n=15, Female=4) and healthy untrained individuals (n=15, Female=12) completed four sets of 10 paced repetitions (15 repetitions per minute) of unilateral leg extension exercise at 60% of predicted 1 repetition maximum. Beat-to-beat blood pressure, MCAv and end-tidal carbon dioxide were measured throughout. Zenith, nadir and zenith-to-nadir difference in mean arterial blood pressure (MAP) and mean MCAv (MCAvmean) for each repetition were averaged across each set. Two-way ANOVA was used to analyse dependent variables (training × sets), Bonferroni corrected t-tests were used for post hoc pairwise comparisons. Group age (26±7 trained vs. 25±6 years untrained, P=0.683) and weight (78±15vs. 71±15kg, P=0.683) were not different. During exercise average MAP was greater for the RE-trained group in sets 2, 3 and 4 (e.g., set 4: 101±11vs. 92±7mmHg for RE trained and untrained, respectively, post hoc tests all P=<0.012). Zenith MAP and zenith-to-nadir MAP difference demonstrated a training effect (P<0.039). Average MCAvmean and MCAvmean zenith-to-nadir difference was not different between groups (interaction effect P=0.166 and P=0.459, respectively). Despite RE-trained individuals demonstrating greater fluctuations in MAP during RE compared to untrained, there were no differences in MCAvmean. Regular RE may lead to vascular adaptations that stabilise MCAv during RE.

A promising approach for quantifying focal stroke modeling and assessing stroke progression: optical resolution photoacoustic microscopy photothrombosis.

JOURNAL/nrgr/04.03/01300535-202507000-00025/figure1/v/2024-09-09T124005Z/r/image-tiff To investigate the mechanisms underlying the onset and progression of ischemic stroke, some methods have been proposed that can simultaneously monitor and create embolisms in the animal cerebral cortex. However, these methods often require complex systems and the effect of age on cerebral embolism has not been adequately studied, although ischemic stroke is strongly age-related. In this study, we propose an optical-resolution photoacoustic microscopy-based visualized photothrombosis methodology to create and monitor ischemic stroke in mice simultaneously using a 532 nm pulsed laser. We observed the molding process in mice of different ages and presented age-dependent vascular embolism differentiation. Moreover, we integrated optical coherence tomography angiography to investigate age-associated trends in cerebrovascular variability following a stroke. Our imaging data and quantitative analyses underscore the differential cerebrovascular responses to stroke in mice of different ages, thereby highlighting the technique's potential for evaluating cerebrovascular health and unraveling age-related mechanisms involved in ischemic strokes.

Multi-modal Magnetic Resonance Imaging to Assess Cerebrovascular Function in Atrial Fibrillation Patients

Atrial fibrillation (AF) is associated with an increased risk of cognitive decline, dementia, and stroke. Low cerebral blood flow (CBF) and low cerebrovascular carbon dioxide reactivity (CVRCO2) are associated with poor brain health outcomes. In the current study we employed magnetic resonance imaging (MRI) to quantify resting CBF and CVRCO2 in patients with AF and age-matched normal sinus rhythm (NSR) controls. We hypothesised that both resting CBF and CVRCO2 would be lower in patients with AF. Patients with AF (n=11, 65±14 years, 2 women) and NSR (n=12, 63±9 years, 7 women) underwent arterial spin labelling (ASL) at rest, and blood oxygen level-dependent (BOLD) MRI during a single-step increase in partial pressure of carbon dioxide (measured by end-tidal carbon dioxide (PETCO2)) induced by changing the fraction of inspired CO2 to 5% (21% O2, balance N2). Region of interest time courses were extracted with grey matter, middle cerebral artery, and posterior cerebral artery territory masks. CVRCO2 was defined as the percentage change (%Δ) in BOLD signal vs %Δ in PETCO2. Baseline CBF was not different between NSR and AF in grey matter (62±17 vs. 58±10 ml/min/100g, respectively; p=0.226), middle cerebral artery (59±16 vs. 56±14 ml/min/100g; p=0.361) and posterior cerebral artery (61±17 vs 53±15 ml/min/100g; p=0.138) territories. BOLD-derived CVRC02 was not different between NSR and AF groups in grey matter (0.11±0.04 vs. 0.12±0.03 %ΔBOLD/%ΔmmHg, respectively; p=0.372), middle cerebral artery (0.09±0.04 vs. 0.10±0.03 %ΔBOLD/%ΔmmHg; p=0.405) and posterior cerebral artery (0.13±0.04 vs. 0.14±0.05 %ΔBOLD/%ΔmmHg; p=0.367) territories. Collectively, these pilot data suggest that MRI-derived cerebrovascular CO2 responsiveness is not different in patients with AF and age-matched NSR controls that have similar resting CBF. Further investigations are required to extend these preliminary findings to a larger cohort to fully elucidate the effects of AF on cerebrovascular function. Support provided by the Royal Society of New Zealand Te Apārangi Marsden Fund (19-UOA-170). 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.

Cerebrovascular Conductance Responses to Carbon Dioxide are Attenuated by the Presence of Hypertension in Patients with Atrial Fibrillation

The cerebral vasculature is highly sensitive to carbon dioxide (CO2) and cerebrovascular CO2 reactivity (CVRCO2) is widely used to index cerebral vascular health. Some studies have shown that both atrial fibrillation (AF) and hypertension (HTN) are independently associated with reduced CVRCO2. However, it is unknown if these effects on CVRCO2 are synergistic when AF and HTN are present together. In this study we tested the hypothesis that CVRCO2 was lower in patients with both AF and HTN (AF+HTN) compared to normotensive patients with AF. Transcranial Doppler ultrasound was used to measure middle cerebral artery blood velocity (MCA Vm) in AF (n=31) and AF+HTN (n=57) during stepped increases and decreases in end-tidal carbon dioxide (PETCO2). The ratio of MCA Vm and mean arterial pressure (MAP) was defined as cerebrovascular conductance index (CVCi). CVRCO2 was taken as the linear slope for MCA Vm and MCA CVCi versus PETCO2. As expected, baseline MAP was higher in AF+HTN than AF (107±9 vs. 98±9 mmHg, respectively; p&lt;0.001). Baseline MCA Vm was numerically lower in AF+HTN than AF, but this did not reach statistical significance (50 [44-60] vs. 52 [45-63] cm.s−1, respectively; p=0.075), while baseline CVCi was lower in AF+HTN compared to AF (0.46 [0.42-0.57] vs. 0.54 [0.44-0.63] cm.s−1.mmHg−1; p&lt;0.001). MCA Vm CVRCO2 was not different between groups (1.70 [1.47-2.19] and 1.74 [1.54-2.52] cm/s/mmHg−2 for AF+HTN and AF, respectively; p=0.221), whereas MCA CVCi CVRCO2 was 13% lower in AF+HTN compared to AF (0.013 ± 0.004 vs. 0.015 ± 0.005 cm.s.mmHg−2; p=0.047). Stepwise linear regression analysis identified that cardiac rhythm during data acquisition (AF or normal sinus rhythm) was a predictor of baseline MCA CVCi and MCA CVCi CVRCO2. In summary, our results demonstrate impaired MCA CVCi CVRCO2 in AF+HTN and suggest that the presence of HTN worsens cerebrovascular function in AF. Such cerebrovascular alterations may be important for the development of cognitive decline and diminished brain health in AF. Funding provided by Bristol-Myers Squibb/Pfizer Alliance Project Grant (CV185-481), British Heart Foundation Project Grant (PG/15/45/31579) and the National Institute of Health Research Clinical Research Network (NIHR CRN). 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 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&lt;0.05). MCA conductance increased at 30-min (+Δ0.04±0.08 cm/s per mmHg, p&lt;0.05), carotid diameter increased at 60-min (+Δ0.13±0.20 mm, p&lt;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.

SEX DIFFERENCES IN CEREBRAL BLOOD FLOW VELOCITY RESPONSES TO EXERCISE IN THE HEAT

INTRODUCTION &amp; AIMS Global warming poses a risk for the development of heat-related physiological impairment, which can be aggravated when exercising in hot conditions. The aim of the present study was to investigate acute effects of exercising in hot conditions on cerebral blood flow velocity and systolic function in healthy individuals and to explore possible sex differences. METHODS The experimental condition consisted of walking on a treadmill, at 5km/h and 2% incline, inside a heat chamber at 40°C (50%RH), for 90 minutes. Middle cerebral artery blood flow velocity (MCAv) and left ventricular global longitudinal strain (GLS; a sensitive index of systolic function), were assessed at baseline and every 30 minutes by means of transcranial Doppler and speckle-tracking echocardiography, respectively. Data is expressed in delta (Δ) and standard error. RESULTS Twenty-six individuals (13♂,13♀ 27.1±1.0yrs, P=0.02) completed the experimental protocol. Both males and females exhibited non-significant increases in MCAv from baseline at 30 minutes (♂Δ=2.55±2.15 P&amp;gt;0.05; ♀Δ=0.54±2.53cm.s-1, P&amp;gt;0.05; interaction P=0.63), followed by significant decreases relative to 30min, at 60min (♂Δ=-4.0±1.23 P=0.04; ♀Δ=-5.41±1.56cm.s-1, P=0.03; interaction P=0.63) and 90 minutes (♂Δ=-6.08±1.37 P&amp;lt;0.01; ♀Δ=-7.39±1.40cm.s-1, P&amp;lt;0.01; interaction P=0.63). In males, there was a significant decrease in GLS from baseline at 30min (Δ=2.44±0.69%, P&amp;lt;0.05), 60 (Δ=2.79±0.73%, P=0.03), and 90 (Δ=3.49±0.89%, P=0.03) minutes; no significant changes were observed in females. CONCLUSION Males and females presented similar patterns of change in cerebral blood flow velocity, including significant decreases with prolonged heat exertion. These changes occur in both sexes, despite changes in systolic strain only being apparent in males. These data suggest that sex differences may exist in the regulation of cerebrovascular responses to exercise in the heat in humans.

The Cardiac and Cerebrovascular Response to Lower Body Negative Pressure in Patients with Postural Orthostatic Tachycardia Syndrome

Introduction: Postural orthostatic tachycardia syndrome (POTS) is characterized by excessive heart rate response upon standing and symptoms that drastically reduce quality of life. Symptoms are often cerebral in nature (e.g., dizziness, headache), however the relationship between the underlying physiology and the symptoms is unknown. We tested the hypothesis that, compared to healthy controls (HC) individuals with POTS would have greater decreases in cardiac, and cerebral hemodynamic function during a simulated orthostatic challenge (lower-body negative pressure; LBNP) measured using magnetic resonance (MR) imaging. Methods: Eleven patients with POTS (17±1yrs; 1 male) and 10 HC (18±2yrs; 1 male) were studied at rest (supine in MRI) and during 20-minutes of -25mmHg LBNP. Symptoms were measured by Vanderbilt Orthostatic Symptom Score (VOSS). Heart rate and blood pressure (BP) were measured using an automated cuff and finger pulse oximeter, respectively. Left and right ventricular volumes, ejection fraction, stroke volume (SV), and cardiac output (Qc) were determined by cardiac MR. Cerebral oxygen utilization (VO2) was calculated as cerebral blood flow (CBF) multiplied by venous oxygen saturation (SVO2), measured by MR phase contrast and susceptomtery-based oximetry in the superior sagittal sinus. Results: At rest, there were no differences between groups for any cardiac hemodynamic measure (p&gt;0.05 for all), however cerebral SvO2 and VO2 were lower in the POTS group (p=0.02 for both). In response to LBNP, patients with POTS had greater VOSS (25±21 vs 5±12; p=0.02). Heart rate increased in response to LBNP (p&lt;0.001), but the increase was not different between groups (HC: +9±8bpm; POTS: +13±11bpm; p=0.35). SV and Qc decreased during LBNP (both, p&lt;0.01), despite no change in mean arterial BP (p=0.13) which did not differ between groups (HC: +9±8mmHg; POTS: 3±6mmHg; p=0.377). Additionally, both left and right ventricular volumes as well as ejection fraction decreased during LBNP (p&lt;0.01 for all). The decreased Qc during LBNP coincided with lower CBF in the superior sagittal sinus (p=0.01) although the response was not different between groups (HC: -17±13ml/min; POTS: -25±32ml/min; p=0.51). Cerebral SvO2 also decreased during LBNP (p=0.03) indicating increased oxygen extraction, resulting in no change in cerebral VO2 during LBNP (p=0.28) and no difference between groups in the VO2 response (HC: -0.2±3.7ml/min; POTS: +1.1±2.0ml/min; p=0.33). Conclusion: In response to a simulated orthostatic challenge (-25mmHg LBNP), patients with POTS do not have impaired cardiac function or cerebral oxygenation despite having a higher symptom score; however, a stronger stimulus may have been necessary to expose differences. Further investigations are needed to elucidate mechanisms of autonomic dysfunction in this population. Women and Children's Health Research Institute. 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 aerobic exercise training on cerebral pulsatile hemodynamics in middle-aged adults with elevated blood pressure/stage 1 hypertension.

Mechanisms behind the protective effects of aerobic exercise on brain health remain elusive but may be vascular in origin and relate to cerebral pulsatility. This pilot study investigated the effects of 12-wk aerobic exercise training on cerebral pulsatility and its vascular contributors (large artery stiffness, characteristic impedance) in at-risk middle-aged adults. Twenty-eight inactive middle-aged adults with elevated blood pressure or stage 1 hypertension were assigned to either moderate/vigorous aerobic exercise training (AET) for 3 days/wk or no-exercise control (CON) group. Middle cerebral artery (MCA) pulsatility index (PI), large artery (i.e., aorta, carotid) stiffness, and characteristic impedance were assessed via Doppler and tonometry at baseline, 6, and 12 wk, whereas cardiorespiratory fitness (V̇o2peak) was assessed via incremental exercise test and cognitive function via computerized battery at baseline and 12 wk. V̇o2peak increased 6% in AET and decreased 4% in CON (P < 0.05). Proximal aortic compliance increased (P = 0.04, partial η2 = 0.14) and aortic characteristic impedance decreased (P = 0.02, partial η2 = 0.17) with AET but not CON. Cerebral pulsatility showed a medium-to-large effect size increase with AET, although not statistically significant (P = 0.07, partial η2 = 0.11) compared with CON. Working memory reaction time improved with AET but not CON (P = 0.02, partial η2 = 0.20). Our data suggest 12-wk AET elicited improvements in central vascular hemodynamics (e.g., proximal aortic compliance and characteristic impedance) along with apparent, paradoxical increases in cerebral pulsatile hemodynamics.NEW & NOTEWORTHY We identify differential central versus cerebrovascular responses to 12 wk of aerobic exercise training in middle-aged adults. Although proximal aortic compliance and characteristic impedance improved after 12 wk of exercise, cerebral pulsatility tended to unexpectedly increase. These data suggest short-term aerobic exercise training may lead to more immediate benefits in the central vasculature, whereas longer duration exercise training may be required for beneficial changes in pulsatility within the cerebrovasculature.

The effect of hypertension on cerebrovascular carbon dioxide reactivity in atrial fibrillation patients

Atrial fibrillation (AF) and hypertension (HTN) are both associated with impaired cerebrovascular carbon dioxide reactivity (CVRCO2), an indicator of cerebral vasodilatory reserve. We hypothesised that CVRCO2 would be lower in patients with both AF and HTN (AF + HTN) compared to normotensive AF patients, due to an additive effect of AF and HTN on CVRCO2. Forty AF (68 ± 9 years) and fifty-seven AF + HTN (68 ± 8 years) patients underwent transcranial Doppler ultrasound measurement of middle cerebral artery blood velocity (MCA Vm) during stepped increases and decreases in end-tidal carbon dioxide (PETCO2). A cerebrovascular conductance index (CVCi) was calculated as the ratio of MCA Vm and mean arterial pressure (MAP). CVRCO2 was determined from the linear slope for MCA Vm and MCA CVCi vs PETCO2. Baseline MAP was higher in AF + HTN than AF (107 ± 9 vs. 98 ± 9 mmHg, respectively; p < 0.001), while MCA Vm was not different (AF + HTN:49.6 [44.1–69.0]; AF:51.7 [45.2–63.3] cm.s−1; p = 0.075), and CVCi was lower in AF + HTN (0.46 [0.42–0.57] vs. 0.54 [0.44–0.63] cm.s−1.mmHg−1; p < 0.001). MCA Vm CVRCO2 was not different (AF + HTN: 1.70 [1.47–2.19]; AF 1.74 [1.54–2.52] cm/s/mmHg−2; p = 0.221), while CVCi CVRCO2 was 13% lower in AF + HTN (0.013 ± 0.004 vs 0.015 ± 0.005 cm.s−1.mmHg−1; p = 0.047). Our results demonstrate blunted cerebral vasodilatory reserve (determined as MCA CVCi CVRCO2) in AF + HTN compared to AF alone. This may implicate HTN as a driver of further cerebrovascular dysfunction in AF that may be important for the development of AF-related cerebrovascular events and downstream cognitive decline.We demonstrated reduced cerebrovascular CO2 responsiveness in atrial fibrillation with hypertension (AF+HTN) vs. atrial fibrillation (AF). Furthermore, AF per se (as opposed to normal sinus rhythm) predicts reduced cerebrovascular CO2 responsiveness. Our findings suggest additional cerebrovascular dysfunction in AF+HTN vs. AF.

Neurovascular Coupling in Acutely Concussed Adolescent Patients.

Neurovascular coupling (NVC) uniquely describes cerebrovascular response to neural activation and has demonstrated impairments following concussion in adult patients. It is currently unclear how adolescent patients experience impaired NVC acutely following concussion during this dynamic phase of physiological development. The purpose of this study was to investigate NVC in acutely concussed adolescent patients relative to controls. We recruited patients presenting to a sports medicine practice within 28 days of a concussion or a musculoskeletal injury (controls). Transcranial Doppler ultrasound was used to measure changes in patients' posterior cerebral artery (PCA) velocity in response to two progressively challenging visual tasks: (1) reading and (2) visual search. Each task was presented in five 1-min trials (20 sec eyes closed/40 sec eyes open). Resting PCA velocity data were derived by averaging PCA velocity across a 2-min baseline period that preceded the visual tasks. Filtered task data were converted to time-series curves representing 40 consecutive 1-sec averages for each trial. Curves were then averaged across the five trials and time-aligned to stimulus onset (eyes open) to generate a single ensemble-averaged 40-sec curve representing NVC response for each participant for each task. Independent t tests were used to assess group differences (concussion vs. control) in resting PCA velocity. Separate linear mixed-effects models were used to evaluate group differences (concussion vs. control) in NVC response profiles for both visual tasks and group-by-task interaction. Twenty-one concussion patients (female = 8 [38.1%]; age = 14.4 ± 1.9 years) and 20 controls (female = 7 [35.0%]; age = 14.4 ± 1.9 years) were included in our analysis. Average resting PCA velocity did not significantly differ between concussion patients (36.6 ± 8.0 cm/sec) and controls (39.3 ± 8.5 cm/sec) (t39 = 1.06; p = 0.30). There were no significant group differences in relative NVC response curves during the reading task (F1,1560 = 2.23; p = 0.14) or the visual search task (F1,1521 = 2.04; p = 0.15). In contrast, the differential response to task (e.g., increase from reading task to visual search task) was significantly greater in concussion patients than in controls (p < 0.0001). The NVC response to the visual search task was 7.1% higher than the response to reading in concussion patients relative to being 5.5% higher in controls. Our data indicate that concussed patients present with a significantly greater response to more difficult tasks than do controls, suggesting that concussed adolescents require increased neural resource allocation as task difficulty increases. The study provides insight into the neurophysiological consequences of concussion in adolescent patients.

Cool head-out water immersion does not alter cerebrovascular reactivity to hypercapnia despite elevated middle cerebral artery blood velocity: A pilot study.

Episodic increases in cerebral blood flow (CBF) are thought to contribute to improved cerebrovascular function and health. Head-out water immersion (HOWI) may be a useful modality to increase CBF secondary to the hydrostatic pressure placed on the body. However, it is unclear whether water temperatures common to the general public elicit similar cerebrovascular responses. We tested the hypothesis that mean middle cerebral artery blood velocity (MCAvmean) and cerebrovascular reactivity to CO2 (CVRCO2) would be higher during an acute bout of thermoneutral (TN; 35°C) vs. cool (COOL; 25°C) HOWI. Ten healthy participants (age: 23±3 y; 4 women) completed two randomized HOWI visits. Right MCAvmean, end-tidal CO2 (PETCO2) mean arterial pressure (MAP), and MCA conductance (MCAvmean/MAP) were continuously recorded. CVRCO2 was assessed using a stepped hypercapnia protocol before (PRE), at 30 minutes of HOWI (HOWI), immediately after HOWI (POST-1), and 45 minutes after HOWI (POST-2). Absolute values are reported as mean ± SD. MCAvmean, PETCO2, MAP, and CVRCO2 were not different between conditions at any timepoint (all P≥0.17). In COOL, MCAvmean increased from PRE (61±9 cm/s) during HOWI (68±11 cm/s), at POST-1 (69±11 cm/s), and POST-2 (72±8 cm/s) (all P<0.01), and in TN from PRE to POST-1 (66±13 vs. 71±14 cm/s; P = 0.05). PETCO2 did not change over time in either condition. In COOL, MAP increased from PRE (85±5 mmHg) during HOWI (101±4 mmHg), at POST-1 (97±7 mmHg), and POST-2 (96±9 mmHg), and in TN from PRE (88±5 mmHg) at HOWI (98±7 mmHg) and POST-1 (99±8 mmHg) (all P<0.01). In COOL, CVRCO2 increased from PRE to HOWI (1.66±0.55 vs. 1.92±0.52 cm/s/mmHg; P = 0.04). MCA conductance was not different between or within conditions. These data indicate that 30 minutes of cool HOWI augments MCAvmean and that the increase in MCAvmean persists beyond cool HOWI. However, cool HOWI does not alter CVRCO2 in healthy young adults.

Pathogenic soluble tau peptide disrupts endothelial calcium signaling and vasodilation in the brain microvasculature

The accumulation of the microtubule-associated tau protein in and around blood vessels contributes to brain microvascular dysfunction through mechanisms that are incompletely understood. Delivery of nutrients to active neurons in the brain relies on capillary calcium (Ca2+) signals to direct blood flow. The initiation and amplification of endothelial cell Ca2+ signals require an intact microtubule cytoskeleton. Since tau accumulation in endothelial cells disrupts native microtubule stability, we reasoned that tau-induced microtubule destabilization would impair endothelial Ca2+ signaling. We tested the hypothesis that tau disrupts the regulation of local cerebral blood flow by reducing endothelial cell Ca2+ signals and endothelial-dependent vasodilation. We used a pathogenic soluble tau peptide (T-peptide) model of tau aggregation and mice with genetically encoded endothelial Ca2+ sensors to measure cerebrovascular endothelial responses to tau exposure. T-peptide significantly attenuated endothelial Ca2+ activity and cortical capillary blood flow in vivo. Further, T-peptide application constricted pressurized cerebral arteries and inhibited endothelium-dependent vasodilation. This study demonstrates that pathogenic tau alters cerebrovascular function through direct attenuation of endothelial Ca2+ signaling and endothelium-dependent vasodilation.