Cerebral Artery Mean Blood Velocity Research Articles

Directional sensitivity of the cerebral pressure-flow relationship during forced oscillations induced by oscillatory lower body negative pressure.

A directional sensitivity of the cerebral pressure-flow relationship has been described using repeated squat-stands. Oscillatory lower body negative pressure (OLBNP) is a reproducible method to characterize dynamic cerebral autoregulation (dCA). It could represent a safer method to examine the directional sensitivity of the cerebral pressure-flow relationship within clinical populations and/or during pharmaceutical administration. Therefore, examining the cerebral pressure-flow directional sensitivity during an OLBNP-induced cyclic physiological stress is crucial. We calculated changes in middle cerebral artery mean blood velocity (MCAv) per alterations to mean arterial pressure (MAP) to compute ratios adjusted for time intervals (ΔMCAvT/ΔMAPT) with respect to the minimum-to-maximum MCAv and MAP, for each OLBNP transition (0 to -90 Torr), during 0.05 Hz and 0.10 Hz OLBNP. We then compared averaged ΔMCAvT/ΔMAPT during OLBNP-induced MAP increases (INC) (ΔMCAvT/) and decreases (DEC) (ΔMCAvT/). Nineteen healthy participants [9 females; 30 ± 6 years] were included. There were no differences in ΔMCAvT/ΔMAPT between INC and DEC at 0.05 Hz. ΔMCAvT/ (1.06 ± 0.35 vs. 1.33 ± 0.60 cm⋅s-1/mmHg; p = 0.0076) was lower than ΔMCAvT/ at 0.10 Hz. These results support OLBNP as a model to evaluate the directional sensitivity of the cerebral pressure-flow relationship.

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.

Comparison of the Buffalo Concussion Treadmill Test With a Physiologically Informed Cycle Test: Calgary Concussion Cycle Test.

Sport-related concussions are a complex injury requiring multifaceted assessment, including physical exertion. Currently, concussion testing relies primarily on a treadmill-based protocol for assessing exertion-related symptoms in persons after concussion. This study compared a modified cycle protocol (Calgary Concussion Cycle Test [CCCT]) with the clinically adopted standard, the Buffalo Concussion Treadmill Test (BCTT), across multiple physiological parameters. Treadmill and cycle matched workload protocols would produce similar results for cerebral blood velocity, mean arterial pressure (MAP), and end-tidal carbon dioxide partial pressure (PETCO2), but heart rate (HR) and oxygen consumption (VO2) would be higher on the treadmill than the cycle modality. Crossover study design. Level 3. A total of 17 healthy adults (8 men, 9 women; age, 26 ± 3 years; body mass index, 23.8 ± 2.7 kg/m2) completed the BCTT and CCCT protocols, 7 days apart in a randomized order. During both exertional protocols, the physiological parameters measured were middle cerebral artery mean blood velocity (MCAv), MAP, PETCO2, VO2, and HR. Analysis of variance with effect size computations, coefficient of variation, and Bland-Altman plots with 95% limits of agreement were used to compare exercise tests. The BCTT and CCCT produced comparable results for both male and female participants with no significant differences for average MCAv, MAP, and PETCO2 (all P > 0.05; all generalized eta squared [η2G] < 0.02 [negligible]; P value range, 0.29-0.99) between stages. When accounting for exercise stage and modality, VO2 (P < 0.01) and HR (P < 0.01) were higher on the treadmill compared with the cycle. Aside from the final few stages, all physiology measures displayed good-to-excellent agreeability/variability. The CCCT was physiologically similar to the BCTT in terms of MCAv, PETCO2, and MAP; however, HR and VO2 differed between modalities. Providing a cycle-based modality to exertional testing after injury mayincrease accessibility to determine symptom thresholds in the future.

Cerebral vascular function in young, healthy non-Hispanic Black and White females

Non-Hispanic Black (BL) individuals are ~2-times more likely to suffer from conditions including cognitive dysfunction and Alzheimer’s disease and related dementias (ADRD) – conditions which are among the fastest growing causes of morbidity and mortality in the US. The prevalence of ADRD is expected to double by 2060 with a more rapid increase in the BL (and Hispanic) population. Importantly, reduced vascular function, particularly in the cerebral circulation, contributes to elevated risk for and prevalence of ADRD. While previous research has provided valuable insight into mechanisms of cerebral vascular dysfunction, this work has been primarily conducted in males and has largely not included socioeconomic/racial discrimination measurements, which are critical to understanding race/ethnicity-related disparities in cerebral vascular health. To our knowledge no studies have specifically examined cerebral vascular function in young, healthy BL females relative to WH females. Therefore, we tested the hypothesis that cerebral vascular function would be blunted in BL relative to WH females. METHODS: Eleven healthy WH (age: 26±7 yr; BMI: 26±3 kg/m2) and 17 healthy (age: 21±2 yr; BMI: 26±4 kg/m2) BL females participated. Beat-to-beat blood pressure, end-tidal carbon dioxide tension, and middle cerebral artery mean blood velocity (MCAVmean) were continuously collected. Transfer function analysis (i.e. gain, phase, and coherence) of blood pressure and MCAVmean were calculated in the very-low, low, and high-frequency ranges to assess cerebral autoregulation. Cerebral vascular function was also assessed as the % increase in MCA vascular conductance (CVCi = MCAVmean/mean arterial pressure) during administration of a hypercapnic gas (6% CO2 gas). Socioeconomic background and psychosocial stress exposures were assessed as: 1) parental education level; 2) adverse childhood experiences (ACEs); and 3) perceived ethnic discrimination (PEDQ). RESULTS: Transfer function analysis of gain, phase, and coherence was similar across all frequency ranges ( P&gt;0.05 for all) and the % increase in CVCi ( P=0.71) during hypercapnia was similar between BL and WH females. Although perceived ethnic discrimination was greater in BL relative to WH females ( P&lt;0.001), there were no group differences in parental education level nor ACEs ( P&gt;0.05 for both). CONCLUSION: These preliminary data suggest that cerebral vascular function is not different between young, healthy BL and WH females of similar socioeconomic background. Future studies should continue to examine these relationships but expand inclusion to a wider age group with a greater diversity in socioeconomic background. Funding: NIH R15 (HL156128, RMB) &amp; AHA Predoctoral Fellowship (915133, ZTM) 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.

Ingestion of carbonated water increases middle cerebral artery blood velocity and improves mood states in resting humans exposed to ambient heat stress

Sugar-free carbonated water is consumed worldwide. The consumption of carbonated water is high in summer, when the heat loss responses of sweating and skin vasodilation are activated, and thermal perceptions (thermal sensation and comfort) and mood states are negatively modulated. However, whether ingesting carbonated water under ambient heat exposure modulates cerebral blood flow index, heat loss responses, thermal perceptions, and mood states remains to be determined. In this study, 17 healthy, habitually active, young adults (eight women) ingested 4 °C noncarbonated or carbonated water under 37 °C ambient heat-stressed resting conditions. Both drinks increased the middle cerebral artery mean blood velocity, an index of cerebral blood flow, and mean arterial pressure, with carbonated water exhibiting higher elevations than noncarbonated water (P < 0.05). However, the heart rate, sweat rate, and skin blood flow during and after drinking remained unchanged between the two conditions (P > 0.05). The thermal sensation and comfort after drinking remained unchanged between the two conditions (P > 0.05); but, a drink-induced reduction in sleepiness was higher, and drink-induced elevations in motivation and exhilaration were higher after ingesting carbonated water than those after ingesting noncarbonated water (P < 0.05). The analyses suggest that in humans under ambient heat-stressed resting conditions, ingestion of cold carbonated water increases the cerebral blood flow index, blood pressure, motivation, and exhilaration, whereas it decreases sleepiness relative to ingestion of noncarbonated cold water. However, ingestion of cold carbonated water fails to modulate thermoregulatory responses and thermal perception as opposed to noncarbonated cold water.

Influence of high‐intensity interval training to exhaustion on the directional sensitivity of the cerebral pressure‐flow relationship in young endurance‐trained men

We previously reported subtle dynamic cerebral autoregulation (dCA) alterations following 6 weeks of high‐intensity interval training (HIIT) to exhaustion using transfer function analysis (TFA) on forced mean arterial pressure (MAP) oscillations in young endurance‐trained men. However, accumulating evidence suggests the cerebrovasculature better buffers cerebral blood flow changes when MAP acutely increases compared to when MAP acutely decreases. Whether HIIT affects the directional sensitivity of the cerebral pressure‐flow relationship in these athletes is unknown. In 18 endurance‐trained men (age: 27 ± 6 years, VO2max: 55.5 ± 4.7 ml·kg−1·min−1), we evaluated the impact of 6 weeks of HIIT to exhaustion on dCA directionality using induced MAP oscillations during 5‐min 0.05 and 0.10 Hz repeated squat‐stands. We calculated time‐adjusted changes in middle cerebral artery mean blood velocity (MCAv) per change in MAP (ΔMCAvT/ΔMAPT) for each squat transition. Then, we compared averaged ΔMCAvT/ΔMAPT during MAP increases and decreases. Before HIIT, ΔMCAvT/ΔMAPT was comparable between MAP increases and decreases during 0.05 Hz repeated squat‐stands (p = 0.518). During 0.10 Hz repeated squat‐stands, ΔMCAvT/ΔMAPT was lower during MAP increases versus decreases (0.87 ± 0.17 vs. 0.99 ± 0.23 cm·s−1·mmHg−1, p = 0.030). Following HIIT, ΔMCAvT/ΔMAPT was superior during MAP increases over decreases during 0.05 Hz repeated squat‐stands (0.97 ± 0.38 vs. 0.77 ± 0.35 cm·s−1·mmHg−1, p = 0.002). During 0.10 Hz repeated squat‐stands, dCA directional sensitivity disappeared (p = 0.359). These results suggest the potential for HIIT to influence the directional sensitivity of the cerebral pressure‐flow relationship in young endurance‐trained men.

Acute Impact of JUUL Electronic Cigarette use on Cerebral Vascular Vasodilator Responsiveness

BackgroundCardiovascular disease is a major cause of death among cigarette smokers and is responsible for ~30% of heart disease related mortality in the U.S each year. Although cigarette smoking rates have declined in recent years, the use of electronic cigarettes (e‐cigarettes) continues to gain popularity in the U.S. and have generated widespread debate within the public health community, mostly due to the lack of scientific evidence regarding their safety and impact on health and behavior. The increasing rates of e‐cigarette use in the U.S have been largely attributed to the recent emergence of the high‐nicotine‐delivery pod‐based devices such as JUUL. Unlike e‐cigarettes, the literature surrounding the health impact of combustible cigarette smoking is well developed with overwhelming evidence of an adverse impact on various cardiovascular outcomes including impaired cerebral perfusion/vascular function. However, the impact of e‐cigarettes on cerebral vascular function remains to be elucidated, representing a major knowledge gap and research priority.HypothesisThis study tested the hypothesis that acute e‐cigarette vaping (JUUL) will impair cerebral vascular function as indexed by the cerebral vasodilatory responsiveness to a hypercapnic stimulus.MethodsA total of 16 adult smokers (mean age=25±5 yrs.) participated in this pilot study which occurred following an overnight fast. Cerebral vascular function was assessed as the hyperemic response to rebreathing‐induced hypercapnia before and ~45 min following a vaping session (10 puffs; 3s each, separated by 30s intervals). Heart rate (ECG), respiration (Pneumotrace), beat‐to‐beat blood pressure (Finometer), middle cerebral artery mean blood velocity (MCAv ‐ transcranial Doppler) and breath‐by‐breath end‐tidal carbon dioxide concentration (PETCO2‐ capnograph) were continuously measured. Cerebral vascular conductance index (CVCi) was calculated as MCAv / mean arterial pressure. Cerebral vasodilatory responsiveness was assessed as % increase in CVCi (%CVCi) during the highest common magnitude of hypercapnia achieved during the pre‐ and post‐vaping trials.ResultsAll CVCi data are reported at the highest common magnitude of hypercapnia achieved during the pre‐ and post‐vaping sessions (ΔPETCO2Pre: 13±2 mmHg, ΔPETCO2 Post: 12±2 mmHg; P=0.11). Cerebral vascular function/vasodilatory responsiveness, as assessed by the CVCi response to the hypercapnic challenge was significantly blunted following the vaping session (Pre: +52±25%, Post: +42±14%; P=0.04).ConclusionsOur preliminary results suggest that e‐cigarette vaping using JUUL acutely impairs cerebral vascular function as indexed by cerebral vasodilatory responsiveness to a hypercapnic challenge. These findings highlight the need for longitudinal studies to assess the long‐term impact of JUUL use on cerebral vascular function as well as other indices of cardiovascular health.

Cerebral haemodynamics during arrhythmia in health, ischaemic heart disease and heart failure with reduced ejection fraction, and in a preclinical swine model.

Ventricular arrhythmias are associated with neurological impairment and could represent a source of cerebral hypoperfusion. In the present study, data from healthy individuals (n=11), patients with ischaemic heart disease (IHD; ejection fraction >40%; n=9) and patients with heart failure with reduced ejection fraction (HFrEF; EF = 31 (5)%, n=11), as well as data from swine surgeries, where spontaneous ventricular arrhythmias were observed during cerebrovascular examination (transcranial Doppler ultrasound in humans and laser Doppler in swine) were analysed retrospectively to investigate the effect of arrhythmia on cerebral microvascular haemodynamics. A subset of participants also completed the Montreal Cognitive Assessment (MoCA). Middle cerebral artery mean blood velocity (MCAVmean ) decreased during premature ventricular contraction (PVC) in all groups, and data from swine indicate PVCs reduced cerebral microvascular perfusion. Overall MCAVmean was decreased in the HFrEF vs. control group. Further, %∆MCAVmean /%∆mean arterial pressure during the PVC was greater in the HFrEF vs. control group and was correlated with decreased MoCA scores. Subanalysis of HFrEF data revealed that during bigeminy MCAVmean decreased owing to reductions during irregular beats only. During non-sustained ventricular tachycardia, MCAVmean decreased but recovered above baseline upon return to sinus rhythm. Also, haemodynamic perturbations during and following the PVC were greater in the brachial artery vs. the MCA. Therefore, ventricular arrhythmias decreased indices of cerebral perfusion irrespective of IHD or HFrEF. The relative magnitude of arrhythmia-induced haemodynamic perturbations appears to be population specific and arrhythmia type and organ dependent. The cumulative burden of arrhythmia-induced deficits may exacerbate existing cerebral hypoperfusion in HFrEF and contribute to neurological abnormalities in this population. KEY POINTS: Irregular heartbeats are often considered benign in isolation, but individuals who experience them frequently have a higher prevalence of cerebrovascular and/or cognitive associated disorders. How irregular heartbeats affect blood pressure and cerebral haemodynamics in healthy and cardiovascular disease patients, those with and without reduced ejection fraction, remains unknown. Here it was found that in the absence of symptoms associated with irregular heartbeats, such as dizziness or hypotension, single, multiple non-sustained and sustained irregular heartbeats influence cerebral haemodynamics in a population-specific, arrhythmia-type and organ-dependent manner. Relative deficits in the index of cerebral blood flow normalized to relative deficits in blood pressure were greatest in patients with heart failure with reduced ejection and inversely related with cognitive performance. Chronic arrhythmias may exacerbate existing cerebral hypoperfusion in heart failure with reduced ejection fraction, thereby providing a mechanistic link between otherwise benign irregular heartbeats and cognitive dysfunction, independent of embolism.

Hypercapnia elicits differential vascular and blood flow responses in the cerebral circulation and active skeletal muscles in exercising humans.

The purpose of this study was to investigate the effects of a rise in arterial carbon dioxide pressure (PaCO2) on vascular and blood flow responses in the cerebral circulation and active skeletal muscles during dynamic exercise in humans. Thirteen healthy young adults (three women) participated in hypercapnia and normocapnia trials. In both trials, participants performed a two‐legged dynamic knee extension exercise at a constant workload that increased heart rate to roughly 100 beats min−1. In the hypercapnia trial, participants performed the exercise with spontaneous breathing while end‐tidal carbon dioxide pressure (PETCO2), an index of PaCO2, was held at 60 mmHg by inhaling hypercapnic gas (O2: 20.3 ± 0.1%; CO2: 6.0 ± 0.5%). In the normocapnia trial, minute ventilation during exercise was matched to the value in the hypercapnia trial by performing voluntary hyperventilation with PETCO2 clamped at baseline level (i.e., 40–45 mmHg) through inhalation of mildly hypercapnic gas (O2: 20.6 ± 0.1%; CO2: 2.7 ± 1.0%). Middle cerebral artery mean blood velocity and the cerebral vascular conductance index were higher in the hypercapnia trial than in the normocapnia trial. By contrast, vascular conductance in the exercising leg was lower in the hypercapnia trial than in the normocapnia trial. Blood flow to the exercising leg did not differ between the two trials. These results demonstrate that hypercapnia‐induced vasomotion in active skeletal muscles is opposite to that in the cerebral circulation. These differential vascular responses may cause a preferential rise in cerebral blood flow.

Directional sensitivity of the cerebral pressure-flow relationship in young healthy individuals trained in endurance and resistance exercise.

What is the central question of this study? Does habitual exercise modality affect the directionality of the cerebral pressure-flow relationship? What is the main finding and its importance? These data suggest the hysteresis-like pattern of dynamic cerebral autoregulation appears present in long-term sedentary and endurance-trained individuals, but absent in resistance-trained individuals. This is the first study to expand knowledge on the directional sensitivity of the cerebral pressure-flow relationship to trained populations. Evidence suggests the cerebrovasculature may be more efficient at dampening cerebral blood flow (CBF) variations when mean arterial pressure (MAP) transiently increases, compared to when it decreases. Despite divergent MAP and CBF responses to acute endurance and resistance training, the long-term impact of habitual exercise modality on the directionality of dynamic cerebral autoregulation (dCA) is currently unknown. Thirty-six young healthy participants (sedentary (n=12), endurance-trained (n=12), and resistance-trained (n=12)) undertook a 5-min repeated squat-stand protocol at two forced MAP oscillation frequencies (0.05 and 0.10Hz). Middle cerebral artery mean blood velocity (MCAv) and MAP were continuously monitored. We calculated absolute (ΔMCAvT /ΔMAPT ) and relative (%MCAvT /%MAPT ) changes in MCAv and MAP with respect to the transition time intervals of both variables to compute a time-adjusted ratio in each MAP direction, averaged over the 5-min repeated squat-stand protocols. At 0.10Hz repeated squat-stands, ΔMCAvT /ΔMAPT and %MCAvT /%MAPT were lower when MAP increased compared with when MAP decreased for sedentary (ΔMCAvT /ΔMAPT : P=0.032; %MCAvT /%MAPT : P=0.040) and endurance-trained individuals (ΔMCAvT /ΔMAPT : P=0.012; %MCAvT /%MAPT P=0.007), but not in the resistance-trained individuals (ΔMCAvT /ΔMAPT : P=0.512; %MCAvT /%MAPT P=0.666). At 0.05Hz repeated squat-stands, time-adjusted ratios were similar for all groups (all P>0.605). These findings suggest exercise training modality does influence the directionality of the cerebral pressure-flow relationship and support the presence of a hysteresis-like pattern during 0.10Hz repeated squat-stands in sedentary and endurance-trained participants, but not in resistance-trained individuals. In future studies, assessment of elite endurance and resistance training habits may further elucidate modality-dependent discrepancies on directional dCA measurements.

Acute Gravitational Stress Selectively Impairs Dynamic Cerebrovascular Reactivity in the Anterior Circulation Independent of Changes to the Central Respiratory Chemoreflex.

Cerebrovascular reactivity (CVR) to changes in the partial pressure of arterial carbon dioxide (PaCO2) is an important mechanism that maintains CO2 or pH homeostasis in the brain. To what extent this is influenced by gravitational stress and corresponding implications for the regulation of cerebral blood flow (CBF) remain unclear. The present study examined the onset responses of pulmonary ventilation (V̇E) and anterior middle (MCA) and posterior (PCA) cerebral artery mean blood velocity (Vmean) responses to acute hypercapnia (5% CO2) to infer dynamic changes in the central respiratory chemoreflex and cerebrovascular reactivity (CVR), in supine and 50° head-up tilt (HUT) positions. Each onset response was evaluated using a single-exponential regression model consisting of the response time latency [CO2-response delay (t0)] and time constant (τ). Onset response of V̇E and PCA Vmean to changes in CO2 was unchanged during 50° HUT compared with supine (τ: V̇E, p = 0.707; PCA Vmean, p = 0.071 vs. supine) but the MCA Vmean onset response was faster during supine than during 50° HUT (τ: p = 0.003 vs. supine). These data indicate that gravitational stress selectively impaired dynamic CVR in the anterior cerebral circulation, whereas the posterior circulation was preserved, independent of any changes to the central respiratory chemoreflex. Collectively, our findings highlight the regional heterogeneity underlying CBF regulation that may have translational implications for the microgravity (and hypercapnia) associated with deep-space flight notwithstanding terrestrial orthostatic diseases that have been linked to accelerated cognitive decline and neurodegeneration.

The middle cerebral artery blood velocity response to acute normobaric hypoxia occurs independently of changes in ventilation in humans

What is the central question of this study? Does the ventilatory response to moderate acute hypoxia increase cerebral perfusion independently of changes in arterial oxygen tension in humans? What is the main finding and its importance? The ventilatory response does not increase middle cerebral artery mean blood velocity during moderate isocapnic acute hypoxia beyond that elicited by reduced oxygen saturation. Hypoxia induces ventilatory, cardiovascular and cerebrovascular adjustments to defend against reductions in systemic oxygen delivery. We aimed to determine whether the ventilatory response to moderate acute hypoxia increases cerebral perfusion independently of changes in arterial oxygenation. Eleven young healthy individuals were exposed to four 15min experimental conditions: (1) normoxia (partial pressure of end-tidal oxygen, =100mmHg), (2) hypoxia ( =50mmHg), (3) normoxia with breathing volitionally matched to levels observed during hypoxia (hyperpnoea; =100mmHg) and (4) hypoxia ( =50mmHg) with respiratory frequency and tidal volume volitionally matched to levels observed during normoxia (i.e., restricted breathing (RB)). Isocapnia was maintained in all conditions. Middle cerebral artery mean blood velocity (MCA Vmean ), assessed by transcranial Doppler ultrasound, was increased during hypoxia (58±12cm/s, P=0.04) and hypoxia + RB (61±14cm/s, P<0.001) compared to normoxia (55±11cm/s), while it was unchanged during hyperpnoea (52±13cm/s, P=0.08). MCA Vmean was not different between hypoxia and hypoxia + RB (P>0.05). These findings suggest that the hypoxic ventilatory response does not increase cerebral perfusion, indexed using MCA Vmean , during moderate isocapnic acute hypoxia beyond that elicited by reduced oxygen saturation.

Caffeine Exacerbates Hyperventilation and Reductions in Cerebral Blood Flow in Physically Fit Men Exercising in the Heat.

Caffeine is an exercise performance enhancer widely used by individuals engaged in training or competition under heat-stressed conditions. Caffeine ingestion during exercise in the heat is believed to be safe because it does not greatly affect body temperature responses, heart rate, or body fluid status. However, it remains unknown whether caffeine affects hyperthermia-induced hyperventilation or reductions in the cerebral blood flow index. We tested the hypothesis that under conditions inducing severe hyperthermia, caffeine exacerbates hyperthermia-induced hyperventilation and reduces the cerebral blood flow index during exercise. Using a randomized, single-blind, crossover design, 12 physically active healthy young men (23 ± 2 yr) consumed a moderate dose of caffeine (5 mg·kg-1) or placebo in the heat (37°C). Approximately 60 min after the ingestion, they cycled for ~45 min at a workload equal to ~55% of their predetermined peak oxygen uptake (moderate intensity) until their core temperature increased to 2.0°C above its preexercise baseline level. In both trials, ventilation increased and the cerebral blood flow index assessed by middle cerebral artery mean blood velocity decreased as core temperature rose during exercise (P < 0.05), indicating that hyperthermia-induced hyperventilation and lowering of the cerebral blood flow occurred. When core temperature was elevated by 1.5°C or more (P < 0.05), ventilation was higher and the cerebral blood flow was lower throughout the caffeine trial than the placebo trial (P < 0.05). A moderate dose of caffeine exacerbates hyperthermia-induced hyperventilation and reductions in the cerebral blood flow index during exercise in the heat with severe hyperthermia.

Dynamic characteristics of cerebrovascular reactivity or ventilatory response to change in carbon dioxide.

What is the central question of this study? What are the dynamic characteristics of cerebrovascular carbon dioxide reactivity and the central respiratory chemoreflex? What is the main finding and its importance? The transfer function gain from the end-tidal partial pressure of carbon dioxide to cerebral blood flow or ventilation decreased in the high frequency range at rest and during exercise. These findings indicate that the dynamic characteristics of both systems were not constant in all frequency ranges, and this trend was not modified by exercise. The purpose of this study was to examine the dynamic characteristics of cerebrovascular reactivity and ventilatory response to change in arterial CO2 in all frequency ranges at rest using frequency domain analysis, and also to examine whether this is modified by dynamic exercise as with the traditionally determined cerebrovascular CO2 reactivity. In nine healthy young subjects, at rest and during exercise (cycling exercise at constant predetermined work rate corresponding to a level of 0.90lmin-1 ), the dynamic characteristics of cerebrovascular CO2 reactivity and the central respiratory chemoreflex were assessed by transfer function analysis using a binary white-noise sequence (0-7% inspired CO2 fraction) from the end-tidal partial pressure of CO2 ( ) to the mean middle cerebral artery mean blood velocity (MCA Vm ) or minute ventilation ( ), respectively. In the high frequency range, both transfer function gains decreased but, interestingly, the cut-off frequency in the transfer function gain from to MCA Vm response was higher than that from to response at rest (0.024 vs. 0.015Hz) and during exercise (0.030 vs. 0.011Hz), indicating that cerebrovascular CO2 reactivity or central respiratory chemoreflex was not constant in all frequency ranges, and this trend was not modified by exercise. These findings suggest that dynamic characteristics of the cerebrovascular CO2 reactivity or central chemoreflex need to be assessed to identify the whole system because the traditional method cannot identify the property of time response of these systems.

The reliability of a breath-hold protocol to determine cerebrovascular reactivity in adolescents.

Cerebrovascular reactivity (CVR) is impaired in adolescents with cardiovascular disease risk factors. A breath-hold test is a noninvasive method of assessing CVR, yet there are no reliability data of this outcome in youth. This study aimed to assess the reliability of a breath-hold protocol to measure CVR in adolescents. Twenty-one 13 to 15 year old adolescents visited the laboratory on two separate occasions, to assess the within-test, within-day and between-day reliability of a breath-hold protocol, consisting of three breath-hold attempts. CVR was defined as the relative increase from baseline in middle cerebral artery mean blood velocity following a maximal breath-hold of up to 30 seconds, quantified via transcranial Doppler ultrasonography. Mean breath-hold duration and CVR were never significantly correlated (r < .31, P > .08). The within-test coefficient of variation for CVR was 15.2%, with no significant differences across breath-holds (P = .88), so the three breath-hold attempts were averaged for subsequent analyses. The within- and between-day coefficients of variation for CVR were 10.8% and 15.3%, respectively. CVR assessed via a three breath-hold protocol can be reliably measured in adolescents, yielding similar within- and between-day reliability. Analyses revealed that breath-hold length and CVR were unrelated, indicating the commonly reported normalization of CVR to breath-hold duration (breath-hold index) may be unnecessary in youth.

No Sex Differences in Cerebral Blood Velocity Responses During Resistance Exercise

IntroductionThe brain requires intricate regulation of blood flow to maintain adequate perfusion to the tissue. Resistance exercise (RE) causes large increases in mean arterial pressure that challenges the regulation of cerebral blood flow. It is unknown, however, if the sex differences in blood pressure regulation may alter how cerebral blood flow responds to the large increases in blood pressure induced during RE.PurposeTo determine if the cerebral blood velocity response during an acute bout of RE differs by sex.MethodsTwenty‐nine young, healthy adults (M/F: 17/12; 25 ± 5 yrs; 23.9 ± 3.3 kg/m2) performed 3 sets of 10 repetitions maximal isokinetic knee flexion/extension exercise. Systolic (SBP), diastolic (DBP), and mean (MAP) arterial pressure were measured using finger photoplethysmography and used to calculate pulse pressure (PP). Transcranial Doppler ultrasound (2 MHz) was used to measure right middle cerebral artery mean blood velocity (MCAmv) and calculate pulsatility index ([MCAsystolic ‐ MCAdiastolic velocity]/MCAmv). Conductance was calculated as MCAmv/MAP. The last 30‐sec of a 10‐min baseline and last 10‐sec of the 3rd RE set were averaged for analyses.ResultsOverall, females had higher MCAmv and conductance compared to males (p&lt;0.05). SBP, DBP, MAP, PP, MCAmv increased and conductance decreased similarly for males and females during RE (p&lt;0.05). Pulsatility index did not change during RE in either sex (p&gt;0.05).ConclusionsThe blood pressure and cerebral hemodynamic response during RE was not different between sexes. These data suggest sex may not effect cerebrovascular responses to a large increase in blood pressure incurred during maximal RE in young healthy adults. Blood pressure and cerebral blood velocity responses at baseline and during an acute bout of resistance exercise in young adults. Male (n= 17) Female (n= 12) p for Interaction Baseline Resistance Exercise Baseline Resistance Exercise SBP (mmHg) * 124 ± 10 172 ± 18 123 ± 7 170 ± 27 0.92 DBP (mmHg) * 73 ± 7 99 ± 10 74 ± 7 103 ± 17 0.58 MAP (mmHg) * 93 ± 8 128 ± 13 96 ± 7 132 ± 10 0.80 PP (mmHg) * 52 ± 7 72 ± 11 50 ± 6 67 ± 14 0.42 MCA Mean Velocity (cm/sec) *, ‡ 55 ± 9 65 ± 12 70 ± 15 81 ± 30 0.89 MCA Pulsatility Index 0.90 ± 0.16 0.82 ± 0.14 0.81 ± 0.15 0.82 ± 0.27 0.27 Conductance (cm/sec/mmHg) *, ‡ 0.60 ± 0.09 0.51 ±0.10 0.74 ± 0.17 0.62 ± 0.24 0.39 All data are presented mean ± standard deviation *Main effect for time (p&lt;0.05) ‡Main effect for sex (p&lt;0.05)

Repeatability of Cerebral Vasomotor Reactivity to Hypercapnia in Humans

Impaired cerebrovascular function is a risk factor for the development of various neurocognitive and cerebrovascular diseases including cognitive dysfunction, dementia, Alzheimer’s disease, and stroke. Since hypercapnia elicits a robust cerebral vasodilator response, cerebrovascular function is commonly assessed as an increase in cerebral blood flow to elevations in arterial carbon dioxide (i.e., cerebral vasomotor reactivity ‐ CVMR). Hypercapnia induced by a rebreathing protocol is one such technique used to assess cerebrovascular function. Although this technique is used to evaluate CVMR within and between subjects before and after interventions, to our knowledge, the repeatability of CVMR assessed by rebreathing has not been comprehensively investigated. Moreover, the National Institute of Health’s recent guidelines emphasize the need for rigor and reproducibility of data collection techniques. Accordingly, this study was designed to determine the within‐day repeatability of CVMR response to rebreathing‐induced hypercapnia. Eleven young healthy males (age = 24 ± 3 years, BMI = 24.3 ± 3.8 kgm−2, mean ± SEM) reported to the laboratory following an overnight fast and performed 3 trials of rebreathing‐induced hypercapnia each separated by approximately 2 hours. Heart rate (ECG), respiration (Pneumotrace), beat‐to‐beat blood pressure (Finometer), middle cerebral artery mean blood velocity (MCAv ‐ transcranial Doppler) and breath‐by‐breath end‐tidal carbon dioxide concentration (PETCO2 ‐ capnograph) were continuously measured. Cerebral vascular conductance index (CVCi) was calculated as MCAv divided by mean arterial pressure. CVMR was assessed as the slope of the linear regression between the increase in %MCAv and %CVCi across the range of change in PETCO2 (ΔPETCO2). The increase in %MCAv and %CVCi was also assessed at a ΔPETCO2 of 15 mmHg which was the highest common change in magnitude of hypercapnia achieved across all rebreathing trials among all participants. Repeatability between the 3 trials was assessed using intra class correlation coefficient (ICC). The slopes of %CVCi vs. ΔPETCO2 (3.9 ± 0.4, 3.8 ± 0.3 and 3.6 ± 0.3 %mmHg−1 for 1st, 2nd and 3rd trial respectively, p = 0.82) was not different and showed very good repeatability (ICC = 0.86, p &lt; 0.001) between the 3 rebreathing‐induced hypercapnia trials. Likewise, the % increase in CVCi at ΔPETCO2 of 15 mmHg was not different (40 ± 4, 38 ± 4 and 36 ± 4% for 1st, 2nd and 3rd trial respectively, p = 0.72) and also demonstrated very good repeatability between trials (ICC = 0.86, p &lt; 0.001). Similar results were obtained when MCAv was used as the dependent variable. These results suggest that within‐day CVMR assessed by rebreathing‐induced hypercapnia is highly repeatable and therefore can be used as a reliable index of cerebrovascular function.Support or Funding InformationSupported by UTA College of Nursing and Health Innovation

Cerebrovascular carbon dioxide reactivity is influenced by sex despite comparable hemodynamic and respiratory chemosensitivity in young fit individuals

Cerebral blood flow (CBF) is generally higher in women compared to men at rest. Although accumulating evidence supports sex differences in CBF regulation, findings remain contradictory for dynamic cerebral autoregulation (dCA) and cerebrovascular reactivity to carbon dioxide (CVRCO2). Cardiorespiratory fitness represents an indicator of cardiovascular health. However, we have recently reported that dCA is reduced in young fit men compared to controls, and that dCA is attenuated in young fit women compared to fit men. However, the influence of sex on CVRCO2 in these young fit individuals remains misunderstood. The aim of this study was to examine the influence of sex on CVRCO2 in young fit individuals. Changes in middle cerebral artery mean blood velocity (MCAvmean; transcranial doppler), mean arterial pressure (MAP; photoplethysmography), heart rate (HR; ECG) and pulmonary ventilation (spirometer) were measured in 29 young fit individuals (women n=10, men n=19), in response to changes in end‐tidal partial pressure of carbon dioxide (PETCO2; gas analyzer) during the modified Duffin hyperoxic rebreathing test. Women were tested in the early follicular phase. CVRCO2, as well as hemodynamic and ventilatory chemosensitivity, were characterized using linear regressions on the rebreathing portion of the test after the determined ventilatory recruitment threshold. While age was not different between groups (26 ± 6 vs. 27 ± 5 years, P = 0.92), height: (1.64 ± 0.06 vs. 1.77 ± 0.08 m; P &lt; 0.0001), body weight (60 ± 6 vs. 72 ± 10 kg; P = 0.0009) and maximal oxygen uptake (48.4 ± 3.8 vs. 57.9 ± 6.8 mL−1kg−1min−1; P &lt; 0.0001) were lower in women. At rest, MCAvmean (72 ± 8 cm/s vs. 62 ± 11 cm/s; P = 0.02) and HR (73 ± 8 vs. 64 ± 11 bpm; P = 0.02) were higher in women, whereas MAP was not different between groups (100 ± 19 vs. 97 ± 10 mm Hg; P = 0.73). CVRCO2 was higher in women compared to men, both in absolute (1.59 ± 0.78 vs. 0.35 ± 1.51 cm/s/mm Hg, P = 0.01) and normalized terms (2.19 ± 0.97 vs. 0.54 ± 2.41 %/mm Hg, P = 0.02). Hemodynamic and respiratory chemosensitivity responses during CO2 rebreathing were not different between groups (all P &gt; 0.05). These results indicate that the cerebrovasculature of young fit women is more sensitive to CO2 than men despite comparable hemodynamic and ventilatory chemosensitivity responses.Support or Funding InformationS.I., L.L. and S.M. have been supported by a doctoral training scholarship from the Fonds de recherche du Québec ‐ Santé (FRQS)

Neurovascular Coupling is Not Attenuated During Reflex‐Mediated Sympathetic Activation via Lower Body Negative Pressure in Humans

IntroductionCerebral blood flow is tightly coupled with local neuronal activation and metabolism (i.e., neurovascular coupling; NVC). Attenuated NVC has been identified in several chronic diseases, including hypertension, but the underlying mechanism(s) remains unknown. Raised peripheral sympathetic vasoconstrictor activity can play a malevolent role in the pathology of hypertension and might also contribute to the blunted NVC as cerebral arteries are autonomic innervated. However, the role of sympathetic nervous system in the regulation of cerebral blood flow remains controversial. Given this, the purpose of the current study was to test the hypothesis that reflex‐mediated sympathetic activation via lower body negative pressure (LBNP) blunts NVC in humans.MethodsNVC was assessed using a visual stimulation protocol (5 cycles of 30 s eyes closed and 30 s of reading) in 10 young and healthy participants (3 women; aged 25 ± 3 years). In a randomized and counterbalanced order, NVC assessments were made under control conditions and during graded sympathetic activation via LBNP at −20 mmHg and −40 mmHg. Posterior (PCA) and middle cerebral artery (MCA) mean blood velocity (vmean) were determined (transcranial Doppler ultrasound). Vertebral artery blood flow (VAflow) was measured using duplex Doppler ultrasound and vessel wall tracking software. Mean arterial pressure (finger photoplethysmography), stroke volume (Modelflow), heart rate (electrocardiogram) and the partial pressure of end‐tidal carbon dioxide (PetCO2; capnograph) were obtained. Data are presented as mean ± SD.ResultsLBNP to −20 mmHg and −40 mmHg evoked an anticipated reduction in stroke volume and increase in heart rate, while mean arterial pressure was unchanged. Prior to visual stimulation, PCAvmean and MCAvmean were not different between control, −20 LBNP and −40 LBNP conditions (P&gt;0.05), while VAflow was reduced at −40 mmHg (P=0.02 vs. control). Under control conditions, the NVC test evoked a robust increase in PCAvmean (Δ22 ± 4%), a modest increase in MCAvmean (Δ10 ± 3%), and a moderate rise in VAflow (Δ14 ± 5%). The magnitude of these responses was unaffected by LBNP at both −20 mmHg and −40mmHg (PCAvmean Δ23 ± 4% and Δ23 ± 4%; MCAvmean Δ10 ± 1% and Δ11 ± 4%; VAflow Δ15 ± 3% and Δ16 ± 6%; P&gt;0.05). PetCO2 decreased at −20 mmHg (37.0 ± 3.1 mmHg) and −40 mmHg (36.3 ± 3.1 mmHg) LBNP trials compared to control (40.2 ± 3.7mmHg; P=0.004).ConclusionIn summary, these findings indicate that reflex‐mediated sympathetic activation via LBNP does not blunt the NVC response in healthy humans.Support or Funding InformationFunding received from Coordination for the Improvement of Higher Education Personnel (Finance Code 001) (MS), the University of Auckland (JPF, JFRP) and the Health Research Council of New Zealand (JPF, JFRP).

Six weeks of high-intensity interval training to exhaustion attenuates dynamic cerebral autoregulation without influencing resting cerebral blood velocity in young fit men.

Elevated cardiorespiratory fitness (CRF) is associated with reduced dynamic cerebral autoregulation (dCA), but the impact of exercise training per se on dCA remains equivocal. In addition, resting cerebral blood flow (CBF) and dCA after high‐intensity interval training (HIIT) in individuals with already high CRF remains unknown. We examined to what extent 6 weeks of HIIT affect resting CBF and dCA in cardiorespiratory fit men and explored if potential changes are intensity‐dependent. Endurance‐trained men were assigned to group HIIT85 (85% of maximal aerobic power, 1–7 min effort bouts, n = 8) and HIIT115 (115% of maximal aerobic power, 30 sec to 1 min effort bouts, n = 9). Training sessions were completed until exhaustion 3 times/week over 6 weeks. Mean arterial pressure (MAP) and middle cerebral artery mean blood velocity (MCAvmean) were measured continuously at rest and during repeated squat‐stands (0.05 and 0.10 Hz). Transfer function analysis (TFA) was used to characterize dCA on driven blood pressure oscillations during repeated squat‐stands. Neither training nor intensity had an effect on resting MAP and MCAvmean (both P > 0.05). TFA phase during 0.10 Hz squat‐stands decreased after HIIT irrespective of intensity (HIIT85: 0.77 ± 0.22 vs. 0.67 ± 0.18 radians; HIIT115: pre: 0.62 ± 0.19 vs. post: 0.59 ± 0.13 radians, time effect P = 0.048). These results suggest that HIIT over 6 weeks have no apparent benefits on resting CBF, but a subtle attenuation in dCA is seen posttraining irrespective of intensity training in endurance‐trained men.