Cerebral Vascular Conductance Research Articles

Indices of cerebral vascular function & health in young healthy adults: impact of sex and race

Background: Cerebral vascular diseases and neurocognitive conditions including stroke, cognitive impairment, & Alzheimer’s disease and related dementias are the fastest growing causes of morbidity and mortality. Studies have demonstrated sex differences in indices of physiological function associated with cardiovascular and metabolic disease risk/prevalence. Further, the incidence of these conditions is elevated in Black (BL) individuals; however, BL females have a reduced age adjusted stroke mortality compared to BL males. Reduced cerebral vascular function/health contributes to the risk for these conditions. Limited studies have examined the influence of sex and race on indices of cerebral vascular function/health. This study examined the potential interaction between race and sex in cerebral pulsatility index (PI: index of cerebral vascular stiffness) and cerebral vasomotor reactivity (CVMR) to a hypercapnic challenge (index of cerebral vasodilatory responsiveness). Hypothesis: We hypothesized: 1) females would have reduced PI and elevated CVMR relative to males. 2) BL individuals would exhibit augmented PI and reduced CVMR. 3) BL females would have reduced PI relative to BL males. 4) Lastly, we posit that CVMR will be negatively correlated with PI. Methods: Data is presented from 136 young healthy individuals. 40 BL males (age: 22±3 yr, BMI: 25±4 kg/m²), 37 BL females (age: 21±3 yr, BMI: 24±4 kg/m²), 39 White (WH) males (age: 24±3 yr, BMI: 25±3 kg/m²), and 20 WH females (age: 25±6 yr, BMI: 23±3 kg/m²). Heart rate, beat-to-beat blood pressure, end-tidal carbon dioxide concentration (PETCO2), and middle cerebral artery blood velocity (MCAv) were continuously recorded (minimum of 6 min). Cerebral vascular function/health was indexed as (a) PI ((MCAVv systolic − MCAv diastolic)/MCAv mean). (b) CVMR assessed as % increase in cerebral vascular conductance (CVCi) slope during a hypercapnic challenge (%CVCi/ΔPETCO2). Results: PI was elevated in males (male: 0.86±0.18, female: 0.77±0.11, P=0.03). There was no difference between races (WH: 0.83±0.19, BL: 0.79±0.13, P=0.27) nor was there a sex x race interaction ( P=0.54). CVMR assessed as %CVCi slope was not different between sexes (male: 2.4±1.7 %/mmHg, female: 2.7±1.2 %/mmHg, P=0.16) or BL & WH (WH: 2.7±1.3 %/mmHg, BL: 2.4±1.1 %/mmHg, P=0.16). CVMR was lower in the BL males relative to the BL females (BL male: 2.0±0.9 %/mmHg, BL female: 2.8±1.2 %/mmHg, P=0.002). There was no difference between WH males and females ( P=0.88). Lastly, there was not a significant correlation between PI and CVMR to hypercapnia ( P=0.16). Conclusion: These preliminary data suggest that relatively young and otherwise health White and Black females have augmented indices of cerebral vascular function/health relative to males. Furthermore, BL males have reduced cerebral vasodilatory responsiveness to a hypercapnic stimuli. The University of Texas at Arlington College of Nursing and Health Innovation and Institutional Start up Funds to Dr. Brothers. 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.

The impact of increased daily peanut consumption on indices of peripheral and cerebral vascular function in non-Hispanic Black individuals

Cardiovascular disease, neurocognitive conditions, and cerebral vascular diseases including cognitive impairment, stroke, and Alzheimer’s disease and related dementias disproportionately impact the Non-Hispanic Black (BL) population. The mechanisms are multifactorial but is related to reduced vascular function/health. Our lab, and others, have demonstrated that reduced nitric oxide (NO) bioavailability secondary to oxidative stress, systemic inflammation, and reduced L-arginine bioavailability contributes to reduced vascular function/health in this population. Increased dietary peanut consumption improves various physiological outcomes including blood pressure, cholesterol, type II diabetes, cognitive health, NO bioavailability, and vascular function/health. This improvement is related to increased bioavailability of L-arginine, reduced systemic inflammation, and antioxidant capacity. This study hypothesized that increased daily peanut consumption would improve indices of peripheral and cerebral vascular function/health in a cohort of BL individuals. Methods: Seventeen people participated (11 non-Hispanic White (WH) and 6 BL (age: WH 25±8, BL 21±2; BMI: WH 23±3, BL 22 ± 4; p>0.05 for both). Measures were made before (pre) and after (post) 56 days of daily lightly salted peanut consumption (2 oz/day for females and 3 oz/day for males). Peripheral macro and microvascular function/health was assessed as brachial artery vasodilation (flow mediated dilation, %FMD) and forearm reactive hyperemia (peak mean forearm blood velocity (FBVmean) respectively following 5-min of suprasystolic cuff inflation. Cerebral vascular function/health was assessed as the cerebral vasodilator response during a hypercapnic challenge, i.e., the slope of % cerebral vascular conductance index (CVCi) relative to the change in end-tidal carbon dioxide concentration (ΔPETCO2). Results: There was no effect of race on peripheral macrovascular function assessed as %FMD (WH: 5.3 ±0.89, BL: 6.3 ±1.9 %, p=0.31) or peripheral microvascular function assessed as FBVmean (WH: 82.90 ± 4.5, BL: 72 ± 6.7 cm·s−1, p=0.13). Likewise, there no effect of treatment on %FMD (Pre: 5.4 ± 0.7, Post: 6.2 ± 2.1 %, p=0.46) or FBVmean (Pre: 81.4 ± 6.7, Post: 73.4 ± 8.8 cm·s−1, p=0.27). Lastly, there were no effect of race (WH: 4.0 ± 0.36, BL: 3.9 ± 0.6 %, p=0.85) or treatment (Pre: 3.9 ± 0.56, Post: 4.0 ± 0.39 %, p=0.79) on cerebral vascular function assessed as %CVCi during hypercapnia. Conclusion: The preliminary data suggest that 56 days of increased daily peanut consumption does not induce measurable improvements in indices of vascular function in a cohort of relatively young BL individuals. Future work will continue to assess this effect in a larger cohort of individuals as well as in individuals with existing conditions or diseases (i.e., hypertension, type II diabetes, etc.). Funding: Peanut Institute (982307). 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.

Attenuated pulsatile transition to the cerebral vasculature during high-intensity interval exercise in young healthy men.

What is the central question of this study? High-intensity interval exercise (HIIE) is recommended for its favourable haemodynamic stimulation, but excessive haemodynamic fluctuations may stress the brain: is the cerebral vasculature protected against exaggerated systemic blood flow fluctuation during HIIE? What is the main finding and its importance? Time- and frequency-domain indices of aortic-cerebral pulsatile transition were lowered during HIIE. The findings suggest that the arterial system to the cerebral vasculature may attenuate pulsatile transition during HIIE as a defence mechanism against pulsatile fluctuation for the cerebral vasculature. High-intensity interval exercise (HIIE) is recommended because it provides favourable haemodynamic stimulation, but excessive haemodynamic fluctuations may be an adverse impact on the brain. We tested whether the cerebral vasculature is protected against systemic blood flow fluctuation during HIIE. Fourteen healthy men (age 24 ± 2 years) underwent four 4-min exercises at 80-90% of maximal workload (Wmax ) interspaced by 3-min active rest at 50-60% Wmax . Transcranial Doppler measured middle cerebral artery blood velocity (CBV). Systemic haemodynamics (Modelflow) and aortic pressure (AoP, general transfer function) were estimated from an invasively recorded brachial arterial pressure waveform. Using transfer function analysis, gain and phase between AoP and CBV (0.39-10.0Hz) were calculated. Stroke volume, aortic pulse pressure and pulsatile CBV increased during exercise (time effect: P<0.0001 for all), but a time-domain index of aortic-cerebral pulsatile transition (pulsatile CBV/pulsatile AoP) decreased throughout the exercise bouts (time effect: P<0.0001). Furthermore, transfer function gain reduced, and phase increased throughout the exercise bouts (time effect: P<0.0001 for both), suggesting the attenuation and delay of pulsatile transition. The cerebral vascular conductance index (mean CBV/mean arterial pressure; time effect: P=0.296), an inverse index of cerebral vascular tone, did not change even though systemic vascular conductance increased during exercise (time effect: P<0.0001). The arterial system to the cerebral vasculature may attenuate pulsatile transition during HIIE as a defence mechanism against pulsatile fluctuation for the cerebral vasculature.

NIH Toolbox Cognitive Battery in non-Hispanic Black individuals: role of cerebral vascular function, pulse wave velocity, and psychosocial stress exposure

Non-Hispanic Black (BL) individuals are ~ 2 times more likely to develop cognitive impairment, Alzheimer’s disease, and related dementias (ADRD) relative to other populations. ADRD prevalence is expected to double by 2060, with a greater increase in BL and Hispanic populations. Reduced cerebral vascular function and large elastic artery health increases risk for cognitive decline and ADRD. In addition, psychosocial stress exposure, including at a young age, is a significant predictor of intellectual function and executive attention. However, the relationship between 1) cerebral &amp; peripheral vascular function/health and indices of cognitive function, and 2) psychosocial stress exposure and indices of cognitive function in relatively young, healthy BL individuals are incompletely understood. We tested the hypothesis that cerebral vascular function and large elastic artery health are blunted in BL individuals, which will be associated with reduced cognitive performance. We also hypothesized that psychosocial stress exposure in the BL individuals is negatively associated with cognitive performance. METHODS: Eight BL (2 males; age: 20±1 yr; BMI: 22±3 kg/m2) and 8 WH (4 males; age: 20±3 yr; BMI: 23±2 kg/m2) individuals participated. Cognitive function was indexed using the NIH Toolbox Cognitive Battery which compiles a fluid score (i.e., capacity for new learning and information processing in novel situations), a crystallized score (i.e., past learning experiences), and a total cognition score. Cerebral vascular function was assessed as the % increase in cerebral vascular conductance (CVCi = middle cerebral artery blood velocity/mean arterial pressure) during hypercapnia (6% CO2). Large elastic artery health was assessed as aortic pulse wave velocity (PWV). Psychosocial stress exposure was assessed as adverse childhood experiences (ACEs). RESULTS: The national percentile and age-adjusted fluid and total scores were lower in the BL individuals ( P&lt;0.05 for each), whereas the crystallized score was not different ( P=0.79). The % increase in CVCi during hypercapnia (BL: 32±15, WH: 54±50%, P=0.26) and PWV (BL: 5.7±0.9, WH: 5.7±0.9 m·s-1, P=0.96) was similar between groups. Within the BL individuals there was not a significant correlation between %CVCi or PWV and the fluid, crystallized, or total scores ( P&gt;0.05 for each) while ACEs tended to be negatively associated with total ( P=0.06) but not fluid or crystallized scores ( P&gt;0.05 for each). CONCLUSION: These preliminary data suggest that young, healthy BL individuals may have reduced indices of cognitive function, particularly in the fluid domain, which may be associated with ACEs. This does not appear to be related to cerebral vascular function or large elastic artery stiffness. Future work will continue to assess these relationships in a population with a wider age range and more diverse life experiences. NIH R15 (HL156128, RMB) &amp; Peanut Institute (982307, RMB) 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.

Cerebral vascular function following the acute consumption of caffeinated artificially- and sugar sweetened soft drinks in healthy adults.

Chronic consumption of sugar- and artificially-sweetened beverages (SSB and ASB) are associated with an increased risk of stroke but it is unclear how acute consumption influences cerebral vascular function. Purpose: We hypothesized that: (1) acute consumption of SSB and ASB would augment dynamic cerebral autoregulation (dCA) and attenuate cerebral vascular reactivity to hypercapnia (CVRCO2) compared to water; and (2) dCA and CVRCO2 would be attenuated with SSB compared to ASB and water. Methods: Twelve healthy adults (age: 23 ± 2 years, four females) completed three randomized trials where they drank 500 ml of water, SSB (Mountain Dew®), or ASB (Diet Mountain Dew®). We measured mean arterial pressure (MAP), middle and posterior cerebral artery blood velocities (MCAv and PCAv), and end-tidal CO2 tension (PETCO2). Cerebral vascular conductance was calculated as cerebral artery blood velocity/MAP (MCAc and PCAc). Twenty min after consumption, participants completed a 5 min baseline, and in a counterbalanced order, a CVRCO2 test (3%, 5%, and 7% CO2 in 3 min stages) and a dCA test (squat-stand tests at 0.10 Hz and 0.05 Hz for 5 min each) separated by 10 min. CVRCO2 was calculated as the slope of the linear regression lines of MCAv and PCAv vs. PETCO2. dCA was assessed in the MCA using transfer function analysis. Coherence, gain, and phase were determined in the low frequency (LF; 0.07-0.2 Hz) and very low frequency (VLF; 0.02-0.07 Hz). Results: MCAv and MCAc were lower after SSB (54.11 ± 12.28 cm/s, 0.58 ± 0.15 cm/s/mmHg) and ASB (51.07 ± 9.35 cm/s, 0.52 ± 1.0 cm/s/mmHg) vs. water (62.73 ± 12.96 cm/s, 0.67 ± 0.11 cm/s/mmHg; all P < 0.035), respectively. PCAc was also lower with the ASB compared to water (P = 0.007). MCA CVRCO2 was lower following ASB (1.55 ± 0.38 cm/s/mmHg) vs. water (2.00 ± 0.57 cm/s/mmHg; P = 0.011) but not after SSB (1.90 ± 0.67 cm/s/mmHg; P = 0.593). PCA CVRCO2 did not differ between beverages (P > 0.853). There were no differences between beverages for coherence (P ≥ 0.295), gain (P ≥ 0.058), or phase (P ≥ 0.084) for either frequency. Discussion: Acute consumption of caffeinated SSB and ASB resulted in lower intracranial artery blood velocity and conductance but had a minimal effect on cerebral vascular function as only MCA CVRCO2 was altered with the ASB compared to water.

Effects of Systemic Hypoxia on Motor Control Performance and Brain Blood Flow in Healthy, Young Humans

The brain is an oxygen dependent organ of the human body and adequate blood flow is imperative. To maintain adequate perfusion, in response to stimuli like hypoxia, vasodilation occurs. Fine motor control skills are essential, particularly for in‐flight piloting. Despite the possibility of encountering hypoxia in flight conditions, there is a lack of data on how motor control may be impacted by hypoxia and the corresponding changes in brain blood flow. We hypothesized that motor control would be impaired during hypoxia, despite increased cerebral blood flow. A group of seven subjects between the ages of 20 to 22 performed a motor control task in two counterbalanced conditions, the control (21% O2, 0.03% CO2, nitrogen balance) and the hypoxic exposure (10% O2 with nitrogen balance mix). The motor control task consisted of lateral joystick movements to adjust the angle of a computer visual beam to roll and stop a ball into one of 4 targets (40 targets total in MATLAB). Throughout each trial, heart rate (HR; 3‐lead ECG), beat‐beat arterial blood pressure (MAP; finger photoplethysmography), end‐tidal CO2 (sampling line) and bilateral middle cerebral artery velocity (MCAv; transcranial doppler), an indicator of cerebral blood flow (CBF), were measured. The motor control program recorded the time to target, beam angle, and ball velocity. In poikilocapnic conditions, hypoxic and normoxic gas mixtures were delivered via facemask and on average the subjects desaturated to an SpO2value of 84.1 ± 4.9%. Contrary to our hypothesis, hypoxia had minimal impact on motor control based on time to task completion for both individual trials and overall task (188.9 ± 21.9 s vs 194.7 ± 19.9 s p=0.613). Physiologically, as anticipated, hypoxia increased heart rate significantly in the transition from normoxic to hypoxic stimulus (86.1 ± 4.6 vs 75.7 ± 7.3 bpm; p&lt;0.001) but was not significantly greater in hypoxic motor control (82.7 ± 9.0 bpm) than hypoxia alone (p=0.180). During the motor control task, MCAv (average of both sides) was similar in normoxic (51.6 ± 7.7 cm/sec) and hypoxic conditions (54.2 ± 8.7 cm/sec; p=0.414). However, MCA during hypoxic motor control was higher than that in hypoxic rest (49.1±10.3 cm/sec; p=0.025), whereas motor control during normoxia did not significantly increase MBV from rest (49.7 ± 7.4; p=0.17). Results were similar when analyzed based on cerebral vascular conductance (MBV/MAP). The present results suggest that mild systemic hypoxia does not impact performance in a simple motor control task, and this may be because of an increase in brain blood flow.

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.

Cerebrovascular Dynamics During Light Exercise

Cerebral blood flow (CBF) dynamic response to moderate‐intensity exercise has a time delay (TD) of ~ 40s. This is dramatically longer compared to other physiological responses to exercise (e.g. skeletal muscle blood flow &lt;10 s) and CBF response to other stimuli (e.g. hypercapnia, thigh cuff occlusion, ~ 10‐20 s). A possible explanation is that a rest‐to‐exercise transition induces a brief hypotensive response due to intensity dependent rapid vasodilation of the periphery (exercise‐onset hypotension, EoH).PurposeTo determine if the magnitude and timing of EoH, effectively reduces CBF at exercise onset causing the longer observed TD. To test this, we modelled CBF kinetic response to light‐intensity exercise to mitigate the magnitude of EoH and determine if components of the CBF response were quickened in young healthy adults.Methods26 young healthy adults (13 Women, 23.8 ± 4 yrs; 23.9 ± 2.9 kg/m2) completed a rest (2min seated quietly, BL) to exercise (3 minutes at 50W, EX) transition on a recumbent cycle ergometer. Middle cerebral artery velocity (MCAv; transcranial doppler) and mean arterial pressure (MAP; finger photoplethysmography) were measured on a heartbeat‐by‐heartbeat basis. End‐tidal CO2 (EtCO2) was measured using breath‐by‐breath capnography. Cerebral vascular conductance index (CVCi) was calculated as (CVCi = MCAv/MAP *100 mmHg). Change in MCAv data (ΔMCAv = MCAvEX‐MCAvBL) were averaged into 2 s bins and fit to a monoexponential model (ΔMCAv(t)= Amp(1‐e‐(t‐TD)/ τ)). Time delay (TD), tau (τ), and mean response time (MRT = TD + τ) were obtained from the model. Several subjects (N=11) exhibited little to no TD (TD &lt; 1 s), these subjects (FAST) were separated out and compared to individuals with longer TDs (TD ≥ 3 s; SLOW). Comparisons were made using an independent t‐test.ResultsAll data is mean±SD. In total, subjects exhibited a TD of 15.4 ± 18.2 s, τ of 79.8 ± 139.7, and MRT of 95.3 ± 134.9 s. This coincided with a ΔMAPNADIR (‐14.5 ± 8.2 mmHg), ΔMCAvNADIR (‐5.7 ± 5.8 cm/s) which occurred at similar times (14.0 ± 17.2 vs. 18.6 ± 14.4 s; p=0.30 MAPNADIR vs. MCAvNADIR), and ΔCVCiMAX (25.3 ± 34.0 cm/s/100mmHg). When data were split, the FAST group experienced a faster TD compared to SLOW (0.01 ± 0.01 vs. 26.8 ± 16.4 s; p&lt;0.001). ΔMCAvNADIR although different (‐1.0 ± 4.0 vs. ‐9.1 ± 4.2 cm/s; p&lt;0.001, FAST vs. SLOW), occurred at similar times (20.5 ± 17.3 vs. 17.3 ± 12.5 s; p=0.59, FAST vs. SLOW). ΔMAPNADIR (‐14.4 ± 10.4 vs. ‐14.6 ± 6.5 mmHg; p=0.97) and CVCiMAX (22.1 ± 25.4 vs. 27.6 ± 39.9 cm/s/100mmHg; p=0.56 FAST vs. SLOW) were not different between groups. There were no other differences between groups regrading demographic, EtCO2, or other kinetic variables.DiscussionOur data indicates EoH is related to the initial drop in CBF and TD during light‐exercise is faster (15.9 s) when compared to previous research during moderate‐intensity exercise (~40 s). However, our data identifies fast responders who have minimal TD and MCAvNADIR responses without differing EoH at the same absolute exercise intensity. Therefore, these data reveal monoexponential CBF models ignore initial perturbances to CBF and disregard potentially important cerebrovascular mechanisms occurring prior to model predicted blood flow increases.

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.

Central command-related increases in blood velocity of anterior cerebral artery and prefrontal oxygenation at the onset of voluntary tapping.

The anterior cerebral artery (ACA) supplies blood predominantly to the frontal lobe including the prefrontal cortex. Our laboratory reported that prefrontal oxygenated-hemoglobin concentration (Oxy-Hb) increased before and at exercise onset, as long as exercise is arbitrarily started. Moreover, the increased prefrontal oxygenation seems independent of both exercise intensity and muscle mass. If so, mean blood velocity of the ACA (ACABV) should increase with "very light motor effort," concomitantly with the preexercise and initial increase in prefrontal Oxy-Hb. This study aimed to examine the responses in ACABV and vascular conductance index (ACAVCI) of the ACA as well as prefrontal Oxy-Hb during arbitrary or cued finger tapping in 12 subjects, an activity with a Borg scale perceived exertion rating of 7 (median). With arbitrary start, ACABV increased at tapping onset (14 ± 9%) via an elevation in ACAVCI. Likewise, prefrontal Oxy-Hb increased at the onset of tapping with a time course resembling that of ACABV. A positive cross correlation between the initial changes in ACABV and prefrontal Oxy-Hb was found significant in 67% of subjects, having a time lag of 2 s, whereas a positive linear regression between them was significant in 75% of subjects. When tapping was forced to start by cue, the initial increases in ACABV, ACAVCI, and prefrontal Oxy-Hb were delayed and blunted as compared with an arbitrary start. Thus, active vasodilatation of the ACA vascular bed occurs at tapping onset, as long as tapping is arbitrarily started, and contributes to immediate increases in blood flow and prefrontal oxygenation.NEW & NOTEWORTHY Anterior cerebral artery blood velocity and vascular conductance index along with prefrontal oxygenated-hemoglobin concentration all increased at the onset of finger tapping, peaking immediately after tapping onset, as long as tapping was arbitrarily started. Positive cross correlation and linear regression between the increases in ACABV and prefrontal Oxy-Hb were significant in 67%-75% of subjects. Active vasodilatation of the ACA vascular bed occurs with arbitrary tapping onset and contributes to increased ACABV and prefrontal oxygenation.

Dynamic Cerebral Autoregulation following the Acute Consumption of Soft‐drinks in Healthy Adults

Chronic consumption of high-fructose corn syrup (HFCS) and artificially sweetened beverages (ASB) are associated with an increased risk of stroke. An attenuation in dynamic cerebral autoregulation (dCA), a measure cerebral vascular function during changes in arterial blood pressure, may indicate cerebral vascular dysfunction. Thus, understanding the acute effects that HFCS and ASB consumption has on dCA may help understand the increased risk of stroke associated with the chronic consumption of these beverages. Purpose We tested the hypothesis that dynamic cerebral autoregulation (dCA) is attenuated following the acute consumption of HFCS and ASB soft-drinks compared to Water. Methods Twelve healthy adults (age: 23±2 y, 4 females) completed three randomized, double-blind trials. Participants drank 500 mL of Water, HFCS (Mountain Dew) or ASB (Diet Mountain Dew). We continuously measured blood pressure (MAP), mean middle cerebral artery blood velocity (MCAv), and end-tidal CO2 tension (PETCO2). Cerebral vascular conductance (CVC) was calculated as mean MCAv/MAP. Twenty minutes after experimental beverage consumption participants completed a 5 minute seated baseline, followed by an oscillatory blood pressure challenge. The oscillatory blood pressure challenge consisted of squat-to-stand intervals at two different frequencies (0.10 Hz and 0.05 Hz) for 5 minutes each separated by 5 minutes of seated rest. dCA was assessed in the MCA using transfer function analysis. Coherence, gain and phase are reported in in predefined frequency domains: low frequency (LF; 0.07-0.2 Hz) and very low frequency (VLF; 0.01-0.07 Hz) for the 0.10 Hz and 0.05 Hz, respectively. Values are reported as mean±SD. Results At baseline, MCAv (HFCS: 53.7±11.5 and ASB: 52.2±10.3 vs. Water: 61.4±10.8 cm/s; p<0.01) and MCA CVC (HFCS: 0.6±0.2 and ASB: 0.5±0.1 vs. Water: 0.7±1 cm/s/mmHg; p<0.02) were lower following HFCS and ASB vs. Water. During the 0.10 Hz squat-to-stand, there were no differences between beverages for coherenceLF (p=0.30) or phaseLF (p=0.68). GainLF was lower following ASB (0.81±0.21 cm/s/mmHg) compared to Water (0.95±0.27 cm/s/mmHg; p=0.01) but there was no difference in gainLF between HFCS (0.92±0.23 cm/s/mmHg) and Water (p=0.53). During the 0.05 Hz squat-to-stand, there were no differences between beverages for coherenceVLF (p=0.83) or gainVLF (p=0.28). PhaseVLF was higher following ASB (45.4±8.5 degrees) compared to Water (39.8±8 degrees; p=0.06) but there was no difference in phaseVLF between HFCS (43.8±10.3 degrees) and Water (p=0.31). Conclusions Our data indicate that acute consumption of an ASB did not consistently alter dCA in both frequency bands. Additionally, dCA was not altered following a HFCS soft-drink. However, future research is warranted to determine the effects of chronic consumption of HFCS and ASB soft-drinks on cerebral vascular function and the increased the risk of stroke.

Differences in Hypercapnia‐Induced Cerebral Vasodilation Between Young, Black Men and Women

In the U.S., stroke prevalence and age-adjusted mortality are greater in the black population than all other racial/ethnic groups. Further, black women (BW) exhibit an ~15% lower age-adjusted stroke mortality than black men (BM), suggesting either cerebrovascular protection in BW or cerebrovascular impairment in BM. While the mechanisms underlying the increased burden of stroke in black individuals remain incompletely understood, vascular dysfunction likely contributes to these negative health outcomes. Our group and others have previously demonstrated impaired vasodilation in the brachial artery, cutaneous microvasculature, and cerebral vasculature in black versus white men and women. However, investigations into gender differences in young, black individuals' cerebral vasodilatory responsiveness remain lacking. Therefore, this study tested the hypothesis that BW and BM exhibit divergent cerebral vasodilatory responses to a rebreathing-induced hypercapnic stimulus. To test this hypothesis, 11 BW and 15 BM (mean ± SD; age: 22 ± 4 vs. 23 ± 3) participated in this study. Each participant was instrumented for the continuous measurement of end-tidal carbon dioxide concentration (PETCO2; capnograph), beat-to-beat mean arterial pressure (MAP; finger photoplethysmography), and middle cerebral artery velocity (MCAv; transcranial Doppler ultrasound) at baseline and during rebreathing induced-hypercapnia. Absolute cerebral vascular conductance index (CVCi = MCAv/MAP) and percent change CVCi (ΔCVCi = [CVCiΔPETCO2 – CVCiBL]/CVCiBL • 100) were calculated at baseline and a ΔPETCO2 of 3, 6, 9, and 12 mmHg (only 8 BW were analyzed at 12 mmHg due to some individuals not reaching this stage). No differences in MAP were observed between BW and BM at baseline or any ΔPETCO2 (BL: 91 ± 9 vs. 89 ± 7 mmHg; Δ3: 88 ± 11 vs. 88 ± 9 mmHg; Δ6: 93 ± 8 vs. 89 ± 8 mmHg; Δ9: 94 ± 8 vs. 90 ± 9 mmHg; Δ12: 95 ± 10 vs. 91 ± 9 mmHg; interaction P = 0.11). At baseline, BW had a greater absolute CVCi than BM (0.80 ± 0.10 vs. 0.68 ± 0.13 cm/s/mmHg; P = 0.04). This pattern was also observed at each ΔPETCO2 stage (Δ3: 0.91 ± 0.11 vs. 0.67 ± 0.13 cm/s/mmHg; Δ6: 0.98 ± 0.10 vs. 0.71 ± 0.12 cm/s/mmHg; Δ9: 1.04 ± 0.09 vs. 0.78 ± 0.13 cm/s/mmHg; Δ12: 1.11 ± 0.11 vs. 0.80 ± 0.16 cm/s/mmHg; all P < 0.001). Despite the baseline differences between groups, BW still exhibited a greater ΔCVCi at each stage of ΔPETCO2 than BM (Δ3: 12.9 ± 5.3 vs. 0.1 ± 9.4%; Δ6: 23.0 ± 6.8 vs. 5.5 ± 10.2%; Δ9: 29.9 ± 12.9 vs. 16.0 ± 11.2%; Δ12: 40.7 ± 16.8 vs. 19.0 ± 12.3%; all P < 0.05). These data suggest that young, BW exhibit greater cerebrovascular responsiveness to a hypercapnic stimulus relative to young, BM, which may partially explain the lower age-adjusted stroke mortality in BW. However, the mechanisms responsible for these observed differences remain undetermined and should be the subject of future research.

Cerebrovascular responses to graded exercise in young healthy males and females.

Although systemic sex‐specific differences in cardiovascular responses to exercise are well established, the comparison of sex‐specific cerebrovascular responses to exercise has gone under‐investigated especially, during high intensity exercise. Therefore, our purpose was to compare cerebrovascular responses in males and females throughout a graded exercise test (GXT). Twenty‐six participants (13 Females and 13 Males, 24 ± 4 yrs.) completed a GXT on a recumbent cycle ergometer consisting of 3‐min stages. Each sex completed 50W, 75W, 100W stages. Thereafter, power output increased 30W/stage for females and 40W/stage for males until participants were unable to maintain 60‐80 RPM. The final stage completed by the participant was considered maximum workload(W max). Respiratory gases (End‐tidal CO2, EtCO2), middle cerebral artery blood velocity (MCAv), heart rate (HR), non‐invasive mean arterial pressure (MAP), cardiac output (CO), and stroke volume (SV) were continuously recorded on a breath‐by‐breath or beat‐by‐beat basis. Cerebral perfusion pressure, CPP = MAP (0. 7,355 distance from heart‐level to doppler probe) and cerebral vascular conductance index, CVCi = MCAv/CPP 100mmHg were calculated. The change from baseline (Δ) in MCAv was similar between the sexes during the GXT (p = .091, ω p 2 = 0.05). However, ΔCPP (p < .001, ω p 2 = 0.25) was greater in males at intensities ≥ 80% W max and ΔCVCi (p = .005, ω p 2 = 0.15) was greater in females at 100% W max. Δ End‐tidal CO2 (ΔEtCO2) was not different between the sexes during exercise (p = .606, ω p 2 = −0.03). These data suggest there are sex‐specific differences in cerebrovascular control, and these differences may only be identifiable at high and severe intensity exercise.

The Influence of Acute Beetroot Juice Consumption on Cerebral Autoregulation during Orthostatic Stress

Beetroot juice (BRJ) supplementation improves cerebrovascular function during exercise. Breathing a mild hypercapnic gas transiently reduces cerebral autoregulation in healthy participants. However, it is unknown if acute BRJ consumption improves cerebral autoregulation while breathing a mild hypercapniac gas.PurposeWe tested the hypothesis that acute BRJ consumption improves cerebral autoregulation while breathing a mild hypercapnic gas during oscillatory lower body negative pressure (LBNP).MethodsEight healthy participants (age: 27±5 y, 3 F) completed a 5 min baseline (BL) followed by 6 min of LBNP intervals (30s at −70 mmHg, 30s at 0 mmHg) while breathing a mild hypercapnic gas (3% CO2, 21% O2, 76% N2). LBNP was performed pre (PRE) and 3 hours after consuming 500 mL of BRJ (BRJ). Mean arterial pressure (MAP), heart rate (HR), end‐tidal carbon dioxide tension (PETCO2), and middle cerebral artery blood velocity (MCAv) were continuously recorded. Cerebral vascular conductance (CVC) was calculated as MCAv divided by MAP. The magnitude of change in MAP, HR, PETCO2, MCAv, and CVC due to LBNP were calculated from the mean change from BL (Δ) obtained during each interval throughout the LBNP protocols. Cerebral autoregulation (i.e., gain and phase) was assessed throughout the LBNP protocols using Fourier transformation and is reported for BL and as the change from BL (Δ). Values are reported as Δ mean±SD.ResultsThere were no differences between conditions at BL for MAP (PRE: 99±8 vs. BRJ: 95±7 mmHg; P=0.10), HR (PRE: 65±9 vs. BRJ: 65±10 bpm; P=0.40), PETCO2 (PRE: 48±3 vs. BRJ: 49±3 mmHg; P=0.30), CVC (PRE: 0.86±0.18 vs. BRJ: 0.83±0.13 cm/s/mmHg; P=0.16) gain (PRE: 0.96±0.29 vs. BRJ: 0.93±0.22 cm/s/mmHg; P=0.31), or phase (PRE: 7±5 vs. BRJ: 10±6°; P=0.19). At BL, MCAv was lower with BRJ (PRE: 84±14 vs. BRJ: 79±11 cm/s; P&lt;0.01). The ΔMAP during −70 mmHg did not differ with BRJ (PRE: −8±5 vs. BRJ: −6±6 mmHg; P=0.51). The ΔMAP did not differ from BL during 0 mmHg PRE (P=0.44) but the ΔMAP was greater during 0 mmHg with BRJ (PRE: 1±3 vs. BRJ: 4±2 mmHg; P=0.03). The ΔHR was greater during −70 mmHg with BRJ (PRE: 13±10 vs. BRJ: 16±11 bpm; P=0.05) but the ΔHR during 0 mmHg did not differ with BRJ (PRE: −5±4 vs. BRJ: −3±3 bpm; P=0.29). The ΔPETCO2 did not differ between PRE and BRJ during −70 mmHg (PRE: −3±1 vs. BRJ: −3±2 mmHg; P=0.91) or 0 mmHg (PRE: −1±1 vs. BRJ: −1±2 mmHg; P=0.91). ΔMCAv did not differ from BL or between PRE and BRJ during −70 mmHg (PRE: −5±18 vs. BRJ: −4±16 cm/s; P=0.76) and 0 mmHg (PRE: −2±14 vs. BRJ: −1±13 cm/s; P=0.76). The ΔCVC did not differ with BRJ during −70 mmHg (PRE: −0.01±0.11 vs. BRJ: −0.03±0.08 cm/s/mmHg; P=0.20) but was greater with BRJ during 0 mmHg (PRE: −0.07±0.05 vs. BRJ: −0.11±0.08 cm/s/mmHg; P=0.02). During LBNP, there were no differences between conditions for Δgain (PRE: −0.03±0.18 vs. BRJ −0.05±0.10 cm/s/mmHg; P=0.41) or Δphase (PRE: −1±5 vs. BRJ: −3±8.2°; P=0.34).ConclusionsThese preliminary data indicate that acute BRJ does not alter cerebral autoregulation during an orthostatic stressor while healthy participants breathed a mild hypercapnic gas. Further investigations are warranted to determine if chornic BRJ ingestion affects cerebral autoregulation.

One Session of High‐Intensity Interval Training Acutely Enhances the Sensitivity of Cerebral Vasoreactivity Post‐Exercise in Young Healthy Males

BackgroundCardiorespiratory fitness and exercise training are associated with improved cerebral vasoreactivity of the middle cerebral artery (MCAvmean). High‐intensity interval exercise training (HIIT) is an effective time‐efficient alternative to long‐duration lower‐intensity exercise that offers similar vascular benefits. It is currently unclear whether HIIT acutely alters cerebral cerebrovascular function.PurposeThis project tested the hypothesis that a single session of HIIT would enhance cerebrovascular reactivity after exercise.MethodsFive healthy active (7‐day activity: 9140±3525 steps·day; VO2max: 55±6.3 mLO2·kg·min−1) adults (22.4±1.9y, 175.9±5.1cm, 77.1±5.1kg) completed one session of HIIT exercise comprised of four bouts of four‐minute intervals at 65% watt max (between 85–95% maximal heart rate [HR]) with three‐minute recovery between at 15% watt max (between 50–65% HRmax). Transcranial Doppler MCAvmean assessed hypercapnia induced cerebral vasoreactivity using a three‐minute rebreathing technique in a supine rest position, before and 30‐minutes after the HIIT. Dose‐response curves (non‐linear log‐transformed) examined the sensitivity of cerebral vasoreactivity to increased concentrations of the partial pressure of end‐tidal CO2 (Torr). Parameters derived from the dose‐response curve included half‐maximal effective concentration (EC50), LogEC50, and HillSlope. Systemic hemodynamics including mean arterial pressure (MAP), systemic vascular resistance (SVR) and HR were also measured during the rebreathe test. MCAvmean cerebral vascular conductance (CVC) was calculated by MCAvmean/MAP. Paired t‐tests were used to compare the pre‐ to post‐HIIT changes in parameters. Alpha prior was set at P&lt;0.05.ResultsThe sensitivity of cerebral vasoreactivity improved from pre to post‐HIIT exercise as reflected by lower MCAvmean EC50 (Δ3.0±1.5 Torr, P&lt;0.006) and LogEC50 (Δ0.03±0.02 Log Torr, P&lt;0.008) post‐exercise. MCAvmean HillSlope showed a trend for significance (P&lt;0.06). Systemically, MAP (Δ9.6±7.7 mmHg, P&lt;0.02) and SVR (Δ343.2±242.5 dynes·s1·cm5, P&lt;0.002) were both lower and HR (Δ18±7 b/min, P&lt;0.002) was increased post‐exercise. When accounted for post‐exercise hypotension, MCAvmean CVC EC50 (Δ4.2±2.0 Torr, P&lt;0.007) and LogEC50 (Δ0.04±0.02 Log Torr, P&lt;0.001) were also improved post‐exercise; however, MCAvmean CVC HillSlope was not different (P=0.30) between conditions.ConclusionThese preliminary data suggest that a single session of HIIT exercise may improve the sensitivity of cerebral vasoreactivity in young healthy males. This may in part be due to changes in peripheral hemodynamics such as baroreflex mediated alterations in MAP, SVR, and HR post‐exercise. These preliminary findings give insight into an integrative relationship between cerebral and peripheral blood flow during recovery from high‐intensity exercise and the benefits of HIIT on cerebrovascular health.

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 Reactivity in Young Adults with Major Depressive Disorder

Cerebral vasodilatory responsiveness is blunted in older adults (~70 yrs) with depressive disorders and thought to contribute to the link between depressive symptomology and increased risk for neurocognitive (e.g., dementia) and cerebral vascular (e.g., stroke) diseases. In young adults with major depressive disorder (MDD), peripheral vascular endothelial dysfunction is evident; however, to date, limited investigations have examined cerebral vasodilatory function in young otherwise healthy adults with MDD. We tested the hypothesis that cerebral vasodilatory responsiveness to a hypercapnic stimulus would be blunted in otherwise healthy young adults with MDD compared to healthy non‐depressed adults (HA). Four HA (22±2yrs) and 6 adults with MDD (23±2yrs; n=2 tested during a major depressive episode) participated. Beat‐to‐beat mean arterial pressure (MAP; finger photoplethysmography), middle cerebral artery blood velocity (MCAv; transcranial Doppler ultrasound), internal carotid artery (ICA) diameter and blood flow (Doppler ultrasound), and end‐tidal carbon dioxide concentration (PETCO2; capnograph) were continuously measured during baseline (i.e., normocapnia) and rebreathing‐induced hypercapnia. Cerebral vascular conductance index (CVCi=MCAv•MAP−1) and ICA blood flow (Vmean•π(d•20−1)2•60) and conductance (CVC=ICA blood flow•MAP−1) were calculated at baseline and at the highest common magnitude of hypercapnia achieved by all subjects during rebreathing (ΔPETCO2 = 9 Torr). At baseline, there were no differences in any outcome variable between groups (all p&gt;0.05). During hypercapnia, there were no group differences in the increase in MAP (Δ3±3 HA vs. Δ3±4 mmHg MDD; p=0.98). The increase in MCAv was blunted in adults with MDD (Δ33±4 HA vs. Δ23±7 cm•s−1 MDD; p=0.03). Both the absolute (Δ0.30±0.02 HA vs. Δ0.20±0.07 cm•s−1•mmHg−1 MDD; p=0.01) and relative (Δ42±7 HA vs. Δ26±9 %baseline MDD; p=0.01) increase in CVCi during hypercapnia were reduced in adults with MDD. There were no group differences in ICA diameter (Δ−0.04±0.22 HA vs. Δ0.05±0.17 mm MDD; p=0.51) or blood flow responses (Δ143±20 HA vs. Δ127±95 mL•min−1 MDD; p=0.49). Although the dilatory response in the ICA was ~50% less in adults with MDD, the increase in CVC was not significantly different between groups (Δ51±26 HA vs. Δ27±22 %baseline MDD; p=0.17). In adults with MDD, there was no relation between habitual physical activity and cerebral vasodilatory responsiveness (R2=0.09; p=0.57). These preliminary data suggest that cerebral vasodilatory reactivity to a hypercapnic stimulus may be blunted in young otherwise healthy adults with MDD, providing further support for the potential mechanistic link between cerebrovascular dysfunction and depression in increased neurocognitive and cerebral vascular disease risk.Support or Funding InformationHL133414 (JLG)

Reduced cerebrovascular and cardioventilatory responses to intermittent hypoxia in elderly

BackgroundThe impact of aging on cerebrovascular function and tissue oxygenation during graded hypoxemia is incompletely known. This study compared the age effect on these variables during cyclic hypoxemia-reoxygenation. MethodsHypoxia-induced changes in arterial (SaO2) and cerebral tissue (ScO2) O2 saturation, middle cerebral arterial flow velocity (VMCA), estimated cerebral vascular conductance (CVC), heart rate (HR) and ventilation were compared between 12 elderly (71 ± 2 yr, 7 women) and 13 young (24 ± 3 yr, 5 women) adults during the first and fifth 5-min exposures to 10% O2. ResultsAlthough pre-hypoxia SaO2 did not differ between the groups, ScO2 was lower (P < 0.05) in the elderly (68.4 ± 1.2%) than young (73.8 ± 0.9%) adults, commensurate with a lower resting VMCA (P < 0.05). SaO2 fell less sharply (P < 0.05) in the elderly subjects during the first and fifth hypoxia exposures. Moreover, the responses of ScO2, VMCA, CVC, HR and breathing frequency to hypoxia were attenuated in the elderly subjects. Systolic and diastolic arterial pressures fell by 2–6 mmHg during hypoxia in both young and elderly. Thus, hypoxemia developed more gradually in elderly than young adults during normobaric hypoxia, concordant with a reduced metabolic demand in the elderly. ConclusionsThe elderly adults safely tolerated cyclic, moderate hypoxemia which lowered SaO2 by 20–25%, despite dampening of cerebrovascular and cardiac responses to hypoxemia.

Effect of time of day on heat‐induced hyperventilation and cerebrovascular response during exercise in the heat

Hyperthermia during exercise leads to increases in minute ventilation independently of metabolic factors. This heat‐induced hyperventilation results in excessive elimination of CO2 from the body, leading to reduced arterial CO2 pressure (PaCO2) and the resultant cerebral hypoperfusion, which may underlie central fatigue during hyperthermia and impaired exercise performance in the heat. We recently reported that time of day has no effect on time course of hyperventilatory response during exercise in the heat, despite the higher core temperatures in the evening (Tsuji et al. Am J Physiol 2016). This was likely due to diurnal variation in the control of ventilation in response to rising core temperature. However, it remains unclear whether cerebrovascular response during exercise in the heat is affected by time of day. This study thus examined the effect of time of day on respiratory and cerebrovascular responses during prolonged exercise in the heat. Eleven healthy subjects performed a cycle exercise at 50% of peak oxygen uptake in the heat (35°C ambient temperature and 40% relative humidity) in the morning (0830) and evening (1830). The exercise was terminated when the exercise duration reached 60 min, esophageal temperature reached 39.0°C or the subject could no longer pedal at 60 rpm. Esophageal temperature and mean arterial pressure were significantly higher in the evening than morning (both P &lt; 0.01), but time of day had no significant effect on minute ventilation, estimated PaCO2, middle cerebral artery blood velocity and cerebral vascular conductance. The ventilatory sensitivity to rising core temperature (i.e., slope of the esophageal temperature‐ventilation relation) was significantly greater in the evening than morning. However, sensitivities of PaCO2 and cerebrovascular responses to rising core temperature were unaffected by time of day. In conclusion, present results suggest that time of day has no effect on the time course of hyperventilation, PaCO2 and cerebral blood flow response during prolonged exercise in the heat.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Fast-food meal reduces peripheral artery endothelial function but not cerebral vascular hypercapnic reactivity in healthy young men.

Consumption of a representative fast‐food meal (FFMeal) acutely impairs peripheral conduit artery vascular function; however, the effect on cerebral vascular function remains unknown. This study tested the hypothesis that a FFMeal would impair cerebral vascular function as indexed by an attenuated increase in cerebral vascular conductance (CVCI) in the middle cerebral artery (MCA) during a hypercapnic challenge. Ten healthy men (age: 24 ± 3 years, BMI: 24.3 ± 3.8 kg/m2) were studied under two conditions; a standardized FFMeal (990 kcals, 50% fat, 36% carbohydrate, 14% protein, and 2120 mg sodium) and a fasting control condition. Basal hemodynamics, cerebral vasomotor reactivity (CVMR), and brachial artery flow‐mediated dilation (BA FMD) were completed after an overnight fast (Pre) and again 2 h and 4 h later both days. To assess CVMR, subjects rebreathed from a 5‐L bag while MCA velocity (MCAV mean) was measured using transcranial Doppler (TCD) ultrasound and converted into CVCI (MCAV mean/mean arterial pressure). Peripheral artery endothelial function was assessed via BA FMD following a standard 5‐min occlusion protocol. As expected, BA FMD was reduced at 2 h (Pre: 6.6 ± 1.7% vs. 5.2 ± 1.8%, P = 0.01). However, despite significant impairment in BA FMD, neither peak CVCI %baseline nor CVMR was affected by the FFMeal (Control–Pre: 1.9 ± 1.1, 2 h: 2.1 ± 1.1, 4 h: 1.7 ± 1.1 ∆CVCI%·∆PETCO 2 −1 vs. FFMeal–Pre: 2.1 ± 1.1, 2 h: 2.2 ± 0.7, 4 h: 1.9 ± 0.9 ∆CVCI%·∆PETCO 2 −1, time × condition P = 0.88). These results suggest that cerebral vascular reactivity to hypercapnia in healthy young men is not altered by an acute FFMeal.