Cerebrovascular Conductance Index Research Articles

Cerebrovascular Responses to Graded Exercise Between Young Healthy Men and Women

BackgroundDysfunctional cerebrovascular control is closely linked to the increased incidence of cerebrovascular and neurodegenerative diseases (e.g. small vessel occlusion, dementia and Alzheimer’s). Epidemiological evidence identifies sex‐specific differences in the course of prevention (risk factor) and treatment (prognosis) of cerebrovascular and brain diseases. Therefore, examining sex differences in cerebral blood flow (CBF) regulation is essential. Exercise provides a unique metabolic environment which influences systemic and CBF responses. Despite previous studies identifying muscle blood flow sex discrepancies to both handgrip and knee extensor exercise, CBF responses during exercise in women are underrepresented in the literature. Therefore, it remains unclear if sex differences in cerebrovascular control to exercise exists.PurposeTo compare CBF and cerebrovascular conductance index (CVCi) over a range of exercise intensities between men (MN) and women (WN).Methods24 young healthy adults (12 WN, 24.0±3.6 yrs) completed a graded‐exercise‐test (GXT, stage length 3‐min, 50W, 75W, 100W; after which MN increases by 40W, WN increased by 30W maintaining 60–80 RPM) on a recumbent cycle ergometer to volitional exhaustion. The highest completed stage was determined as Maximal Wattage (Wmax). Middle cerebral artery velocity (MCAv; transcranial Doppler ultrasound) and mean arterial pressure (MAP; finger photoplethysmography, CPP was calculated MAP – [0.7355* vertical distance of TCD probe from heart‐level]), were measured on a beat‐by‐beat basis to calculate CVCi = MCAv/CPP*100mmHg.ResultsMean ± SD, effect size using Ω2. MN and WN exhibited similar MCAv responses to changes in exercise intensity where peak MCAv was obtained ~ 60% Wmax (ΔMCAv, WN = 17.9 ± 3.6, MN = 16.0 ±7.01 cm/s, p = 0.4) and declined as intensity increased. There was a trend for WN to have a greater ΔMCAv with increasing relative exercise intensity (p = 0.05, Ω2 = 0.02) with the greatest difference between WN and MN observed at 100%Wmax (ΔMCAv, WN= 10.7±2.2, MN= 5.5± 1.3cm/s, p<0.01). Interestingly, MN had a greater exercise cerebral prefusion pressor response with increasing exercise intensity (p < 0.01, Ω2 = 0.05) with the largest difference being observed at 100% Wmax (ΔCPP, WN 37.7 ± 3.0, MN 47.3 ± 5.6 mmHg, p < 0.01). However, these differences did not compute into differences in ΔCVCi between the sexes over any exercise intensity (p = 0.8, Ω2 = 0.0).ConclusionsOur data suggest cerebrovascular responses to exercise are similar between sexes. However, the small effect sizes in MCAv and differences in ΔCPP indicate the study may be underpowered to detect differences in cerebrovascular control during high intensity exercise. Therefore, we conclude men and women have similar cerebrovascular responses during low to moderate exercise. However, further research into cerebrovascular and exercise pressor responses during high intensity exercise are warranted as our data remain inconclusive and literature has identified exercise sex differences in systemic and non‐cerebral peripheral circulations.

The Influence of Age at Natural Menopause on Cerebrovascular Reactivity

The onset of menopause coincides with a loss of the vasoprotective effects of estrogen. Early menopause is associated with increased cardiovascular risk factors and cardiovascular disease; however, the specific cerebrovascular outcomes regarding the timing at natural menopause are not understood. The purpose of this study was to investigate how the age of natural menopause influences cerebrovascular reactivity, a measure of cerebrovascular function. We studied 37 women with earlier (Early; n = 20; age at onset of menopause = 46 ± 3 y; age at time of study = 61 ± 4 y) and later (Late; n = 17; age at onset of menopause = 55 ± 2 y; age at time of study = 62 ± 3 y) onset of natural menopause. Supine brachial blood pressure was taken in triplicate using a sphygmomanometer before study procedures. Middle cerebral artery velocity (MCAv), mean arterial blood pressure (MAP), and end‐tidal carbon dioxide (ETCO□) were continuously recorded during hypercapnia to measure cerebrovascular reactivity. Cerebrovascular conductance index (CVCi) was calculated as MCAv/MAP. Reactivity was calculated as the slope of the relationship between ETCO□ and each variable of interest. There were no significant differences in MCAv reactivity (Early: 2.0 ± 0.2 cm/s/mmHg; Late: 2.3 ± 0.2 cm/s/mmHg; p = 0.09), MAP reactivity (Early: 1.0 ± 0.3 mmHg/mmHg; Late: 1.0 ± 0.2 mmHg/mmHg; p = 0.50), or CVCi reactivity (Early: 0.01 ± 0.002 cm/s/mmHg2; Late: 0.02 ± 0.001 cm/s/mmHg2; p = 0.16) between women who experienced an earlier or later onset of menopause. However, the Early and Late groups had a statistically significant difference in supine brachial MAP at rest (Early: 99.5 ± 1.9 mmHg, Late: 91.6 ± 2.9 mmHg; p < 0.05), which may confound cerebrovascular reactivity to hypercapnia. When brachial MAP was added as a covariate, the Early group had a significantly lower MCAv reactivity (p < 0.05) than the Late group. These results suggest that the age at natural menopause may influence cerebrovascular function in postmenopausal women, as women who experience an earlier onset of menopause have lower cerebrovascular reactivity after resting MAP is accounted for. Future studies should examine intervention strategies, such as menopausal hormone therapy, in order to mitigate these discrepancies in cerebral blood flow regulation.Support or Funding InformationResearch funded through a grant from the Alzheimer’s Association.

Epinephrine Increases Middle Cerebral Artery Blood Velocity in Response to Progressive Central Hypovolemia in Healthy Humans

ObjectivesWe aimed to determine if epinephrine played a beneficial role on middle cerebral artery velocity (MCAv) during physiologically stressful stimuli prior to cardiovascular collapse. MCAv was assessed during lower body negative pressure (LBNP) under conditions of a saline or epinephrine infusion. We hypothesized that (1) epinephrine would augment the change in MCAv from baseline to LBNP tolerance, (2), epinephrine would increase MCAv for a given LBNP stimulus, (3) at a given percent of LBNP tolerance epinephrine and saline will be similar and (4) that epinephrine would improve LBNP tolerance.MethodsNine participants (35±9yrs, n=5 male, 4 female) underwent a LBNP protocol to physiological tolerance during two study visits, performed at least two weeks apart, and randomized to saline or epinephrine (dose=0.1μg/kg/min) infusions (peripherally‐ inserted central catheter). Blood pressure (radial artery catheter) and middle cerebral artery velocity (transcranial Doppler) were assessed. MCAv and cerebrovascular conductance index (CvCi) were analyzed during baseline (three minutes), physiological tolerance (one minute), during LBNP at a given stimulus (three minutes; −15, −30, −45 mmHg of LBNP), and during relative percentages of LBNP tolerance [three minutes; 20, 40, 60, and 80% of LBNP tolerance time (s)]. Baseline was defined as measures taken after 15 minutes of saline or epinephrine infusion.ResultsIn both saline and epinephrine conditions, MCAv and CvCi decreased from baseline to tolerance (Saline MCAv: 69.7±7.5 vs 44.9±4.9 cm/s, p<0.05; Epinephrine MCAv: 80.9±5.9 vs 56.5±6.7 cm/s, p<0.05; Saline CvCi: 0.69±0.06 vs 0.58±0.067 cm/s/mmHg, p>0.05; Epinephrine CvCi: 0.80±0.06 vs 0.70±0.078 cm/s/mmHg, p<0.05). Epinephrine augmented MCAv at a given LBNP stimulus from baseline to −15, −30, and −45 mmHg (MCAv: Treatment effect: p<0.05; CvCi: Treatment effect: p=0.05). At a relative percent of LBNP tolerance, epinephrine increased MCAv, but when blood pressure was controlled for with CvCi there was no treatment effect between epinephrine and saline (MCAv: Treatment effect: p<0.05; CvCi: Treatment effect: p>0.05). Time to tolerance was not significantly different between saline and epinephrine conditions (1469±168 vs. 1445±82s, p=0.88).ConclusionsEpinephrine increased MCAv during LBNP. These data suggest that epinephrine plays a beneficial role during stressful physiological stimuli such as hemorrhage in humans by augmenting cerebral blood flow prior to cardiovascular collapse. However, epinephrine did not improve LBNP tolerance.Support or Funding InformationThe United States Department of Defense W81XWH‐13‐2‐0038

Reactive oxygen species and cyclooxygenase products explain the majority of hypoxic cerebral vasodilation in healthy humans.

The role of reactive oxygen species (ROS) in human cerebral blood flow (CBF) during hypoxia is largely unknown. Additionally, it is unknown whether ROS interact with cyclooxygenase-derived signals during hypoxia to increase CBF. We hypothesized ROS inhibition would reduce hypoxic CBF, and combined inhibition of cyclooxygenase (COX) and ROS would decrease hypoxic CBF more than ROS suppression alone. We measured middle cerebral artery velocity with transcranial Doppler ultrasound in 12 healthy adults during normoxia and 2 isocapnic hypoxia trials. Intravenous ascorbic acid infusion during the first hypoxia trial suppressed ROS. Oral indomethacin inhibited COX between hypoxia trials. The second bout of hypoxia tested the combined effects of ROS and COX inhibition. Middle cerebral artery velocity was normalized for blood pressure as cerebrovascular conductance index. Hypoxia increased cerebrovascular conductance index in both trials (P<0.05). Ascorbic acid infusion did not alter cerebrovascular conductance index during hypoxia. Combined ascorbic acid and indomethacin significantly reduced hypoxia-mediated increases in cerebrovascular conductance index from 17±2 to 4±1 cm s-1 100 mmHg-1 (P<0.05). ROS are not obligatory for hypoxic cerebral vasodilation. Current data indicate ROS and COX together may account for the majority of the increase in CBF through the middle cerebral artery during hypoxia. These data are the first to demonstrate compensatory hypoxic vasodilatory signalling in human cerebral circulation.

Reduced heart rate variability and lower cerebral blood flow associated with poor cognition during recovery following concussion.

Although physiological deficits such as altered cerebral blood flow (CBF), and autonomic nervous system (ANS) dysregulation have been reported following a concussion, the relationship between CBF and ANS with functional outcome post-injury remains unclear. Our present study was designed to examine heart-rate variability (HRV) using percentage of successive NN intervals (pNN50) and CBF on day-3 (T1), day-21 (T2), and day-90 (T3) following a concussion in collegiate athletes (N = 31) in comparison to non-injured controls (N = 31). Continuous RR-interval (3-lead electrocardiogram), middle cerebral artery blood velocity (MCAV; transcranial Doppler ultrasonography), mean arterial pressure (MAP; finger photoplethysmography) were obtained at rest. Cerebrovascular conductance index (CVCi) was estimated as a ratio of MCAV to MAP. Cognition was evaluated with standard assessment of concussion (SAC), and Trails A & B. Compared to the controls, lower HRV (43 ± 15 vs. 27 ± 20%; p < 0.0001) was observed at T1 with normalization at T2 and T3. No difference in MCAV between the control and the concussed groups across the three time points were observed. However, post-hoc analyses indicated a positive relationship between MCAV at T1 phase with HRV and CVCi during T2, and T3 phases. Higher MCAV at T1 was also associated with better cognition scores during the asymptomatic T2 phase in the concussed athletes. Therefore, our results indicate ANS dysregulation during the acute recovery phase after a concussion. Differences in CBF may be one of the underlying causes behind heterogeneity in clinical symptoms and functional outcomes after a concussion and future studies are warranted to validate this finding.

The Effects of Age and Cyclooxygenase Inhibition on the Cerebrovascular Response to a Metabolic Stimulus

BackgroundProstaglandins, such as cyclooxygenase (COX), may play an important role in regulating the cerebral blood flow response to a stimulus. We have previously shown that the vasodilatory response to a chemical stimulus decreases with age, and this difference is abolished by COX inhibition. However, the effects of COX inhibition on the cerebrovascular response to an increase in metabolic demand during a cognitive challenge is unknown. This information is important due to the frequent use of COX inhibitors for pain management. Thus, the purpose of this study was to determine the effect of COX inhibition on the cerebrovascular response to a metabolic stimulus in young and older adults.MethodsSeventy‐six participants, including 42 young adults (YA; 26 ± 5 y) and 34 older adults (OA; 64 ± 6 y) completed the Stroop Color Word Test, which is a test of executive function. A subset of 42 participants (n = 22 YA, n = 20 OA) also completed the N‐back Test, which is a test of working memory. Beat‐to‐beat middle cerebral artery velocity (MCAv) and mean arterial pressure (MAP) were measured at baseline and in response to each cognitive test. Cerebrovascular conductance index (CVCi) was calculated as MCAv/MAP. The response to each cognitive test was calculated as the peak percent change (%Δ) from baseline. Oral administration of the COX inhibitor Indomethacin (Indo) was given at 1.2mg/kg. Cognitive tests were then repeated after a 120‐minute wash‐in period.ResultsAt baseline, YA had higher MCAv, CVCi, and lower MAP (p&lt;0.01 for all) compared to OA. There were no significant differences between groups in the %Δ from baseline during the Stroop or N‐back test (p&gt;0.05). During Indo, YA had higher MCAv (p&lt;0.01), CVCi (p&lt;0.01), and lower MAP (p&lt;0.05) compared to OA. Indo decreased baseline MCAv and CVCi in both groups (p&lt;0.01 for all) but had no effect on MAP (p&gt;0.05). During Indo, the %Δ in MCAv during Stroop and N‐back was lower in YA (p&lt;0.01) compared to baseline in YA. During Indo, the %Δ in MCAv was lower during Stroop in OA (p&lt;0.01), with a trend for significance in OA during N‐back (p=0.06) compared to baseline. In YA during Indo, the %Δ in MAP was lower during Stroop (p&lt;0.01) with a trend for significance during Nback (p=0.08) compared to baseline. In OA, the %Δ in MAP during N‐back was lower during Indo compared to baseline (p&lt;0.05). Indo had no effect on the %Δ in CVCi (p&gt;0.05). Importantly, there were group differences in the %Δ in MAP during Indo, such that the change was greater in OA compared with YA during Stroop (14.1 ± 1.3% vs. 10.6 ± 1.0%; p&lt;0.05).ConclusionAfter administration of Indo, OA increased MAP to a greater extent during the Stroop test when compared to YA. These results suggest that OA required a larger increase in blood pressure to complete a test of executive function during COX inhibition. Because some COX inhibitors attenuate cerebral blood flow, OA may need to augment blood pressure to complete this metabolically‐challenging task.Support or Funding InformationThis research was funded by NIH grant HL118154.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Cerebrovascular Reactivity in Resistance Trained Young Men

Cerebrovascular reactivity is a measure of cerebrovascular function and is often used as an indicator of cerebrovascular health. There is evidence that habitual exercise can influence cerebrovascular reactivity; however, the effect of habitual exercise has only been examined in aerobic trained individuals or under the context of cardiorespiratory fitness. Therefore, the purpose of our study was to investigate the effect of chronic resistance training on cerebrovascular reactivity. We recruited 22 young men, including 11 untrained (UT; age = 27 ± 4 yr) and 11 resistance trained (RT; age = 24 ± 4 yr) individuals. Middle cerebral artery velocity (MCAv), beat‐to‐beat mean arterial blood pressure (MAP), and end‐tidal CO2 (ETCO2) were continuously monitored during a stepped hypercapnia protocol. In order to account for the influence of blood pressure on MCAv, cerebrovascular conductance index (CVCi) was calculated as MCAv/MAP × 100. MCAv, MAP, and CVCi reactivities were calculated as the linear relationship between each respective variable and ETCO2. There were no group differences in MCAv, MAP, CVCi, or ETCO2 during baseline or any level of the stepped hypercapnia (p &gt; 0.05 for all). There was a trend for RT adults to have a higher MCAv reactivity, compared to UT adults (RT: 2.4 ± 0.4 cm/s/mmHg vs. UT: 1.7 ± 0.2 cm/s/mmHg; p = 0.06); however, there were no group differences in CVCi reactivity (RT: 1.5 ± 0.6 cm/s/mmHg2 vs. UT: 1.6 ± 0.2 cm/s/mmHg2; p = 0.41). Additionally, the MAP response to hypercapnia differed between the groups, as RT adults had a greater MAP reactivity compared with UT adults (RT: 0.98 ± 0.40 mmHg/mmHg vs. UT: 0.25 ± 0.08 mmHg/mmHg; p &lt; 0.05). In conclusion, chronic resistance training likely influences cerebrovascular reactivity, as RT individuals had a larger MAP reactivity and a trend for greater MCAv reactivity, compared with UT individuals. Our results suggest that in young men, chronic resistance training may influence the hemodynamic response to a physiological stimulus, such as hypercapnia.Support or Funding InformationSupported by National Institute of Health grant HL118154This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The influence of microgravity on cerebral blood flow and electrocortical activity.

Changes in gravity conditions have previously been reported to influence brain hemodynamics as well as neuronal activity. This paper attempts to identify a possible link between changes in brain blood flow and neuronal activity during microgravity. Middle cerebral artery flow velocity (MCAv) was measured using Doppler ultrasound. Brain cortical activity (i.e., cortical current density) was measured using electroencephalography. Finger blood pressure was recorded and exported to generate beat-by-beat systolic (SBP), diastolic (DBP) and mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), and cerebrovascular conductance index (CVCi). Seventeen participants were evaluated under normal gravity conditions and microgravity conditions, during 15 bouts of 22-s intervals of weightlessness during a parabolic flight. Although MAP decreased and CO increased, MCAv remained unchanged in the microgravity condition. CVCi as the quotient of MCAv and MAP increased in microgravity. Cortical current density showed a global decrease. Our data support earlier data reporting a decrease in the amplitude of event-related potentials recorded during microgravity. However, the general decrease in neural excitability in microgravity seems not to be dependent on hemodynamic changes.

Cerebrovascular reactivity after cessation of menopausal hormone treatment

Objective: Women who are currently using menopausal hormone therapy (MHT) have higher cerebrovascular reactivity when compared with postmenopausal women who are not taking MHT; however, the effect of cessation of MHT on cerebrovascular reactivity is not known. Given that MHT can have structural and activational effects on vascular function, this study was performed to characterize cerebrovascular reactivity following cessation of MHT in women at low risk for cerebrovascular disease. Methods: Cerebrovascular reactivity was measured in a subset of women from the Kronos Early Estrogen Prevention Study (KEEPS) 3 years after cessation of the study drug (oral conjugated equine estrogen, transdermal 17β-estradiol, or placebo [PLA]).Results: Age, body mass index, and blood pressure were comparable among groups. At rest, the middle cerebral artery velocity (MCAv), cerebrovascular conductance index, mean arterial pressure, and cerebral pulsatility index did not differ among groups. Slope-based summary measures of cerebrovascular reactivity did not differ significantly among groups. However, utilizing repeated-measures modeling, there was a significant upward shift in MCAv responses (p = 0.029) in the combined MHT group compared with the PLA group.Conclusion: MHT has a marginal sustained effect on cerebrovascular reactivity when measured 3 years after cessation of hormone treatment.

Cerebrovascular Reactivity and Central Arterial Stiffness in Habitually Exercising Healthy Adults.

Reduced cerebrovascular reactivity to a vasoactive stimulus is associated with age-related diseases such as stroke and cognitive decline. Habitual exercise is protective against cognitive decline and is associated with reduced stiffness of the large central arteries that perfuse the brain. In this context, we evaluated the age-related differences in cerebrovascular reactivity in healthy adults who habitually exercise. In addition, we sought to determine the association between central arterial stiffness and cerebrovascular reactivity. We recruited 22 young (YA: age = 27 ± 5 years, range 18–35 years) and 21 older (OA: age = 60 ± 4 years, range 56–68 years) habitual exercisers who partake in at least 150 min of structured aerobic exercise each week. Middle cerebral artery velocity (MCAv) was recorded using transcranial Doppler ultrasound. In order to assess cerebrovascular reactivity, MCAv, end-tidal carbon dioxide (ETCO2), and mean arterial pressure (MAP) were continuously recorded at rest and during stepwise elevations of 2, 4, and 6% inhaled CO2. Cerebrovascular conductance index (CVCi) was calculated as MCAv/MAP. Central arterial stiffness was assessed using carotid–femoral pulse wave velocity (PWV). Older adults had higher PWV (YA: 6.2 ± 1.2 m/s; OA: 7.5 ± 1.3 m/s; p < 0.05) compared with young adults. MCAv and CVCi reactivity to hypercapnia were not different between young and older adults (MCAv reactivity, YA: 2.0 ± 0.2 cm/s/mmHg; OA: 2.0 ± 0.2 cm/s/mmHg; p = 0.77, CVCi reactivity, YA: 0.018 ± 0.002 cm/s/mmHg2; OA: 0.015 ± 0.001 cm/s/mmHg2; p = 0.27); however, older adults demonstrated higher MAP reactivity to hypercapnia (YA: 0.4 ± 0.1 mmHg/mmHg; OA: 0.7 ± 0.1 mmHg/mmHg; p < 0.05). There were no associations between PWV and cerebrovascular reactivity (range: r = 0.00–0.39; p = 0.07–0.99). Our results demonstrate that cerebrovascular reactivity was not different between young and older adults who habitually exercise; however, MAP reactivity was augmented in older adults. This suggests an age-associated difference in the reliance on MAP to increase cerebral blood flow during hypercapnia.

Cerebral Blood Flow Responses to a Memory Test in Young and Older Habitual Exercisers

In a healthy brain, the cerebral microvessels respond to increased metabolic demand by vasodilating to increase blood flow. Reduced cerebrovascular responses to stimuli are indicative of impaired cerebrovascular functioning, and this mismatch may be a mechanism underlying age‐related reductions in cognition. The purpose of this study was to investigate how the cerebral blood flow (CBF) response to a metabolic stimulus differs between young and older participants. It has been shown that older adults have lower CBF response to chemical stimuli compared to young adults, and we hypothesized there would also be age‐associated differences in the CBF response to metabolic stimuli. We evaluated 15 young (25±1 y) and 11 older (64±1 y) habitual exercisers. Participants were instrumented with a transcranial Doppler ultrasound to measure middle cerebral artery velocity (MCAv) and a Finometer to measure beat‐to‐beat mean arterial pressure (MAP) at baseline and during two difficulty levels of the n‐back memory test. Cerebrovascular conductance index (CVCi) was calculated as MCAv/MAP. There were no group differences in BMI or resting heart rate. The older adults had a significantly higher MAP at rest compared with young adults (96±4 mmHg vs. 86±2 mmHg, respectively; p&lt;0.05). There were no differences in MCAv at baseline. However, baseline CVCi was lower in the older adults compared with young adults (0.55±0.04 cm/s/mmHg vs. 0.70±0.06 cm/s/mmHg respectively; p&lt;0.05). There were no differences in MCAv during either level of the test. During the level 1 test, older adults had higher MAP compared with young adults (111±6 mmHg vs. 96±3 mmHg respectively; p&lt;0.05). During the level 2 test, the older adults again demonstrated augmented MAP compared with young adults (108±5 mmHg vs. 94±3 mmHg; p&lt;0.05). Interestingly, older adults had a greater percent increase in CVCi compared with young adults during the level 2 test (13±3% vs. 7±2% respectively; p&lt;0.05). Thus, while older adults had lower baseline CVCi and lower CVCi during the test, they had a greater increase in CVCi during the higher difficulty test. In summary, there were no age‐associated differences in baseline MCAv or change in MCAv during the cognitive tests, yet MAP was higher in the older adults. Therefore, our results suggest that the CBF response to an acute cognitive challenge is similar in young and older adults, but the regulatory mechanism may be different.Support or Funding InformationSupported by National Institute of Health grant HL118154, and the American Physiological Society Undergraduate Research Excellence Fellowship.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The Impact of Grey Matter Normalization on Cerebrovascular Reactivity

Grey matter atrophy occurs with age; however, most studies on cerebral blood flow responses to hypercapnia and age do not normalize to grey matter volume. It is possible that adults with lower brain blood flow and lower brain blood flow responses simply have less grey matter. This is especially relevant in the context of aging, where grey matter declines 0.83% per year. Therefore, the purpose of this study was to determine the impact of grey matter volume (GM) normalization on the cerebrovascular reactivity quantification in young and older healthy adults. We recruited 15 young (YA: age = 26 ± 4 y; BMI = 23 ± 1 kg/m2) and 10 older (OA: age= 64 ± 3 y; BMI= 22 ± 3 kg/m2) habitually exercising men and women. Middle cerebral artery velocity (MCAv), mean arterial pressure (MAP), and end‐tidal carbon dioxide (ETCO2) were measured continuously at rest and during a stepped hypercapnia protocol. GM was calculated from a T‐1 weighted scan on a 3T MRI scanner and segmented using SPM12. Cerebrovascular conductance index (CVCi) was calculated as CVCi = MCAv/MAP. Reactivity was calculated as the linear relationship between the change in ETCO2 and the change in MCAv and CVCi. GM normalization was performed by dividing MCAv and CVCi by GM. GM was significantly higher in the young compared with the older adults (YA: 0.71±0.02 L; OA: 0.62±0.01 L; p&lt;0.001). MCAv reactivity values normalized to GM were significantly higher than those of raw MCAv reactivity in both young (YA: Raw: 1.7±0.3 cm/s/mmHg; Norm: 2.3±0.4 cm/s/L/mmHg; p&lt;0.001) and older adults (OA: Raw: 2.0±0.3 cm/s/mmHg; Norm: 3.3±0.4 cm/s/L/mmHg; p&lt;0.001). However, MCAv reactivity was not different between groups for both the raw and GM normalized data (p&gt;0.05). Similar results were found for CVCi reactivity such that CVCi reactivity values normalized to GM were higher than raw CVCi reactivity for both young (YA: Raw: 0.017±0.002 cm/s/mmHg2; Norm: 0.023±0.003 cm/s/L/mmHg2; p&lt;0.001) and older adults (OA: Raw: 0.015±0.002 cm/s/mmHg2; Norm: 0.024±0.003 cm/s/L/mmHg2; p&lt;0.001). However, there were no significant differences in CVCi reactivity between young and older adults for both raw and normalized data (p&gt;0.05). These results suggest that GM normalization changes reactivity values similarly between young and older habitually exercising adults.Support or Funding InformationSupported by National Institute of Health grant HL118154.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Cerebrovascular Reactivity in Habitually Exercising Healthy Adults

Cerebrovascular reactivity to hypercapnia declines with age and low reactivity may be a biomarker of cognitive decline. Central elastic arteries that perfuse the brain stiffen with age, increasing their transmission of pulsatile mechanical forces into the cerebral microvasculature and impairing cerebral microvessel function. Habitual physical activity, however, has been shown to reduce central arterial stiffness and is associated with better cognitive function. Therefore, the purpose of this study was to evaluate cerebrovascular reactivity in young and older healthy adults who habitually exercise. We hypothesized that older adults who habitually exercised would have similar cerebrovascular reactivity when compared with young adults. However, because the underlying mechanisms of cerebral blood flow regulation may differ with age, we also evaluated blood pressure and central hemodynamic measures. We recruited 25 young (YA: age = 27 ± 1 y) and 20 older (OA: age = 59 ± 1 y) habitual exercisers. Middle cerebral artery velocity (MCAv) was recorded using transcranial Doppler ultrasound. In order to assess cerebrovascular reactivity, mean arterial pressure (MAP), end‐tidal carbon dioxide (ETCO2), and MCAv were continuously recorded at rest and during stepwise elevations of inhaled CO2. Cerebrovascular conductance index (CVCi) was calculated as MCAv/MAP. Reactivity was calculated as the linear relationship between the change in ETCO2 and the change in each variable of interest (MCAv, CVCi and MAP). Central arterial stiffness (carotid‐femoral pulse wave velocity, PWV) and central hemodynamics (augmentation index, AIx) were assessed by applanation tonometry. Older adults had higher MAP (YA: 85 ± 2 mmHg; OA: 90 ± 3 mmHg; p&lt;0.05) and AIx (YA: 0 ± 3 %; OA: 20 ± 2 %; p&lt;0.05) at rest compared with young adults. PWV was not statistically different between groups (YA: 4.9 ± 0.3 cm/s; OA: 5.7 ± 0.5 cm/s; p=0.18). MCAv and CVCi reactivity to hypercapnia were similar between young and older adults (MCAv reactivity, YA: 2.0 ± 0.2 cm/s/mmHg; OA: 2.2 ± 0.1 cm/s/mmHg; p=0.46, CVCi reactivity, YA: 0.018 ± 0.002 cm/s/mmHg2; OA: 0.016 ± 0.001 cm/s/mmHg2; p=0.42); however, older adults demonstrated higher MAP reactivity to hypercapnia (YA: 0.3 ± 0.1 a.u.; OA: 0.8 ± 0.1 a.u.; p&lt;0.05). PWV and AIx were not associated with MCAv, CVCi, or MAP reactivity to hypercapnia (p&gt;0.05). Our results suggest that habitual exercise preserves cerebrovascular reactivity; however, MAP reactivity is augmented with aging allowing older adults to sufficiently increase cerebral blood flow during hypercapnia.Support or Funding InformationSupported by National Institute of Health grant HL118154This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Effect of acute hypoxemia on cerebral blood flow velocity control during lower body negative pressure.

The ability to maintain adequate cerebral blood flow and oxygenation determines tolerance to central hypovolemia. We tested the hypothesis that acute hypoxemia during simulated blood loss in humans would cause impairments in cerebral blood flow control. Ten healthy subjects (32 ± 6 years, BMI 27 ± 2 kg·m−2) were exposed to stepwise lower body negative pressure (LBNP, 5 min at 0, −15, −30, and −45 mmHg) during both normoxia and hypoxia (FiO2 = 0.12–0.15 O2 titrated to an SaO2 of ~85%). Physiological responses during both protocols were expressed as absolute changes from baseline, one subject was excluded from analysis due to presyncope during the first stage of LBNP during hypoxia. LBNP induced greater reductions in mean arterial pressure during hypoxia versus normoxia (MAP, at −45 mmHg: −20 ± 3 vs. −5 ± 3 mmHg, P < 0.01). Despite differences in MAP, middle cerebral artery velocity responses (MCAv) were similar between protocols (P = 0.41) due to increased cerebrovascular conductance index (CVCi) during hypoxia (main effect, P = 0.04). Low frequency MAP (at −45 mmHg: 17 ± 5 vs. 0 ± 5 mmHg2, P = 0.01) and MCAv (at −45 mmHg: 4 ± 2 vs. −1 ± 1 cm·s−2, P = 0.04) spectral power density, as well as low frequency MAP‐mean MCAv transfer function gain (at −30 mmHg: 0.09 ± 0.06 vs. −0.07 ± 0.06 cm·s−1·mmHg−1, P = 0.04) increased more during hypoxia versus normoxia. Contrary to our hypothesis, these findings support the notion that cerebral blood flow control is not impaired during exposure to acute hypoxia and progressive central hypovolemia despite lower MAP as a result of compensated increases in cerebral conductance and flow variability.

Acute impact of drinking coffee on the cerebral and systemic vasculature.

Previous studies have suggested that the risk of ischemic stroke increases immediately after drinking coffee. Indeed, drinking coffee, that is, caffeine, acutely increases arterial stiffness as well as blood pressure and peripheral vascular resistance. On the other hand, it has been reported that arterial stiffening is associated with elevation in the pulsatility index (PI) of cerebral blood flow (CBF), which increases the risk of brain disease. However, the effect of drinking coffee on the PI of the CBF and its interaction with arterial stiffness remain unknown. Against this background, we hypothesized that an acute increase in arterial stiffness induced by drinking coffee augments cerebral pulsatile stress. To test this hypothesis, in 10 healthy young men we examined the effects of drinking coffee on the PI of middle cerebral artery blood velocity (MCAv) and brachial‐ankle pulse wave velocity (baPWV) as indices of cerebral pulsatile stress and arterial stiffness, respectively. Mean arterial blood pressure and baPWV were higher (P < 0.01 and P = 0.02), whereas mean MCAV and mean cerebrovascular conductance index were lower upon drinking coffee (P = 0.02 and P < 0.01) compared with a placebo (decaffeinated coffee). However, there was no difference in the PI of MCAv between drinking coffee and the placebo condition. These findings suggest that drinking coffee does not increase cerebral pulsatile stress acutely despite an elevation in arterial stiffness in the systemic circulation.

Transcranial Doppler-determined change in posterior cerebral artery blood flow velocity does not reflect vertebral artery blood flow during exercise.

We examined whether a change in posterior cerebral artery flow velocity (PCAv) reflected the posterior cerebral blood flow in healthy subjects during both static and dynamic exercise. PCAv and vertebral artery (VA) blood flow, as an index of posterior cerebral blood flow, were continuously measured during an exercise trial using transcranial Doppler (TCD) ultrasonography and Doppler ultrasound, respectively. Static handgrip exercise significantly increased both PCAv and VA blood flow. Increasing intensity of dynamic exercise further increased VA blood flow from moderate exercise, while PCAv decreased to almost resting level. During both static and dynamic exercise, the PCA cerebrovascular conductance (CVC) index significantly decreased from rest (static and high-intensity dynamic exercise, -11.5 ± 12.2% and -18.0 ± 16.8%, means ± SD, respectively) despite no change in the CVC of VA. These results indicate that vasoconstriction occurred at PCA but not VA during exercise-induced hypertension. This discrepancy in vascular response to exercise between PCA and VA may be due to different cerebral arterial characteristics. Therefore, to determine the effect of exercise on posterior cerebral circulation, at least, we need to carefully consider which cerebral artery to measure, regardless of exercise mode.NEW & NOTEWORTHY We examined whether transcranial Doppler-determined flow velocity in the posterior cerebral artery can be used as an index of cerebral blood flow during exercise. However, the changes in posterior cerebral artery flow velocity during exercise do not reflect vertebral artery blood flow.

Lack of correlation between cerebral vasomotor reactivity and dynamic cerebral autoregulation during stepwise increases in inspired CO2 concentration.

Cerebral vasomotor reactivity (CVMR) and dynamic cerebral autoregulation (CA) are measured extensively in clinical and research studies. However, the relationship between these measurements of cerebrovascular function is not well understood. In this study, we measured changes in cerebral blood flow velocity (CBFV) and arterial blood pressure (BP) in response to stepwise increases in inspired CO2 concentrations of 3 and 6% to assess CVMR and dynamic CA in 13 healthy young adults [2 women, 32 ± 9 (SD) yr]. CVMR was assessed as percentage changes in CBFV (CVMRCBFV) or cerebrovascular conductance index (CVCi, CVMRCVCi) in response to hypercapnia. Dynamic CA was estimated by performing transfer function analysis between spontaneous oscillations in BP and CBFV. Steady-state CBFV and CVCi both increased exponentially during hypercapnia; CVMRCBFV and CVMRCVCi were greater at 6% (3.85 ± 0.90 and 2.45 ± 0.79%/mmHg) than at 3% CO2 (2.09 ± 1.47 and 0.21 ± 1.56%/mmHg, P = 0.009 and 0.005, respectively). Furthermore, CVMRCBFV was greater than CVMRCVCi during either 3 or 6% CO2 (P = 0.017 and P < 0.001, respectively). Transfer function gain and coherence increased in the very low frequency range (0.02-0.07 Hz), and phase decreased in the low-frequency range (0.07-0.20 Hz) when breathing 6%, but not 3% CO2 There were no correlations between the measurements of CVMR and dynamic CA. These findings demonstrated influences of inspired CO2 concentrations on assessment of CVMR and dynamic CA. The lack of correlation between CVMR and dynamic CA suggests that cerebrovascular responses to changes in arterial CO2 and BP are mediated by distinct regulatory mechanisms.

Cerebrovascular vasoconstrictor responses in young and older adults: effect of age and exercise

Recent research focuses on the cerebrovascular response to vasodilatory stimuli as an index of cerebrovascular health; however, vasoconstrictor responses in the brain are likely equally important. We previously have shown that cerebral vasoconstrictor responses to hypocapnia are not affected by aging; however, this was evaluated in primarily sedentary adults. Therefore, we hypothesized that middle cerebral artery velocity (MCAv) vasoconstrictor responses to hypocapnia are dependent on age and habitual physical activity. We evaluated 13 young physically active (YA; age = 30±5 y; VO2max = 45±8 mL/kg/min), 6 young sedentary (YS; age = 29±4 y; VO2max = 26±3 mL/kg/min), 10 older physically active (OA; age= 61±6 y; VO2max =35±7 mL/kg/min) and 8 older sedentary (OS; age = 65±8 y; VO2max 23±2 mL/kg/min) adults during the recovery from inhaled 6% CO2 to room air. Mean arterial pressure (MAP) end tidal CO2 (ETCO2) and MCAv were recorded throughout. Using a breath‐by breath analysis, cerebrovascular conductance index (CVCi=MCAv/MAP) reactivity was calculated as a slope of CVCi and ETCO2 and used to quantify vasoconstrictor responses. CVCi reactivity was higher in YA adults (slope=2.74±0.9 AU) compared with both YS (slope=2.20±1.1 AU) and older groups (OA: slope=2.08±0.5 AU; OS: slope=2.07±0.7 AU; p&lt;0.05 for all). There were no significant differences in CVCi reactivity between YS and either OA or OS (p=0.94, p=0.99 respectively). Additionally, CVCi negatively correlated with age (r=−0.38, p&lt;0.05). Our results indicate that aging attenuates the cerebral vasoconstrictor response to hypocapnia in older adults in comparison to physically‐active young adults, but not compared to sedentary young controls. A sedentary lifestyle resulted in attenuated vasoconstrictor responses in the young sedentary group, as their responses were not different than the older adults. It remains unclear how habitual physical activity preserves the cerebral vasoconstrictor response to hypocapnia in young people, and if a structured exercise training intervention would impact this response in older adults.Support or Funding InformationNIH HL118154

The analysis of cardio-respiratory signals and cerebral autoregulation based on CO2 reactivity with healthy subjects and Parkinson's patients.

Current paper focus on Parkinson's patients with autonomic dysfunction and how their interactions between cerebral autoregulation and ventilatory control are affected. The experimental data of dynamic CA assessment from the ANS Laboratory of CCGH was accessed for further processing and analysis. The subjects were classified into the groups of healthy and with Parkinson's disease. Based on the accessed ventilation and CBF data, the percentage changes in ventilation and CBF responses to PETCO2 were examined. To minimize effects of changes in ABP on cerebral vasomotor reactivity (CVMR) estimation, cerebrovascular conductance index (CVCi) was calculated, and CBFV-PETCO2 and CVCi-PETCO2 relationships were quantified by nonlinear logistic regression. The interaction between ventilation responses and CBF autoregulation will be modeled and parameters will be validated.

Arterial stiffness is associated with age-related differences in cerebrovascular conductance

To determine if arterial stiffness is associated with age-related differences in cerebrovascular conductance and reactivity, twenty-eight apparently healthy sedentary young (25±1years; n=15) and older (67±1years; n=13) adults were studied. Brachial-ankle pulse wave velocity (baPWV) was measured as an index of arterial stiffness. Cerebrovascular reactivity was determined by measuring changes in mean blood velocity in the middle cerebral artery under normocapnic, hypocapnic and hypercapnic conditions. Mean baPWV was greater (p<0.05) in older compared with young adults. At baseline, mean cerebral blood flow velocity and cerebrovascular conductance index were lower (p<0.05) in older compared with young adults under normocapnic, hypocapnic and hypercapnic conditions. There were no significant group differences in cerebrovascular reactivity when they were adjusted for stimuli (i.e., end-tidal CO2 concentrations) in most perturbation conditions except for the normocapnia to hypercapnia condition. baPWV was negatively associated with cerebrovascular conductance index at all conditions (all p<0.05). We concluded that arterial stiffness was associated with age-related differences in cerebrovascular conductance and that there were no apparent age-associated differences in cerebrovascular reactivity.