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Matched increases in cerebral artery shear stress, irrespective of stimulus, induce similar changes in extra-cranial arterial
diameter in humans
*Kurt J Smith1 PhD, *Ryan L Hoiland2 MSc, Ryan Grove1BSc (Hon), Hamish McKirdy1 BSc (Hon), Louise Naylor 1 PhD, Philip N Ainslie2 PhD, Daniel J Green1,3 PhD
1Cardiovascular Research Group, School of Human Sciences (Exercise and Sport Science),
The University of Western Australia, Perth, Australia;2Centre for Hearth Lung and Vascular Health, School of Health and Exercise Sciences,
University of British Columbia,3Research Institute for Sport and Exercise Sciences, John Moores Liverpool University, UK
*Authors contributed equally to this manuscript
Corresponding Author:Kurt J. Smith
Kurt.smith@uwa.edu.au610431698502
School of Human Sciences M40835 Stirling Highway, Nedlands, 6000The University of Western Australia
Word Count: 4571Tables: 2Figures: 2
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Abstract
The mechanistic role of arterial shear stress in the regulation of cerebrovascular responses to
physiological stimuli (exercise and hypercapnia) is poorly understood. We hypothesized that,
if shear stress is a key regulator of arterial dilation, then matched increases in shear induced
by distinct physiological stimuli, would induce similar dilation of the large extra-cranial
arteries. Participants (n=10), participated in three 30-min experimental interventions, each
separated by ≥48hours: 1) mild hypercapnia (FICO2:~0.045); 2) submaximal cycling (EX;
60%HRreserve); or 3) resting (time-matched control, CTRL). Blood flow, diameter and shear
rate were assessed (via Duplex ultrasound) in the internal carotid and vertebral arteries (ICA,
VA) at baseline, during and following the interventions. Hypercapnia and EX produced
similar elevations in blood flow and shear rate through the ICA and VA (p<0.001), which
were both greater than CTRL. Elevations in ICA and VA diameter from baseline in response
to hypercapnia (5.3±0.8 and 4.4±2.0%) and EX (4.7±0.7 and 4.7±2.2%) were also similar,
and greater than CTRL (p<0.001). Our findings indicate that matched levels of shear,
irrespective of their driving stimulus, induce similar extra-cranial artery dilation. We
demonstrate, for the first time in humans, an important mechanistic role for the endothelium
in regulating cerebrovascular response to common physiological stimuli in vivo.
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Introduction
In conduit arteries such as the coronary,1 brachial,2 radial,3 and femoral,4,5 it is well
established that intra-arterial shear stress regulates endothelium-dependent vasoreactivity. It
is also well-known that episodic increases in shear can induce anti-atherogenic adaptation in
paracrine transduction pathways, including the nitric oxide (NO)-dilator system [reviewed in:
6]. Shear-mediated stimulation of the endothelium is a key mechanism responsible for
vasodilation through these conduit arteries in humans.6
Exercise increases blood flow to the brain in humans.7 Traditionally, the explanation for this
has been attributed to a combination of physiological stimuli, including changes in arterial
blood gases, blood pressure and metabolism. 8,9 Another possible mechanism, however,
involves changes in arterial shear stress and consequent endothelium-mediated dilation.10
Recently, we demonstrated vasodilation of extra-cranial feed arteries as a result of
hypercapnia induced increases in brain blood flow and shear stress in vivo.11,12 However, the
impact of shear stress on cerebrovascular responses during exercise has not previously been
investigated.
In the current study, we propose that shear stress is involved in regulating cerebrovascular
function during exercise in humans. We therefore examined the impact of matched elevations
in arterial shear stress, induced by distinct and common physiological mechanisms: Exercise
or hypercapnia. We examined the hypothesis that similar patterns of dilation of the large
extra-cranial arteries would be observed irrespective of the different stimuli induced by
exercise or hypercapnia.
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Methods
Participants
Ten healthy male participants (age, 25±6 years; weight, 74.14±7.03kg; height, 2.11±0.21m)
were recruited for the study. All participants were non-smokers, with a body mass index <30,
free of cardiovascular, respiratory, cerebrovascular, musculoskeletal and/or metabolic
diseases. The study was approved by the University of Western Australia’s Human Research
Ethics Committee. The participants were informed of all experimental procedures and
associated risk. Participants provided written informed consent before the commencement of
the study.
Experimental design
After inclusion, participants were tested at the Cardiovascular Research Laboratory on three
occasions separated by ≥48hours at the same time of day. Each visit consisted of one of three
randomly assigned interventional protocols (Control [CTRL], Hypercapnia [CO2], or
Exercise [EX]). Subjects arrived after fasting for a minimum of 6 hrs, with 24 hr abstinence
from alcohol, caffeine and vigorous exercise. Upon arrival, participants were instrumented
and underwent a 10 min rest period in a semi-recumbent position. Baseline (BL) recordings
of the primary outcome measures were then collected during a further 5-minute period of
quiet rest. Following baseline measures, subjects participated in one of three interventions: 1)
30-minutes of hypercapnia (see below); 2) 30-minutes of exercise at ~60% heart rate (HR)
reserve; or 3) 30-minutes of rest (time-control day). Cerebrovascular (transcranial Doppler
and duplex vascular ultrasound) and cardiorespiratory assessments were collected throughout
each condition.
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Experimental procedures
Cerebrovascular assessments
Non-invasive insonation via 2MHz transcranial Doppler ultrasound (TCD; Spencer
Technologies, Seattle, WA) was used to assess blood velocity in the middle (MCAv) and
posterior (PCAv) cerebral arteries. The cerebral arteries were identified and optimised
according to their signal depth, waveform and velocities, according to previously published
guidelines.13 The MCAv and PCAv were continuously recorded at baseline, throughout the
30-minutes of each intervention, and during post-intervention assessments.
Blood velocity and diameter of the internal carotid artery (ICA) and vertebral (VA) arteries
(VA) were measured using a 10-15MHz multi-frequency linear array vascular ultrasound
(Terason T3200, Teratech, Burlington, MA).14 Whilst ICA recordings were captured at 10,
20 and 30 minutes of the intervention, the VA recording were captured at 15 and 25 minutes
of the intervention. Ultrasound assessments were performed by one scanner and required
approximately 5-minutes to achieve a single scan. Thus, a standardized timing of ICA and
VA collection was applied to ensure similar time-points were collected throughout each
experimental condition. Baseline and post-intervention recordings (5–10 minutes post) were
collected for both the ICA and VA. All of the ICA and VA recordings were screen captured
and stored as video files for offline analysis.15
Cardiorespiratory measurements
All cardiorespiratory variables were sampled continuously throughout the protocol at 1000Hz
via an analogue-to-digital converter (Powerlab, 16/30; ADInstruments, Colorado Springs,
CO). Partial pressure of oxygen (PETO2) and carbon dioxide (PETCO2) were assessed using a
gas analyser (ADInstruments, Colorado Springs, CO), heart rate (HR) was measured by a 3-
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lead electrocardiogram (ECG; ADI bioamp ML132), and beat-to-beat blood pressure by
finger photoplethysmography (Finometer PRO, Finapres Medical Systems, Amsterdam,
Netherlands).
Experimental interventions
Hypercapnia (CO2) condition
Hypercapnia was used as a stimulus to elevate cerebral blood flow (CBF) and shear stress for
30 minutes via breathing an air mixture (4.5% CO2, 21% O2, and balanced N2) through a
spirometer connected to a Douglas bag. The participants were seated throughout in a semi-
recumbent position. Simultaneous assessment of intracranial velocity (measured by
transcranial Doppler of the left MCA and right PCA) and beat-by-beat extracranial blood
flow (measurement by Duplex ultrasonography of the ICA and VA) was assessed along with
beat-to-beat arterial pressure (Finometer Pro, Amsterdam, Netherlands). Continuous
monitoring of MCAv was used as an index of real-time change in cerebrovascular shear
stress. If necessary, the concentration of inspired CO2 was altered (range 3-6%) to achieve the
desired increase in arterial shear stress (~30% above baseline). The decision to use a 30%
increase in shear stress was chosen based off of pilot data indicating this to be the most
reliable increase achievable in both CO2 and EX protocols. This allowed CO2 and EX shear to
be matched irrespective of study order.
Exercise condition
Participants cycled at submaximal intensity [~60% heart rate (HR) reserve = 100-120bpm]
for 30-minutes to maintain a steady increase in CBF measures throughout the exercise
condition. As with the hypercapnia intervention, continuous intracranial blood velocity and
extra-cranial blood flow were measured at the same time points during the intervention. The
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MCAv during the 30-minute intervention was closely monitored to ensure that an elevated
CBF and shear stress was achieved (~30% above baseline, to match the CO2 condition).
Time-control condition
Participants sat in a semi-recumbent position for 30-minutes. Continuous intracranial blood
velocity and extra-cranial blood flow were measured at the same time points as the
interventions above.
Statistics
Statistical and graphing analysis was performed using GraphPad PRISM 6.01 software
(GraphPad Software, LaJolla, CA, USA). All parameters were compared within-subjects
using 2-way ANOVA repeated-measures. Bonferroni-correction for multiple comparisons
were used for all post-hoc analysis. Statistical significance was assumed at p<0.05. All data
are reported as mean ± SD unless otherwise specified.
Results
All cardiorespiratory and cerebrovascular values, for the anterior (ICA, MCA) and posterior
(VA, PCA) cerebral arteries, are provided in tables 1 and 2.
Cardiorespiratory measures
No changes were observed for any of the cardiorespiratory measures assessed during the 30-
minute CTRL condition (Table 1 and 2).
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During the CO2 and EX, MAP increased (p<0.01), but returned toward baseline values post-
intervention (Tables 1 and 2). The magnitude of increase in MAP was similar between the
CO2 and EX conditions, except for the post-intervention time point (EX was lower;
p<0.001).,\ Both CO2 and EX MAP data were significantly higher throughout the intervention
period compared to the CTRL trial (p<0.001).
The CO2 and CTRL conditions did not elicit any changes in HR. In contrast, the EX
condition was associated with an elevated HR compared to baseline values and by
comparison to the other conditions during the intervention period. Both PETO2 and PETCO2
were elevated throughout the CO2 intervention (p<0.001), compared to baseline values and
also when compared to the CTRL condition. EX had a small increase on PETCO2 compared to
baseline values, but not to the same extent as the CO2 condition.
Cerebrovascular measures
No changes in either MCAv or PCAv were observed during CTRL. When all time points
were considered, similar mean increases, from BL, were observed in response to CO2
(28.1±3.4 and 23.3±2.8%) and EX (27.7±3.8 and 19.6 ± .3.0%) in the in MCAv and PCAv,
respectively (p<0.001). All MCAv and PCAv values were greater during the EX and CO2
conditions relative to the CTRL data (Figure 1; p<0.001). Both the EX and CO2 conditions
stimulated similar magnitudes of increase in blood flow, blood velocity and shear rate (p <
0.001) in the ICA and VA, relative to baseline value. Furthermore, blood flow, velocity and
shear rate data collected under the CO2 and EX conditions were elevated compared to CTRL
throughout the intervention period (Figure 1; p<0.001).
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No changes ICA or VA diameter were observed during CTRL. In contrast, ICA and VA
diameters increased from baseline values during both CO2 and EX (Table 1; p<0.001). The
increases in diameter, in both arteries, were higher than the changes observed in the CTRL
condition at all time-points, except for the VA diameters 10 minutes post intervention (Figure
2). There were no differences in the changes in diameter observed when the CO2 and EX
conditions were compared.
Linear Regression
Linear regression analysis between the peak changes in diameter and shear stress indicated
significant correlation coefficient during the CO2 (R2 = 0.47; p< 0.01) and EX (R2 = 0.31;
p<0.01) conditions (see Figure 4). Multiple regression analysis using changes in blood
pressure as a covariate to predict the relationship between shear stress and ICA dilation
during the CO2 condition revealed an enhanced correlation coefficient (R2 = 0.61; p< 0.01);
however, no significant improvement was observed using changes in CO2 as a covariate. In
contrast, multiple regression analysis using changes in CO2 as a covariate during the EX
condition, revealed an enhanced correlation coefficient between the peak shear and dilation
(R2 = 0.53; p< 0.01), but not for changes in BP. No significant change in the improvement in
the covariate linear regression was observed between shear stress and diameter using changes
in both CO2 and blood pressure during either the CO2 or EX conditions.
Discussion
Our findings indicate that matched increases in cerebrovascular shear stress, irrespective of
the eliciting stimulus (CO2 or EX), induce similar increases in extra-cranial artery diameter in
humans. This study therefore provides novel evidence that arterial shear stress, alongside
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changes in blood gases and pressure, is an important stimulus regulating cerebral conduit
artery dilation in vivo. Given that repetitive episodic increases in shear stress beneficially
impact arterial function and structure,6 our novel observation provides a mechanistic basis for
linking exercise, physical activity and cerebrovascular health in humans.
It is well established that endothelium-dependent mechanisms play a key role in shear stress
mediated vasodilation of coronary and peripheral arteries in humans.1,3-5,16 These studies have
established a role for paracrine hormones such as NO and prostacyclin in vasomotor
regulation, for example, in response to exercise. In animals, classic studies have established
that in vivo increases in flow and shear stress through cerebral conduit arteries (e.g. basilar
artery) trigger endothelial-mediated vasodilation.17 Recently, in a well-controlled mouse
model, Raignault et al.18 illustrated that the cerebrovascular endothelium optimally couples
shear stress to eNOS-mediated dilation under physiological pulse pressures, in contrast to
static flow conditions. These findings strongly infer that changes in the diameter of cerebral
arteries are responsive to a pulsatile environment and that shear stress sensitivity and
consequent production of NO are optimised under in vivo conditions.18 It is also well
established that carotid artery remodelling as a result of chronic changes in flow is dependent
upon the presence of a functional endothelial layer,19 implicating shear- and NO-mediated
mechanisms in arterial structural adaptation. Collectively these findings, in animals, support a
key role for shear-mediated endothelial-dependent dilation of extra- and intra-cranial cerebral
conduit arteries, although it is also true that some studies indicate a role for non-shear
mediated NO-dependent (ie. eNOS) pathways in cerebral microvascular dilation 20-22. Few
studies, however, have addressed the impact of changes in arterial shear on human cerebral
vasodilator function in vivo.
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Recently we characterised the time-course and response of ICA dilation to changes in shear
using duplex ultrasound with high temporal resolution edge-detection and wall-tracking in
healthy subjects.11 We concluded that, in response to a sustained hypercapnic stimulus (5-
mins), dilation of the ICA occurs subsequent to marked increases in intra-arterial blood flow
and shear stress. Carter et al.,10 observed a significant relationship (R2 = 0.46) between the
peak shear response and the magnitude of ICA dilation during hypercapnic stimulus. In a
subsequent follow-up experiment,12 a more transient increase in PETCO2 (30 secs) triggered
similar ICA vasodilation to those observed during a sustained 4-min stimulus. Hoiland et
al.,11 also observed a significant relationship (R2 = 0.44) between the shear stress area under
the curve and the magnitude of ICA dilation following the transient hypercapnic bolus. Since
the transient changes in PETCO2 elicited vasodilation following the hypercapnic stimulus, the
notion of shear-mediated dilation of the ICA was further confirmed. The current study
advances these findings by illustrating that similar changes in shear stress during moderate
intensity exercise - and hypercapnia - elicit a similar increases in extra-cranial artery dilation
of both the ICA and VA in humans. This is further corroborated by the observed relationship
(Fig 4) between the peak changes in shear stress and the maximal dilation of the ICA during
exercise (R2 = 0.34) and CO2 (R2 = 0.47).
This study is one of the few to have assessed extra-cranial artery responses to exercise in
humans. Whilst some previous studies have assessed blood flow responses in the ICA during
exercise,7,23,24 these have not specifically focused on changes in arterial diameter or shear
stress. Furthermore, to the best of our knowledge, no study has reported changes in ICA and
VA diameter or shear during and following a commonly undertaken bout of exercise. We
observed significant ICA and VA dilation during exercise in all subjects. Our findings
therefore raise the possibility that exercise-mediated and shear-driven increases in the
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bioavailability of endothelium-derived dilators such as NO may counteract other vasoactive
pathways, such as the increase in sympathetic drive associated with some forms of exercise.
Indeed, functional sympatholysis is a well-established phenomenon in skeletal muscle
arterioles during exercise.25,26 However, the role of sympatholysis in the brain is unclear, and
mechanism(s) of vasomotion and adrenoceptor distribution differ from the large to smaller
cerebral arteries.27
This is the first study that has assessed VA diameter and shear relationships during EX, CO2
and CTRL conditions in humans. Our findings indicate that the vertebral arteries exhibit
dilator responses which are similar to those observed in the ICA. Only two previous studies,
to our knowledge, have recorded VA blood flows during exercise in humans, but these did
not address changes observed in either diameter or shear.7,24 When considered in concert with
our contemporaneous MCA and PCA observations, our ICA and VA data therefore indicate
that cerebral shear and artery dilation occur in both the anterior and posterior cerebral
circulation in response to both EX and CO2 in humans.
An interesting secondary finding of the present study relates to change in shear and artery
diameter following the cessation of exercise. We continued data collection in the post-
exercise period, at different time-points in the ICA (5 minutes post) and VA (10 minutes
post). Dilation remained elevated 5 minutes post-exercise, whereas it had returned to near
resting baseline levels 10-min post-exertion. These findings provide some insight into the
time-course of change in extra-cranial artery diameter following a physiological relevant
exercise duration and intensity.
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There are several limitations of the current experiment. We recruited and studied young male
subjects. The impact of cyclical changes in sex hormones on shear-mediated cerebrovascular
function and health would be an important follow up study in women (as would aging and
menopause). Although our findings suggest that exercise or hypercapnia elicited shear-
mediated endothelial dependent dilation of the ICA and VA, we did not utilize a NO
antagonist to address specific endothelial pathways. However, a previous study following a
sublingual administration of an NO donor (nitroglycerin spray) observed vasodilation in the
common carotid artery28 that was of similar magnitudes to the dilation that we observed in the
ICA. Future studies, involving more invasive approaches, for example endothelial denudation
and/or pharmacological blockade, would advance our understanding of the endothelial
dependency of extra-cranial dilation. Similarly, experiments involving deliberate
manipulation of the magnitude of shear (e.g., different levels of exercise or PETCO2) and
assessment of consequential diameter change in extra-cranial arteries are germane. It is
unlikely that our findings are explained solely as a result of the increases in blood pressure,
per se. Increases in intra-arterial pressure, and associated transmural pressure, are typically
associated with myogenic mediated vasoconstriction,29 however, it is unknown how this
directly influences shear mediated vasodilation in extracranial arteries. Our multiple linear
regression calculations suggest that changes in BP during sustained hypercapnia positively
reinforce shear mediated dilation. Also, PETCO2 was somewhat elevated above baseline in
each condition, and linear regression analysis between ICA dilation and shear stress during
exercise is enhanced when changes in PETCO2 was used as a covariate. We are therefore
unable to exclude the possibility that CO2 directly induces extra-cranial dilation. However,
we have recently provided evidence10,11 that part of the influence of CO2 on extra-cranial
vasodilation is likely due, in part, to shear stress which is supported by our findings of an
enhanced linear regression analysis when CO2 is used as a covariate (Fig 4). Indeed, when a
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bolus of CO2 is administered and arterial diameter is measured following restoration of
PETCO2 and BP to normal values, vasodilation occurs. This vasodilation is approximately
50% in magnitude of the vasodilation observed during a steady state, or persistent CO2
stimulus. Therefore, while data to support direct vasodilatory mechanisms on dilation in the
ICA or VA do not currently exist in humans, a decrease in small intracranial arteriole
resistance and consequent increase in extracranial shear stress clearly possesses a significant
role in cerebrovascular regulation. Stimulation of the peripheral chemoreceptors is associated
with sympathoexcitation, and usually associated with systemic arterial vasoconstriction rather
than the dilation we observed. Finally, we acknowledge that the limitations of TCD impair
our ability to extrapolate our extracranial diameter responses to changes in shear stress, to
intracranial changes that may have simultaneously occurred in the MCA and PCA. However,
the intention of our study was to focus on the ICA and VA responses, with intracranial
measures collected primarily in order to confirm that matching of shear in each intervention
was successful.
Conclusion
We have demonstrated, for the first time in humans, that matched increases in shear stress
through the extra-cranial cerebral conduit arteries in response to distinct stimuli induce
similar levels of vasodilation. Alongside previous evidence, largely derived from animal and
in situ preparations 30,31, our findings regarding vasodilator changes in both the anterior and
posterior extra-cranial conduit arteries suggest an important mechanistic role for the
endothelium in regulating cerebrovascular function in humans in response to both 30 minutes
of moderate hypercapnia and exercise. Since previous studies indicate that some clinical
population’s (stroke, Alzheimer’s, etc)32,33 exhibit impaired carotid and MCA responses to
physiological challenges , our cerebral flow mediated dilation approach may prove useful in
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the characterisation of cerebrovascular health in humans. Interventions that enhance
endothelial function may mitigate age-related decline in cerebrovascular vasodilator function
in humans.
Disclosures: None
Acknowledgements
Kurt J Smith, is supported by a Natural Sciences and Engineering Council of Canada Post-
Doctoral Fellowship. Ryan L. Hoiland was supported by a UBC School of Medicine
Friedman’s Scholarship. Prof’ Ainslie is a Canadian Research Chair in Cerebrovascular
Physiologist. Winthrop Professor Green is a National Health and Medical Research Council
Principal Research Fellow (1080914). This work was supported by NHMRC Project grant
(APP1045204)
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List of Tables
Table 1. Anterior cerebral blood flow and cardiorespiratory measurements during control
(CTRL), carbon dioxide (CO2), and exercise (EX) interventions (n=10).
Table 2. Posterior cerebral blood flow measurements during control (CTRL), carbon dioxide
(CO2), and exercise (EX) interventions (n=8)
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Table 1. Anterior cerebral blood flow and cardiorespiratory measurements during control (CTRL), carbon dioxide (CO2), and exercise (EX) interventions (n=10).
Time (min)Measure Condition BL 10 20 30 Post INT
Mean SD Mean SD Mean SD Mean SD Mean SD
MAP (mmHg)CTRL 88 11 90 8 90 8 93 8 91 9
**CO2 87 7.6 100*φ 10 104*φ 14 102*φ 14 96 11EX 82φ 11 102*φ 10 102*φ 9.5 100*φ 7.7 86*ѱ 15.8
HR (bpm)CTRL 64 7 64 9 67 7 67 7 63 7
**CO2 66 8 70 9 74 9 70 7 63 7EX φѱ 70 8 115φѱ 11 115φѱ 7 118φѱ 7 80φѱ 11
PetO2 (mmHg)CTRL 95.2 6.8 97.7 3.2 98.5 5 100.4 6.9 96 6.2
**CO2 φ 97.4 5 128*φ 2.9 130*φ 1.9 130 *φ 2.3 96 7.8EX ѱ 95.2 6.5 96.6ѱ 7.8 95.8ѱ 7.6 96.0ѱ 7.8 96.8 4.1
PetCO2 (mmHg)CTRL 42.7 4 42.4 2.7 41.9 3.6 41.3 3.6 41.6 3.4
**CO2 φ 42.3 3 46.9*φ 2.4 46.3*φ 2.3 46.2*φ 2.2 41.3 2.5EX 41.6 3.1 44.7* 4.9 44.7* 4.5 44.4φ 5.2 40.8 2.4
QICA (ml.min-1)CTRL 297 24.8 289 20.8 278 21.4 278 24.4 264 24.1
**CO2 262 18.8 368*φ 23.8 380*φ 30.5 354*φ 25.1 256 16.1EX 274 16.9 361*φ 19.7 368*φ 29.6 394*φ 26 282 24.1
ICA Diam (mm)CTL 5.2 0.2 5.2 0.2 5.2 0.2 5.2 0.2 5.2 0.2
**CO2 5.0 φ 0.1 5.3* 0.1 5.3* 0.1 5.4* φ 0.1 5.2 0.1EX 5.1 0.2 5.2 0.2 5.4* 0.2 5.4* φ 0.2 5.3 0.2
ICA Vel (cm.s-1)CTRL 41.1 1.5 40.8 1.2 39.7 1.7 39.6 1.6 38.3 2.2
**CO2 39 2.1 49.5*φ 2.8 49.7*φ 2.7 49.3*φ 2.5 36.9 1.4EX 38 1.6 47.5*φ 1.5 47.4*φ 2.3 49.8*φ 2.5 39.7 1.9
ICA shearCTRL 316 11.3 314 12.1 305 14.2 304 12.9 294 16.6
**CO2 309 15.5 372* 18.0 369*φ 17.4 362*φ 14.2 286 12.2EX 297 12.4 366* 14.6 354*φ 14.1 371*φ 18.0 298 17.0
MCAv (cm.s-1)CTRL 66 3 66 3 65 3 63 3 63 3
**CO2 64 6 83*φ 7 83*φ 7 82*φ 7 68 5EX 58 3 75*φ 4 75*φ 5 74*φ 5 60 3
CVC(ml.min-1/mmHg)
CTRL3.4 0.3 3.2 0.3 3.1 0.3 3.0 0.3 2.9 0.3
NSCO23.0 0.2 3.7 0.2 3.7 0.2 3.5 0.3 2.7 0.1
EX3.5 0.3 3.5 0.2 3.6 0.3 3.9 0.2 3.5 0.4
Time: * = different from BL; p < 0.05, COND: φ = different from CTRL; ѱ = different from CO2; p < 0.01, INT: ** = significant COND x TIME interaction; φ = different from CTRL; ѱ = different from CO2; p < 0.001
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Table 2. Posterior cerebral blood flow and cardiorespiratory measurements during Control (CTRL), carbon dioxide (CO2), and Exercise (EX)(n=8)
Time (min)Measure Condition BL 15 25 Post Int
Mean SD Mean SD Mean SD Mean SD
MAP (mmHg)
CTRL 92 3 93 3 90 4 93 4**CO2 94 3 102 5 106*φ 6 98 5
EX 87 4 102*φ 3 101*φ 3 88 4
HR (BPM)
CTRL 63 2 65 3 65 3 64 3**CO2 64 2 69 3 72*φ 3 65 3
EX ѱ 68 2 114*φѱ 2 118*φѱ 2 80*φѱ 3
PetO2(mmHg)
CTRL 97.5 2.4 104.7 5.3 100 1.4 99.3 1.3**CO2 φ 97.5 2.4 129.9*φ 0.8 130.3*φ 1.3 100.1 0.9
EX φ ѱ 95.9 1.7 94.1 φѱ 3.0 96.0ѱ 2.2 97.9 1.6
PetCO2(mmHg)
CTRL 40.2 2.3 40.4 4.5 40.2 2.2 41 0.9**CO2 φ 41.3 1.3 46.4*φ 0.8 46.1*φ 1 41 0.9
EXφ 41.4 1.1 45.7φ 1.9 44.5 1.5 40.1 1.1
QVA
(ml.min-1)
CTRL 113 20.6 111 21.6 103 19.7 103 17.9**CO2 100 13.1 141* 16.1 142* 20 95 12.9
EX 90 16.1 140* 26.2 143* 26.1 87 12.3
VA Diam(cm)
CTL 3.9 0.1 3.9 0.2 3.9 0.2 3.9 0.1CO2 3.9φ 0.2 4.2φ 0.2 4.2*φ 0.2 4.0φ 0.1 **EX 3.7φ ѱ 0.2 3.9*ѱ 0.2 4.1*ѱ 0.2 3.7φѱ 0.1
VA Vel(cm.s-1)
CTRL 27.7 3.3 27.3 3.3 25.5 2.9 24.4* 3**CO2 24.7 φ 1.9 31.6* φ 2.2 31.2* 2.2 23.4 2
EX 24.7 φ 2.0 31.1* φ 2.6 31.5* 2.5 24.1 1.7
VA shearCTRL 282 28 279 27 261 25 249* 26
**CO2 251 φ 14 305*φ 19 297*φ 16 237 17EX 268 16 322*φ 20 316*φ 20 261 16
PCAv(cm.s-1)
CTRL 49 3 47 3 47 3 46 3**CO2 φ 51 4 63*φ 5 63*φ 4 52 4
EX 48 4 58*φѱ 5 56*φѱ 4 45*ѱ 3
CVC(ml.min-1/mmHg)
CTRL 1.2 0.2 1.2 0.3 1.1 0.2 0.9 0.1NSCO2 1.1 0.1 1.4 0.2 1.4 0.2 1.0 0.1
EX 1.1 0.2 1.4 0.3 1.5 0.3 1.0 0.2Time: * = different from BL; p < 0.05, COND: φ = different from CTRL; ѱ = different from CO2; p < 0.01, INT: ** = significant COND x TIME interaction; φ = different from CTRL; ѱ = different from CO2; p < 0.001
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Figures
Figure 1. Middle (MCAv) and posterior (PCAv) cerebral blood flow velocity (Panels A &
C), internal carotid (ICA) and vertebral (VA) artery Shear (Panels B and D), pre
(BL) during (10,15, 25, 30 minutes, respectively) and POST (5 and 10 minutes
respectively) of the control (CTRL), carbon dioxide (CO2) and exercise (EX)
interventions. φ indicate differences between CO2 and CTRL (p<0.001); τ indicates
differences between EX and CTRL (p<0.001).
Figure 2. Changes in diameter in the internal carotid (ICA), and vertebral (VA) arteries
during (10, 15, 20, 25 and 30 mins, respectively) as well as POST (5 and 10 min,
respectively) control (CTRL) carbon dioxide (CO2) and exercise (EX)
interventions. Straight line connectors indicate significance between experimental
and control conditions (p<0.001).
Figure 3. Arterial blood pressure [MAP]) and end-tidal carbon dioxide [PETCO2] at baseline
(BL), during (10, 15, 20, 25, 30 mins) as well as post exercise during the control
(CTRL), carbon dioxide (CO2) and exercise (EX) conditions. φ indicate differences
between CO2 and CTRL (p<0.001); τ indicates differences between EX and CTRL
(p<0.001).
Figure 4. Relationship between changes in arterial shear stress and dilation of the internal
carotid artery during the carbon dioxide (CO2; r = 0.69) and exercise (EX; r = 0.58)
conditions. Control data is included in both the CO2 and EX figures (p<0.01).
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