Dynamic Cerebral Autoregulation Is Maintained

during High-Intensity Interval Exercise

HAYATO TSUKAMOTO1,2, TAKESHI HASHIMOTO2,3, NIELS D. OLESEN4,5, LONNIE G. PETERSEN4,6,
HENRIK SKRENSEN5, HENNING B. NIELSEN5,7, NIELS H. SECHER5, and SHIGEHIKO OGOH8
1
Neurovascular Research Laboratory, Faculty of Life Sciences and Education, University of South Wales, Pontypridd,
UNITED KINGDOM; 2Research Organization of Science and Technology, Ritsumeikan University, Kyoto, JAPAN; 3Faculty of
Sport and Health Science, Ritsumeikan University, JAPAN; 4Department of Biomedical Sciences, University of Copenhagen,
Copenhagen, DENMARK; 5Department of Anesthesia, The Copenhagen Muscle Research Centre, Rigshospitalet, University of
Copenhagen, Copenhagen, DENMARK; 6Department of Orthopedic Surgery, University of California, San Diego, CA; 7Sanos
Clinic, Herlev, DENMARK; 8Department of Biomedical Engineering, Toyo University, Saitama, JAPAN
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ABSTRACT
TSUKAMOTO, H., T. HASHIMOTO, N. D. OLESEN, L. G. PETERSEN, H. SKRENSEN, H. B. NIELSEN, N. H. SECHER,
and S. OGOH. Dynamic Cerebral Autoregulation Is Maintained during High-Intensity Interval Exercise. Med. Sci. Sports Exerc., Vol. 51,
No. 2, pp. 372–378, 2019. Introduction: High-intensity interval exercise (HIIE) is more effective at increasing metabolic and cardiovascular
health compared with moderate-intensity continuous exercise for patients with cardiovascular disease, but exhaustive high-intensity con-
tinuous exercise attenuates dynamic cerebral autoregulation (CA). This study assessed the effect of HIIE on dynamic CA. Methods: Nine
healthy men (age, 24 T 3 yr; mean T SD) warmed up at 50%–60% maximal workload (Wmax) for 5 min before HIIE including four 4-min
bouts of exercise at 80%–90% Wmax interspaced by four 3-min bouts at 50% to 60% Wmax. Transcranial Doppler determined middle cerebral
artery mean blood velocity (MCA Vmean), and brachial artery catheterization determined mean arterial pressure (MAP). Dynamic CA was
evaluated by transfer function analysis of changes in MAP and MCA Vmean. Results: The HIIE increased MAP (from 92 T 9 to 104 T 10 mm Hg;
P G 0.0125), whereas MCA Vmean did not change. Transfer function phase increased and coherence decreased during HIIE (P G 0.0125 vs rest,
respectively), whereas gain was unchanged. Conclusions: The results suggest that dynamic CA is unaffected during HIIE, indicating that the
brain is protected from fluctuations in MAP. Thus, we propose that HIIE may be beneficial for brain-related health as maintenance of
cerebral perfusion in contrast to high-intensity continuous exercise. Key Words: CEREBRAL BLOOD FLOW, BLOOD PRESSURE,
BRAIN HEALTH, EXERCISE MODALITY, TRANSFER FUNCTION ANALYSIS

H
igh-intensity exercise training offers advantages rel-
ative to low- and moderate-intensity exercise with
regards to body fat, level of fitness, mitochondrial
biogenesis, and endothelial function in both healthy young
and elderly subjects and in the presence of type 2 diabetes,
chronic obstructive pulmonary disease, and heart failure (1,2).
Additionally, Rognmo et al. (3) suggest that high-intensity
interval exercise (HIIE), as well as moderate-intensity exercise,
do not increase the risk of a cardiovascular event even in car-
diac rehabilitation and some studies recommend high-intensity
exercise to prevent cardiovascular disease (4,5).
However, the potential dangers of high-intensity exercise
for the risk of a cerebrovascular event may not be neglected.
Address for correspondence: Takeshi Hashimoto, Ph.D., F.A.C.S.M., Faculty
of Sport and Health Science, Ritsumeikan University 1-1-1 Nojihigashi,
Kusatsu, Shiga 525-8577, Japan; E-mail: thashimo@fc.ritsumei.ac.jp.
Submitted for publication May 2018.
Accepted for publication September 2018.
0195-9131/19/5102-0372/0
MEDICINE & SCIENCE IN SPORTS & EXERCISEÒ
Copyright Ó 2018 by the American College of Sports Medicine
DOI: 10.1249/MSS.0000000000001792
Indeed, high-intensity exercise of a short duration (around
5 min) does not affect dynamic cerebral autoregulation (CA)
(6), which describes the ability to maintain cerebral blood
flow (CBF) in the face of rapid fluctuations in mean arterial
pressure (MAP) to support cerebral metabolism and protect the
brain from the potentially damaging effects of hypoperfusion
and hyperperfusion (7–9). In contrast, dynamic CA is impaired
during exhaustive high-intensity continuous exercise (HICE)
(6). High-intensity continuous exercise–induced impairment
of dynamic CA may render the brain vulnerable to changes in
MAP during exercise and may thereby increase the risk of a
cerebrovascular event, especially in elderly hypertensive pa-
tients who demonstrate high fluctuation in perfusion pressure
(10) and patients with impaired CA (e.g., stroke, diabetes, and
dementia) (11).
The exercise-induced improvement in cognitive executive
function is greater following HIIE than moderate-intensity
continuous exercise (12). Yet, executive function is dimin-
ished by prolonged HICE (13) but not by HIIE including a
similar duration of high-intensity exercise (12). Thus, even if
the total duration of high-intensity exercise is prolonged,
brain function appears not to be impaired by repeated short
bouts of high-intensity exercise. Therefore, we hypothesized
that dynamic CA would not be impaired during HIIE. We

372

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evaluated whether acute HIIE affects dynamic CA, which
holds implications for training and rehabilitation protocols to
promote and maintain cognitive and cardiovascular function.
METHODS
Subjects. Fourteen healthy, male subjects participated
in the study. All subjects were free from neurologic, cardio-
vascular, or pulmonary disorders, did not take any medication,
and were nonsmokers. The subjects were informed of the
experimental procedures and potential risks and provided
written consent as previously described (14). All procedures
conformed to the Declaration of Helsinki and were approved
by the local ethics committee in Copenhagen (H-15011242).
Data from this study concerning post-HIIE cerebral function
and metabolism were already published (14).
Experimental procedure. Cycling was on a Krogh
ergometer attached to a bed with the upper body at a 40-
inclination. At rest the subjects_ legs were extended and re-
laxed on the bed and during exercise strapped to the pedals
of the cycle. At least 5 d before the experiment, maximal
workload (Wmax) was determined to calculate the intensity
required for the HIIE protocol. The maximal workload test
began at 30 W for 3 min, and thereafter, workload was in-
creased by 15 WIminj1 until the subject could not maintain
a cadence of 60 rpm (task failure of a pedaling rate of at least
55 rpm over 5 s despite maximal effort) and Wmax was de-
termined as the highest workload maintained for at least 30 s.
The HIIE protocol was performed on another day and
preceded by a warm-up at 50% to 60% Wmax for 5 min and
included four 4-min bouts of exercise at 80%–90% Wmax
interspaced by four 3-min bouts at 50% to 60% Wmax for a
total of 28 min. The subjects were instructed to maintain a
cadence of 60 rpm. If the subject could not maintain the
cadence despite verbal encouragement, the high-intensity
workload was reduced by 15 W.
Measurement. As an index of CBF, right (n = 5) or left
(n = 4) mean MCA V (MCA Vmean) was measured using
transcranial Doppler ultrasonography (DWL, Sipplingen,
Germany) with a 2-MHz probe placed over the temporal
ultrasound window. An optimal signal-to-noise ratio was
obtained at a depth of 48 to 60 mm, and the probe was fixed
with an adjustable headband. Subjects were familiarized with
the evaluation of MCA V on the day Wmax was determined.
HR was monitored by a lead II electrocardiogram. With
the subject placed slightly head-down on the bed, guided by
ultrasound, a catheter (1.6 mm; 14 G; ES-04706; Arrow
International, Reading, PA) was inserted under cover of lo-
cal anesthesia (lidocaine 2%) retrograde in the right internal
jugular vein and the tip advanced to the bulb of the vein.
Blood sampled from this site was considered to represent the
outlet from the brain, although the potential for a small
contribution from cerebrospinal fluid drained through the
sagittal sinus is recognized. A catheter (1.1 mm ID, 20 G)
was placed in the brachial artery of the nondominant arm for
blood sampling and determination MAP using a pressure
INTERVAL EXERCISE ON CEREBRAL AUTOREGULATION
Copyright © 2018 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
transducer (Baxter, Uden, the Netherlands), zeroed at the
level of the right atrium was interfaced with a Dialogue 2000
monitor (IBC-Danica, Copenhagen, Denmark). Stroke vol-
ume (SV) was estimated offline using the ModelflowÒ
method (Beatscope; FMS, Amsterdam, The Netherlands),
which simulates aortic flow waveforms from an arterial
pressure signal using a nonlinear three-element model of the
aortic input impedance (15) taking height, weight, age, and
sex into account. ModelflowÒ reliably estimates changes in
SV and cardiac output (CO) during a variety of experimental
protocols including dynamic exercise (16). Subjects rested
supine for 1 h after catheterization prior to collection of any
experimental data to offset changes in cerebral metabolism
caused by arousal and nociceptive stimuli (17).
The psychological response during exercise, rating of
perceived exertion (RPE) for breathing and leg effort, and
arousal level were evaluated using the Borg 6 to 20 scale,
APPLIED SCIENCES
Borg CR10 scale, and felt arousal scale, respectively
(18,19). The Borg 6 to 20 scale ranges from 6 (no exertion)
to 20 (maximal exertion). The Borg CR10 scale ranges from
0 (nothing at all) to 10 (almost max). The felt arousal scale
ranges from 1 (low arousal; ‘‘relaxation’’) to 6 (high arousal;
‘‘excitement’’).
Arterial and jugular venous blood (1-mL) for immediate
determination of blood gas variables, glucose, lactate, he-
moglobin, and hematocrit were drawn anaerobically at rest
and during each moderate-intensity exercising (i.e., after each
high-intensity exercise; ABL 800, Radiometer, Copenhagen,
Denmark). The arterial-venous differences across the brain
(a-v diffsubstrate) for oxygen, glucose, and lactate were
determined from paired arterial and internal jugular venous
samples, and fractional extraction (Esubstrate) was also
calculated by dividing the a-v diffsubstrate by the arterial
concentration. For assessment of dehydration, hemoglobin
(Hb) and hematocrit (Hct) were used to calculate changes
in relative plasma volume as follows (20):
relative blood volume ðrBV; %Þ ¼ baseline Hb=Hb
relative red cell volume ðrRCV; %Þ ¼ rBVðHct=100Þ
relative plasma volume ð%Þ ¼ rBV j rRCV
Data analysis. The MCA Vmean, MAP and electrocar-
diogram data were sampled at 100 Hz (LabChart v7.3 and
Powerlab; ADInstruments, Bella Vista, NSW, Australia).
Beat-to-beat MAP and MCA Vmean were obtained by inte-
grating analog signals within each cardiac cycle and were
linearly interpolated and resampled at 2 Hz for spectral
analysis of dynamic CA over 3 min (21). Dynamic CA was
calculated at rest and during the last 3 min of each high-
intensity exercise bout to allow for CBF regulation to reach
steady state, as the transfer function phase and gain shift
between fluctuations in MAP and MCA Vmean (21). Transfer
function analysis was not done in case of excessive noise/
artifact in the recording of arterial pressure or MCA V,
Medicine & Science in Sports & Exercised 373
according to the recommendations from the International
Cerebral Autoregulation Research Network (CARNet) (22).
Subjects for whom transfer function analysis was not done
were excluded from the study. Short periods of strong arti-
fact (up to three beats) were removed and replaced by linear
interpolation (22). The transfer function phase and gain shift
reflect the relative amplitude and time relationship between
changes in MAP and MCA Vmean over a specified frequency
range. From the temporal sequences of MAP and MCA
Vmean, the frequency-domain transformations were computed
using a fast Fourier transformation algorithm. The transfer
function H( f ) between the two signals was calculated as
H( f ) = Sxy( f )/Sxx( f ), where Sxx( f ) is the autospectrum of
changes in MAP and Sxy( f ) is the cross-spectrum between the
two signals. The transfer function magnitude |H( f )| and phase
spectrum |6( f )| were obtained from the real part HR( f ) and
imaginary part HI( f ) of the function:
h i1=2
jH ð f Þj ¼ HR ð f Þ2 þ H1 ð f Þ2
6ð f Þ ¼ tanj1 ½H1 ð f Þ=HR ð f Þ
The squared coherence function MSC( f ) was estimated as
2  and thus, were excluded whereby data from nine healthy
MSCð f Þ ¼ jSxx ð f Þj = Sxx ð f ÞSyy ð f Þ
where Syy( f ) is the autospectrum of changes in MCA Vmean.
Spectral power of mean value of transfer function phase, gain,
and coherence function were calculated in the low-frequency
(LF; 0.07 to 0.20 Hz) range (21) that is independent of re-
spiratory frequency and reflect CA mechanisms (6,21). In-
creased transfer function gain and diminished phase indicate
an impairment of dynamic CA (21). The squared coherence
function reflects the fraction of output power (i.e., MCA
Vmean) that can be linearly related to the input power (i.e.,
MAP) at each frequency. Similar to a correlation coefficient,
this value varies between 0 and 1 with 0 indicating no CA
(G0.5 indicated low coherence (21)) and 1 indicating com-
plete CA with no changes in MCA Vmean by changes in
MAP. Resting measurements were made during a 3-min data
collection segment, whereas during exercise, the latter 3 min
of each high-intensity exercise period were used. Dynamic
CA was not evaluated during moderate intensity as the 3-min
requirement was not met due to blood sampling from the
arterial catheter.
Statistical analysis. We did not perform a power cal-
culation but the present study had adequate statistical power
to detect dynamic CA responses (n = 9, see results section
for description; statistical power for phase = 0.99, and for
coherence = 1.00). The data are expressed as mean T SD or
median (IQR) if not normally distributed. The data were
analyzed by one-way repeated-measures analysis of variance
when normal data distribution was confirmed. If the sphericity
assumption was not met, Greenhouse–Geisser corrections were
used. Specific differences were identified with a Bonferroni
post hoc test. Not normally distributed data (i.e., arterial
374 Official Journal of the American College of Sports Medicine
Copyright © 2018 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
oxygen, a-v diffoxygen, a-v difflactate, Elactate, and psychological
data) were analyzed using the Friedman test. In the event of a
significant Friedman test, specific differences were identified
with a Wilcoxon signed rank sum test after Bonferroni cor-
rection. The statistical significance level was defined at P G
0.05. The Bonferroni-corrected P values for the physiological
data and psychological data to detect specific differences data
were set at 0.0125 (vs rest) and 0.0167 (vs first high-intensity
exercise phase), respectively. Cohen_s d effect sizes using the
means and pooled SD were calculated, along with the 95%
confidence interval, to determine the magnitude of differences
in outcome variables between rest and exercise. The strength
of effect sizes was interpreted as weak (d e 0.40), moderate
(0.40 e d e 0.79), and large (0.80 e d) (23). Moreover, to
assess CO2 reactivity, Pearson_s correlation evaluated rela-
tionship between the average of MCA Vmean and arterial car-
bon dioxide tension (PaCO2) at each blood sampling time
point during HIIE. All statistical analyses were conducted
using IBM SPSS software (version 24.0; International Busi-
ness Machines Corp, NY).
RESULTS
Five subjects had excessive noise/artifact in the recordings
subjects were used in the analysis (age 24 T 3 yr, height 180 T
7 cm, weight 75 T 9 kg, Wmax 238 T 35 W; mean T SD). Seven
subjects completed HIIE at the protocolled workload whereas
workload for two subjects during high-intensity exercise was
reduced by 15 W beginning from the second and third high-
intensity exercise phase, respectively (Table 1).
Effect of HIIE on cardiovascular responses and
dynamic CA. Cardiovascular responses before and during
HIIE are presented in Table 2. The HIIE increased MAP,
HR, SV, and CO and decreased total peripheral resistance.
In contrast, there was no change in MCA Vmean during HIIE.
LF transfer function phase, gain, and coherence between
MAP and MCA Vmean before and during the HIIE protocols
are presented in Figure 1. The HIIE increased phase in the
LF range at the second and third high-intensity exercise with
a tendency to an increase in the fourth bout as compared to
rest (P G 0.0125, d = 1.83; P G 0.0125, d = 1.74; and P =
0.0156 d = 1.66, respectively), whereas the coherence was
reduced and gain was maintained during HIIE.
Blood variables. Compared to rest, HIIE increased ar-
terial oxygen content and thus the a-v diffoxygen (Table 3).
Moreover, PaCO2, arterial glucose, pH, and relative plasma
volume were reduced, while Eglucose, arterial lactate, a-v
TABLE 1. Intensity of each HIE during HIIE.
Main
During HIIE Effect
First HIE Second HIE Third HIE Fourth HIE P
Exercise workload, W 202 T 32 200 T 30 198 T 33 198 T 33 0.20
% Wmax 85 T 3 84 T 2 83 T 3 83 T 3 0.21
Values are mean T SD. W; watt, Wmax; maximal workload.
HIE, high-intensity exercise.
http://www.acsm-msse.org
TABLE 2. Cardiovascular variables before and during HIIE.
During HIIE Main Effect
Rest First HIE Second HIE Third HIE Fourth HIE P
MAP, mm Hg 92 T9 114 T 8* 108 T 9* 105 T 10* 104 T 10* G0.01
MCA Vmean, cmIsj1 58 T 12 64 T 17 60 T 14 58 T 15 56 T 18 0.12
HR, bpm 70 T9 162 T 9* 171 T 9* 174 T 11* 177 T 11* G0.01
SV, % 100 T0 127 T 10* 132 T 7* 129 T 11* 128 T 11* G0.01
Cardiac output, % 100 T0 299 T 46* 332 T 53* 330 T 49* 329 T 58* G0.01
Total peripheral resistance, % 100 T0 47 T 9* 39 T 5* 38 T 6* 36 T 6* G0.01
Values are mean T SD. HIE, high-intensity exercise during the HIIE protocol. MCA Vmean, middle cerebral artery mean blood velocity.
*P G 0.0125 vs rest.

difflactate, and arterial hemoglobin were increased during DISCUSSION

HIIE. The PaCO2 was associated with MCA Vmean during
HIIE (r2 = 0.91; P G 0.05). On the other hand, there were no
significant changes in Eoxygen, a-v diffglucose, and Elactate
throughout HIIE.
The present study examined the effect of HIIE on dy-
namic CA as evaluated by transfer function analysis be-
tween MAP and MCA Vmean. The transfer function phase in
the LF range was temporarily increased during HIIE, while

Psychological HIIE responses. Psychological pa-
rameters before and during HIIE are presented in Table 4.
Both breathing and leg effort RPE values gradually increased
during HIIE while arousal level was maintained.
FIGURE 1—Averaged low-frequency (0.07–0.2 Hz) transfer function
phase (A), gain (B), and coherence (C) between MAP and middle ce-
rebral artery mean blood velocity (MCA Vmean) at rest and during
HIIE. The values are mean T SD. *P G 0.0125 vs rest.
APPLIED SCIENCES
gain in the LF range did not change indicating that HIIE did
not impair dynamic CA. Thus, HIIE appears to protect the
brain from changes in perfusion pressure during exercise
whereas HICE is reported to impair dynamic CA in men (6).
Benefits of HIIE on human health. Exercise training
volume (product of intensity, duration, and frequency) and
mode are important for maintaining and increasing human
health, such as enhancing fitness capacity and mitochondrial
content (24). In particular, exercise intensity appears to have
a stronger impact on physical fitness than exercise duration
and frequency (24). In terms of continuous exercise modal-
ities, an acute higher intensity exercise, if not too exhaustive,
is more beneficial for postexercise executive function com-
pared with lower intensity exercise (25). Thus, increasing
the intensity of aerobic exercise is an appealing strategy for
promoting and maintaining human health, but HICE at 90%
peak oxygen uptake can lead to exhaustion in approximately
6 min (26). In other words, HICE is not feasible for suffi-
cient duration of exercise and if sustained, HICE leads to
attenuation of brain function. For instance, HICE at 80% HR
reserve for 40 min diminishes executive function (13).
Clinical HIIE rehabilitation protocols often include 4-min
intervals of intense exercise at 85% to 95% of maximal HR,
separated by 3-min low-intensity active recovery thereby
allowing for longer duration of high-intensity work than
HICE (11,24,27). A meta-analysis showed that such a HIIE
protocol as compared to moderate-intensity continuous ex-
ercise, enhances fitness level and muscle mitochondrial
biogenesis in patients with heart failure and metabolic syn-
drome and thus may be relevant for cardiac rehabilitation
(27). Moreover, HIIE and moderate-intensity exercise pro-
tocols for cardiac rehabilitation has been shown to carry very
low risk of acute adverse cardiovascular events in a large
population (3). In addition, we previously demonstrated that
the post-HIIE executive function improvement is greater
than after volume-matched moderate-intensity exercise (12).
Among high-intensity exercise, we suggest that HIIE might
enhance cognitive function with better protection of cerebral
perfusion as compared to HICE.

INTERVAL EXERCISE ON CEREBRAL AUTOREGULATION Medicine & Science in Sports & Exercised 375

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TABLE 3. Blood variables before and during HIIE.
During HIIE Main Effect
Rest First HIE Second HIE Third HIE Fourth HIE P
PaCO2, mm Hg 41 T 2 36 T 4* 34 T 3* 34 T 4* 32 T 4* G0.01
Oxygen
Arterial conc., mM 9.2 (8.6–9.4) 9.8 (9.4–10.1)* 10.0 (9.5–10.1)* 10.0 (9.4–10.2)* 10.0 (9.4–10.2)* G0.01
a-v difference, mM 2.9 (2.7–3.3) 3.7 (3.2–4.4) 3.5 (3.4–4.7)* 4.1 (3.3–4.8)* 3.9 (3.4–4.9) G0.01
Eoxygen, % 33.5 T 3.2 38.2 T 6.0 39.6 T 6.6 41.4 T 7.0* 41.8 T 9.1 G0.01
Glucose
Arterial conc., mM 6.9 T 0.8 4.8 T 0.6* 4.7 T 0.6* 4.6 T 0.7* 4.6 T 0.8* G0.01
a-v difference, mM 0.6 T 0.1 0.5 T 0.2 0.7 T 0.2 0.7 T 0.2 0.7 T 0.2 0.05
Eglucose, % 9.1 T 2.1 10.5 T 4.0 15.5 T 2.9* 15.6 T 3.1* 14.9 T 2.6* G0.01
Lactate
Arterial conc., mM 1.2 T 0.3 7.9 T 2.6* 8.4 T 3.1* 8.1 T 3.1* 8.9 T 3.3* G0.01
a-v difference, mM 0.0 (0.0–0.1) 0.4 (0.3–0.7)* 0.4 (0.3–0.6)* 0.5 (0.2–0.8)* 0.5 (0.2–0.7)* G0.01
Elactate, % 0.0 (0.0–6.9) 6.0 (4.4–6.8) 4.1 (3.4–8.0) 6.3 (3.7–8.1) 4.8 (2.9–7.2) 0.29
Arterial pH 7.41 T 0.01 7.35 T 0.04* 7.34 T 0.04* 7.36 T 0.03* 7.37 T 0.03* G0.01
Plasma volume, % 0 T0 j12 T 4* j14 T 4* j14 T 5* j15 T 5* G0.01
Hematocrit, % 46 T2 49 T 3* 49 T 2* 49 T 3* 49 T 3* G0.01
Hemoglobin, mM 9.2 T 0.5 9.9 T 0.5* 10.0 T 0.5* 10.0 T 0.6* 10.0 T 0.5* G0.01
Values are mean T SD or median (IQR).
*P G 0.0125 vs rest.

Exercise and dynamic CA. Few studies have exam-
ined dynamic CBF regulation during exercise. Brys et al.
(28) found that dynamic moderate-intensity exercise does
not alter dynamic CA despite an increase in HR, MAP, and
end-tidal CO2. Similarly, static exercise increases MAP with
no effect on dynamic CA (9). These findings suggest that
different exercise modes (i.e., dynamic or static exercise)
probably do not modify dynamic CA, and that dynamic CA
is maintained during moderate-intensity exercise.
In contrast, prolonged high-intensity exercise (more than
10 min) impairs dynamic CA (6), indicating that an extended
duration of high-intensity exercise affects dynamic CA. It
seems likely that high-intensity exercise induces a greater
improvement of human health than moderate-intensity ex-
ercise, but exhaustive HICE-induced impairment of dynamic
CA could increase the risk of a cerebrovascular event, espe-
cially in patients with impaired CA (e.g., stroke, diabetes,
and dementia) (11).
On the other hand, dynamic CA appears to be maintained
during HIIE, that allows for a total high-intensity exercise
duration of about 16 min. Thus, even if high-intensity exercise
is repeated, dynamic CA is not impaired which may relate to
the interspaced moderate-intensity exercise. Regarding use of
HIIE training in rehabilitation programs, the present findings
can be interpreted to mean that HIIE might enhance cardio-
vascular- and brain-related health without increasing the risk
of cardio- and cerebrovascular events. However, before rec-
ommendations can be made, the effect of HIIE on dynamic
CA and the risk of vascular events needs to be tested in a
clinical population.
Mechanisms underlying dynamic CA during exercise.
CO2 is a potent cerebral vasodilator and CA is attenuated
during hypercapnia and augmented by cerebral vasoconstric-
tion during hypocapnia (29). However, dynamic CA is im-
paired during HICE despite a hyperventilation-induced
reduction in PaCO2 and MCA Vmean (6). During moderate-
intensity exercise, end-tidal CO2 tension and MCA Vmean
increase up to an intensity of approximately 60% maximal
oxygen uptake while both variables decrease at higher in-
tensities (30). In contrast to HICE-induced reduction in MCA
Vmean, MCA Vmean was not significantly decreased during
HIIE. Yet, MCA Vmean tended to decline while PaCO2
gradually decreased during HIIE. Perhaps, HIIE may thus
offer an appropriate balance, in which moderate hyper-
ventilation-induced hypocapnia contributes to maintaining
MCA Vmean and dynamic CA.
Although autonomic neural control of CBF remains debated
(31), augmented sympathetic tone has been suggested as a factor
for impairment of dynamic CA (32,33). The HR increased
similarly during HIIE as reported for HICE (6) whereby the
impact of augmented sympathetic tone as reflected by HR on
dynamic CA might be comparable. Additionally, CO influences
CBF regulation both at rest and during exercise (34). During
HICE, CO is elevated and increases further with extended
duration of HICE (6), whereas CO was maintained high
throughout HIIE in the present study (see Table 2). The

TABLE 4. Psychological variables before and during HIIE.

During HIIE Main Effect
Rest First HIE Second HIE Third HIE Fourth HIE P
RPE
Borg 6–20 scale — 14.0 (11.5–15.0) 15.0 (14.0–15.5)* 16.0 (13.5–17.0)* 16.0 (15.0–19.0)* G0.01
Borg CR10 scale — 4.0 (3.0–6.0) 5.0 (4.5–6.0) 7.0 (5.0–7.5) 7.0 (6.0–9.0)* G0.01
Arousal level 2.0 (1.0–3.0) 2.0 (2.0–3.5) 3.0 (2.0–4.0) 4.0 (2.0–4.5) 4.0 (2.0–5.0) 0.17
Values are median (IQR).
*P G 0.0167 first HIE vs following HIE.

376 Official Journal of the American College of Sports Medicine http://www.acsm-msse.org

Copyright © 2018 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
maintained CO during HIIE might contribute maintaining
CBF and dynamic CA.
Limitations. The present study has several limitations.
Although MCA diameter remains relatively constant under a
variety of conditions (35), estimating changes in CBF via
MCA Vmean could be influenced by changes in diameter of
the vessel by changes in PaCO2 (36). Assessment of CBF
responses to exercise using duplex ultrasound of the internal
carotid and vertebral arteries would be valuable (37). For
this initial study, we recruited young healthy men because
CBF regulation may be influenced by the menstrual cycle.
For instance, high concentrations of plasma estrogen in the
luteal phase are associated with substantial increases in CBF
and decreases in external carotid artery blood flow (38).
Nevertheless, Deegan et al. (39) demonstrated similar dy-
namic CA in young men and women in response to thigh-
cuff release without consideration of the menstrual cycle. On
the other hand, Deegan et al. (40) also demonstrated that LF
transfer function gain between MAP and MCA Vmean in el-
derly women is lower than in elderly men, indicating that
elderly women have better dynamic CA than elderly men.
Future studies should examine the impact of both HIIE and
HICE on dynamic CA in women and the possible effects of
fluctuations of endogenous estrogen across the menstrual
cycle. Moreover, maintenance of dynamic CA may be more
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Research from the Japanese Ministry of Education, Culture, Sports,
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H. T., T. H., and S. O. conceived and designed of research. H. T.,
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