Access to this full-text is provided by Frontiers.
Content available from Frontiers in Physiology
This content is subject to copyright.
ORIGINAL RESEARCH
published: 05 January 2017
doi: 10.3389/fphys.2016.00674
Frontiers in Physiology | www.frontiersin.org 1January 2017 | Volume 7 | Article 674
Edited by:
Gregoire P Millet,
University of Lausanne, Switzerland
Reviewed by:
Samuel Verges,
Université Joseph Fourier, France
Philip J Millar,
University of Guelph, Canada
*Correspondence:
François Billaut
francois.billaut@kin.ulaval.ca
Specialty section:
This article was submitted to
Exercise Physiology,
a section of the journal
Frontiers in Physiology
Received: 27 September 2016
Accepted: 20 December 2016
Published: 05 January 2017
Citation:
Paradis-Deschênes P, Joanisse DR
and Billaut F (2017) Sex-Specific
Impact of Ischemic Preconditioning on
Tissue Oxygenation and Maximal
Concentric Force.
Front. Physiol. 7:674.
doi: 10.3389/fphys.2016.00674
Sex-Specific Impact of Ischemic
Preconditioning on Tissue
Oxygenation and Maximal
Concentric Force
Pénélope Paradis-Deschênes 1, 2, Denis R. Joanisse 1, 2 and François Billaut 1, 2, 3*
1Département de kinésiologie, Université Laval, Québec, QC, Canada, 2Institut Universitaire de Cardiologie et de
Pneumologie de Québec, Québec, QC, Canada, 3Institut National du Sport du Québec, Montréal, QC, Canada
Prior peripheral hypoxia induced via remote ischemic preconditioning (IPC) can improve
physical performance in male athletes through improved O2delivery and utilization. Since
females may have an innate protective mechanism against ischemia-reperfusion injury,
and since muscle metabolism during contraction differs between sexes, it is relevant to
examine the impact of sex in response to IPC to determine whether it is also ergogenic
in females. In a randomized, crossover, single-blind study, we investigated muscle
performance, hemodynamic and O2uptake in strength-trained males (n=9) and females
(n=8) performing five sets of 5 maximum voluntary knee extensions on an isokinetic
dynamometer, preceded by either IPC (3 ×5-min ischemia/5-min reperfusion cycles at
200 mmHg) or SHAM (20 mmHg). Changes in deoxy-hemoglobin (1[HHb], expressed
in percentage of arterial occlusion and considered an index of O2extraction), and total
hemoglobin (1[THb]) concentrations of the vastus lateralis muscle were continuously
monitored by near-infrared spectroscopy. The metabolic efficiency of the contractions
was calculated as the average force/1[HHb]avg ratio. Cohen’s effect sizes (ES) ±90%
confidence limits were used to estimate IPC-induced changes and sex differences. IPC
increased total muscular force in males only (13.0%, ES 0.64, 0.37;0.90), and this
change was greater than in females (10.4% difference, ES 0.40, 0.10;0.70). Percent
force decrement was only attenuated in females (−19.8%, ES −0.38, −0.77;0.01),
which was clearly different than males (sex difference: ES 0.45, −0.16;1.07). IPC also
induced different changes between sexes for average muscle O2uptake in set 2 (males:
6.4% vs. females: −16.7%, ES 0.21, −0.18;0.60), set 3 (males: 7.0% vs. females:
−44.4%, ES 0.56, −0.17;1.29), set 4 (males: 9.1% vs. females: −40.2%, ES 0.51,
−0.10;1.13), and set 5 (males: 10.2% vs. females: −40.4%, ES 0.52, −0.04;1.09).
However, metabolic efficiency was not meaningfully different between conditions and
sexes. IPC increased muscle blood volume (↑[THb]) at rest and during recovery between
sets, to the same extent in both sexes. Despite a similar IPC-induced initial increase in
O2delivery in both sexes, males displayed greater peripheral O2extraction and greater
strength enhancement. This ergogenic effect appears to be mediated in part via an up
regulated oxidative function in males. We conclude that strength-trained males might
benefit more from IPC than their female counterparts during repeated, maximal efforts.
Keywords: blood flow restriction, muscle function, oxygenation, performance, sex differences, athletes
Paradis-Deschênes et al. Ischemic Preconditioning in Males and Females
INTRODUCTION
Ischemic preconditioning of a limb (IPC) is a non-invasive
technique inducing transient peripheral hypoxia to subsequently
enhance tissue tolerance against ischemia-reperfusion injury.
This technique promotes local vasodilation, improves O2delivery
(Enko et al., 2011; Bailey et al., 2012a), and enhances the efficiency
of muscular contraction (Pang et al., 1995; Moses et al., 2005).
Higher muscle O2utilization was also demonstrated in the
quadriceps of strength-trained male athletes after performing
IPC compared to placebo compressions (Paradis-Deschenes
et al., 2016). It is not surprising, therefore, to observe that
IPC can improve maximal physical performance in various
exercise modes in male participants (De Groot et al., 2010;
Bailey et al., 2012a; Paradis-Deschenes et al., 2016), although
this is not a universal finding (Incognito et al., 2015). Before
exercise sport performance applications, IPC was originally
studied for its potential clinical relevance, and in this context,
it is interesting to note that females appeared to display smaller
clinical benefits compared with their male counterparts. In a
cohort of 382 subjects, a failure to induce preconditioning effects
during percutaneous coronary intervention was noted in females
(Laskey and Beach, 2003), presumably due to the innate, multiple,
protective actions of estrogens (Pitcher et al., 2005). Moreover,
since physiological responses to exercise (in particular metabolic
pathway utilization and perfusion) may differ between sexes, and
that exercise performance data from females is almost inexistent,
it is relevant and timely to examine the impact of IPC on females
compared to males to more precisely evaluate the potency of this
technique for exercise performance applications.
Females have been reported to exhibit less fatigue than
males during intense exercise (Parker et al., 2007; Hunter,
2016), but not under conditions of ischemia (Russ and Kent-
Braun, 2003), suggesting that muscle perfusion and oxygenation
may be involved in the sex-related difference (Russ and Kent-
Braun, 2003; Clark et al., 2005; Hunter et al., 2006). Indeed,
females exhibit greater vasodilation in the limbs during single
knee extensions (Parker et al., 2007), and may have a greater
proportional area of type I fibers (Simoneau et al., 1985;
Staron et al., 2000) and greater capacity for utilizing oxidative
metabolism than males (Kent-Braun et al., 2002). Thus, females
exhibit a greater reliance on oxidative metabolism compared with
males, which could challenge the ergogenic impact of IPC.
Prior evidence examining sex-related differences in the
response to IPC during exercise is limited. Gibson et al.
(2015) reported no performance difference between male and
female team-sport athletes during five repeated 6-s sprints after
performing 3 ×5-min occlusions at 220 mmHg to both legs.
However, the IPC procedure used in that study failed to improve
performance in either sex, making the sex comparison moot.
Another study demonstrated the positive impact of IPC (2 ×
3-min at 220-mmHg) on recovery from squat jump test and
running sprint performance 24 h after an initial, fatiguing session
in males, but the female cohort was too small to draw any
firm conclusion (Beaven et al., 2012). Considering the scarcity
of studies and that none have attempted to measure relevant
physiological responses to provide sex-specific mechanistic
insights, any conclusion on the usefulness of IPC for female
athletes cannot robustly be drawn.
The aim of the current investigation was therefore
to determine the impact of IPC on muscle force and
haemodynamics (blood volume and O2extraction) derived
from near-infrared spectroscopy in males vs. females during
repeated maximal efforts separated with incomplete recovery
periods. We chose isolated contractions specifically to avoid
confounding effects that inspiratory muscle fatigue can have on
limb blood flow and O2uptake (Kayser et al., 1997).
MATERIALS AND METHODS
Participants
Strength-trained (power and weight lifters, cross-fit and
taekwondo athletes) males (n=9, age 25 ±2 year; height 1.78
±0.02 m; weight 86.5 ±4.9 kg) and females (n=8, age 22 ±
1 year; height 1.66 ±0.02 m; weight 60.8 ±2.7 kg) volunteered
to take part in this study. All performed 3–5 weight training
sessions per week. All participants were non-smokers, free of
health problems, did not use any medication, and were asked to
avoid vigorous exercise, alcohol and caffeine 24 h before the tests.
All but one female (who was amenorrheic) were tested in their
follicular phase. Participants provided written informed consent
after being informed of experimental procedures, associated risks
and potential benefits. The study was approved by the Ethics
committee of Université Laval, and adhered to the principles
established in the Declaration of Helsinki.
Experimental Design
Participants visited the laboratory for one familiarization and
two experimental trials. Resting heart rate and blood pressure
(inclusion criteria <140/100 mmHg) were taken prior to every
trial. During the first visit, height, weight and thigh circumference
were measured. Thigh circumference (males: 61.3 ±1.9 cm;
females: 57.2 ±1.9 cm) was measured by the same experimenter,
1 cm under the gluteal line. Participants then completed a
familiarization session with the experimental set-up, comprising
one 3-min compression at a pressure of 200 mmHg, and a
standardized warm-up consisting of 5 min of cycling on a
Monark ergometer (Ergomedic 828 E) at 100 W. The warm-up
was continued with 3–5 right-leg extensions on an isokinetic
dynamometer (Kin-Com 500 H, Chattecx Corp., Hixson, TN)
at 20◦/s, with effort perception progressing from 3 to 9 out
of a scale of 10. After 2 min of rest while seated on the
dynamometer, participants completed three complete sets of the
exercise protocol described below.
Following familiarization, participants were randomized into
IPC or SHAM groups in a single-blind, crossover design. In both
conditions, participants were seated comfortably on a bed with
both legs outstretched, and a non-elastic nylon blood pressure
cuff (WelchAllyn, Skaneateles Falls, NY, USA, width: 21 cm)
was positioned around the right upper thigh under the gluteal
line. In IPC, the cuff was rapidly inflated to 200 mmHg for 5
min, and this was repeated three times with each compression
episode separated by 5 min of reperfusion (cuff release) in the
same position. A plateau in the NIRS-derived deoxy-hemoglobin
Frontiers in Physiology | www.frontiersin.org 2January 2017 | Volume 7 | Article 674
Paradis-Deschênes et al. Ischemic Preconditioning in Males and Females
concentration signal (see NIRS procedure below) was observed in
every subject by 5 min, and taken as a sign of effective occlusion
and ischemia. In SHAM, the cuff was inflated to 20 mmHg.
To minimize any placebo effect, participants were told that the
purpose of the study was to compare the impact of two different
cuff pressures that could both alter performance.
The familiarization session and experimental trials were
separated by a minimum of 3 days to eliminate the potential
effects of the second window of protection caused by IPC
(Bolli, 2000), and a maximum of 7 days. All trials were
performed at the same time of day for every participant to
avoid potentially confounding circadian rhythm effects. The
laboratory temperature was controlled and constant (20.31 ±
0.02◦C) throughout all trials.
Exercise Protocol
The exercise protocol started 18.5 ±0.1 min after the end of
the last cycle of compression. Participants were seated in an
upright position on the isokinetic dynamometer, and a strap was
secured tightly across the pelvis. The right leg was fixed to the
dynamometer with a strap above the ankle external malleoli, and
the axis of rotation was aligned to the lateral femoral condyle of
the knee joint.
The protocol consisted of five sets of 5 maximum voluntary
knee extensions (60◦range of motion from 80 to 20◦; 0◦
corresponding to knee fully extended) at 20◦/s angular velocity
(one extension lasting ∼3.0 s). Participants were instructed to
contract as hard as they could throughout the extension, and
were strongly encouraged during all contractions. Contraction
was stopped during flexion when the dynamometer arm
automatically returned to 80◦at angular velocity of 120◦/s
(lasting less than 0.5 s), and started immediately after the return
of the arm. Subjects rested quietly and relaxed for 30 s between
each set and after the last set. After the exercise, participants
moved back to the bed to perform an arterial occlusion with
the cuff at 200 mmHg (∼3–5 min) to obtain a physiological
calibration of the NIRS signals. The cuff pressure was released
after the deoxy-hemoglobin signal had reached a plateau (see
Near-infrared spectroscopy procedure below). Participants were
also asked which condition between IPC and SHAM they felt had
the greatest impact on their performance, and their verbal answer
recorded.
The force produced by participants was measured with
a force transducer connected at the end of the level arm
of the dynamometer, which was calibrated according to
the manufacturer’s recommendations before every trial
(manufacturer typical error 0.5%). The intra- and inter-
day coefficient of variation for force obtained by the main
experimenter was 2.4%. Force signals were analyzed in Matlab R
between a starting point defined when velocity was ≥18◦/s,
angle was ≥80◦and force was ≥100 N, and an end point when
velocity was ≥18◦/s and angle was ≥20◦. In every set, peak and
average force were calculated. Total force was then calculated as
the sum of the average force produced in all sets. Percent force
decrement across all sets was calculated as follows: 100 −([total
force output/ideal force output] ×100), where total and ideal
force outputs are the sum of average force values from all sets
and the highest average force was multiplied by five, respectively.
Near-Infrared spectroscopy (NIRS)
NIRS is a versatile, non-invasive methodology providing semi-
quantitative measures of tissue oxygenation, and is easily
applied to study a variety of tissue regions in individuals.
NIRS quantifies the changes in hemodynamics from changes
in the absorption of near-infrared light by oxyhemoglobin
(HbO2) and deoxyhemoglobin (HHb) (Mccully and Hamaoka,
2000). With this technique, oxygenation can be measured
in a discrete region of a tissue in a working physiological
setting, which enhances specificity and has distinct advantages
as compared to more cumbersome methods. Muscle tissue
oxygenation measured by NIRS reflects the balance of O2delivery
to working muscles and muscle O2consumption in capillary
beds (De Blasi et al., 1993; Ferrari et al., 2004). Assessment
of de- and re-oxygenation kinetics during and after dynamic
exercise has become increasingly popular in recent years as a
means to non-invasively assess the aerobic function of skeletal
muscle. In the current protocol, muscle blood volume and
oxygenation were assessed using a portable spatially resolved,
dual wavelength NIRS apparatus (PortaMon, Artinis Medical
Systems BV, Netherlands). The NIRS device was installed on the
distal part of the right vastus lateralis belly (approximately 15 cm
above the proximal border of the patella). Skinfold thickness was
measured at the site of the application of the NIRS (males: 8.7
±0.9 mm; females: 10.7 ±2.0 mm) using a Harpenden skinfold
caliper (Harpenden Ltd) during the familiarization session, and
was less than half the distance between the emitter and the
detector (i.e., 20 mm). This thickness is adequate to let near-
infrared light through muscle tissue (Mccully and Hamaoka,
2000). The skin was cleaned with an alcohol swab, and the device
was fixed using double-sided stick disks and tape. Black bandages
were used to cover the device to eliminate potentially interfering
background light. The position of the apparatus was marked with
an indelible pen for repositioning during the subsequent visit.
The pressure cuff was positioned above the NIRS device, which
did not affect the placement of the device during occlusions.
A modified form of the Beer-Lambert law, using two
continuous wavelengths (760 and 850 nm) and a differential
optical path length factor of 4.95, was used to calculate
micromolar changes in tissue oxy-hemoglobin (1[HbO2]),
deoxy-hemoglobin (1[HHb]) and total hemoglobin (1[THb] =
[HbO2]+[HHb]; used as an index of change in regional blood
volume). NIRS data were acquired at 10 Hz. At rest, once the
signal was stabilized, 1 min of baseline values were analyzed pre
IPC and SHAM treatments. Then, NIRS signals were analyzed 2-
min post treatment for a duration of 1 min to assess the impact of
IPC on resting blood volume (1[THb]rest,µM). During exercise,
NIRS analysis was limited to 1[HHb] since this variable is less
sensitive than [HbO2] to perfusion variations and abrupt blood
volume changes during contraction and recovery (De Blasi et al.,
1993; Ferrari et al., 2004). The [HHb] signal was averaged over the
last second of every contraction and over every set to obtain peak
(1[HHb]peak, % arterial occlusion) and mean (1[HHb]avg , %
arterial occlusion) O2extraction, respectively. These [HHb] data
Frontiers in Physiology | www.frontiersin.org 3January 2017 | Volume 7 | Article 674
Paradis-Deschênes et al. Ischemic Preconditioning in Males and Females
were then normalized to express the magnitude of changes from
baseline, and expressed in percentage of the maximal amplitude
calculated during an arterial occlusion performed at the end
of exercise. Contraction metabolic efficiency was calculated as
the average force/1[HHb]avg ratio. Finally, during recovery
periods between exercise sets, the muscle reoxygenation rate
(1Reoxy, µM.s−1) was calculated as the rate of change in [HHb]
from the end of the exercise set to the end of the subsequent
recovery period (i.e., the recovery of [HHb]; Billaut and Buchheit,
2013). During this period, the amplitude of change in [THb]
(1[THb]rec) was also analyzed.
Statistical Analysis
All data are reported as means ±standard error (SE) or
percentage changes from SHAM. The IPC-SHAM differences
within the same group and between sexes were analyzed using
Cohen’s effect sizes (ES) ±90% confidence limits (Batterham
and Hopkins, 2006; Hopkins et al., 2009). Except for 1[THb]rest
and 1[THb]rec, all variables were log-transformed prior to
analysis (Hopkins et al., 2009). Magnitudes of difference between
conditions were determined with an effect size of 0.2 set to
evaluate the smallest worthwhile change. Standardized effects
were classified as small (>0.2), moderate (>0.5) or large
(>0.8). The effect was deemed “unclear” if chances of having
better/greater or poorer/lower change in performance and
physiological variables were both >5% (Batterham and Hopkins,
2006; Hopkins et al., 2009).
RESULTS
All 17 participants met all criteria, completed the entire protocol,
and tolerated the IPC procedure without complications. None of
the participants could tell what condition produced the greatest
change in performance.
Performance
Force parameters for males and females are displayed in Table 1
and Figures 1,2. After the IPC manoeuver, total force clearly
increased in males (13.0%, ES 0.64, 0.37;0.90), but the change
was trivial in females (2.3%, ES 0.10, −0.17;0.38). &&&The
sex difference for this parameter was clear (ES 0.40, 0.10;0.70;
Figure 1). Specifically, the IPC-induced increase in average force
was greater in males than females in every set of the protocol (set
1–males: 15.2% vs. females: 0.7%, ES 0.53, 0.16;0.90, set 2–males:
15.6% vs. females: 3.6%, ES 0.43, 0.10;0.76, set 3–males: 11.1% vs.
females: 2.6%, ES 0.31, 0.02;0.61, set 4–males: 14.5% vs. females:
3.1%, ES 0.41, 0.07;0.76, set 5–males: 8.4% vs. females: 1.7%, ES
0.25, −0.06;0.56; Figure 2).
Importantly, although IPC did not increase average force in
females, it clearly augmented 1-s peak force in sets 1–3 (Table 1),
whereas males displayed benefits in sets 1, 2, 4, and 5. This effect
was higher in males compared to females in sets 2 and 5.
Percent force decrement was attenuated in females after IPC
(−19.8%, ES −0.38, −0.77;0.01), which was clearly different than
males (sex difference: ES 0.45, −0.16;1.07).
Muscle Hemodynamics and Oxygenation
Physiological variables are displayed in Table 2. No difference
was observed between IPC and SHAM in both groups for NIRS
variables during baseline before the manoeuver. IPC increased
1[THb]rest to the same extent in males and females (males: 1.5%
vs. females: 1.5%, ES 0.00, −0.80;0.79). After IPC, 1[THb]rec
was increased in males after sets 1 (1.2%, ES 0.33, −0.14;0.80)
and 5 (1.5% ES 0.44, 0.17;0.70). In females, 1[THb]rec was only
enhanced after sets 2 (0.7%, ES 0.23, −0.09;0.54) and 3 (1.8%
ES 0.54, 0.04;1.04). This change in 1[THb]rec was higher in
males compared to females in set 5 only (sex difference: ES 0.48,
0.10;0.87). There was no change in 1Reoxy within the same
group and between sexes.
TABLE 1 | Performance variables in IPC and SHAM conditions for males and females.
Females Males Sex difference
SHAM IPC % difference
(ES) 90% CL
SHAM IPC % difference (ES)
90% CL
(ES) 90% CL
Peak force S1 (N) 449.1 ±37.2 481.3 ±42.1 7.2%, ES 0.24*,
−0.07;0.56
627.9 ±45.1 685.3 ±35.7 10.2%, ES 0.41*,
0.23;0.59
ES 0.10,
−0.24;0.44
Peak force S2 (N) 421.1 ±32.8 446.3 ±33.1 6.4%, ES 0.22*,
0.00;0.43
566.3 ±31.3 648.9 ±47.6 13.7%, ES 0.54*,
0.32;0.75
ES 0.24*,
−0.03;0.50
Peak force S3 (N) 402.5 ±22.7 429.5 ±28.3 6.3%, ES 0.22*,
0.05;0.38
558.8 ±35.7 581.6 ±41.7 3.8%, ES 0.16,
−0.01;0.32
ES −0.09,
−0.29;0.12
Peak force S4 (N) 402.5 ±24.7 422.0 ±25.0 5.1%, ES 0.18,
−0.06;0.41
526.3 ±29.8 574.6 ±43.2 8.4%, ES 0.34*,
0.06;0.61
ES 0.11,
−0.20;0.42
Peak force S5 (N) 401.8 ±27.1 397.5 ±24.5 −0.7%,
ES −0.02,
−0.17;0.12
506.9 ±28.3 544.0 ±39.1 6.7%, ES 0.27*,
0.01;0.54
ES 0.26*,
0.00;0.51
Force decrement (%) 10.4 ±1.5 8.4 ±1.4 −19.8%,
ES −0.38*,
−0.77;0.01
13.7 ±2.7 15.2 ±2.2 6.0%, ES0.12,
−0.54;0.77
ES 0.45*,
−0.16;1.07
Values are mean ±SE.
Asterisks (*) denote “clear” effect sizes (see statistics section).
Frontiers in Physiology | www.frontiersin.org 4January 2017 | Volume 7 | Article 674
Paradis-Deschênes et al. Ischemic Preconditioning in Males and Females
FIGURE 1 | Individual and average total force developed in SHAM and
IPC conditions for males () and females (•). The IPC-induced change in
total force was clearly higher in males than females. Values are mean ±SE.
FIGURE 2 | Average force produced during the five sets in males
(SHAM: IPC: ) and females (SHAM: IPC: ◦). Asterisks (*) denote
“clear” differences between sexes (see statistics section). Values are mean
±SE.
The IPC maneuver did not alter muscle 1[HHb]peak across
sets nor between sexes (Table 2). However, 1[HHb]avg were
higher after IPC in males for set 1 (18.1%, ES 0.31, −0.11;0.73),
and lower in females for sets 3 (−44.4%, ES −0.25, −0.61;0.11),
4 (−40.2%, ES −0.22, −0.52;0.08), and 5 (−40.4%, ES −0.22,
−0.50;0.06). There was a clear sex difference in the impact of
IPC on global muscle deoxygenation in sets 2–5 (Figure 3). The
contraction metabolic efficiency ratio was not altered by IPC
during the sets or between sexes (Table 2).
DISCUSSION
Summary of Main Findings
This study investigated the impact of sex on performance
and vasoactive and oxidative responses to IPC in strength-
trained athletes during repeated, maximal contractions. The
main findings were that IPC (1) increased muscle force to a
greater extent in males than females; (2) increased resting blood
volume similarly in both sexes; and (3) increased O2extraction
in males but decreased it in females. These results challenge the
general applicability of IPC on physical performance. While it
may be recommended to enhance exercise capacity in males,
this preconditioning technique appears less effective in females
during maximal efforts.
Muscle Force Parameters
IPC affected muscle force production and the ability to resist
neuromuscular fatigue differently between sexes. While male
athletes increased peak and average maximal concentric force
in every set of the protocol following IPC, the benefits in
females were lesser (Figures 1,2). Females only displayed small
improvements in peak force in the first three sets, while average
force changes were trivial across all sets. Importantly, while IPC
yielded acute positive responses in every male, four females out
of eight experienced a decrease in performance. Another study
did not report any sex difference in repeated-sprint performance,
but the IPC protocol employed did not yield any positive effects
in either males or females and, therefore, sex-related differences
could not be truly assessed (Gibson et al., 2015). Although not
studying sex differences per se, Gibson and colleagues (Gibson
et al., 2013) reported altered 30-m running sprint times after
IPC in females, while males displayed no added benefit. Taken
together, these results highlight the importance of considering
inter-individual responses to IPC in sports, particularly in
female athletes. Considering the complex sex modulation of
preconditioning mechanisms (such as mitochondrial KATP
channel activation, reactive oxygen species generation, nitric
oxide synthase activity, and inflammatory mediator production),
as well as robust data documenting that females experience an
innate protective mechanism after several forms of acute injury
(for review see Pitcher et al., 2005), one could expect a sex-
specific impact of remote IPC on physical performance. That
said, both sexes are capable of being preconditioned (Pitcher
et al., 2005). Hence, it is possible that females in the current
study did not reach a sufficient threshold for preconditioning
to occur. Thus, contrary to the proposition of a responder vs.
non-responder pattern (Beaven et al., 2012; Gibson et al., 2013,
2015), the current data coupled with other clinical studies rather
suggest that females may require a greater stimulus for effect. This
remains to be elucidated by investigating the influence of varying
numbers of IPC cycles and/or the number of limbs occluded at
one time.
The sex-specific impact of IPC on fatigability has not been
robustly assessed in the literature. The present data demonstrated
clear differences between sexes; compared with males, females
exhibited a lower force decrement over the five sets of maximal,
isokinetic contractions. The lack of change in males is in keeping
with previous studies reporting no differences between SHAM
and IPC conditions in the measured fatigue index, despite higher
peak and mean power outputs during the first repetitions of
a series of ten 6 s cycle sprints (Patterson et al., 2015), or
higher average force during maximal voluntary knee extensions
after IPC (Paradis-Deschenes et al., 2016). This apparent sex
Frontiers in Physiology | www.frontiersin.org 5January 2017 | Volume 7 | Article 674
Paradis-Deschênes et al. Ischemic Preconditioning in Males and Females
TABLE 2 | Muscle hemodynamic and oxygenation variables in IPC and SHAM conditions for males and females.
Females Males Sex difference
SHAM IPC % difference
(ES) 90% CL
SHAM IPC % difference (ES)
90% CL
(ES) 90% CL
[HHb]base (µM) 25.3 ±1.3 25.2 ±1.1 −0.20%, ES
−0.01,
−0.35;0.33
37.5 ±2.7 37.8 ±2.8 0.85%, ES 0.03,
−0.14;0.21
−5.39;7.92
[THb]base (µM) 46.1 ±3.5 43.8 ±3.3 −4.80%, ES
−0.21,
−0.50;0.08
72.2 ±5.3 72.6 ±5.6 0.42%, ES 0.02,
−0.12;0.15
ES 0.16,
−0.06;0.38
1[THb]rest (µM) 0.1 ±0.4 1.6 ±0.5 1.5%, ES 1.06*,
0.13;1.99
3.6 ±0.6 5.1 ±0.8 1.5%, ES 0.69*,
−0.17;1.55
ES 0.00,
−0.80;0.79
1[THb]rec S1 (µM) 7.3 ±1.0 7.8 ±0.7 0.53%, ES 0.16,
−0.27;0.59
9.1 ±1.1 10.3 ±1.3 1.16%, ES 0.33*,
−0.14;0.80
ES 0.21,
−0.46;0.88
1[THb]rec S2 (µM) 5.0 ±0.8 5.8 ±0.5 0.75%, ES 0.23*,
−0.09;0.54
6.4 ±0.9 6.5 ±1.5 0.14%, ES 0.04,
−0.50;0.58
ES −0.20,
−0.88;0.48
1[THb]rec S3 (µM) 3.7 ±0.8 5.5 ±0.8 1.77%, ES 0.54*,
0.04;1.04
6.0 ±1.0 6.5 ±1.4 0.57%, ES 0.16,
−0.21;0.53
ES −0.40,
−1.04;0.25
1[THb]rec S4 (µM) 4.7 ±1.1 5.2 ±0.7 0.58%, ES 0.18,
−0.24;0.59
5.3 ±1.1 5.9 ±1.0 0.64%, ES 0.18,
−0.26;0.62
ES 0.02,
−0.62;0.66
1[THb]rec S5 (µM) 5.5 ±0.9 5.6 ±0.77 0.08%, ES 0.02,
−0.23;0.28
3.9 ±0.9 5.4 ±1.1 1.54%, ES 0.44*,
0.17;0.70
ES 0.48*,
0.10;0.87
1Reoxy (µM.s−1) 0.1 ±0.0 0.1 ±0.02 −21.0%„ ES
−0.32,
−0.89;0.26
0.2 ±0.1 0.2 ±0.1 −4.0%„ ES −0.05,
−0.38;0.028
ES 0.21,
−0.29;0.70
1[HHb]peak S1 (%AO) 59.0 ±5.5 45.8 ±13.3 −29.5%, ES
−0.97,
−2.86;0.92
69.8 ±5.4 73.9 ±3.9 7.3%, ES 0.26,
−0.38;0.90
ES 1.35,
−0.92;3.61
1[HHb]peak S2 (%AO) 72.6 ±7.3 57.3 ±11.7 −10.3%, ES
−0.30,
−0.91;0.31
79.0 ±5.6 83.9 ±4.3 7.4%, ES 0.27,
−0.35;0.89
ES 0.58,
−0.24;1.40
1[HHb]peak S3 (%AO) 75.0 ±7.8 60.7 ±11.8 −42.8%, ES
−1.55,
−4.11;1.01
80.4 ±5.7 85.5 ±3.9 7.7%, ES 0.28,
−0.36;0.92
ES 2.04,
−0.99;5.06
1[HHb]peak S4 (%AO) 71.7 ±7.3 61.4 ±11.4 −29.1%, ES
−0.95,
−2.42;0.51
79.7 ±6.8 86.3 ±4.2 10.5%, ES 0.38,
−0.24;0.99
ES 1.43,
−0.32;3.17
1[HHb]peak S5 (%AO) 68.4 ±5.7 58.8 ±11.5 −33.7%, ES
−1.14,
−2.64;0.36
82.7 ±7.1 86.2 ±4.2 6.4%, ES 0.23,
−0.40;0.86
ES 1.52,
−0.27;3.31
CMER S1 10.5 ±1.4 5.6 ±4.3 −4.4%, ES
−0.12,
−1.84;1.59
13.2 ±2.5 11.8 ±1.2 −2.4%, ES −0.04,
−0.49;0.41
ES 0.05,
−1.42;1.52
CMER S2 5.7 ±1.3 7.2 ±9.2 23.3%, ES 0.57,
−0.57;1.72
5.6 ±0.6 6.1 ±0.8 8.7%, ES 0.14,
−0.21;0.49
ES −0.29,
−1.29;0.72
CMER S3 5.1 ±1.1 9.9 ±5.7 22.2%, ES 0.55,
−0.46;1.56
5.1 ±0.6 5.2 ±0.6 3.8%, ES 0.06,
−0.24;0.37
ES −0.37,
−1.26;0.52
CMER S4 4.9 ±1.0 17.3 ±8.8 72.4%, ES 1.49,
−0.42;3.41
4.7 ±0.6 4.9 ±0.5 5.0%, ES 0.08,
−0.25;0.41
ES −1.13,
−2.75;0.49
CMER S5 4.8 ±0.9 19.3 ±11.4 70.5%, ES 1.46,
−0.30;3.23
4.6 ±1.8 4.5 ±0.5 −1.6%, ES −0.03,
−0.36;0.30
ES −1.25,
−2.75;0.25
Values are mean ±SE.
Asterisks (*) denote “clear” effect sizes (see statistics section). AO, arterial occlusion; CMER, contraction metabolic efficiency ratio; base, baseline before the IPC manoeuver; ∆Reoxy,
reoxygenation rate of the muscle; S, sets.
difference in response to IPC could be attributed in part to the
fact that males increased their initial and total force leading to
greater subsequent metabolic and ionic perturbations (Balsom
et al., 1994; Glaister, 2005). However, this cannot be the only
explanation, as females clearly improved their resistance to
fatigue across the sets by approximately 2%. Sex differences in the
availability and use of O2could shed some light on these differing
responses to IPC.
Frontiers in Physiology | www.frontiersin.org 6January 2017 | Volume 7 | Article 674
Paradis-Deschênes et al. Ischemic Preconditioning in Males and Females
FIGURE 3 | Average changes in (1[HHb]avg ), expressed as a fraction of
the maximal values obtained during a transient arterial occlusion (AO)
in males (SHAM: IPC: ) and females (SHAM: IPC: ◦). Asterisks (*)
denote “clear” differences between sexes (see statistics section). Values are
mean ±SE.
Muscle Hemodynamic and Oxygenation
IPC is known to increase blood flow in both ipsilateral (Kraemer
et al., 2011) and contralateral limbs (Enko et al., 2011). It also
up-regulates endothelial function at rest (Moro et al., 2011), after
local transient ischemia (Kharbanda et al., 2001; Loukogeorgakis
et al., 2005), and prevents the decline in flow-mediated dilation
observed after strenuous exercise (Bailey et al., 2012a) in males.
By investigating the NIRS-derived [THb] changes from pre-
to post-IPC, we confirmed the acute increase in local blood
volume at rest in males, and extended this hyperperfusion
finding to females. In fact, these moderate to large hemodynamic
changes from baseline were similar in both sexes, of a magnitude
of 1.5%. Such data from female participants are very scarce
in the literature, and results do vary. While Kharbanda and
colleagues reported no sex difference in flow-mediated dilation
response during ischaemia-reperfusion after IPC (Kharbanda
et al., 2001), the same response was found to be higher in
females compared with males immediately post-preconditioning
(Moro et al., 2011). There is, however, stronger evidence of
a sex difference in vasodilator responsiveness. Females display
higher brachial artery flow-mediated dilation (Levenson et al.,
2001) and forearm vasodilatory response to acetylcholine and
β2-adrenergic receptor stimulation (Dietz, 1999; Kneale et al.,
2000) relative to males. At first glance, these sex-based differences
in intrinsic physiological responses could explain the differing
impact of IPC on performance in males vs. females observed in
the current study. Greater effects on endothelial function should
improve contractile activity (and/or efficiency) by allowing a
better O2supply to skeletal muscles during intense exercise. It
is not clear why males had a greater increase in muscle force
than females for a similar percent increase in 1[THb]rest, but one
could argue that males might benefit more than females from
an up-regulated endothelial function since they possess a lower
intrinsic vasodilator responsiveness. Nevertheless, NIRS does not
offer a robust assessment of blood flow since it does not detect
change in blood velocity (Delorey et al., 2003). Studies using
Doppler ultrasound are warranted to investigate vasodilation and
potential blood flow changes following IPC in males and females.
An augmented blood volume before exercise could facilitate
O2delivery to active skeletal muscles. While IPC-induced
changes in peak muscle O2extraction were trivial in males,
they displayed meaningful changes in 1[HHb]avg across the
sets (Figure 3). Males extracted more O2than females after
IPC in sets 2–5, with clearly increased muscle force. IPC has
been reported to increase systemic maximal O2uptake (De
Groot et al., 2010), as well as local tissue deoxygenation at
task failure during handgrip exercise at 45% maximal voluntary
contraction (Barbosa et al., 2015), and decrease blood lactate
accumulation during submaximal running exercise (Bailey et al.,
2012b). IPC also accelerates muscle deoxygenation dynamics and
enhances performance during whole-body cycling and sustained
isometric contraction of the knee in males (Kido et al., 2015;
Tanaka et al., 2016). However, despite large 1[THb]rest, IPC
decreased 1[HHb]avg in females in the current study. The above
studies exclusively recruited males, thus the current study adds
to the literature by demonstrating that IPC might not induce
similar metabolic responses in female athletes. Although we
did not measure blood flow per se, the similar 1[THb]rest
after IPC in both sexes suggest that the sex difference in O2
extraction might not be directly related to a difference in O2
availability. Furthermore, intramuscular pressure is positively
correlated with contraction intensity, and it is accepted that
occlusion of muscle blood flow occurs at 50–60% maximal
voluntary contraction (Wigmore et al., 2004), thereby limiting
its impact on sex differences observed in O2metabolism when
contractions are performed maximally as in the current study.
In fact, the excessive intramuscular pressures of the contractions
made our [THb] data collected during contractions unusable.
And along this line of reasoning, it is of note that sex differences
in fatigue development and performance disappear when blood
flow is occluded (Maughan et al., 1986; Yoon et al., 2007). This
could suggest that O2availability does not explain the current
finding of upregulated O2extraction in males only. Caution is
of course needed when interpreting NIRS-derived results due
to methodological confounding factors such as subcutaneous
fat layer thickness (although it was below the recommended
emitter-receptor distance in both sexes) and possible NIRS
sensor movement on the skin. Finally, muscle re-perfusion and
thereby re-oxygenation occurring between maximal efforts is
correlated with the recovery of muscle performance mainly via
the resynthesis of phosphocreatine and by-products removal
(Kime et al., 2003; Billaut and Buchheit, 2013). However, sex
differences in 1[THb]rec were mostly unclear, as was the case for
1Reoxy. Based on these data, the sex-specific impact of IPC on
exercise performance does not appear to be attributed to recovery
processes.
There is also the possibility of a preferential impact of IPC
on type II muscle fibers. A lower proportional area of type I
fibers has been found in the vastus lateralis of males compared
with females (Simoneau et al., 1985; Staron et al., 2000). Type II
fibers display greater fractional O2extraction with faster kinetics
and lower microvascular O2partial pressure (i.e., better muscle
Frontiers in Physiology | www.frontiersin.org 7January 2017 | Volume 7 | Article 674
Paradis-Deschênes et al. Ischemic Preconditioning in Males and Females
O2diffusion index), despite a lower overall O2consumption
(Mcdonough et al., 2005). Interestingly, extraneous infusion of
adenosine, which is a key acting molecule released during IPC,
preferentially enhances vasodilation of arterioles to type II fibers
(Wunsch et al., 2000). Therefore, due to the greater O2extraction
of type II fibers when highly perfused (Wilson et al., 1977), it
has been suggested that these fibers might benefit more from an
increase in blood perfusion than the more aerobic type I fibers
(Faiss et al., 2013; Paradis-Deschenes et al., 2016), which could
explain the higher 1[HHb]avg in strength-trained males in the
present study.
In conclusion, this applied study demonstrated that strength-
trained males might benefit more clearly from IPC than their
female counterparts during repeated, maximal contractions. This
strengthens clinical observations that sex may be a confounder in
the response to this stimulus. Despite a similar increase in blood
volume (↑[THb]) in both sexes immediately after IPC, and thus
presumably similar increase in O2availability, males displayed
greater peripheral O2extraction (↑1[HHb]). This ergogenic
effect therefore appears to be mediated in part via an upregulation
of oxidative function in males, possibly within type II muscle
fibers.
AUTHOR CONTRIBUTIONS
PPD, DRJ, and FB conceptualized and designed the research
project; PPD acquired the data and conducted the statistical
analysis; PPD interpreted results with assistance from DRJ and
FB; PPD wrote the manuscript with revisions from DRJ and FB.
All authors reviewed and agreed upon the final manuscript.
ACKNOWLEDGMENTS
The authors thank the athletes for their participation in the study.
We also sincerely thank Pr Normand Teasdale and Mr. Marcel
Kaszap for their valuable technical support and assistance.
REFERENCES
Bailey, T. G., Birk, G. K., Cable, N. T., Atkinson, G., Green, D. J., Jones, H.,
et al. (2012a). Remote ischemic preconditioning prevents reduction in brachial
artery flow-mediated dilation after strenuous exercise. Am. J. Physiol. Heart
Circ. Physiol. 303, H533–H538. doi: 10.1152/ajpheart.00272.2012
Bailey, T. G., Jones, H., Gregson, W., Atkinson, G., Cable, N. T., and
Thijssen, D. H. J. (2012b). Effect of ischemic preconditioning on lactate
accumulation and running performance. Med. Sci. Sports Exerc. 44, 2084–2089.
doi: 10.1249/MSS.0b013e318262cb17
Balsom, P. D., Gaitanos, G. C., Ekblom, B., and Sjödin, B. (1994). Reduced oxygen
availability during high intensity intermittent exercise impairs performance.
Acta Physiol. Scand. 152, 279–285. doi: 10.1111/j.1748-1716.1994.tb09807.x
Barbosa, T. C., Machado, A. C., Braz, I. D., Fernandes, I. A., Vianna, L. C.,
Nobrega, A. C. L., et al. (2015). Remote ischemic preconditioning delays fatigue
development during handgrip exercise. Scand. J. Med. Sci. Sports 25, 356–364.
doi: 10.1111/sms.12229
Batterham, A. M., and Hopkins, W. G. (2006). Making meaningful
inferences about magnitudes. Int. J. Sports Physiol. Perform. 1, 50–57.
doi: 10.1123/ijspp.1.1.50
Beaven, C. M., Cook, C. J., Kilduff, L., Drawer, S., and Gill, N. (2012). Intermittent
lower-limb occlusion enhances recovery after strenuous exercise. Appl. Physiol.
Nutr. Metab. 37, 1132–1139. doi: 10.1139/h2012-101
Billaut, F., and Buchheit, M. (2013). Repeated-sprint performance and vastus
lateralis oxygenation: effect of limited O2 availability. Scand. J. Med. Sci. Sports
23, e185–e193. doi: 10.1111/sms.12052
Bolli, R. (2000). The late phase of preconditioning. Circ. Res. 87, 972–983.
doi: 10.1161/01.RES.87.11.972
Clark, B. C., Collier, S. R., Manini, T. M., and Ploutz-Snyder, L. L.
(2005). Sex differences in muscle fatigability and activation patterns
of the human quadriceps femoris. Eur. J. Appl. Physiol. 94, 196–206.
doi: 10.1007/s00421-004-1293-0
De Blasi, R. A., Cope, M., Elwell, C., Safoue, F., and Ferrari, M. (1993).
Noninvasive measurement of human forearm oxygen consumption by near
infrared spectroscopy. Eur. J. Appl. Physiol. 67, 20–25. doi: 10.1007/BF00
377698
De Groot, P. C., Thijssen, D. H., Sanchez, M., Ellenkamp, R., and Hopman, M. T.
(2010). Ischemic preconditioning improves maximal performance in humans.
Eur. J. Appl. Physiol. 108, 141–146. doi: 10.1007/s00421-009-1195-2
Delorey, D. S., Kowalchuk, J. M., and Paterson, D. H. (2003). Relationship
between pulmonary O2 uptake kinetics and muscle deoxygenation
during moderate-intensity exercise. J. Appl. Physiol. 95, 113–120.
doi: 10.1152/japplphysiol.00956.2002
Dietz, N. M. (1999). Gender and nitric oxide-mediated vasodilation in humans.
Lupus 8, 402–408. doi: 10.1177/096120339900800515
Enko, K., Nakamura, K., Yunoki, K., Miyoshi, T., Akagi, S., Yoshida, M., et al.
(2011). Intermittent arm ischemia induces vasodilatation of the contralateral
upper limb. J. Physiol. Sci. 61, 507–513. doi: 10.1007/s12576-011-0172-9
Faiss, R., Léger, B., Vesin, J. M., Fournier, P. E., Eggel, Y., Deriaz, O., et al. (2013).
Significant molecular and systemic adaptations after repeated sprint training in
Hypoxia. PLoS ONE 8:e56522. doi: 10.1371/journal.pone.0056522
Ferrari, M., Mottola, L., and Quaresima, V. (2004). Principles, techniques, and
limitations of near infrared spectroscopy. Can. J. Appl. Physiol. Rev. 29,
463–487. doi: 10.1139/h04-031
Gibson, N., Mahony, B., Tracey, C., Fawkner, S., and Murray, A. (2015). Effect of
ischemic preconditioning on repeated sprint ability in team sport athletes. J.
Sports Sci. 33, 1182–1188. doi: 10.1080/02640414.2014.988741
Gibson, N., White, J., Neish, M., and Murray, A. (2013). Effect of ischemic
preconditioning on land-based sprinting in Team-Sport Athletes. Int. J. Sports
Physiol. Perform. 8, 671–676. doi: 10.1123/ijspp.8.6.671
Glaister, M. (2005). Multiple sprint work - Physiological responses, mechanisms
of fatigue and the influence of aerobic fitness. Sports Med. 35, 757–777.
doi: 10.2165/00007256-200535090-00003
Hopkins, W. G., Marshall, S. W., Batterham, A. M., and Hanin, J. (2009).
Progressive statistics for studies in sports medicine and exercise science. Med.
Sci. Sports Exerc. 41, 3–13. doi: 10.1249/MSS.0b013e31818cb278
Hunter, S. K. (2016). The relevance of sex differences in performance fatigability.
Med. Sci. Sports Exerc. 48, 2247–2256. doi: 10.1249/MSS.0000000000000928
Hunter, S. K., Schletty, J. M., Schlachter, K. M., Griffith, E. E., Polichnowski, A.
J., and Ng, A. V. (2006). Active hyperemia and vascular conductance differ
between men and women for an isometric fatiguing contraction. J. Appl.
Physiol. 101, 140–150. doi: 10.1152/japplphysiol.01567.2005
Incognito, A. V., Burr, J. F., and Millar, P. J. (2015). The effects of ischemic
preconditioning on human exercise performance. Sports Med. 46, 531–544.
doi: 10.1007/s40279-015-0433-5
Kayser, B., Sliwinski, P., Yan, S., Tobiasz, M., and Macklem, P. T. (1997).
Respiratory effort sensation during exercise with induced expiratory-flow
limitation in healthy humans. J. Appl. Physiol. (1985) 83, 936–947.
Kent-Braun, J. A., Ng, A. V., Doyle, J. W., and Towse, T. F. (2002).
Human skeletal muscle responses vary with age and gender during fatigue
due to incremental isometric exercise. J. Appl. Physiol. 93, 1813–1823.
doi: 10.1152/japplphysiol.00091.2002
Kharbanda, R. K., Peters, M., Walton, B., Kattenhorn, M., Mullen, M., Klein,
N., et al. (2001). Ischemic preconditioning prevents endothelial injury and
systemic neutrophil activation during ischemia-reperfusion in humans in vivo.
Circulation 103, 1624–1630. doi: 10.1161/01.CIR.103.12.1624
Frontiers in Physiology | www.frontiersin.org 8January 2017 | Volume 7 | Article 674
Paradis-Deschênes et al. Ischemic Preconditioning in Males and Females
Kido, K., Suga, T., Tanaka, D., Honjo, T., Homma, T., Fujita, S., et al. (2015).
Ischemic preconditioning accelerates muscle deoxygenation dynamics and
enhances exercise endurance during the work-to-work test. Physiol. Rep.
3:e12395. doi: 10.14814/phy2.12395
Kime, R., Katsumura, T., Hamaoka, T., Osada, T., Sako, T., Murakami, M.,
et al. (2003). “Muscle reoxygenation rate after isometric exercise at various
intensities in relation to muscle oxidative capacity,” in Oxygen Transport to
Tissue Xxiv, eds J. F. Dunn and H. M. Swartz (New York, NY: Springer
Science+Business Media), 497–507.
Kneale, B. J., Chowienczyk, P. J., Brett, S. E., Coltart, D. J., and Ritter,
J. M. (2000). Gender differences in sensitivity to adrenergic agonists
of forearm resistance vasculature. J. Am. Coll. Cardiol. 36, 1233–1238.
doi: 10.1016/S0735-1097(00)00849-4
Kraemer, R., Lorenzen, J., Kabbani, M., Herold, C., Busche, M., Vogt, P. M.,
et al. (2011). Acute effects of remote ischemic preconditioning on cutaneous
microcirculation–a controlled prospective cohort study. BMC Surg. 11:32.
doi: 10.1186/1471-2482-11-32
Laskey, W. K., and Beach, D. (2003). Frequency and clinical significance of
ischemic preconditioning during percutaneous coronary intervention. J. Am.
Coll. Cardiol. 42, 998–1003. doi: 10.1016/S0735-1097(03)00909-4
Levenson, J., Pessana, F., Gariepy, J., Armentano, R., and Simon, A.
(2001). Gender differences in wall shear-mediated brachial artery
vasoconstriction and vasodilation. J. Am. Coll. Cardiol. 38, 1668–1674.
doi: 10.1016/S0735-1097(01)01604-7
Loukogeorgakis, S. P., Panagiotidou, A. T., Broadhead, M. W., Donald, A.,
Deanfield, J. E., and Macallister, R. J. (2005). Remote ischemic preconditioning
provides early and late protection against endothelial ischemia-reperfusion
injury in humans: role of the autonomic nervous system. J. Am. Coll. Cardiol.
46, 450–456. doi: 10.1016/j.jacc.2005.04.044
Maughan, R. J., Harmon, M., Leiper, J. B., Sale, D., and Delman, A. (1986).
Endurance capacity of untrained males and females in isometric and dynamic
muscular contractions. Eur. J. Appl. Physiol. Occup. Physiol. 55, 395–400.
doi: 10.1007/BF00422739
Mccully, K. K., and Hamaoka, T. (2000). Near-infrared spectroscopy: what can it
tell us about oxygen saturation in skeletal muscle? Exerc. Sport Sci. Rev. 28,
123–127.
Mcdonough, P., Behnke, B. J., Padilla, D. J., Musch, T. I., and Poole, D. C.
(2005). Control of microvascular oxygen pressures in rat muscles comprised of
different fibre types. J. Physiol. 563, 903–913. doi: 10.1113/jphysiol.2004.079533
Moro, L., Pedone, C., Mondi, A., Nunziata, E., and Antonelli Incalzi, R. (2011).
Effect of local and remote ischemic preconditioning on endothelial function in
young people and healthy or hypertensive elderly people. Atherosclerosis 219,
750–752. doi: 10.1016/j.atherosclerosis.2011.08.046
Moses, M. A., Addison, P. D., Neligan, P. C., Ashrafpour, H., Huang, N., Zair,
M., et al. (2005). Mitochondrial KATP channels in hindlimb remote ischemic
preconditioning of skeletal muscle against infarction. Am. J. Physiol. Heart Circ.
Physiol. 288, H559–H567. doi: 10.1152/ajpheart.00845.2004
Pang, C. Y., Yang, R. Z., Zhong, A. G., Xu, N., Boyd, B., and Forrest, C.
R. (1995). Acute ischemic preconditioning protects against skeletal-muscle
infarction in the pig. Cardiovasc. Res. 29, 782–788. doi: 10.1016/S0008-6363(96)
88613-5
Paradis-Deschenes, P., Joanisse, D. R., and Billaut, F. (2016). Ischemic
preconditioning increases muscle perfusion, oxygen uptake, and force
in strength-trained athletes. Appl. Physiol. Nutr. Metab. 41, 938–944.
doi: 10.1139/apnm-2015-0561
Parker, B. A., Smithmyer, S. L., Pelberg, J. A., Mishkin, A. D., Herr, M. D.,
and Proctor, D. N. (2007). Sex differences in leg vasodilation during graded
knee extensor exercise in young adults. J. Appl. Physiol. 103, 1583–1591.
doi: 10.1152/japplphysiol.00662.2007
Patterson, S. D., Bezodis, N. E., Glaister, M., and Pattison, J. R. (2015). The effect
of ischemic preconditioning on repeated sprint cycling performance. Med. Sci.
Sports Exerc. 47, 1652–1658. doi: 10.1249/MSS.0000000000000576
Pitcher, J. M., Wang, M., Tsai, B. M., Kher, A., Turrentine, M. W., Brown, J.
W., et al. (2005). Preconditioning: gender effects. J. Surg. Res. 129, 202–220.
doi: 10.1016/j.jss.2005.04.015
Russ, D. W., and Kent-Braun, J. A. (2003). Sex differences in human skeletal
muscle fatigue are eliminated under ischemic conditions. J. Appl. Physiol. 94,
2414–2422. doi: 10.1152/japplphysiol.01145.2002
Simoneau, J. A., Lortie, G., Boulay, M. R., Thibault, M. C., Thériault, G.,
and Bouchard, C. (1985). Skeletal muscle histochemical and biochemical
characteristics in sedentary male and female subjects. Can. J. Physiol.
Pharmacol. 63, 30–35. doi: 10.1139/y85-005
Staron, R. S., Hagerman, F. C., Hikida, R. S., Murray, T. F., Hostler, D. P.,
Crill, M. T., et al. (2000). Fiber type composition of the vastus lateralis
muscle of young men and women. J. Histochem. Cytochem. 48, 623–629.
doi: 10.1177/002215540004800506
Tanaka, D., Suga, T., Tanaka, T., Kido, K., Honjo, T., Fujita, S., et al.
(2016). Ischemic preconditioning enhances muscle endurance during sustained
isometric exercise. Int. J. Sports Med.. doi: 10.1055/s-0035-1565141
Wigmore, D. M., Damon, B. M., Pober, D. M., and Kent-Braun, J. A.
(2004). MRI measures of perfusion-related changes in human skeletal
muscle during progressive contractions. J. Appl. Physiol. 97, 2385–2394.
doi: 10.1152/japplphysiol.01390.2003
Wilson, D. F., Erecinska, M., Drown, C., and Silver, I. A. (1977). Effect of oxygen
tension on cellular energetics. Am. J. Physiol. 233, C135–C140.
Wunsch, S. A., Muller-Delp, J., and Delp, M. D. (2000). Time course of vasodilatory
responses in skeletal muscle arterioles: role in hyperemia at onset of exercise.
Am. J. Physiol. Heart Circ. Physiol. 279, H1715–H1723.
Yoon, T., Schlinder Delap, B., Griffith, E. E., and Hunter, S. K. (2007). Mechanisms
of fatigue differ after low- and high-force fatiguing contractions in men and
women. Muscle Nerve 36, 515–524. doi: 10.1002/mus.20844
Conflict of Interest Statement: The authors declare that the research was
conducted in the absence of any commercial or financial relationships that could
be construed as a potential conflict of interest.
Copyright © 2017 Paradis-Deschênes, Joanisse and Billaut. This is an open-access
article distributed under the terms of the Creative Commons Attribution License (CC
BY). The use, distribution or reproduction in other forums is permitted, provided the
original author(s) or licensor are credited and that the original publication in this
journal is cited, in accordance with accepted academic practice. No use, distribution
or reproduction is permitted which does not comply with these terms.
Frontiers in Physiology | www.frontiersin.org 9January 2017 | Volume 7 | Article 674
Content uploaded by François Billaut
Author content
All content in this area was uploaded by François Billaut on Jan 13, 2017
Content may be subject to copyright.