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fphys-09-01621 November 13, 2018 Time: 14:48 # 1
ORIGINAL RESEARCH
published: 15 November 2018
doi: 10.3389/fphys.2018.01621
Edited by:
François Billaut,
Laval University, Canada
Reviewed by:
Oliver R. Gibson,
Brunel University London,
United Kingdom
Martin Burtscher,
Universität Innsbruck, Austria
*Correspondence:
Jamie F. Burr
burrj@uoguelph.ca
Specialty section:
This article was submitted to
Exercise Physiology,
a section of the journal
Frontiers in Physiology
Received: 11 September 2018
Accepted: 26 October 2018
Published: 15 November 2018
Citation:
Slysz JT and Burr JF (2018)
Enhanced Metabolic Stress
Augments Ischemic Preconditioning
for Exercise Performance.
Front. Physiol. 9:1621.
doi: 10.3389/fphys.2018.01621
Enhanced Metabolic Stress
Augments Ischemic Preconditioning
for Exercise Performance
Joshua T. Slysz and Jamie F. Burr*
Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, Canada
Purpose: To identify the combined effect of increasing tissue level oxygen consumption
and metabolite accumulation on the ergogenic efficacy of ischemic preconditioning (IPC)
during both maximal aerobic and maximal anaerobic exercise.
Methods: Twelve healthy males (22 ±2 years, 179 ±2 cm, 80 ±10 kg,
48 ±4 ml.kg−1.min−1) underwent four experimental conditions: (i) no IPC control,
(ii) traditional IPC, (iii) IPC with EMS, and (iv) IPC with treadmill walking. IPC involved
bilateral leg occlusion at 220 mmHg for 5 min, repeated three times, separated by 5 min
of reperfusion. Within 10 min following the IPC procedures, a 30 s Wingate test and
subsequent (after 25 min rest) incremental maximal aerobic test were performed on a
cycle ergometer.
Results: There was no statistical difference in anaerobic peak power between the
no IPC control (1211 ±290 W), traditional IPC (1209 ±300 W), IPC +EMS
(1206 ±311 W), and IPC +Walk (1220 ±288 W; P= 0.7); nor did VO2max change
between no IPC control (48 ±2 ml.kg−1.min−1), traditional IPC (48 ±6 ml.kg−1.min−1),
IPC +EMS (49 ±4 ml.kg−1.min−1) and IPC +Walk (48 ±6 ml.kg−1.min−1;P= 0.3).
However, the maximal watts during the VO2max increased when IPC was combined
with both EMS (304 ±38 W) and walking (308 ±40 W) compared to traditional IPC
(296 ±39 W) and no IPC control (293 ±48 W; P= 0.02).
Conclusion: This study shows that in a group of participants for whom a traditional
IPC stimulus was not effective, the magnification of the IPC stress through muscle
contractions while under occlusion led to a subsequent exercise performance response.
These findings support that amplification of the ischemic preconditioning stimulus
augments the effect for exercise capacity.
Keywords: exercise, hypoxia, occlusion, cycling, metabolites
INTRODUCTION
It has been demonstrated that brief periods of circulatory occlusion and reperfusion, or ischemic
preconditioning (IPC), can act to improve exercise performance (Jean-St-Michel et al., 2011;Bailey
et al., 2012). Multiple studies have demonstrated that IPC performed in the minutes to hours
preceding aerobic (De Groot et al., 2010) or anaerobic (Patterson et al., 2015;Cruz et al., 2016)
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Slysz and Burr Enhanced Metabolic Stress Augments IPC
exercise can improve performance but there appears to be
great variability in response and, at present, the magnitude
and consistency of the IPC effect across populations is not
clear for either aerobic (Bailey et al., 2012;Hittinger et al.,
2014;Sabino-Carvalho et al., 2017) nor anaerobic (Lalonde and
Curnier, 2014;Paixao et al., 2014) exercise. Contributing to
the lack of clarity around IPC as an effective ergogenic aid is
the fact that the physiological signaling stimuli and associated
downstream responses remain incompletely characterized. Of the
leading physiological theories, local hypoxia [leading to HIF-
1 signaling (Eckle et al., 2008)] and metabolite accumulation
[such as adenosine, bradykinin, ROS, and opioids (Cohen et al.,
2000;Marongiu and Crisafulli, 2014)] have received considerable
attention; however, the existence of a dose-response relationship
or identification of a threshold to trigger the biochemical
pathways leading to the IPC effect remain unconfirmed (Cohen
et al., 2000;Marongiu and Crisafulli, 2014). Given the many
variations of IPC methodology reported in the current literature
(i.e., differences in duration and number of cycles, occlusion
pressure, volume of restricted muscle mass, local exercising, or
remote muscle group) defining a pattern of the most efficacious
method remains a challenge.
The metaboreflex is a key factor in controlling sympathetic
outflow during exercise (Alam and Smirk, 1937) and studies
utilizing ischemia to amplify metabolites and provide increased
afferent feedback have shown an elevated sympathetic outflow
and blood pressure response (Rowell et al., 1991;Tschakovsky
and Hughson, 1999). Provided that the accumulation of
metabolites is adequate, IPC could promote metaboreflex-
induced increases in sympathetic outflow and blood pressure,
preparing the body for subsequent exercise. IPC alone, however,
has not been shown to elicit a sympathetic response, whereas the
combination of cyclic bouts of blood flow restriction-reperfusion
and treadmill exercise at 65% heart rate max has (Sprick and
Rickards, 2017). It remains unclear if this combination can lead to
improvements in performance, but it is possible that a sufficient
metabolic stimulus (intramuscular perturbation) of IPC may be a
crucial factor to elicit the desired effect.
By combining IPC with light exercise, such as walking, the
muscle contractions thus evoked could function to amplify
the hypoxic and/or metabolic preconditioning stimulus. As
exercising while under blood flow occlusion may not be feasible
or practical in certain situations (e.g., limited mobility during
travel or when other temporal or spatial limitations exist in
warm-up), the passive technique of electrical muscle stimulation
(EMS) may be a more suitable option to similarly combine muscle
contractions with IPC. Thus, we were interested in attempting to
amplify the IPC performance effect by combining IPC with either
active walking or passive EMS to enhance the stimulus evoked
during a single treatment session. Both the active and passive
models represent possible pre-competition strategies to increase
tissue level hypoxia and metabolite accumulation compared with
IPC alone.
Ischemic preconditioning is most commonly performed using
supra-arterial occlusion pressures, dictating that both arterial
inflow and venous outflow are subsequently restricted. As such
there is a direct, and perhaps unavoidable, link between a greater
emphasis on anaerobic metabolism and metabolite accumulation
under these conditions which is challenging to meaningfully
disentangle (Scott et al., 2014). Therefore, the purpose of this
study was to identify the combined effect of increasing tissue level
oxygen consumption and subsequent metabolite accumulation
on the ergogenic efficacy of IPC during both maximal aerobic
and maximal anaerobic exercise. It was hypothesized that IPC
combined with muscle contractions induced by slow walking or
electrical muscle stimulation would augment the ergogenic IPC
effect, as demonstrated by greater aerobic and anaerobic power
outputs.
MATERIALS AND METHODS
Subjects
Twelve healthy males (22 ±2 years, 179 ±2 cm, 80 ±10 kg,
47.7 ±4 ml.kg−1.min−1) volunteered to participate in this
study which employed a randomized cross-over design. All
participants were recreationally active non-smokers. Participants
had no medical history of chronic disease and were safe to
exercise as confirmed through completion of a PARQ+screening
questionnaire (Warburton et al., 2014). This study was carried
out in accordance with the recommendations of the University
of Guelph’s human ethics research board with written informed
consent from all subjects. All subjects gave written informed
consent in accordance with the Declaration of Helsinki. The
protocol was approved by the University of Guelph’s human
ethics research board (REB# 15SE019).
Protocol and Measurements
All participants refrained from alcohol, caffeine, and intensive
physical exercise for a least 24 h prior to testing. On each
of four visits to the lab, participants performed both a 30 s
anaerobic Wingate test with a standardized 5-min warm-
up and warm-down and, after a 25-min rest, a subsequent
incremental maximal exercise test. Both tests were completed on
a cycle ergometer (Velotron Inc., Seattle, WA, United States).
The four experimental visits were performed at least 1 week
apart and at the same time of day. Each visit involved
either (i) baseline control involving no IPC, (ii) traditional
IPC, (iii) IPC in combination with EMS, and (iv) IPC in
combination with treadmill walking (2 mph at 0% grade).
Ten minutes following the IPC procedures (described below),
the performance tests were initiated as per the graphical
representation of the protocol presented in Figure 1. To
eliminate possible training, learning, or familiarization effects,
all conditions were assigned in a random order. Participants,
who otherwise had little in the way of expectations concerning
the expected effects, were blinded to all performance data and
were not informed a priori as to the expected outcomes of
the study to avoid introducing possible placebo or nocebo
effects.
Ischemic Preconditioning
Ischemic preconditioning was performed prior to exercise in a
seated position using bilateral arterial occlusion. The occlusion
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Slysz and Burr Enhanced Metabolic Stress Augments IPC
FIGURE 1 | Study protocol including experimental and control visits, which were performed in random order. IPC ischemic preconditioning, EMS electrical muscle
stimulation. Black boxes represent arterial occlusion on both the right and left leg, white boxes represent no occlusion.
cuffs (Zimmer ATS 1500; United States) were positioned
around the proximal thigh and inflated to 220 mmHg for
5 min. This procedure, which is most commonly used in
the IPC exercise performance literature (Incognito et al.,
2016), promotes complete occlusion of both the arterial
inflow and venous outflow in the lower limbs throughout
the 5 min (Kooijman et al., 2008) as was confirmed in the
present study using a near-infrared spectroscopy (MOXY, MN,
United States), and the disappearance of a distal pulse. This
ischemic procedure was repeated three times, each separated
by 5 min of reperfusion (Incognito et al., 2016). IPC in
combination with EMS was also performed in a seated position
and involved the above-mentioned IPC protocol with electrically
evoked muscle contractions throughout. The EMS (Compex
International, Mi-Runner Sport, United Kingdom) involved
two surface electrodes placed on both the Vastus Medialis
and Vastus Lateralis at the distal and proximal position that
best elicited a muscular contraction. Stimulation was applied
using a pulse train length of 400 µs, delivered at a frequency
of 50–100 Hz at a maximally tolerable intensity level. As
participants accommodated to the stimulation during a session,
the stimulation intensity was progressively increased. IPC in
combination with walking involved the above-mentioned IPC
protocol with slow walking on a standard motor driven treadmill
(Sole F63 treadmill, Canada) at 2 mph (Sakamaki et al.,
2011).
30 s Anaerobic Wingate Test
The 30 s Anaerobic Wingate test included a “flying start,” which
consisted of 40 s of low load (100 W) pedaling prior to the
introduction of the resistance (7.5% body weight), against which
participants aimed to maintain maximal pedal revolutions for
30 s. Integrated Wingate testing software was used to calculate
peak power output in watts.
Incremental Maximal Aerobic Capacity
Test
The incremental exercise test began with a resistance of 100 W
and increased continuously at 1 watt every 3 s until exhaustion
(i.e., the participant was unable to maintain a pedaling frequency
of ≥50 rpm). Starting 1-min prior, and continuing throughout
the maximal exercise test, oxygen consumption (VO2) was
measured via indirect calorimetry using a face mask and optical
turbine connected to a gas analyser with a sampling line
(Cosmed Quark CPET, Rome, Italy). The maximal values were
recorded as the highest reading that occurred after the data
was smoothed using a rolling 30 s average. Attainment of
true physiological max was confirmed for all subjects by the
presentation of a plateau in VO2(increase in ≤50 mL/min
at VO2peak and the closest neighboring data point), or
respiratory exchange ratio (RER) ≥1.15 (Astorino et al., 2000).
During the graded exercise test, VO2at submaximal intensities
were recorded and compared every 20 W between 120 and
200 W to investigate possible effects on submaximal exercise
efficiency.
Statistics
A Shapiro–Wilk test was used to confirm normality of data, prior
to analysis. Comparisons between conditions were performed
using repeated measures ANOVA, with LSD post hoc tests,
as was appropriate. Statistical analyses were conducted using
SPSS software (version 25; IBM, Chicago, IL, United States),
with differences considered to be statistically significant at
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Slysz and Burr Enhanced Metabolic Stress Augments IPC
P<0.05. All data is presented as mean ±SD, unless specified
otherwise.
RESULTS
30 s Anaerobic Wingate Test
Peak anaerobic power was 1211 ±290 W during the no IPC
control and 1209 ±300 W following traditional IPC. When
IPC was combined with EMS and walking, peak anaerobic
power was recorded to be 1206 ±311 W and 1220 ±288 W,
respectively. There were no statistical differences between any
groups (P= 0.7).
Incremental Maximal Aerobic Capacity
Test
Baseline VO2max was 47.7 ±4 ml.kg−1.min−1and
48.4 ±6 ml.kg−1.min−1following traditional IPC.
When IPC was combined with EMS and then walking,
VO2max was recorded to be 49.1 ±4 ml.kg−1.min−1and
48 ±6 ml.kg−1.min−1, respectively. There were no statistical
differences between any groups (P= 0.3; Figures 2A,B).
Submaximal oxygen consumption increased as the test
progressed from 120 to 200 W, but these increases in VO2
every 20 W were similar in their pattern and magnitude across
all conditions (Table 1).
Peak watts, recorded at the point of exhaustion during the
incremental maximal aerobic test, was 293 ±48 W during the
no IPC control and 296 ±39 W following traditional IPC
treatment. When IPC was combined with EMS and walking, peak
watts increased to 304 ±38 W and 308 ±40 W, respectively
(Figures 3A,B). Statistical analyses revealed significant increases
in peak watts when combing IPC with EMS (P= 0.02) and
walking (P= 0.03) compared to IPC alone. There were also
significant increases in peak watts when combining IPC with
EMS (0.04) and walking (P= 0.002) compared to the control
group.
DISCUSSION
The present study sought to compare the effects of traditional
IPC with an enhanced preconditioning stimulus, involving
IPC combined with EMS or walking, for augmenting either
aerobic and anaerobic performance. The main novel findings
were that (1) IPC, when combined with walking or EMS
significantly improved peak watt output in the maximal aerobic
test to exhaustion, despite traditional IPC causing no significant
benefit; (2) neither IPC nor an augmented adaptation of IPC
improved maximal oxygen consumption; (3) neither IPC alone
nor augmented IPC improved maximal anaerobic power. These
findings suggest that a certain magnitude of metabolic and/or
hypoxic stimulus may, thus, be important for stimulating the
positive effects of IPC on exercise capacity, but that this effect
was not driven by a change in aerobic or anaerobic maximal
capacity.
FIGURE 2 | (A) Mean maximal oxygen uptake ml.kg−1.min−1from the incremental maximal aerobic test for each intervention and baseline. (B) Maximal oxygen
uptake ml.kg−1.min−1from the incremental maximal aerobic test for each intervention and baseline. Data is presented as mean ±SE.
TABLE 1 | Oxygen consumption at submaximal exercise intensities during an incremental cycling test after no intervention (Control) ischemic preconditioning (IPC),
ischemic preconditioning combined with electrical muscle stimulation (IPC +EMS), and ischemic preconditioning performed during slow walking at 2 mph (IPC +Walk).
Control IPC IPC +EMS IPC +Walk P-value
VO2120 W (ml O2·kg−1·min−1) 25 ±3 25 ±4 25 ±3 25 ±2 0.9
VO2140 W (ml O2·kg−1·min−1) 28 ±2 27 ±4 28 ±3 27 ±3 0.5
VO2160 W (ml O2·kg−1·min−1) 30 ±4 30 ±4 30 ±2 30 ±3 0.8
VO2180 W (ml O2·kg−1·min−1) 33 ±4 32 ±4 33 ±3 33 ±3 0.5
VO2200 W (ml O2·kg−1·min−1) 35 ±4 35 ±4 36 ±3 35 ±3 0.8
Data is presented as mean ±SD.
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FIGURE 3 | (A) Mean peak watts from the incremental maximal aerobic test for each intervention and baseline. Data is presented as mean ±SE and the differences
were considered significant at P≤0.05. ∗Represents statistically different from baseline; #Represents statistically different from IPC alone. (B) Individual peak watts
from the incremental maximal aerobic test for each intervention and baseline.
Exercise Performance
Previous studies have demonstrated increases in cycling peak
power output (of 1.6–3.7%) following IPC treatment during
maximal tests (De Groot et al., 2010;Crisafulli et al., 2011).
The current data demonstrate traditional IPC to be ineffective
for increasing peak power output during a maximal cycling
test; however, when IPC was augmented with either passive
twitches or active light-intensity muscular contractions, power
output thereafter increased. More specifically, we observed a
3.8% increase in power with the addition of EMS to IPC and
a 5% increase in power when slow walking was performed
during the IPC treatment. The effect of an 11–15 W increase
in max power could be quite meaningful in a competition
situation, and when modeled using the current participants’
weight and the assumption of zero grade and wind while cycling,
these augmentations in power would be expected to result
in a 0.5–0.7 kph improvement in speed (Cycling Power Lab,
2018). While it is difficult to compare directly the muscular
stress while under IPC, it is likely that the added stress
of walking was greater than that of EMS. It is also likely
that this utilized additional muscle mass, thus, the increased
efficacy with walking is logical. Furthermore, it was observed
that of the 12 participants, 8 did not initially demonstrate
improvements in power output with traditional IPC. However,
when a greater metabolic stress was imposed, 7 of the 8
“non-responders” became “responders” and increased maximal
power output, which is in line with previous evidence that a
greater physiologic stimulus reduces the rate of non-response
to a given perturbation (Ross et al., 2015). Comparing to
previous literature, it is worth noting that the one study which
previously reported no change in peak power output during
cycling following IPC also used the lowest occlusion pressure
(Hittinger et al., 2014), and it is thus possible that the induced
metabolic stress was lower, similar to the pattern we report
here.
In line with the current model of increasing the accumulation
of metabolic waste products, Crisafulli et al. (2011) have
similarly attempted to magnify this effect by occluding leg
circulation (for 3 min) immediately following submaximal
cycling exercise. In partial agreement with our findings, this
group reported that IPC consistently increased peak power
output compared to a control test; however, augmenting the
metabolic stress through a post-exercise occlusion did not
demonstrate further benefit compared to traditional IPC. This
may suggest that the initial IPC provided a sufficient stimulus
to elicit an optimal performance effect, or that the addition
of a brief 3-min augmented IPC period was insufficient to
further amplify the response. In our study, in which we invoked
muscle contractions throughout all cycles of the IPC, this
stress was prolonged and repeated and may account for the
differences in response. While we did not observe efficacy
of traditional (using similarly matched) IPC protocol and
graded cycling test with male participants, the addition of
metabolic stress led to a response of similar magnitude. The
discrepancy regarding the efficacy of traditional IPC between
studies may be attributable to IPC protocol differences or
participant training status, as subjects in the current study
reached ∼10% higher peak watts, and thus a higher threshold
of metabolic stress during IPC may have been required to elicit
a similar response. The specific role of training status on the
efficacy of IPC for affecting exercise performance requires further
study.
Maximal Aerobic Capacity
As is consistent with the majority of other studies, compared
to the control group, there was no increase in VO2max
after traditional IPC (Bailey et al., 2012;Hittinger et al.,
2014;Sabino-Carvalho et al., 2017). Despite improvements in
exercise performance (peak watts), when metabolic IPC stress
was augmented with the addition of either passive or active
muscle contractions VO2max remained unaltered compared
to the control. This suggests that performance gains are not
the result of an increase in maximal capacity. There was
also no change in submaximal VO2during cycling following
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Slysz and Burr Enhanced Metabolic Stress Augments IPC
traditional IPC, or following IPC combined with EMS or
walking. This too is consistent with current literature (Clevidence
et al., 2012) showing no change with traditional IPC, while
also providing evidence that increasing the magnitude of
the metabolic stimulus during IPC may have no effect on
submaximal efficiency. Interestingly, 4 weeks of applying IPC
after sprint interval training has been shown to increase
VO2max (Taylor et al., 2016), suggesting an augmented IPC
stress may be important in long-term aerobic adaptation
rather than a short-term change. It must be recognized
that it is possible our VO2measures were affected by a
preceding anaerobic test. If true, this is a potential explanation
for the disagreement between a previous study (De Groot
et al., 2010) that reported an increase in VO2max with
traditional IPC; however, this is unlikely as our findings are
consistent with the majority of the existing literature (Bailey
et al., 2012;Hittinger et al., 2014;Sabino-Carvalho et al.,
2017).
Anaerobic Capacity
Using a standard 30 s anaerobic Wingate test, there was no
change in anaerobic peak power following traditional IPC or
following IPC combined with EMS or walking. This finding
agrees with previous studies (Lalonde and Curnier, 2014;
Paixao et al., 2014) showing no ergogenic effect of IPC on
anaerobic exercise, while also providing novel evidence that
the magnitude of the metabolic stimulus during IPC may
have little impact on anaerobic exercise. A select few studies
have shown a beneficial effect of IPC on anaerobic exercise
(Patterson et al., 2015;Cruz et al., 2016), with positive effects
typically occurring when IPC is employed further in advance
(i.e., 30–60 min) of the exercise test; whereas studies that
showed reduced or unchanged anaerobic performance used
shorter periods (i.e., 5–15 min) (Lalonde and Curnier, 2014;
Paixao et al., 2014) between IPC and the exercise test. Of
note, the anaerobic test used in the current study occurred
in the shorter time frame. The specific role of timing on
the efficacy of IPC for affecting maximal anaerobic capacity
needs to be further investigated. In addition, the studies that
have shown positive effects of IPC on anaerobic exercise
(Patterson et al., 2015;Cruz et al., 2016) appear to employ
longer anaerobic effects (≥60 s) compared to the studies
(Lalonde and Curnier, 2014;Paixao et al., 2014) that show
no effect (30 s). The current study did not show any changes
in peak or average power with IPC during the first or last
10 s of the 30 s Wingate test, suggesting that IPC does
not assist with short-term energy provision. It is possible
that IPC assists with energy provision with longer anaerobic
efforts, but this remains speculative and requires further
investigation.
The specific mechanism by which IPC works remains unclear.
It is possible that the combination of IPC and rhythmic muscle
contractions sufficiently altered local oxygen and metabolites
to activate afferent feedback leading to a metaboreflex-induced
sympathetic response during exercise, while IPC alone did not.
This increase in sympathetic activity to non-active muscle could
lead to greater blood flow and perfusion of the active muscle beds
(Boulton et al., 2018), and if preconditioning were performed
locally, the proper distribution of blood flow could be further
aided by sympatholysis during treatment (Horiuchi et al., 2015).
Nevertheless, we observed no change in whole body VO2max.
An alternative explanation may be that IPC permits an enhanced
central motor efferent command by attenuating inhibitory
signals originating from metabolic sensory muscle afferents
(Crisafulli et al., 2011). This would, thus, allow participants
to exercise slightly beyond their individual critical threshold
of exhaustion for the exercise, which fits with our finding of
increased power. Indeed, a complete blockade of muscle afferent
feedback during exercise, using an intrathecal administration of
fentanyl, results in large increases in central motor drive and
power output (Amann et al., 2011). de Oliveira Cruz et al.
(2015) have observed an increase in aerobic energy provision
with IPC, possibly reducing the utilization rate of anaerobic
energy stores, lowering fatigue signals and delaying exhaustion.
While the current study also does not offer any mechanistic
insight, future studies will need to include more invasive
measurements of blood flow, oxygen delivery, and arteriovenous
oxygen difference across the working limb to determine whether
IPC results in tissue specific improvements in these variables,
which may be responsible for small improvements in peak
watts.
Limitations
As with most performance research, there were potential
limitations to the current study that should be recognized.
The inclusion of a sham control for each IPC intervention
was omitted, both for practicality and to avoid introducing
a potential training effect of excessive repeated testing of the
same subjects. As such, it is possible that that a placebo effect
could have occurred, if participants believed the treatment
would help. However, participants were naïve to the expected
treatment outcomes and it is conceivable that placebo effects
were no more likely to occur than nocebo effects. It is
undeniable that that this area of research, as a whole has
struggled to find an effective sham control, and while previous
research has used low-pressure sham conditions in which
the cuff is only inflated to 10–20 mmHg (Jean-St-Michel
et al., 2011;Bailey et al., 2012), this low pressure is easily
distinguishable from true IPC. In addition, it is still unknown
if the low-pressure itself can elicit a preconditioning response,
thus we chose not to employ this technique in the current
study and compared to a simple control condition. Finally,
the current study was conducted with participants that are
young and recreationally active, thus, the relevance of these
interventions in an athletic or clinical population remain to be
tested.
CONCLUSION
In a group of participants for whom a traditional IPC stimulus
was not effective, the amplification of an IPC stress through
muscle contractions while under occlusion led to a subsequent
increase in exercise performance. These findings support the
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Slysz and Burr Enhanced Metabolic Stress Augments IPC
hypothesis that there needs to be a sufficient metabolic and/or
hypoxic stimulus for IPC to elicit an ergogenic action. From
a practical standpoint, the addition of either passive or active
muscle contractions to the standard IPC protocol of 3 sets of
5-min cycles of occlusion and reperfusion, may improve the
efficacy and decrease “non-response” to IPC treatment, and
this highlights that new variations of the IPC protocol should
be explored in an effort to optimize the desired effect. Thus,
augmenting the metabolic or hypoxic stress through muscle
contractions may be an important and functional way to ensure
the required metabolic/hypoxic stimulus is met for IPC to
improve exercise capacity.
AUTHOR CONTRIBUTIONS
JB and JS had met the guidelines for authorship, and this
manuscript had been read and approved by both authors.
FUNDING
This work was supported by the Natural Sciences and
Engineering Research Council of Canada under Grant 03974;
Mitacs under Grant IT05783; and the Canada Foundation for
Innovation under Grant 460597.
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Conflict of Interest Statement: The authors declare that the research was
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