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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.
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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.kg1.min1) 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.kg1.min1), traditional IPC (48 ±6 ml.kg1.min1),
IPC +EMS (49 ±4 ml.kg1.min1) and IPC +Walk (48 ±6 ml.kg1.min1;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.kg1.min1) 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 Guelphs 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 Guelphs 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.kg1.min1and
48.4 ±6 ml.kg1.min1following traditional IPC.
When IPC was combined with EMS and then walking,
VO2max was recorded to be 49.1 ±4 ml.kg1.min1and
48 ±6 ml.kg1.min1, 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.kg1.min1from the incremental maximal aerobic test for each intervention and baseline. (B) Maximal oxygen
uptake ml.kg1.min1from 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·kg1·min1) 25 ±3 25 ±4 25 ±3 25 ±2 0.9
VO2140 W (ml O2·kg1·min1) 28 ±2 27 ±4 28 ±3 27 ±3 0.5
VO2160 W (ml O2·kg1·min1) 30 ±4 30 ±4 30 ±2 30 ±3 0.8
VO2180 W (ml O2·kg1·min1) 33 ±4 32 ±4 33 ±3 33 ±3 0.5
VO2200 W (ml O2·kg1·min1) 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 P0.05. 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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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.
REFERENCES
Alam, M., and Smirk, F. H. (1937). Observations in man upon a blood pressure
raising reflex arising from the voluntary muscles. J. Physiol. 89, 372–383.
doi: 10.1113/jphysiol.1937.sp003485
Amann, M., Runnels, S., Morgan, D. E., Trinity, J. D., Fjeldstad, A. S., Wray, D. W.,
et al. (2011). On the contribution of group III and IV muscle afferents to the
circulatory response to rhythmic exercise in humans. J. Physiol. 589(Pt 15),
3855–3866. doi: 10.1113/jphysiol.2011.209353
Astorino, T. A., Robergs, R. A., Ghiasvand, F., Marks, D., and Burns, S. (2000).
Incidence of the oxygen plateau at VO2max during exercise testing to volitional
fatigue. J. Exerc. Physiol. Online 3, 1–12.
Bailey, T. G., Jones, H., Gregson, W., Atkinson, G., Cable, N. T., and Thijssen,
D. H. J. (2012). Effect of ischemic preconditioning on lactate accumulation and
running performance. Med. Sci. Sport Exerc. 44, 2084–2089. doi: 10.1249/MSS.
0b013e318262cb17
Boulton, D., Taylor, C. E., Green, S., and Macefield, V. G. (2018). The metaboreflex
does not contribute to the increase in muscle sympathetic nerve activity to
contracting muscle during static exercise in humans. J. Physiol. 596, 1091–1102.
doi: 10.1113/JP275526
Clevidence, M. W., Mowery, R. E., and Kushnick, M. R. (2012). The effects
of ischemic preconditioning on aerobic and anaerobic variables associated
with submaximal cycling performance. Eur. J. Appl. Physiol. 112, 3649–3654.
doi: 10.1007/s00421-012- 2345-5
Cohen, M. V., Baines, C. P., and Downey, J. M. (2000). Ischemic preconditioning:
from adenosine receptor to KATP channel. Annu. Rev. Physiol. 62, 79–109.
doi: 10.1146/annurev.physiol.62.1.79
Crisafulli, A., Tangianu, F., Tocco, F., Concu, A., Mameli, O., Mulliri, G., et al.
(2011). Ischemic preconditioning of the muscle improves maximal exercise
performance but not maximal oxygen uptake in humans. J. Appl. Physiol. 111,
530–536. doi: 10.1152/japplphysiol.00266.2011
Cruz, R. S., de Aguiar, R. A., Turnes, T., Salvador, A. F., and Caputo, F.
(2016). Effects of ischemic preconditioning on short-duration cycling
performance. Appl. Physiol. Nutr. Metab.41, 825–831. doi: 10.1139/apnm-2015-
0646
Cycling Power Lab. (2018). Cycling Power Lab. Available at: http://www.
cyclingpowerlab.com/PowerSpeedScenarios.aspx
De Groot, P. C. E., Thijssen, D. H. J., Sanchez, M., Ellenkamp, R., and Hopman,
M. T. E. (2010). Ischemic preconditioning improves maximal performance
in humans. Eur. J. Appl. Physiol. 108, 141–146. doi: 10.1007/s00421-009-1
195-2
de Oliveira Cruz, R. S., De Aguiar, R. A., Turnes, T., Pereira, K. L., and Caputo, F.
(2015). Effects of ischemic preconditioning on maximal constant-load cycling
performance. J. Appl. Physiol. 119, 961–967. doi: 10.1152/japplphysiol.00498.
2015
Eckle, T., Köhler, D., Lehmann, R., El Kasmi, K. C., and Eltzschig, H. K.
(2008). Hypoxia-inducible factor-1 is central to cardioprotection: a new
paradigm for ischemic preconditioning. Circulation 118, 166–175. doi: 10.1161/
CIRCULATIONAHA.107.758516
Hittinger, E. A., Maher, J. L., Nash, M. S., Perry, A. C., Signorile, J. F., Kressler, J.,
et al. (2014). Ischemic preconditioning does not improve peak exercise capacity
at sea level or simulated high altitude in trained male cyclists. Appl. Physiol.
Nutr. Metab. 40, 65–71. doi: 10.1139/apnm-2014-0080
Horiuchi, M., Endo, J., and Thijssen, D. H. J. (2015). Impact of ischemic
preconditioning on functional sympatholysis during handgrip exercise in
humans. Physiol. Rep. 3:e12304. doi: 10.14814/phy2.12304
Incognito, A. V., Burr, J. F., and Millar, P. J. (2016). The effects of ischemic
preconditioning on human exercise performance. Sport Med. 46, 531–544.
doi: 10.1007/s40279-015- 0433-5
Jean-St-Michel, E., Manlhiot, C., Li, J., Tropak, M., Michelsen, M. M., Schmidt,
M. R., et al. (2011). Remote preconditioning improves maximal performance in
highly trained athletes. Med. Sci. Sport Exerc. 43, 1280–1286. doi: 10.1249/MSS.
0b013e318206845d
Kooijman, M., Thijssen, D. H. J., De Groot, P. C. E., Bleeker, M. W. P., Van
Kuppevelt, H. J. M., Green, D. J., et al. (2008). Flow-mediated dilatation in the
superficial femoral artery is nitric oxide mediated in humans. J. Physiol. 586,
1137–1145. doi: 10.1113/jphysiol.2007.145722
Lalonde, F., and Curnier, D. (2014). Can anaerobic performance be improved
by remote ischemic preconditioning? J. Strength Cond. Res. 29, 80–85.
doi: 10.1519/JSC.0000000000000609
Marongiu, E., and Crisafulli, A. (2014). Cardioprotection acquired through
exercise: the role of ischemic preconditioning. Curr. Cardiol. Rev. 10, 336–348.
doi: 10.2174/1573403X10666140404110229
Paixao, R. C., da Mota, G. R., and Marocolo, M. (2014). Acute effect
of ischemic preconditioning is detrimental to anaerobic performance
in cyclists. Int. J. Sports Med. 35, 912–915. doi: 10.1055/s-0034-137
2628
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.000000000000
0576
Ross, R., de Lannoy, L., and Stotz, P. J. (2015). Separate effects of intensity and
amount of exercise on interindividual cardiorespiratory fitness response. Mayo
Clin. Proc. 90, 1506–1514. doi: 10.1016/j.mayocp.2015.07.024
Rowell, L. B., Savage, M. V., Chambers, J., and Blackmon, J. R. (1991).
Cardiovascular responses to graded reductions in leg perfusion in exercising
humans. Am. J. Physiol. 261(5 Pt 2), H1545–H1553. doi: 10.1152/ajpheart.1991.
261.5.H1545
Sabino-Carvalho, J. L., Lopes, T. R., Obeid-Freitas, T., Ferreira, T. N., Succi, J. E.,
Silva, A. C., et al. (2017). Effect of ischemic preconditioning on endurance
performance does not surpass placebo. Med. Sci. Sports Exerc. 49, 124–132.
doi: 10.1249/MSS.0000000000001088
Sakamaki, M., Bemben, M. G., and Abe, T. (2011). Legs and trunk muscle
hypertrophy following walk training with restricted leg muscle blood flow.
J. Sports Sci. Med. 10, 338–340.
Scott, B. R., Slattery, K. M., Sculley, D. V., and Dascombe, B. J. (2014). Hypoxia and
resistance exercise: a comparison of localized and systemic methods. Sport Med.
44, 1037–1054. doi: 10.1007/s40279-014- 0177-7
Sprick, J. D., and Rickards, C. A. (2017). Combining remote ischemic
preconditioning and aerobic exercise: a novel adaptation of blood flow
restriction exercise. Am. J. Physiol. Integr. Comp. Physiol. 313, R497–R506.
doi: 10.1152/ajpregu.00111.2017
Frontiers in Physiology | www.frontiersin.org 7November 2018 | Volume 9 | Article 1621
fphys-09-01621 November 13, 2018 Time: 14:48 # 8
Slysz and Burr Enhanced Metabolic Stress Augments IPC
Taylor, C. W., Ingham, S. A., and Ferguson, R. A. (2016). Acute and chronic effect
of sprint interval training combined with postexercise blood-flow restriction in
trained individuals. Exp. Physiol. 101, 143–154. doi: 10.1113/EP085293
Tschakovsky, M. E., and Hughson, R. L. (1999). Ischemic muscle chemoreflex
response elevates blood flow in nonischemic exercising human forearm muscle.
Am. J. Physiol. 277, H635–H642. doi: 10.1152/ajpheart.1999.277.2.H635
Warburton, D. E., Jamnik, V. K., Bredin, S. S. D., and Gledhill, N. (2014). The 2014
physical activity readiness questionnaire for everyone (PAR-Q+) and electronic
physical activity readiness medical examination (ePARmed-X+). Health Fit. J.
Can. 7, 80–83.
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 © 2018 Slysz and Burr. 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) and
the copyright owner(s) are credited and that the original publication in this journal
is cited, in accordance with accepted academic practice. No use, distribution or
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Frontiers in Physiology | www.frontiersin.org 8November 2018 | Volume 9 | Article 1621
... Enhanced Metabolic Stress Augments Ischemic Preconditioning for Exercise Performance by Slysz, J. T., and Burr, J. F. (2018). Front. ...
... Our research group has published several papers involving ischemic preconditioning (IPC) and exercise performance (Marocolo et al., 2017(Marocolo et al., , 2018. Thus, we read with interest the paper of Slysz and Burr (2018). The aim of their study was to identify the combined effect of increasing tissue level oxygen consumption and metabolite accumulation on the ergogenic efficacy of ischemic preconditioning (IPC) during maximal aerobic and maximal anaerobic exercise. ...
... Briefly, the authors concluded that IPC combined with walking or electrical muscle stimulation (EMS) improved performance in a maximal aerobic test to exhaustion, but traditional (i.e., isolated) IPC no. Also, they found no effects from all treatments on maximal oxygen consumption and maximal anaerobic power (Slysz and Burr, 2018). Although their article is relevant and feasible, we would like to promote intellectual discussion aiming to full the topic. ...
... However, the literature is not yet conclusive regarding the efficacy of RIPC for performance enhancement (Incognito et al. 2016;Salvador et al. 2016), and at least some of the discrepancy in results may stem from the existence of responders and non-responders among subject populations (Koch et al. 2014;Incognito et al. 2016;). An augmented form of RIPC involving concurrent muscle contraction (RIPC aug ) seems to reduce the frequency of non-response to promote enhanced performance, suggesting a potential dose-response with stimulus intensity, or perhaps a critical metabolic threshold (Slysz and Burr 2018). Using an incremental maximal cycling test, Slysz et al. found that peak watts were improved following RIPC aug using concurrent muscle activation via walking or electrical stimulation, compared to no improvement in the same participants using traditional RIPC (Slysz and Burr 2018). ...
... An augmented form of RIPC involving concurrent muscle contraction (RIPC aug ) seems to reduce the frequency of non-response to promote enhanced performance, suggesting a potential dose-response with stimulus intensity, or perhaps a critical metabolic threshold (Slysz and Burr 2018). Using an incremental maximal cycling test, Slysz et al. found that peak watts were improved following RIPC aug using concurrent muscle activation via walking or electrical stimulation, compared to no improvement in the same participants using traditional RIPC (Slysz and Burr 2018). A similar protocol coined "active preconditioning" designed by Aebi et al. (Aebi et al. 2019) found no improvement in repeated sprint exercises. ...
... A similar protocol coined "active preconditioning" designed by Aebi et al. (Aebi et al. 2019) found no improvement in repeated sprint exercises. However, their ability to reach this critical threshold may have been limited by using a reduced occlusion pressure, and there is weak empirical support for RIPC or RIPC aug as an ergogenic aid with sprint exercise (Gibson et al. 2013;Incognito et al. 2016;Salvador et al. 2016;Slysz and Burr 2018). ...
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Purpose: While the possible ergogenic benefits of remote ischemic preconditioning (RIPC) make it an attractive training modality, the mechanisms of action remain unclear. Alterations in neural tone have been demonstrated in conjunction with circulatory occlusion, yet investigation of the autonomic nervous system following RIPC treatment has received little attention. We sought to characterize alterations in autonomic balance to both RIPC and augmented RIPC (RIPC aug) performed while cycling, using acute and sustained autonomic indices. Methods: Thirteen participants (8M:5F) recorded baseline waking heart rate variability (HRV) for 5 days prior to treatment. Participants then completed control exercise (CON), RIPC, and RIPC aug interventions in a randomized cross-over design. Cardiovascular measurements were recorded immediately before and after each intervention at rest, and during an orthostatic challenge. Waking HRV was repeated the morning after each intervention. Results: RIPC resulted in acutely reduced resting heart rates (HR) (∆ − 4 ± 6 bpm, P = 0.02) and suppressed HR 30 s following the orthostatic challenge compared to CON (64 ± 10 vs 74 ± 9 bpm, P = 0.003). RIPC aug yielded elevated HRs compared to CON and RIPC prior to (P = 0.003) and during the orthostatic challenge (P = 0.002). RIPC aug reduced LnSDNN (Baseline 4.39 ± 0.27; CON 4.44 ± 0.39; RIPC 4.41 ± 0.34; RIPC aug 4.22 ± 0.29, P = 0.02) and LnHfa power (Baseline 7.82 ± 0.54; CON 7.73 ± 1.11; RIPC 7.89 ± 0.78; RIPC aug 7.23 ± 0.87, P = 0.04) the morning after treatment compared to all other conditions. Conclusions: Our data suggest that RIPC may influence HR acutely, possibly through a reduction in cardiac sympathetic activity, and that RIPC aug reduces HRV through cardiac vagal withdrawal or increased cardiac sympathetic modulation, with alterations persisting until the following morning. These findings imply a dose-response relationship with potential for optimization of performance.
... The aforementioned findings were unexpected given that previous literature demonstrates an improved exercise performance after IPC administration without corresponding improvements in aerobic metabolism (Cook et al., 1997;Crisafulli et al., 2011;Slysz and Burr, 2018). It is still possible that IPC improves exercise performance through perceptual modulation, as the mechanism by which IPC modulates an individual's perception to cold pain may not equate to how IPC modulates his/her perception of exercise. ...
... It is important to note that the pain of a cold-pressor test is driven by a single external stimulus, whereas the discomfort of intense exercise is internal and dependent on multiple signals across organs. Along these lines, it has been alternatively theorized that IPC may improve performance by modulating sensitivity to fatigue rather than pain (Crisafulli et al., 2011;Slysz and Burr, 2018). Future research should continue to investigate the possibility that IPC-induced improvements in exercise performance are related to perceptual changes during the exercise task. ...
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Purpose The purpose of this study was to examine whether an individual’s IPC-mediated change in cold pain sensitivity is associated with the same individual’s IPC-mediated change in exercise performance. Methods Thirteen individuals (8 males; 5 females, 27 ± 7 years, 55 ± 5 ml.kgs –1 .min –1 ) underwent two separate cold-water immersion tests: with preceding IPC treatment and without. In addition, each participant undertook two separate 5-km cycling time trials: with preceding IPC treatment and without. Pearson correlation coefficients were used to assess the relationship between an individual’s change in cold-water pain sensitivity following IPC with their change in 5-km time trial performance following IPC. Results During the cold-water immersion test, pain intensity increased over time ( p < 0.001) but did not change with IPC ( p = 0.96). However, IPC significantly reduced the total time spent under pain (−9 ± 7 s; p = 0.001) during the cold-water immersion test. No relationship was found between an individual’s change in time under pain ( r = −0.2, p = 0.6) or pain intensity ( r = −0.3, p = 0.3) following IPC and their change in performance following IPC. Conclusion These findings suggest that IPC can modulate sensitivity to a painful stimulus, but this altered sensitivity does not explain the ergogenic efficacy of IPC on 5-km cycling performance.
... 9,10 An alternative form of IPC is the application of voluntary exercise or electrically evoked muscle contractions during the episodes with a reduced blood flow (ischemic exercise preconditioning [IPC-Ex]). 11 In the only study of IPC-Ex published to date, IPC-Ex was reported to increase incremental peak power output (iPPO) by ∼4% relative to IPC-rest in recreationally trained men (VO 2 max = 48 mL/kg/min), indicating a larger ergogenic potential of IPC-Ex versus IPC-rest in less trained individuals. Clearly, the ergogenic value of IPC for well-trained subjects warrants further evaluation, including what mechanisms can explain any improvements in performance. ...
Article
Purpose: This study tested the hypothesis of whether ischemic exercise preconditioning (IPC-Ex) elicits a better intense endurance exercise performance than traditional ischemic preconditioning at rest (IPC-rest) and a SHAM procedure. Methods: Twelve men (average V˙O2max ∼61 mL·kg-1·min-1) performed 3 trials on separate days, each consisting of either IPC-Ex (3 × 2-min cycling at ∼40 W with a bilateral-leg cuff pressure of ∼180 mm Hg), IPC-rest (4 × 5-min supine rest at 220 mm Hg), or SHAM (4 × 5-min supine rest at <10 mm Hg) followed by a standardized warm-up and a 4-minute maximal cycling performance test. Power output, blood lactate, potassium, pH, rating of perceived exertion, oxygen uptake, and gross efficiency were assessed. Results: Mean power during the performance test was higher in IPC-Ex versus IPC-rest (+4%; P = .002; 95% CI, +5 to 18 W). No difference was found between IPC-rest and SHAM (-2%; P = .10; 95% CI, -12 to 1 W) or between IPC-Ex and SHAM (+2%; P = .09; 95% CI, -1 to 13 W). The rating of perceived exertion increased following the IPC-procedure in IPC-Ex versus IPC-rest and SHAM (P < .001). During warm-up, IPC-Ex elevated blood pH versus IPC-rest and SHAM (P ≤ .027), with no trial differences for blood potassium (P > .09) or cycling efficiency (P ≥ .24). Eight subjects anticipated IPC-Ex to be best for their performance. Four subjects favored SHAM. Conclusions: Performance in a 4-minute maximal test was better following IPC-Ex than IPC-rest and tended to be better than SHAM. The IPC procedures did not affect blood potassium, while pH was transiently elevated only by IPC-Ex. The performance-enhancing effect of IPC-Ex versus IPC-rest may be attributed to a placebo effect, improved pH regulation, and/or a change in the perception of effort.
... 8 Contrastingly, adding low-intensity treadmill walking exercise to a "standard" ischemic preconditioning protocol of three sets of 5-minute cycles of occlusion (cuff pressure = 220 mm Hg) and reperfusion led to a ∼5% improvement in peak wattage at exhaustion during a graded exercise test. 11 Confounding factors such as differences in cuff sizes, patterns of occlusion (continuous or intermittent application), and/or occlusive pressures (partial vs complete occlusion) makes it difficult to compare outcomes across studies. 12 Altogether, the existing data suggest that "classic" (ie, at rest) preconditioning seems more effective than the "active" (ie, combined with exercise) method, yet without clear explanations for the differences. ...
Purpose: The authors compared the effects of active preconditioning with local and systemic hypoxia during submaximal cycling. Methods: On separate visits, 14 active participants completed 4 trials. Each visit was composed of 1 preconditioning phase followed, after 40 minutes of rest, by 3 × 6-minute cycling bouts (intensity = 85% of critical power; rest = 6 min). The preconditioning phase consisted of 4 × 5-minute cycling bouts at 1.5 W·kg-1 (rest = 5 min) in 4 conditions: control (no occlusion and normoxia), blood flow restriction (60% of total occlusion), HYP (systemic hypoxia; inspired fraction of oxygen = 13.6%), and blood flow restriction + HYP (local and systemic hypoxia combined). Results: During the preconditioning phase, there were main effects of both systemic (all P < .014) and local hypoxia (all P ≤ .001) on heart rate, arterial oxygen saturation, leg discomfort, difficulty of breathing, and blood lactate concentration. Cardiorespiratory variables, gross efficiency, energy cost, and energy expenditure during the last minute of 6-minute cycling bouts did not differ between conditions (all P > .105). Conclusion: Local and systemic hypoxic stimuli, or a combination of both, during active preconditioning did not improve physiological responses such as cycling efficiency during subsequent submaximal cycling.
... In the case of IPC, a recent meta-analysis identified a small effect of IPC on overall exercise performance, the largest effect being on aerobic exercise (51). Importantly, in some cases certain individuals may require a combination of both MP and IPC to see a performance-enhancing effect (53). In the present study the condition of reduced O 2 D while maintaining exercise is the equivalent of a combined IPC and MP condition. ...
Article
Key points: The immediate increase in skeletal muscle blood flow following contraction is greater when the contracting muscle is below vs. above heart level. This has been attributed to muscle pump-mediated venous emptying and subsequent widening of the arterial to venous pressure gradient which can occur below but not above heart level. However, alternate explanations could include greater rapid onset vasodilatation and/or transmural pressure-mediated mechanical distension of resistance vessels, but these remain unexplored. We demonstrate that active vasodilatation is not responsible for greater post-contraction hyperaemia below heart. Instead, an increased transmural pressure-mediated mechanical distension of resistance vessels is a key mechanism responsible for this phenomenon. Our findings establish the importance of considering/accounting for local mechanical arteriolar distension effects when investigating exercise hyperaemia. They also inform the application of exercise for rehabilitative purposes and prompt investigation into whether arteriolar distension accompanying vasodilation is reduced with diseases or aging, thereby compromising exercising muscle perfusion. Abstract: We tested the hypotheses that increased post-contraction hyperaemia in higher (H; below heart) vs. lower (L; above heart) transmural pressure conditions is due to 1) greater active vasodilatation or 2) greater transmural pressure-mediated arteriolar distension. Participants (n = 20, 12 male, 8 female, combined 24.5 ± 2 yrs) performed a 2 s isometric handgrip contraction, where arm position was maintained within or changed between H and L during contraction, resulting in 4 starting-finishing arm position conditions (LL, HL, LH, HH). Post-contraction forearm blood flow (FBF; echo and Doppler ultrasound) was higher with contraction release in H vs. L environments (P < 0.05). However, contraction initiated in H did not result in greater vasodilatation (forearm vascular conductance; FVC) than contraction initiated in L, regardless of contraction release condition (peak FVC; LL 217 ± 104 vs. HL 204 ± 92 ml/min/100 mmHg; P = 0.313, LH 229 ± 8 vs. HH 225 ± 85 ml/min/100 mmHg; P = 0.391; first post-contraction cardiac cycle FVC, same comparisons both P = 0.317). However, FVC of the first post-contraction cardiac cycle was greater for contractions released in H vs. L regardless of pre-contraction condition (LL 106 ± 67 vs. LH 152 ± 76 ml/min/100 mmHg, P < 0.05; HL 80 ± 51 vs. HH 119 ± 58 ml/min/100 mmHg, P < 0.05). These findings refute the hypothesis that greater hyperaemia following a single contraction in higher transmural pressure conditions is due to greater active vasodilatation. Instead, our findings reveal a key role for increased transmural pressure-mediated mechanical distension of arterioles in creating a greater increase in vascular conductance for a given active vasodilatation following skeletal muscle contraction. rapid onset vasodilatation, transmural pressure, myogenic vasodilatation, distension, forearm blood flow, muscle contraction This article is protected by copyright. All rights reserved.
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RESUMO: O pré-condicionamento isquêmico [do termo em inglês ischemic preconditioning (IPC)] é uma estratégia caracterizada por breves ciclos de restrição do fluxo sanguíneo seguidos de reperfusão, realizados nos membros superiores ou inferiores com o objetivo de melhorar o desempenho físico. Essa intervenção tem chamado atenção devido a sua característica não invasiva, seu baixo custo e a fácil aplicação. Uma vez que não há um consenso sobre a sua efetividade como uma estratégia ergogênica, o objetivo deste estudo foi investigar o seu estado atual de produção científica, o efeito sobre o desempenho físico e o efeito do nível de treinamento dos participantes e diferentes exercícios/testes utilizados para avaliação do desempenho. Sessenta e sete artigos, envolvendo 984 participantes (177 mulheres) de diferentes níveis de treinamento, preencheram os critérios de inclusão. Sete exercícios (ciclismo, exercício resistido, corrida, natação, patinação, futebol, remo) e cinco níveis de treinamento (destreinados, recreacionalmente treinados, treinados, bem treinados, profissional) foram identificados. A maioria da produção científica sobre IPC e desempenho físico foi publicada a partir de 2015. Mais da metade dos estudos apresentaram um efeito positivo do IPC sobre o desempenho físico (59,7%, n=40). O teste exato de Fischer mostrou que existe uma relação entre o efeito do IPC sobre o desempenho físico e o nível de treinamento dos participantes [X2(8) = 15,149; p = 0,026], mas não entre o efeito do IPC e exercício/teste [X2(12) = 19,528; p = 0,129]. Na última década, houve um aumento substancial na produção cientifica sobre IPC e desempenho físico. Nossos achados sustentam um efeito benéfico do IPC na melhora do desempenho físico, sendo este efeito mais pronunciado em indivíduos destreinados e recreacionalmente treinados, independente do exercício/teste realizado.
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Ischemic preconditioning (IPC) has been repeatedly reported to augment maximal exercise performance over a range of exercise durations and modalities. However, an examination of the relevant literature indicates that the reproducibility and robustness of ergogenic responses to this technique are variable, confounding expectations about the magnitude of its effects. Considerable variability among study methodologies may contribute to the equivocal responses to IPC. This review focuses on the wide range of methodologies used in IPC research, and how such variability likely confounds interpretation of the interactions of IPC and exercise. Several avenues are recommended to improve IPC methodological consistency, which should facilitate a future consensus about optimizing the IPC protocol, including due consideration of factors such as: location of the stimulus, the time between treatment and exercise, individualized tourniquet pressures and standardized tourniquet physical characteristics, and the incorporation of proper placebo treatments into future study designs.
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Key points: It is not clear how sympathetic activity to contracting muscle is controlled. We recorded muscle sympathetic nerve activity (MSNA) to the ipsilateral tibialis anterior muscle during 4 min of isometric dorsiflexion of the ankle and 6 min of post-exercise ischaemia, which was repeated contralaterally. MSNA to the contracting muscle increased within 1 min of static exercise and returned to pre-contraction levels at the end. Unlike the increase in MSNA seen in the non-contracting muscle, post-exercise ischaemia had no effect on MSNA to the contracted muscle. We conclude that central command is the primary mechanism responsible for increasing MSNA to contracting muscle and also that the metaboreflex is not expressed in contracting muscle. Abstract: Both central command and metaboreflex inputs from contracting muscles increase muscle sympathetic nerve activity (MSNA) to non-contracting muscle during sustained isometric exercise. We recently showed that MSNA to contracting muscle also increases in an intensity-dependent manner, although whether this can be sustained by the metaboreflex is unknown. MSNA was recorded from the left common peroneal nerve and individual spikes of MSNA extracted from the nerve signal. Eleven subjects performed a series of 4 min dorsiflexions of the left ankle at 10% of maximum voluntary contraction under three conditions: without ischaemia, with 6 min of post-exercise ischaemia, and with ischaemia during and after exercise; these were repeated in the right leg. Compared with pre-contraction values, MSNA to the contracting muscles increased and plateaued in the first minute of contraction (50 ± 18 vs. 34 ± 10 spikes min-1, P = 0.01), returned to pre-contraction levels within 1 min of the contraction ending and was not influenced by ischaemia during or after contraction. Conversely, MSNA to the non-contracting muscles was not different from pre-contraction levels in the first minute of contraction (34 ± 9 vs. 32 ± 5 spikes min-1, P = 0.48), whereas it increased each minute and was significantly greater by the second minute (44 ± 8 spikes min-1, P = 0.01). Ischaemia augmented the MSNA response to contraction (63 ± 25 spikes min-1after 4 min, P < 0.05) and post-exercise ischaemia (63 ± 27 spikes min-1after 6 min, P < 0.01) for the non-contracting muscles only. These findings support our conclusion that the metaboreflex is not expressed in the contracting muscle during sustained static exercise.
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Purpose: Recent studies have reported ischemic preconditioning (IPC) can acutely improve endurance exercise performance in athletes. However, placebo and nocebo effects have not been sufficiently controlled, and the effect on aerobic metabolism parameters that determine endurance performance [e.g., oxygen cost of running, lactate threshold, and maximal oxygen uptake (V[Combining Dot Above]O2max)] has been equivocal. Thus, we circumvented limitations from previous studies to test the effect of IPC on aerobic metabolism parameters and endurance performance in well-trained runners. Methods: Eighteen runners (14 men/4 women) were submitted to three interventions, in random order: IPC; sham intervention (SHAM); and resting control (CT). Subjects were told both IPC and SHAM would improve performance compared to CT (i.e., similar placebo induction) and IPC would be harmless despite circulatory occlusion sensations (i.e., nocebo avoidance). Next, pulmonary ventilation and gas exchange, blood lactate concentration, and perceived effort were measured during a discontinuous incremental test on a treadmill. Then, a supramaximal test was used to verify the V[Combining Dot Above]O2max and assess endurance performance (i.e., time to exhaustion). Results: Ventilation, oxygen uptake, carbon dioxide output, lactate concentration, and perceived effort were similar among IPC, SHAM, and CT throughout the discontinuous incremental test (P > 0.05). Oxygen cost of running, lactate threshold, and V[Combining Dot Above]O2max were also similar among interventions (P > 0.05). Time to exhaustion was longer after IPC (mean ± SEM, 165.34 ± 12.34 s) and SHAM (164.38 ± 11.71 s) than CT (143.98 ± 12.09 s; P = 0.02 and 0.03, respectively), but similar between IPC and SHAM (P = 1.00). Conclusions: IPC did not change aerobic metabolism parameters, whereas improved endurance performance. The IPC improvement, however, did not surpass the effect of a placebo intervention.
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Background Ischemic preconditioning (IPC) is the exposure to brief periods of circulatory occlusion and reperfusion in order to protect local or systemic organs against subsequent bouts of ischemia. IPC has also been proposed as a novel intervention to improve exercise performance in healthy and diseased populations. Objective The purpose of this systematic review is to analyze the evidence for IPC improving exercise performance in healthy humans. Methods Data were obtained using a systematic computer-assisted search of four electronic databases (MEDLINE, PubMed, SPORTDiscus, CINAHL), from January 1985 to October 2015, and relevant reference lists. Results Twenty-one studies met the inclusion criteria. The collective data suggest that IPC is a safe intervention that may be capable of improving time-trial performance. Available individual data from included studies demonstrate that IPC improved time-trial performance in 67 % of participants, with comparable results in athletes and recreationally active populations. The effects of IPC on power output, oxygen consumption, rating of perceived exertion, blood lactate accumulation, and cardiorespiratory measures are unclear. The within-study heterogeneity may suggest the presence of IPC responders and non-responders, which in combination with small sample sizes, likely confound interpretation of mean group data in the literature. Conclusion The ability of IPC to improve time-trial performance is promising, but the potential mechanisms responsible require further investigation. Future work should be directed toward identifying the individual phenotype and protocol that will best exploit IPC-mediated exercise performance improvements, facilitating its application in sport settings.
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