Literature Review

A Review on the Mechanisms of Blood-Flow Restriction Resistance Training-Induced Muscle Hypertrophy

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DOI: 10.1007/s40279-014-0264-9 · Source: PubMed
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Abstract
It has traditionally been believed that resistance training can only induce muscle growth when the exercise intensity is greater than 65 % of the 1-repetition maximum (RM). However, more recently, the use of low-intensity resistance exercise with blood-flow restriction (BFR) has challenged this theory and consistently shown that hypertrophic adaptations can be induced with much lower exercise intensities (<50 % 1-RM). Despite the potent hypertrophic effects of BFR resistance training being demonstrated by numerous studies, the underlying mechanisms responsible for such effects are not well defined. Metabolic stress has been suggested to be a primary factor responsible, and this is theorised to activate numerous other mechanisms, all of which are thought to induce muscle growth via autocrine and/or paracrine actions. However, it is noteworthy that some of these mechanisms do not appear to be mediated to any great extent by metabolic stress but rather by mechanical tension (another primary factor of muscle hypertrophy). Given that the level of mechanical tension is typically low with BFR resistance exercise (<50 % 1-RM), one may question the magnitude of involvement of these mechanisms aligned to the adaptations reported with BFR resistance training. However, despite the low level of mechanical tension, it is plausible that the effects induced by the primary factors (mechanical tension and metabolic stress) are, in fact, additive, which ultimately contributes to the adaptations seen with BFR resistance training. Exercise-induced mechanical tension and metabolic stress are theorised to signal a number of mechanisms for the induction of muscle growth, including increased fast-twitch fibre recruitment, mechanotransduction, muscle damage, systemic and localised hormone production, cell swelling, and the production of reactive oxygen species and its variants, including nitric oxide and heat shock proteins. However, the relative extent to which these specific mechanisms are induced by the primary factors with BFR resistance exercise, as well as their magnitude of involvement in BFR resistance training-induced muscle hypertrophy, requires further exploration.
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Sports Medicine
ISSN 0112-1642
Sports Med
DOI 10.1007/s40279-014-0264-9
A Review on the Mechanisms of Blood-
Flow Restriction Resistance Training-
Induced Muscle Hypertrophy
Stephen John Pearson & Syed Robiul
Hussain
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REVIEW ARTICLE
A Review on the Mechanisms of Blood-Flow Restriction
Resistance Training-Induced Muscle Hypertrophy
Stephen John Pearson Syed Robiul Hussain
ÓSpringer International Publishing Switzerland 2014
Abstract It has traditionally been believed that resistance
training can only induce muscle growth when the exercise
intensity is greater than 65 % of the 1-repetition maximum
(RM). However, more recently, the use of low-intensity
resistance exercise with blood-flow restriction (BFR) has
challenged this theory and consistently shown that hyper-
trophic adaptations can be induced with much lower
exercise intensities (\50 % 1-RM). Despite the potent
hypertrophic effects of BFR resistance training being
demonstrated by numerous studies, the underlying mech-
anisms responsible for such effects are not well defined.
Metabolic stress has been suggested to be a primary factor
responsible, and this is theorised to activate numerous other
mechanisms, all of which are thought to induce muscle
growth via autocrine and/or paracrine actions. However, it
is noteworthy that some of these mechanisms do not appear
to be mediated to any great extent by metabolic stress but
rather by mechanical tension (another primary factor of
muscle hypertrophy). Given that the level of mechanical
tension is typically low with BFR resistance exercise
(\50 % 1-RM), one may question the magnitude of
involvement of these mechanisms aligned to the adapta-
tions reported with BFR resistance training. However,
despite the low level of mechanical tension, it is plausible
that the effects induced by the primary factors (mechanical
tension and metabolic stress) are, in fact, additive, which
ultimately contributes to the adaptations seen with BFR
resistance training. Exercise-induced mechanical tension
and metabolic stress are theorised to signal a number of
mechanisms for the induction of muscle growth, including
increased fast-twitch fibre recruitment, mechanotransduc-
tion, muscle damage, systemic and localised hormone
production, cell swelling, and the production of reactive
oxygen species and its variants, including nitric oxide and
heat shock proteins. However, the relative extent to which
these specific mechanisms are induced by the primary
factors with BFR resistance exercise, as well as their
magnitude of involvement in BFR resistance training-
induced muscle hypertrophy, requires further exploration.
Key Points
Mechanical tension and metabolic stress are both
primary mechanisms of resistance training-induced
muscle hypertrophy.
Metabolic stress may play the dominant role in
mediating the potent hypertrophic effects seen with
blood-flow restriction (BFR) resistance training, but
mechanical tension also plays a part.
Mechanical tension and metabolic stress act
synergistically to mediate numerous secondary
associated mechanisms, all of which stimulate
autocrine and/or paracrine actions for the induction
of muscle hypertrophy with BFR resistance training.
1 Background
During resistance exercise, motor units, and hence muscle
fibres, are recruited according to the ‘size principle’ [1], in
which the smaller motor units associated with type I
S. J. Pearson (&)S. R. Hussain
Centre for Health, Sport and Rehabilitation Sciences Research,
University of Salford, Manchester M6 6PU, UK
e-mail: s.pearson@salford.ac.uk
123
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DOI 10.1007/s40279-014-0264-9
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muscle fibres are activated initially at low intensities, and
the larger motor units associated with type II muscle fibres
are recruited at higher exercise intensities with increasing
level of contractile force. In order to increase muscle mass
and strength, it is important to activate type II muscle fibres
during training, since these fibres have been shown to be
more responsive to hypertrophy than type I fibres [2,3] and
are generally larger. Therefore, previously it has been
suggested that only moderate–high-intensity resistance
exercise with intensities [65 % of the 1-repetition maxi-
mum (RM) can induce significant gains in muscle mass and
strength [4,5].
However, more recent research has demonstrated the
effectiveness of exercise training with blood-flow restric-
tion (BFR), which can produce hypertrophic adaptations
with much lower exercise intensities than previously
believed [617]. In particular, most studies appear to have
utilised a low-intensity (\50 % 1RM) resistance exercise
protocol with BFR [611] for the induction of muscle
hypertrophy, although some have also shown the utility of
a low-intensity walking intervention (2-min bouts at 50 m/
min) [14]. The BFR in such exercise protocols is typically
achieved by restricting blood flow to the muscle with the
application of external pressure via a tourniquet [18],
pressurised cuff [19], or elastic banding [20] that is applied
over the proximal portion of the upper or lower extremities.
It has been suggested that the external pressure applied is
sufficient to maintain arterial inflow whilst occluding
venous outflow of blood distal to the occlusion site [16],
although here, it is difficult to envisage sufficient arterial
inflow, since such restricted venous return is likely to
reduce inflow of blood to the muscle. This reduced blood
flow is thought to induce an ischemic/hypoxic environment
that enhances the training effect in exercising muscle,
leading to increased muscle mass and strength [610,14].
Despite the fact that the robust effects of BFR resistance
training in producing muscle hypertrophy have previously
been documented by numerous studies [617], the under-
lying mechanisms responsible for such effects remain
poorly understood. The resultant hypertrophic effects of
resistance training with BFR have been primarily attributed
to increased levels of metabolic stress (i.e., build-up of
metabolites as a result of the ischemic/hypoxic environ-
ment) [21], which is theorised to induce muscle growth by
acting on other factors, including the increased recruitment
of fast-twitch muscle fibres [22,23], elevations of systemic
hormones [24,25], cell swelling [26], and increased pro-
duction of reactive oxygen species (ROS) [16,27]. How-
ever, it must be noted that some of these mechanisms (i.e.
increased recruitment of fast-twitch muscle fibres and ROS
production) are not activated to the greatest extent by
metabolic stress, and are more associated with high levels
of mechanical tension (another primary factor of muscle
growth) as that seen with high-intensity resistance training
[19,2830], which perhaps questions their level of con-
tribution in BFR resistance training-induced hypertrophy,
given its low-intensity nature.
Despite the low level of mechanical tension, it is pos-
sible that the effects induced by the primary factors
(mechanical tension and metabolic stress) are in fact
additive, which ultimately contributes to the adaptations
seen with BFR resistance training. However, the specific
extent to which these primary factors activate the particular
mechanisms for the induction of muscle growth with BFR
resistance exercise, as well as their magnitude of involve-
ment to BFR resistance training-induced muscle hypertro-
phy, is largely unknown. This topic is obviously very
complex, and further exploration is required to provide a
better understanding of the potential relative contributions
of the mechanisms involved.
Thus, it is the purpose of this article to review the existing
literature and explore in detail how muscle growth is induced
with BFR resistance training, with particular regard to the
relative contribution of mechanical tension and metabolic
stress, as well as their associated mechanisms.
2 Literature Search Methodology
The National Library of Medicine (PubMed) database was
used to search for relevant articles between January 2000
and June 2014. The specific search terms used in isolation
and/or combination were ‘occlusion training’, ‘blood flow
restriction’, ‘muscle hypertrophy’, ‘human’, ‘skeletal
muscle’, ‘molecular signalling’, ‘kaatsu training’, ‘resis-
tance training’, ‘adaptation’, ‘mechanical loading’, ‘meta-
bolic stress’, ‘hormones’, ‘cellular’, and ‘anabolic
hormones’. Reference lists of articles obtained from this
search were also examined for additional relevant articles.
The inclusion/exclusion criteria for studies were based on
their potential relevance to the acute and/or chronic
responses of resistance exercise with BFR. In addition,
studies utilising other modalities of exercise with BFR
were also considered if relevant information with regards
to the mechanisms of hypertrophy with BFR resistance
exercise was detailed.
3 Modes of Action
The mechanisms suggested to stimulate muscle growth
from exercise-induced metabolic stress and/or mechanical
tension include increased fast-twitch fibre recruitment,
mechanotransduction, muscle damage, systemic and
localised hormone production, cell swelling, and the pro-
duction of ROS and its variants, including nitric oxide
S. J. Pearson, S. R. Hussain
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(NO) and heat shock proteins [1113,2029,31,32]. It is
plausible that mechanical tension and metabolic stress
activate similar mechanisms to promote hypertrophy and
thus the effects may be additive and synergistic; however,
it seems reasonable that some of these mechanisms would
be more mediated (activated to a greater degree) by
mechanical tension (i.e. fast-twitch fibre recruitment) and
others by metabolic stress (i.e. systemic hormone produc-
tion). To speculate, it is possible that the magnitude of
contribution of the primary factors and their associated
mechanisms in producing muscle hypertrophy actually
depends on the training intensity/modality employed. For
instance, high-intensity resistance exercise may induce a
higher level of mechanical tension and a lower level of
metabolic stress than moderate-intensity resistance exer-
cise and low-intensity resistance exercise with BFR [4,33,
34], whereas low-intensity BFR resistance exercise may
induce a lower degree of mechanical tension but a higher
level of metabolic stress than moderate- and high-intensity
resistance exercise [14,24,35]. Thus, moderate-intensity
resistance exercise may induce an optimal combination of
both mechanical tension and metabolic stress, perhaps
lending itself to the greatest hypertrophic potential (see
Fig. 1).
Based on the above intensity/modality-specific mecha-
nisms theory, metabolic stress appears to play the dominant
role in mediating muscle hypertrophy with BFR resistance
training. However, it would still seem of significant
importance to not categorically exclude the potential role
of mechanical tension, since it would most likely be this
combination of complex cascades that ultimately contrib-
utes to muscle growth.
4 Primary Mechanisms
The following sub-sections discuss the primary factors in
greater detail with respect to their relative contribution to
BFR resistance training-induced hypertrophy.
4.1 Mechanical Tension
A large body of research indicates that mechanical tension
acts as a primary mechanism of muscle growth. This was
first noted by Goldberg et al. [36] where induced
mechanical ‘‘strain’’ on muscle was found to attenuate the
atrophy caused by unloading, suggesting that mechanical
tension is a critical factor initiating compensatory muscle
growth. Subsequently, Spangenburg et al. [37] reported an
increased mechanical load to induce muscle hypertrophy in
a rat model, and Vandenburgh and Kaufman [38] also
reported mechanical stretch to be an important factor for
hypertrophy using an in vitro model.
The mechanisms put forward by which mechanical
tension induces muscle hypertrophy include mechano-
transduction [31,39,40], increased localised hormone
production [41], muscle damage [42], ROS production [42,
43] and increased fast-twitch fibre recruitment [17,28,30].
All of the above have been reported to increase protein
synthesis through activation of signalling pathways [44,
45], and/or satellite cell activation and proliferation [41]
for the induction of muscle growth. Although it can be
argued that the low level of mechanical tension associated
with BFR resistance exercise would not induce these
mechanisms to any great extent, metabolic stress has also
been shown to mediate similar mechanisms, and as such
the effects may be additive.
4.2 Metabolic Stress
Metabolic stress (i.e. accumulation of metabolites during
exercise) has been reported as being equally as important
as mechanical tension, if not more, for the induction of
muscle growth [9,12,28,31,46]. To illustrate, Goto et al.
[47] compared the acute and chronic effects of two volume/
intensity-matched resistance exercise protocols (3–5 sets of
10 reps at 75 % 1RM), with the only difference being that
one protocol included a 30-s rest period in the midway
point of each set to try and reduce the degree of metabolic
build-up, whereas the other did not. Results showed blood
lactate concentrations to be significantly higher following
the without-rest protocol relative to the with-rest protocol.
Additionally, following 12 weeks of training, the without-
rest regimen was found to significantly increase muscle
cross-sectional area (CSA), whereas no such differences
were observed following the with-rest protocol, indicating
a direct link between metabolic stress and muscle
hypertrophy.
Indeed, such levels of metabolic stress are also magni-
fied under ischemic/hypoxic conditions as that seen during
BFR resistance exercise [24,35]. Blood lactate concen-
trations have previously been shown to be significantly
higher following low-intensity resistance exercise per-
formed under ischemic conditions such as BFR [24] and
hypoxia [35] compared with the same exercise protocol
performed under normal conditions. The potential hyper-
trophic effects of the metabolic stress associated with BFR
resistance exercise have also been demonstrated by
numerous studies where a period of low-intensity resis-
tance exercise (*30–50 % 1RM) with BFR
(*110–200 mmHg) was found to result in a significantly
greater increase in muscle CSA than the same training
programmes performed without BFR [68]. In addition,
direct relationships between other indices of metabolic
stress (Pi and intramuscular pH) and muscle hypertrophy
following a period of low-intensity (20 % 1RM) resistance
Mechanisms of Blood-Flow Restricted Resistance Exercise-Induced Hypertrophy
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exercise with BFR have also been reported elsewhere in the
literature [9]. This perhaps highlights the prominent role of
metabolic stress in mediating hypertrophic adaptations
following resistance training with BFR. It has been theor-
ised that exercise-induced metabolic stress mediates mus-
cle hypertrophy via a number of mechanisms, including
elevated systemic hormone production [25], increased fast-
twitch fibre recruitment [6,7], cell swelling [26], muscle
damage [31,48] and increased production of ROS [13,27,
31,49], all of which are thought to mediate muscle protein
signalling and/or satellite cell proliferation for the induc-
tion of muscle growth.
5 Secondary Mechanisms
As outlined earlier, the primary factors are expected to act
on a number of associated secondary mechanisms for the
induction of muscle growth. The following sub-sections
discuss these secondary factors in greater detail in terms of
their extent of activation by mechanical tension/metabolic
stress and their magnitude of involvement in BFR resis-
tance training-induced hypertrophy.
5.1 Mechanotransduction
Mechanical tension leads to morphological adaptations
through the process of mechanotransduction, whereby
sarcolemmal-bound mechanosensors, such as integrins and
focal adhesions, convert mechanical energy into chemical
signals that mediate intracellular anabolic and catabolic
pathways, ultimately leading to a shift in muscle protein
balance that favours synthesis over degradation [40]. Baar
and Esser [45] reported increased phosphorylation of
p70S6 kinase (p70S6k) following high-resistance length-
ening contractions, which also correlated to percent
increases in muscle mass (r=0.998). This process of
mechanotransduction could in theory occur at the level of
Fig. 1 The relative contributions of mechanical tension and meta-
bolic stress in mediating muscle hypertrophy, dependant on the
training intensity and/or modality. Arrows highlight potential degrees
of activation of resultant intermediate secondary mechanisms and
their possible relationships. Vertical arrows (l) represent higher/
lower degree of activation, horizontal arrows ($) represent no effect,
interconnecting arrows represent potential relationships between
secondary mechanisms, dotted interconnecting arrows indicate
equivocal relationships. BFR blood flow restriction, HSP heat shock
proteins, NOS nitric oxide synthase, ROS reactive oxygen species
S. J. Pearson, S. R. Hussain
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the lipid bilayer and/or at the matrix of the integrin cyto-
skeleton [50]. It has been proposed that, during damage or
repair to the lipid bilayer, vesicle plugs can form whereby
intracellular components can fuse with the bilayer and
release insulin-like growth factor (IGF)-1, which ultimately
up-regulates protein synthesis via activation of phospho-
inositide 3-kinase (PI3K)/Akt [51]. Other associated
mechanisms here include changes in the permeability of
the bilayer by stretch, leading to activation of G proteins
and subsequent muscle hypertrophy [38]. In addition, the
mechanical stretch can also increase production of neuro-
nal NO in muscle fibres, causing release of intracellular
calcium, which has also been shown to activate the mam-
malian target of rapamycin (mTOR) signalling pathway
[49], promoting muscle anabolism.
Collectively, there is a large body of research empha-
sising mechanotransduction as an important mechanism of
muscle hypertrophy. However, no evidence yet exists with
regards to its potential contribution to the training-induced
effects of resistance exercise with BFR; although it is
questionable whether such mechanotransduction processes
would contribute to BFR resistance training-induced
hypertrophy given its low mechanical stress nature.
5.2 Muscle Damage
Exercise-induced muscle damage (EIMD) is purported to
be an essential regulator of satellite cell-mediated com-
pensatory muscle growth (see later section) [5254]. The
greatest damage to muscle tissue is seen with eccentric
exercise, where muscles are forcibly lengthened [55]. Thus,
support for the potential anabolic role of EIMD perhaps
stems from studies that have reported the hypertrophic
response [56] to be blunted when the eccentric phase is
omitted from training. In addition, a meta-analysis by Roig
et al. [57] suggests that eccentric training is superior to
concentric training in mediating muscle hypertrophy.
Taken together, these studies support the notion that EIMD
(eccentric exercise) is a potent stimulus for muscle growth.
However, the ‘repeated bout effect’ phenomenon suggests
that, although one bout of eccentric exercise may induce
muscle damage, repeated bouts of the same exercise are not
associated with such effects [58], which perhaps contra-
dicts any association of EIMD to hypertrophy, as multiple
exercise sets and chronic training are, in this sense, likely
to lessen the muscle damage response.
It is currently unclear whether EIMD plays a role in the
hypertrophic adaptations of BFR resistance exercise, as
previous research is somewhat diverse. Through the use of
indirect markers (i.e. maximal voluntary contraction
[MVC] torque, muscle soreness), Thiebaud and colleagues
[59,60] showed BFR resistance exercise to induce only
minimal levels of muscle damage (lasting less than 1 day),
whereas Umbel et al. [61] have reported a sufficient degree
of EIMD by BFR resistance exercise (lasting 48 h post-
exercise). These discrepancies could perhaps be accounted
for by differences in methodologies between the studies,
including the prescribed exercise intensity, volume, and
time under BFR [5961].
Additionally, direct markers such as interleukin (IL)-6,
which may provide a more accurate reflection of EIMD, have
also been examined in response to BFR resistance exercise,
with studies showing no increases [11,62]. Although some
studies [24,63] have reported a gradual increase in IL-6
following low-intensity resistance exercise with BFR
(110 mmHg; 214 mmHg), the overall effect sizes were very
small, with levels reaching only one-quarter of those repor-
ted in response to high-intensity eccentric exercise [64].
These findings perhaps suggest that only high mechanical
tension-associated exercise can induce the sufficient amount
of muscle damage required for the production of IL-6 and
subsequent compensatory muscle growth. Thus, EIMD may
not contribute to BFR resistance training-induced hypertro-
phy, due to its low-intensity nature.
5.3 Systemic and Localised Hormones
Another popular theory proposed by several researchers to
explain the hypertrophic effects of BFR resistance training
is that the increased metabolic stress triggers a strong ana-
bolic hormonal response post-exercise [24]. Numerous
studies have reported low-intensity resistance exercise with
BFR to facilitate the expression of many systemic hor-
mones, including growth hormone (GH) [24,25,65] and
IGF-1 [19], although the latter is not consistent in all trials
[65]. However, it must be noted that such increases in
systemic hormones do not appear to be associated with
increased muscle protein synthesis [6669] or long-term
hypertrophic adaptations [70]. West and Phillips [69]
reported an increase in myofibrillar protein synthesis
(*78 %) in response to a resistance exercise protocol
(unilateral elbow flexion), independent of any changes in
the systemic levels of GH, IGF-1 and testosterone, respec-
tively. Also, Mitchell et al. [70] found 16 weeks (four
sessions per week) of resistance training to significantly
increase muscle fibre CSA of the vastus lateralis (*20 %)
as well as leg press strength (*61 %), without any asso-
ciated increases in GH, free testosterone and IGF-1.
Conversely, mechanical tension-induced localised
hormones may in fact contribute to such hypertrophic
adaptations. To illustrate, an animal model in which the
IGF-1Ea (systemic form) receptor was knocked out dem-
onstrated that animals were still able to undergo muscle
hypertrophy [37]. This could be attributable to the pro-
duction of the localised IGF-1 isoform, IGF-1Ec, better
known as mechano-growth factor (MGF), which is
Mechanisms of Blood-Flow Restricted Resistance Exercise-Induced Hypertrophy
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believed to be principally responsible for the hypertrophic
effects with resistance training, as opposed to the systemic
forms of IGF-1 (IGF-1Ea and IGF-1Eb) [21,71]. Although
each of these isoforms is expressed in muscle tissue [72],
only IGF-1Ec appears to be locally activated by mechani-
cal stimuli and cellular damage [73,74]. Because of its
rapid expression following mechanical loading, MGF is
thought to help ‘kick start’ the post-exercise hypertrophic
response and facilitate local repair of damaged tissue [75].
MGF gene expression is thought to carry out signalling
through multiple anabolic cascades including mTOR [76],
mitogen-activated protein kinase (MAPK) [77], and vari-
ous calcium-dependent pathways [78], thereby directly
mediating muscle protein synthesis. In addition, MGF
could also induce muscle growth through satellite cell
activation, proliferation, and differentiation [79,80],
highlighting its utility in autocrine and paracrine actions.
However, the extent to which these mechanical tension-
induced localised factors exist following resistance exercise
with BFR and contribute to the hypertrophic adaptations
seen with BFR resistance training is yet to be elucidated.
5.4 Cell Swelling
One of the more novel mechanisms involved in the
hypertrophic adaptations of BFR resistance exercise has
been reported to be the increase in intracellular hydration, a
phenomenon known as ‘cell swelling’. Previously, it has
been reported that hydration-mediated cell swelling results
in an increase in protein synthesis and a decrease in pro-
teolysis in a variety of different cell types, including
hepatocytes, osteocytes, breast cells and muscle fibres [81].
Increased accumulation of metabolites via BFR creates a
pressure gradient favouring the flow of blood into the muscle
fibres (intracellular space). The resulting enhanced reperfu-
sion and subsequent intracellular swelling is believed to
threaten the structural integrity of the cell membrane [26],
which causes the cell to initiate a signalling response that
chronically leads to a reinforcement of its ultrastructure [32,
82]. There is evidence that signalling is carried out via
integrin-associated volume osmosensors within cells [83].
The sensors, in turn, activate anabolic protein kinase trans-
duction pathways, possibly mediated by autocrine effects of
growth factors [84,85]. Research indicates that anabolic
functions are carried out in an mTOR-independent fashion
[86], with MAPK modules being the primary mediator of
swelling-induced anabolism [87,88], although it has been
reported that cell swelling could also induce muscle growth
through the proliferation and fusion of satellite cells [89].
However, Gundermann et al. [90] recently reported no sig-
nificant increases in muscle protein synthesis following a
simulation of the reactive hyperaemia response via a phar-
macological vasodilator, suggesting that reperfusion may
not be responsible for the hypertrophic adaptations of BFR
resistance exercise.
Research is currently very scarce concerning the
potential contribution of cell swelling to hypertrophic
adaptations and so any definitive statements at this time
would be premature. Also in question is whether cell
swelling is solely mediated by metabolic stress or whether
mechanical tension also plays a part.
5.5 Reactive Oxygen Species
The acute production of ROS by muscles during exercise
[91] is believed to be an important mechanism mediating
post-workout anabolic adaptations [9295]. ROS produc-
tion has been shown to promote growth in both smooth and
cardiac muscle [96], and previous work also suggests that it
may play a role in the hypertrophic effects of BFR resis-
tance training [6,43,97], since hypoxia and subsequent
reperfusion is thought to further heighten the production of
ROS [98,99]. However, evidence supporting its potential
contribution to BFR resistance training-induced hypertro-
phy is conflicting. Although hypoxia and subsequent
reperfusion associated with arterial occlusion has been
shown to increase ROS production [98,99], Takarada et al.
[24] and Goldfarb et al. [29] both reported no significant
increases in markers of ROS (lipid peroxide and protein
carbonyl) following a low-intensity resistance exercise
protocol with BFR. These disparate findings could perhaps
be explained by differences in the applied length of the
BFR stimulus between the studies. Most BFR resistance
exercise protocols last 5–10 min [24,29], and as such may
not elevate ROS levels to the same extent as longer
occlusive stimuli (4 h) [98].
Interestingly, previous work appears to support the
notion that mechanical load is the dominant factor
responsible for the production of ROS, as opposed to
metabolic stress. Goldfarb et al. [29] compared the ROS
responses between volume-matched moderate-intensity
resistance exercise and low-intensity resistance exercise
with BFR and found plasma protein carbonyl levels and
blood glutathione ratio (markers of ROS) to be signifi-
cantly greater following the moderate-intensity resistance
exercise protocol, suggesting that mechanical tension plays
the dominant role in generating ROS. Hence, it is perhaps
not surprising that previous studies utilising BFR resistance
exercise protocols have reported no significant increases in
ROS [24,29], as these typically involve low levels of
mechanical tension (*20 % 1RM) and thus work.
5.6 Nitric Oxide
A particular variant of ROS that has been linked to com-
pensatory muscle hypertrophy is NO, an important cellular
S. J. Pearson, S. R. Hussain
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signalling molecule produced constitutively at high levels
in muscle by neuronal nitric oxide synthase (NOS)-1 [100
102]. Previous research indicates that NO can stimulate
satellite cell activation and proliferation [103], possibly via
synthesis of hepatocyte growth factor [42]. Interestingly,
NO production has also been shown to directly mediate
protein synthesis through the activation of the transient
receptor potential cation channel, subfamily V, member 1
(TRPV1) within the sarcoplasmic reticulum via peroxyni-
trite-dependent mechanisms, resulting in mTOR activation
and subsequent protein synthesis [104].
NO production appears to be primarily increased in
response to high mechanical tension [105], and so, it seems
unlikely that NO would play a part in BFR resistance
training-induced hypertrophy given its low-intensity nat-
ure. However, there is evidence suggesting a potential
increase in NO production with a BFR resistance exercise
protocol. A number of studies have reported low-intensity
BFR resistance exercise to increase conduit-artery maximal
dilation [106,107], which itself is dependent on NO pro-
duction [108]. In fact, the contribution of NO to conduit-
artery vasodilation is enhanced under ischemic/hypoxic
conditions compared with normoxic conditions [109,110],
augmenting the up-regulation of endothelial NOS (eNOS).
This, combined with the protective effects of ischemic
preconditioning [111,112] has been shown to contribute to
an increase in NO bioavailability [113]. In addition,
Kawada and Ishii [27] have also reported an increased
expression of NOS-1 following 2 weeks of chronic occlu-
sion in an animal model. Thus, NO production may in fact
be evident with BFR resistance exercise, which could
potentially contribute to hypertrophic effects via autocrine
[104] and/or paracrine [105] actions.
5.7 Heat Shock Proteins
ROS may also indirectly influence anabolism by mediating
transcription of highly conserved stress proteins called heat
shock proteins (HSPs). Under normal physiological condi-
tions, HSPs act as chaperones, aiding in the assembly and
translocation of proteins [114], but when the body is sub-
jected to stress, they are thought to play a role in modulating
the effects of the stress to maintain cellular homeostasis (i.e.
limiting oxidative damage caused by ROS production)
[115]. It should be noted that, in addition to ROS-mediated
transcription, HSPs are also induced by heat, hypoxia,
acidosis, and ischemia–reperfusion [116], which may sug-
gest that metabolic stress can also regulate HSP activity,
similarly to mechanical tension-induced ROS.
Kawada and Ishii [27] first reported that HSP72 was
significantly elevated in the plantaris muscle of rats fol-
lowing 2 weeks of exercise with BFR. These findings were
associated with a significant increase in muscle
hypertrophy, suggesting that HSPs may contribute to the
hypertrophic adaptations of BFR resistance exercise.
However, Fry et al. [62] reported no significant increases in
HSP70 content following a low-intensity (20 % 1RM)
resistance exercise protocol with BFR (200 mmHg). These
conflicting data could perhaps be accounted for by the
different HSPs examined. It is possible that only certain
HSPs (HSP72) are increased with BFR exercise, whereas
others are not (HSP70), and, as such, only specific HSPs
may play a role in hypertrophy. Further research is clearly
required on varying HSPs to identify the specific HSP
isoforms that may have an important post-exercise anabolic
role.
5.8 Fibre Recruitment
The increased recruitment of type II muscle fibres with
BFR resistance exercise has been proposed to be a critical
factor responsible for the potent hypertrophic effects [21,
117]. According to the size principle for neuromotor con-
trol [1], fast-twitch muscle fibres are only recruited at
higher exercise intensities. However, BFR resistance
training research has demonstrated that recruitment of fast-
twitch muscle fibres is possible even at very low intensities,
likely due to the inadequate oxygen supply for slow-twitch
fibres and high metabolite accumulation [22,117,118].
Both reduced oxygen and metabolite accumulation can
increase fibre recruitment, mechanistically speaking,
through the stimulation of group III and IV afferents, which
may cause inhibition of the alpha motorneuron, resulting in
an increased fibre recruitment to maintain muscular force
and protect against conduction failure [21,119]. This is
also supported by many reports in the literature showing
higher motor unit recruitment/firing frequency and activa-
tion of fast-twitch muscle fibres via electromyography
(EMG) during low-intensity BFR resistance exercise, rel-
ative to the same exercise protocol without BFR [6,7,21
23]. Indeed, such increased electrical activity could stim-
ulate muscle protein synthesis via the transcriptional ca
2?
/
calmodulin—phosphatase calcineurin and/or the ca
2?
/cal-
modulin-dependant kinase pathways [120].
However, increased recruitment of fast-twitch muscle
fibres may not always be observed with BFR resistance
exercise, since Wernbom et al. [97] and Kacin and Strazar
[121] both reported similar levels of quadriceps EMG
activity during low-intensity knee extension exercise with
and without BFR. It is also important to note that BFR
resistance exercise does not necessarily recruit as many
fast-twitch muscle fibres as high-intensity resistance exer-
cise [17,28,30], which may suggest that mechanical ten-
sion plays a greater role than metabolic stress in mediating
fast-twitch fibre recruitment. However, taken together, it
would seem that increased fast-twitch fibre recruitment is
Mechanisms of Blood-Flow Restricted Resistance Exercise-Induced Hypertrophy
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responsible for at least some of the hypertrophic adapta-
tions seen with BFR resistance training.
6 Autocrine/Paracrine Actions
Muscle growth is ultimately brought about by autocrine
(i.e. stimulation of protein synthesis through an increase in
anabolic and/or decrease in catabolic signalling pathways)
and/or paracrine (i.e. increased satellite cell activation,
proliferation, and fusion) actions. The two primary mech-
anisms are thought to act on their associated secondary
mechanisms that subsequently stimulate protein synthesis
(autocrine) and/or satellite cell activity (paracrine), for the
induction of muscle hypertrophy. The following sections
discuss the potential autocrine and paracrine mechanisms
involved in BFR resistance training-induced hypertrophy.
6.1 Autocrine: Protein Synthesis
6.1.1 IGF-1/PI3K/Akt/mTOR Signalling Pathway
The IGF-1/PI3K/Akt signalling pathway plays a key role in
the regulation of muscle mass [44,122,123], and promotes
muscle hypertrophy by stimulating overall protein synthesis
and suppressing proteolysis. In skeletal muscle, activation
of Akt by IGF-1 stimulates protein translation through the
induction of mTOR, which is involved in the regulation of
messenger RNA (mRNA) translation initiation and has been
reported to play a significant role in exercise-induced
muscle protein synthesis and training-induced hypertrophy
[44,45,124,125]. Low-intensity (20 % 1RM) resistance
exercise with BFR (200 mmHg) has also been shown to
stimulate the mTOR signalling pathway via its associated
downstream effectors (ribosomal S6 kinase 1 [S6K1] and
ribosomal protein S6 [rpS6] phosphorylation) [11,62],
highlighting its potential contribution to the potent effects
of BFR resistance training. In addition, the enhanced mTOR
signalling to S6K1 also inhibits the activity of eukaryotic
translation elongation factor 2 (eEF2) kinase, which sig-
nificantly reduces eEF2 phosphorylation [11] and thus
promotes translation initiation and elongation [126].
6.1.2 Myostatin Smad2/3 Signalling Pathway
Myostatin is a member of the transforming growth factor
(TGF)-bsuper-family that negatively regulates muscle
growth [127132] via the Smad2/3 phosphorylation-
induced inhibition of myoblast and myotube differentiation
[133136].
Theoretically, any potential decrease in myostatin
expression would indicate an increased signalling in favour
of muscle hypertrophy. Previous research has also shown
the expression of myostatin to be diminished in response to
BFR resistance exercise, highlighting its potential contri-
bution to training-induced effects [27,137,138]. More-
over, previous research has also demonstrated that
decreased myostatin expression following 8 weeks of
resistance exercise with BFR (20 % 1RM at 95 mmHg) is
concomitant with increased muscle mass and strength (6.3
and 40 %) [138], thus emphasising the inhibitory role of
myostatin in BFR resistance training-induced hypertrophy.
The specific mode of action by which myostatin is
decreased with BFR resistance exercise may be attributable
to the increased activation of mTOR, which has been
shown to play an important role in regulating myostatin’s
inhibition of muscle growth [136]. However, increased
mTOR activation may not be the only factor blunting
myostatin-induced effects, as previous research has dem-
onstrated that blocking mTOR activity does not fully pre-
vent the increases in protein synthesis and hypertrophy
phenotype associated with myostatin inhibition [139,140].
Thus, other factors may also coexist with respect to
inhibiting myostatin and promoting muscle growth. One
such factor may be JunB transcription, which has also been
associated with myostatin inhibition [141], but no research
yet exists with respect to its potential activation with BFR
resistance exercise.
6.1.3 FOXO Transcription Factors
One downstream target of the PI3K/Akt pathway is the
Forkhead box O (FOXO) class of transcription factors,
which interestingly enough has contrasting effects to the
PI3K/Akt/mTOR pathway. Activation of the FOXO tran-
scription factors has been shown to be associated with
muscle wasting and the induction of muscle atrophy [142
144]. However, in growing muscles, FOXO transcription
factors are maintained in an inactive state by phosphory-
lation via the PI3K/Akt signalling cascade [142]. In con-
trast, during atrophic conditions, the activity of the PI3K/
Akt signalling pathway decreases, causing dephosphoryl-
ation of FOXO transcription factors and subsequent stim-
ulation of muscle protein breakdown [145], via the
ubiquitin–proteasome [142,143] and autophagic/lysosomal
pathways [146,147] (see next sections). Based on these
considerations, it appears that a suppression of FOXO
transcription would in fact promote anabolism. The ability
of the PI3K/Akt pathway to suppress the activation of
FOXO transcription factors may therefore present another
mechanism by which BFR resistance exercise induces
hypertrophic adaptations. In other words, the Akt-induced
activation of mTOR and its associated downstream targets
may stimulate muscle protein synthesis, while the phos-
phorylation of FOXO transcription factors by Akt leave
them inactive in the cytosol. Together, these changes may
S. J. Pearson, S. R. Hussain
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lead to a positive muscle protein balance and ultimately
muscle hypertrophy.
6.1.4 Ubiquitin–Proteasome Pathway
One mechanism by which FOXO transcription factors
negatively regulate muscle growth is through activation of
the ubiquitin–proteasome pathway [142,143,148,149]. In
particular, muscle RING finger-containing protein 1
(MuRF1) and muscle atrophy Fbox protein (MAFbx) are
genes that encode for E3 ubiquitin ligases [150,151].
Empirical evidence supporting their prominent catabolic
roles is provided by Bodine et al. [150], who showed under
atrophic conditions that mice null for either gene (MuRF1
or MAFbx) exhibit a resistance to muscle mass loss com-
pared with wild-type controls, respectively.
MuRF1 induces muscle atrophy, at least in part, by
directly ubiquitinating the thick filament of the sarcomere
and causing the proteolysis of myosin proteins [152,153],
whereas MAFbx down-regulates protein synthesis via the
ubiquitination of eIF3-f, a protein initiation factor [154].
Although no research currently exists with respect to the
potential contribution of MuRF1 and MAFbx to BFR
resistance training-induced hypertrophy, it is likely that any
inhibition or decreased expression of these genes also plays
some part in promoting hypertrophic adaptations. Interest-
ingly, previous research has also shown that MuRF1 and
MAFbx transcription can be at least partially inhibited by
the activation of mTOR [155,156], which has convincingly
been shown to significantly increase in response to resis-
tance exercise with BFR [11,62]. It has been reported that
mTOR activation blocks MuRF1 and MAFbx activity by
inhibiting glucocorticoid activity [156], which is thought to
synergise with FOXO transcription factors for the induction
of these E3 ubiquitin ligases [157,158]. Thus, it could
perhaps be speculated that the increased activation of
mTOR with BFR resistance exercise also inhibits MuRF1
and MAFbx activity to some degree, thereby promoting an
increased signalling in favour of muscle hypertrophy.
6.1.5 Autophagic/Lysosomal Pathway
The other mechanism by which FOXO transcription factors
induce muscle atrophy is via the autophagic/lysosomal
system, which is independent of the ubiquitin–proteasome
pathway [146,147]. FOXO3 transcription, in particular,
has been shown to stimulate autophagy in skeletal muscle
for protein breakdown and atrophy [146] via a set of
autophagy-related genes, including microtubule-associated
protein 1 light chain 3 (LC3) and BCL2/adenovirus E1B
19-kDa interacting protein 3 (BNIP3) [146,147]. FOXO3-
induced LC3 up-regulation alone is not considered to be
sufficient for triggering muscle autophagy [159,160], but
BNIP3 expression may, in fact, contribute to such muscle
autophagic effects and act as a key mediator of FOXO3-
induced atrophy [146,161].
No information currently exists with regards to the
potential role of the autophagic/lysosomal system in BFR
resistance training-induced hypertrophy. However, it could
perhaps be speculated once again that the potential acti-
vation of Akt/P13K in response to BFR resistance exercise
would inhibit FOXO transcription to some extent [142],
which in turn may blunt the BNIP3 response for muscle
autophagy, ultimately increasing the potential for hyper-
trophy. This is indeed an attractive area for future research.
6.2 Paracrine: Satellite Cell Activity
Satellite cells are muscle-specific stem cells located under
the basal lamina of muscle fibres and that are responsible for
muscle regeneration [162]. They also contribute to the
increase in the number of myonuclei during postnatal
muscle growth [162] and compensatory muscle hypertrophy
[163] by proliferating and fusing with the existing myofi-
bres. Following EIMD, satellite cells undergo rapid prolif-
eration, leading to subsequent muscle growth and
remodelling. Multiple signals appear to trigger this activa-
tion, including the generation of sphingosine-1-phosphate
in the inner side of the plasma membrane of the satellite
cell, as well as NO production, which stimulates satellite
cell activation, via increased activation of matrix metallo-
proteinases, ultimately leading to the release of hepatocyte
growth factor from the extracellular matrix [42].
It seems unlikely that satellite cell mechanisms of muscle
growth would be activated to a significant degree with BFR
resistance exercise considering its low mechanical tension
and minimal muscle damage-inducing nature [49]. How-
ever, interestingly, increases in satellite cell proliferation
have been demonstrated in response to acute BFR resistance
exercise in association with increased muscle protein syn-
thesis [122] as well as chronic BFR resistance exercise
concomitant with muscle hypertrophy [164], thus present-
ing a novel paracrine mechanism by which BFR resistance
training mediates muscle growth. In addition, the coexisting
increase in muscle protein synthesis with satellite cell
activity [122] may lend some support to the notion that there
is a synergism between autocrine and paracrine mecha-
nisms that ultimately contributes to the hypertrophic adap-
tations of BFR resistance training.
7 Conclusions
A growing body of research has demonstrated the robust
hypertrophic effects of resistance training with BFR, which
can produce positive training adaptations at intensities
Mechanisms of Blood-Flow Restricted Resistance Exercise-Induced Hypertrophy
123
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lower than previously believed (\50 % 1RM). Although
the use of BFR resistance exercise is indeed intriguing and
effective, the mechanisms underpinning the hypertrophic
adaptations are yet to be fully determined. It has been
suggested that increased levels of metabolic stress is the
primary driving stimulus in this process, which is theorised
to activate a number of other mechanisms (i.e. systemic
hormone production, increased fast-twitch fibre recruit-
ment), all of which are thought to mediate muscle growth
via autocrine and/or paracrine actions. However, the extent
to which these mechanisms are activated with metabolic
stress is unclear. In fact, previous research suggests that
some of these mechanisms are more mediated by
mechanical tension (another primary impetus of muscle
growth) rather than metabolic stress, which perhaps ques-
tions their level of contribution in BFR resistance training-
induced hypertrophy given its low-intensity nature.
Despite the low level of mechanical tension associated
with BFR resistance training, both mechanical tension and
metabolic stress are primary factors of muscle hypertrophy,
so it seems reasonable to conclude that both of these would
synergistically contribute to the hypertrophic adaptations of
BFR resistance training, with metabolic stress playing the
dominant role. Both factors may mediate muscle hyper-
trophy through a combination of mechanisms as outlined
above, all of which are thought to stimulate muscle protein
synthesis by modulating signalling pathways in favour of
muscle hypertrophy and/or increase satellite cell activation
and proliferation. However, specific identification of the
mechanisms most associated with the primary factors, as
well as the particular extent of activation of each of the
mechanisms by the primary factors requires further inves-
tigation. A complication with attributing causal description
is that mechanical tension and metabolic stress occur in
tandem, making it difficult to determine the relative
involvement of each of them. This can potentially result in
misinterpretation of the mechanisms thought to be associ-
ated with metabolic stress when in fact they are more
mediated by mechanical tension, or vice versa.
A better understanding of the above mechanisms will
lead to the development of optimal training programmes
that maximise morphological adaptations. These approa-
ches can then be applied in many clinical, rehabilitation,
and athletic settings.
Acknowledgments No funding was provided in the preparation of
this review, and the authors have no conflicts of interest that are
directly relevant to the contents of the review.
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  • ... The main mechanisms responsible for the adaptive responses associated with training under BFR conditions include increased mechanical tension and elevated metabolic stress compared with traditional resistance training (1). Resistance training under BFR conditions leads to increased metabolic stress (34,46), cell swelling (21), enhanced intramuscular signaling (16,27), increased recruitment of fast twitch muscle fibers (26,45), and enhanced responses of the endocrine system (38,42). Furthermore, the hyperemia experienced after occlusion may play a significant role in nitric oxide production (39), increased phosphocreatine resynthesis, altered oxy-deoxyhemoglobin kinetics (3), and increased oxygen uptake (2). ...
    Article
    Wilk, M, Krzysztofik, M, Filip, A, Zajac, A, Bogdanis, GC, and Lockie, RG. Short-term blood flow restriction increases power output and bar velocity during the bench press. J Strength Cond Res XX(X): 000–000, 2020—This study examined the effect of blood flow restriction (BFR) with 2 different types of cuffs on peak power output (PP), mean power output (MP), peak bar velocity (PV), and mean bar velocity (MV) in the bench press exercise (BP). Fourteen healthy strength-trained male athletes (age = 27.6 ± 3.5 years; body mass = 84.1 ± 8.0 kg; height = 175.8 ± 6.7 cm; BP 1 repetition maximum [RM] = 138.6 ± 17.8 kg) performed 3 different testing protocols as follows: without BFR (NO-BFR), BFR with a narrow cuff (BFRNARROW), and BFR with a wide cuff (BFRWIDE) in a randomized crossover design. During all sessions, subjects performed one set of 3 repetitions of the BP exercise using 70% 1RM. Cuff pressure was set to approximately 90% full arterial occlusion pressure of the upper limb at rest. Analyses of variance showed an increase in PP (by 21%, p < 0.01; effect size [ES] = 1.67), MP (by 16%, p < 0.01; ES = 0.93), PV (by 22%, p < 0.01; ES = 1.79), and MV (by 21%, p < 0.01; ES = 1.36) during BFRWIDE compared with NO-BFR and a significant increase in PP (by 15%, p < 0.01; ES = 1.07), MP (by 17%, p < 0.01; ES = 0.78), PV (by 18%, p < 0.01; ES = 1.65), and MV (by 13% p < 0.01; ES = 1.00) during BFRWIDE compared with BFRNARROW. There were no significant differences in any of the variable between NO-BFR and BFRNARROW. The results of the study indicate that short-term BFR training increases power output and bar velocity during the BP exercise. However, only BFRWIDE significantly influenced bar velocity and power output, which indicates that the width of the cuff is a critical factor determining acute exercise adaptation during BFR resistance training.
  • ... Die bisherige Forschung auf diesem Gebiet zeigt, dass ein Training unter diesen Bedingungen -selbst bei niedrigen Intensitäten (NI) (20-30% der Maximalkraft) -zu vergleichbaren Muskelquerschnittsanpassungen wie ein konventionelles hoch-intensives (HI) Krafttraining führen kann [18,19]. Als potenzielle physiologische Mechanismen, welche die beobachteten Hypertrophieeffekte des NI-BFR Trainings erklären könnten, werden mehrere Faktoren wie eine metabolische Akkumulation, erhöhte Typ-II Faser-Rekrutierung, Zellschwellung sowie eine veränderte Hormonreaktionen diskutiert [20,21]. Obwohl die derzeitige Evidenzlage der muskulären Adaptationen auf das BFR Training bei jungen und gesunden Personen gut zu sein scheint [22], ist der Transfer dieser Trainingsmethode in die klinische Praxis noch unzureichend beschrieben. ...
    Zusammenfassung Die medizinische und sportwissenschaftliche Forschung der letzten Jahre konnte zeigen, dass ein niedrig-intensives (20-30% des Einwiederholungsmaximums, 1RM) Krafttraining (NI) mit gleichzeitiger Blutflussrestriktion (engl.: Blood Flow Restriction, BFR) ähnliche muskuläre Adaptionen hervorruft wie ein konventionelles hoch-intensives Krafttraining (70-85% 1RM). Obwohl die positiven Effekte dieser neuen Trainingsmethode für junge und gesunde Probanden nachgewiesen sind, sind deren Auswirkungen in der Rehabilitation bisher nur unzureichend beschrieben. Das Ziel des vorliegenden PRISMA-konformen Reviews war es die Effekte von NI-BFR Training auf die Muskelstruktur und -funktion bei Patienten mit Rekonstruktion des vorderen Kreuzbandes (VKB) und Kniearthrose systematisch zu untersuchen. Von N = 5213 Artikeln wurden insgesamt N = 9 Studien identifiziert und einem Qualitätsassessment mittels PEDro-Skala unterzogen. Die Ergebnisse zeigen, dass das NI-BFR Training eine effektive Methode in der Rehabilitation darstellt, um den funktionellen Outcome (Muskelkraft und -funktion) zu verbessern und mit niedriger Gewichtsbelastung den Rehabilitationsprozess zu optimieren. Hierbei sind sowohl bei VKB Rupturen als auch bei Patienten mit Kniearthrose funktionelle und strukturelle Effekte im Sinne einer verbesserten Muskelkraft und -funktion sowie einer verringerten Muskelatrophie zu beobachten. Aufgrund der geringen Anzahl an Studien, sind weitere Forschungsarbeiten notwendig, um die Evidenz im klinischen Kontext zu stärken. Hierbei ist insbesondere eine bessere Standardisierung wichtig, um die Vergleichbarkeit von Studien gewährleisten zu können.
  • ... Besides, strength adaptations were believed to be maximized with heavy-load training, and hypertrophy and strength gains observed with low-load training may not be as great as those achieved with heavy-load training (41). However, the usage of low-intensity resistance exercise with blood flow restriction (BFR) has challenged this theory and consistently presented that hypertrophic adaptations can be induced with much lower load (,50% 1RM) (14,38). Blood flow restriction is achieved through the application of external pressure over the proximal portion of the upper or lower extremities. ...
    Article
    Effects of blood flow restriction training on muscle strength and architecture. J Strength Cond Res XX(X): 000-000, 2020-The aim of this study was to compare the effect of the traditional resistance (RES) training and low-intensity resistance training with blood flow restriction (BFR) protocols on quadriceps and hamstring muscle strength, and rectus femoris (RF) and vastus lateralis architecture, in youth team soccer players. Twenty-three young trained soccer team players were divided into 2 groups: the RES group that practiced traditional high-intensity resistance training (80% 1 repetition maximum [1RM], 4 sets, 12 rep.) (n = 12) and the BFR group that performed low-intensity resistance exercise with BFR (30% 1RM, 4 sets, 30-15-15-15 rep) (n = 11)-unilateral knee extension exercise-twice a week for 6 weeks. Muscle strength (isokinetic concentric peak torque of the quadriceps and hamstring muscles) and ultrasonographic parameters (muscle thickness, pennation angle, and fascicle length) were assessed. Bilateral knee flexor and extensor strength was increased in both groups compared with pre-exercise. The increase in dominant side extensor muscle strength (60°·s p = 0.02, ηp = 0.256, 180°·s p = 0.019, ηp = 0.271) and RF thickness (p = 0.002, ηp = 0.361) was statistically higher in the BFR group than in the RES group. These findings support that occlusion training can provide better benefits than traditional strength training to improve muscle hypertrophy. In addition, the novelty of our study is that BFR training may affect the muscle structure measured by ultrasonography.
  • ... The sample size was calculated in 30 subjects(15 hypertensive and 15 normotensive), considering a mean standard deviation of the main outcome variables of ten units, with a statistical power of 80%, a significance level of 0.05 (two-tailed distribution), a detectable difference between treatment of 10.6 units. Considering the strict exclusion criteria related to missing the training sessions (missing no more than three consecutive sessions or five sessions during the six months of intervention), the initial sample consisted of 50 women (25 hypertensive and 25 normotensive). ...
    Article
    Full-text available
    Background Although the positive effects of resistance training (RT) on strength and functional capacity have been well evidenced in the scientific literature, the effects of RT on blood pressure and the relationship of these responses with performance improvement are not yet well established. Objective This study aimed to analyze the effects of three and six months of RT on the hemodynamic parameters and functional capacity of hypertensive and normotensive women. Method Sixteen hypertensive and 15 normotensive elderly women participated in a RT protocol designed to increase muscle strength and hypertrophy, lasting six months, twice a week. Results Systolic blood pressure (SBP) had a reduction at six months only in hypertensive patients, while diastolic blood pressure (DBP) decreased at six months of intervention in both groups (p < 0.05). SBP showed differences between the groups in the pretest (p < 0.05), but not at three and six months of intervention (p > 0.05). Heart rate (HR) was reduced at three months in hypertensive patients, and at six months in the normotensive (p < 0.05). The strength and functional mobility of both hypertensive and normotensive individuals significantly increased at three and six months of intervention (p < 0.05). Hypertensive women showed increased strength at all moments, while normotensive ones showed improvement only at six months. Conclusion Moderate to high intensity RT improves the hemodynamic parameters of hypertensive and normotensive women differently, and independently of strength gain and functional capacity improvement.
  • Article
    PurposeBlood flow restriction (BFR) is an innovation in fitness to train muscles with low loads at low oxygen levels. Low-level laser therapy (LLLT) is a bio-energetic approach to alleviate muscle fatigue during resistance training. This study investigated the immediate effect of LLLT pre-conditioning on BFR that accelerates muscle fatigue due to ischemia.Methods Fifteen young adults participated in this study of a crossover randomized design. They completed a low-load contraction with various pre-conditioning (blood flow restriction with low-level laser therapy (LLLT + BFR), blood flow restriction with sham low-level laser therapy (BFR), and control). Force fluctuation dynamics, muscle oxygen saturation of hemoglobin and myoglobin (SmO2), and discharge patterns of motor units (MU) were compared.ResultsNormalized SmO2 during low-load contractions significantly varied with the pre-contraction protocols (Control (83.6 ± 3.0%) > LLLT + BFR (70.3 ± 2.8%) > BFR (55.4 ± 2.4%). Also, force fluctuations and MU discharge varied with the pre-contraction protocols. Multi-scale entropy and mean frequency of force fluctuations were greater in the LLLT + BFR condition (31.95 ± 0.67) than in the BFR condition (29.47 ± 0.73). The mean inter-spike interval of MUs was greater in the LLLT + BFR condition (53.32 ± 2.70 ms) than in the BFR condition (45.04 ± 1.08 ms). In particular, MUs with higher recruitment thresholds exhibited greater LLLT-related discharge complexity (LLLT + BFR (0.201 ± 0.012) > BFR (0.154 ± 0.006)).ConclusionsLLLT pre-conditioning can minimize the BFR-related decline in muscle oxygen saturation, leading to force gradation and MU discharge in a cost-effective and complex manner.
  • Article
    Full-text available
    98 * ‫ﻣﮑﺎﺗﺒﻪ:‬ ‫آدرس‬ ‫اردﺑﯿﻞ‬ ‫اردﺑﯿﻠﯽ،‬ ‫ﻣﺤﻘﻖ‬ ‫داﻧﺸﮕﺎه‬ ‫ورزﺷﯽ،‬ ‫ﻋﻠﻮم‬ ‫و‬ ‫ﺑﺪﻧﯽ‬ ‫ﺗﺮﺑﯿﺖ‬ ‫ﮔﺮوه‬ ‫اﯾﺮان‬ ،. ‫ﭘﺴﺖ‬ ‫اﻟﮑﺘﺮوﻧﯿﮏ:‬ l_bilboli@uma.ac.ir ‫ﺗ‬ ‫ﺎ‬ ‫ﺛﯿﺮ‬ ‫ﺣﺎد‬ ‫ﺟﺮﯾﺎن‬ ‫ﻣﺤﺪودﯾﺖ‬ ‫ﺑﺎ‬ ‫ﻣﻘﺎوﻣﺘﯽ‬ ‫ﺗﻤﺮﯾﻦ‬ ‫ﻋﺎﻣﻞ‬ ‫رﺷﺪ،‬ ‫ﻫﻮرﻣﻮن‬ ‫ﺑﺮ‬ ‫ﺗﻨﺎوﺑﯽ‬ ‫و‬ ‫ﺗﺪاوﻣﯽ‬ ‫ﺧﻮن‬ ‫ﺷﺒﻪ‬ ‫اﻧﺴﻮﻟﯿﻨﯽ‬-1 ‫ﻻﮐﺘﺎت‬ ‫و‬ ‫ﻏﯿﺮورزﺷﮑﺎر‬ ‫ﺟﻮان‬ ‫ﻣﺮدان‬ ‫در‬ ‫ﮐﻼﻧﺘ‬ ‫ﺣﺴﻨﻌﻠﯽ‬ ‫ﺮ‬ ‫ي‬ 1 ، ‫ﺑﻠﺒ‬ ‫ﻟﻄﻔﻌﻠﯽ‬ ‫ﻠ‬ ‫ﯽ‬ 2 * ، ‫ﺳﯿﺎﻫﮑﻮﻫﯿﺎن‬ ‫ﻣﻌﺮﻓﺖ‬ 3 1-‫ورزﺷ‬ ‫ﻓﯿﺰﯾﻮﻟﻮژي‬ ‫دﮐﺘﺮي‬ ‫داﻧﺸﺠﻮي‬ ‫ﺗﻨﻔﺲ‬ ‫و‬ ‫ﻋﺮوق‬ ‫و‬ ‫ﻗﻠﺐ‬ ‫ﯽ‬ ‫اردﺑﯿﻠﯽ‬ ‫ﻣﺤﻘﻖ‬ ‫داﻧﺸﮕﺎه‬ ‫ورزﺷﯽ،‬ ‫ﻋﻠﻮم‬ ‫و‬ ‫ﺑﺪﻧﯽ‬ ‫ﺗﺮﺑﯿﺖ‬ ‫ﮔﺮوه‬ ، ‫اردﺑﯿﻞ‬ ، ‫اﯾﺮا‬ ، ‫ن‬ 2-‫داﻧﺸﯿ‬ ‫ورزﺷ‬ ‫ﻓﯿﺰﯾﻮﻟﻮژي‬ ‫ﺎر‬ ‫ﯽ‬ ‫اردﺑﯿﻞ‬ ‫اردﺑﯿﻠﯽ،‬ ‫ﻣﺤﻘﻖ‬ ‫داﻧﺸﮕﺎه‬ ‫ورزﺷﯽ،‬ ‫ﻋﻠﻮم‬ ‫و‬ ‫ﺑﺪﻧﯽ‬ ‫ﺗﺮﺑﯿﺖ‬ ‫ﮔﺮوه‬ ، ‫اﯾﺮان‬ ، 3-‫ورزﺷ‬ ‫ﻓﯿﺰﯾﻮﻟﻮژي‬ ‫اﺳﺘﺎد‬ ‫ﯽ‬ ، ‫اردﺑﯿﻞ‬ ‫اردﺑﯿﻠﯽ،‬ ‫ﻣﺤﻘﻖ‬ ‫داﻧﺸﮕﺎه‬ ‫ورزﺷﯽ،‬ ‫ﻋﻠﻮم‬ ‫و‬ ‫ﺑﺪﻧﯽ‬ ‫ﺗﺮﺑﯿﺖ‬ ‫ﮔﺮوه‬ ‫اﯾﺮان‬ ، ‫دوره‬ / ‫ﯾﺎﻓﺘﻪ‬ ‫ﯾﮑﻢ‬ ‫و‬ ‫ﺑﯿﺴﺖ‬ ‫ﺷﻤﺎره‬ / 4 / ‫ز‬ ‫ﻣﺴﺘﺎن‬ 98 ‫ﻣﺴﻠﺴﻞ‬ / 82 ‫ﻣﻘﺎﻟﻪ:‬ ‫درﯾﺎﻓﺖ‬ 2 / 8 / 98 ‫ﻣﻘﺎﻟﻪ:‬ ‫ﭘﺬﯾﺮش‬ 27 / 9 / 98 ‫ﻣﻘﺪﻣﻪ‬ : ‫ﻣﻘﺎﯾﺴﻪ‬ ‫ﭘﮋوﻫﺶ،‬ ‫اﯾﻦ‬ ‫از‬ ‫ﻫﺪف‬ ‫ﻣﻘﺎوﻣﺘﯽ‬ ‫ﺗﻤﺮﯾﻦ‬ ‫ﻧﻮع‬ ‫ﺳﻪ‬ ‫ﺑﻪ‬ ‫ﻣﺘﺎﺑﻮﻟﯿﮑﯽ‬ ‫و‬ ‫ﻫﻮرﻣﻮﻧﯽ‬ ‫ﻫﺎي‬ ‫ﭘﺎﺳﺦ‬ ‫در‬ ‫ﻏﯿﺮ‬ ‫ﺟﻮان‬ ‫ﻣﺮدان‬ ‫ورزﺷﮑ‬ ‫ﺑﻮد.‬ ‫ﺎر‬ ‫روش‬ ‫و‬ ‫ﻣﻮاد‬ ‫ﻫﺎ:‬ 40 ‫آزﻣﻮدﻧﯽ‬ ‫ﺑﺎ‬ ‫ﻣﯿﺎﻧﮕﯿﻦ‬ ‫ﺳﻨﯽ‬ 50 / 1 ± 56 / 22 ‫ﺳﺎل‬ ‫و‬ ‫ﺗﻮده‬ ‫ﺷﺎﺧﺺ‬ ‫ﺑﺪﻧﯽ‬ 55 / ± 75 / 23 ‫ﻣﺘﺮ‬ ‫ﺑﺮ‬ ‫ﮐﯿﻠﻮﮔﺮم‬ ‫ﻣﺮﺑﻊ‬ ‫ﺑﻪ‬ ‫ﻃﻮر‬ ‫ﮔﺮﻓﺘﻨﺪ‬ ‫ﻗﺮار‬ ‫ﻣﺴﺎوي‬ ‫ﮔﺮوه‬ ‫ﭼﻬﺎر‬ ‫در‬ ‫ﺗﺼﺎدﻓﯽ‬ 1-‫ﻣﻘﺎوﻣﺘﯽ‬ ‫ﺗﻤﺮﯾﻦ‬ ‫ﭘﺎﯾﯿﻦ‬ ‫ﺷﺪت‬) 20 ‫ﺑﯿﺸﯿﻨﻪ‬ ‫ﺗﮑﺮار‬ ‫%ﯾﮏ‬ (‫ﺟ‬ ‫ﻣﺤﺪودﯾﺖ‬ ‫ﺑﺎ‬ ‫ﺧﻮن‬ ‫ﺮﯾﺎن‬ ‫ﺗﺪاوﻣﯽ‬ 2-‫ﻣﻘﺎوﻣﺘﯽ‬ ‫ﺗﻤﺮﯾﻦ‬ ‫ﭘﺎﯾﯿﻦ‬ ‫ﺷﺪت‬) 20 ‫ﺑﯿﺸﯿﻨﻪ‬ ‫ﺗﮑﺮار‬ ‫%ﯾﮏ‬ (‫ﺑﺎ‬ ‫ﺗﻨ‬ ‫ﺧﻮن‬ ‫ﺟﺮﯾﺎن‬ ‫ﻣﺤﺪودﯾﺖ‬ ‫ﺎوﺑﯽ‬ 3-‫ﺗ‬ ‫ﺳﻨﺘﯽ‬ ‫ﻣﻘﺎوﻣﺘﯽ‬ ‫ﻤﺮﯾﻦ‬) 80 ‫ﺑﯿﺸﯿﻨﻪ(‬ ‫ﺗﮑﺮار‬ ‫%ﯾﮏ‬ ‫ﺑﺪون‬ ‫اﻧﺴﺪاد‬ 4-‫ﮐﻨﺘﺮل‬ ‫ﮔﺮوه‬. ‫ﻫﺎ‬ ‫آزﻣﻮدﻧﯽ‬ ‫ﻫﺎﻟﺘﺮ‬ ‫ﺑﺎ‬ ‫ﺑﺎزو‬ ‫ﺟﻠﻮ‬ ‫ﺣﺮﮐﺖ‬ ‫در‬ ‫را‬ 4 ‫ﻧﻮﺑﺖ‬ ‫و‬ ‫ﺧﺴﺘﮕﯽ‬ ‫ﺣﺪ‬ ‫ﺗﺎ‬ ‫ﻓﺎﺻﻠﻪ‬ ‫ﺑﺎ‬ 1 ‫دﻗﯿﻘﻪ‬ ‫ﻫﺎ‬ ‫ﺳﺖ‬ ‫ﺑﯿﻦ‬ ‫اﺳﺘﺮاﺣﺖ‬ ‫دادﻧﺪ‬ ‫اﻧﺠﺎم‬ ‫و‬ ‫ﻗﺒﻞ‬ ‫ﺧﻮﻧﯽ‬ ‫ﮔﯿﺮي‬ ‫ﻧﻤﻮﻧﻪ‬. ‫ﺳﺎﻋﺖ‬ ‫ﯾﮏ‬ ‫ﺟﻠﺴﻪ‬ ‫از‬ ‫ﺑﻌﺪ‬ ‫ﻫ‬ ‫داده‬ ‫ﺗﺤﻠﯿﻞ‬ ‫ﺑﺮاي‬ ‫ﺷﺪ.‬ ‫اﻧﺠﺎم‬ ‫ﺗﻤﺮﯾﻦ‬ ‫آزﻣ‬ ‫از‬ ‫ﺎ‬ ‫ﻮن‬ ‫واﺑﺴﺘﻪ‬ ‫ﺗﯽ‬ ‫ﺗﺤﻠﯿﻞ‬ ‫و‬ ‫ﮔﺮوﻫﯽ(‬ ‫درون‬ ‫ي‬ ‫)ﻣﻘﺎﯾﺴﻪ‬ ‫ﯾﮑﻄﺮﻓﻪ‬ ‫وارﯾﺎﻧﺲ‬ ‫ﺷﺪ‬ ‫اﺳﺘﻔﺎده‬ ‫ﮔﺮوﻫﯽ(‬ ‫ﺑﯿﻦ‬ ‫ي‬ ‫)ﻣﻘﺎﯾﺴﻪ‬) 05 / 0 P≤ .(
  • Chapter
    Obese individuals generally have a reduced muscle strength and mass, which result in an increased risk of disability. In this perspective, strength training represents a good strategy for enhancing function and reducing the obesity-related disability. This chapter aims to provide a general overview on the potential effects of strength training in obese patients. We include a brief description of the strength-related variables that may be useful for practitioners for understanding, planning and structuring resistance training programs appropriate for obese individuals. Given the importance of reducing mechanical stress, leading to increased systolic blood pressure and risk of orthopaedic injuries, recommendations for practitioners in the field are needed. In this chapter we focus on low-intensity, low-velocity resistance training programs which appear to be particularly suited for the obese population.
  • Preprint
    Full-text available
    Hintergrund und Ziel: Während der Rehabilitation von Kniepathologien spielen Muskelschwäche und Muskelabbau, eine große Rolle. Wodurch Krafttraining eine notwendige Maßnahme in der Nachbehandlung von Kniepathologien darstellt. Okklusionstraining (OT) führt bei gesunden Menschen zu einem signifikanten Kraft- und Muskelaufbau und könnte deshalb eine effektive Methode für die Rehabilitation sein. Ziel: Den Effekt von OT nach Kniearthroskopie zu untersuchen. Methodik: Anhand einer systematische Literaturrecherche wurden Studien mittels der Datenbanken PubMed, SURF und PEDro gesucht. Die Studien wurden anhand der PEDro-Skala und des „Quality Assessment Tool for Case Series Studies“ auf ihre Qualität hin bewertet. Ergebnisse: Sechs Studien wurden eingeschlossen. Fünf von sechs Studien zeigten einen positiven Effekt auf die Veränderung von Kraft oder Muskelmasse. Schlussfolgerung: OT hat einen signifikanten Effekt auf Kraft und Muskelmasse. OT kann anderen Interventionen überlegen sein kann. Doch aufgrund der limitierenden Studienlage und Heterogenität der Studien kann keine eindeutige Aussage getroffen werden.
  • Article
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    تمرین مقاومتی و عوامل هایپرتروفی کلانتري و همکاران 57 / یافته، دوره بیست و یکم،زمستان 98 The Acute Effect of Resistance Exercise Training with Continuous and Intermittent Blood Flow Restriction on Growth Hormone, Insulin-Like Factor- 1 and Lactate in Non-Athletic Young Men Kalantari HA1 , Bolboli LA*2, Siahkohian M3 1. PhD Student of Exercise Physiology in the Field of Cardiovascular and Respiration, Department of Physical Education and Sport Sciences, University of Mohaghegh Ardabili, Ardabil, Iran. 2.Associate Professor of Exercise Physiology, Department of PhysicalEducation and Sport Sciences, University of Mohaghegh Ardabili, Ardabil, Iran, l_bilboli@uma.ac.ir 3. Professor of Exercise Physiology, Department of Physical Education and Sport Sciences, University of Mohaghegh Ardabili, Ardabil, Iran. Received: Nov. 25, 2019 Accepted: Dec. 18, 2019 Abstract Background: The aim of this study was to compare hormonal and metabolic responses to three types of resistance exercise trainings in non-athlete young men. Materials and Methods: 40 subjects with the mean age of 22.56 ± 1.50 and the BMI of 23.75 ± 55.5 kg/m2 were randomly divided into four equal groups: (a) low intensity resistance training (20% one repetition maximum) with continuity of blood flow restriction (BFR), (b) low intensity resistance training (20% one repetition maximum) with intermittent BFR, (c) traditional resistance training (80% repetition maximum) with no BFR, and (d) the control group. Subjects performed the barbell curl 4 times until exhaustion and with a 1-minute rest between the sets. Blood sampling was performed before and one hour after the exercise session. Dependent T-Test (intra-group comparison) and One-Way Anova (inter-groups comparison) were used to analyze the data (P≤0.05). Results: The levels of growth hormone and lactate in all three three experimental groups showed a significant increase compared to the baseline (P≤0.001), while insulin-like growth factor was not increased significantly in any of the groups. Inter-group results showed that after a training session, the levels of growth hormone and lactate were not changed significantly between the three experimental groups. Conclusion: It seems that low-intensity resistance exercise trainings and continuous and intermittent blood flow restriction are effective in terms of hormonal and metabolic changes similar to traditional resistance exercise trainings. Key words: blood flow restriction; resistance exercise; hormonal response. *Citation: Kalantari HA, Bolboli LA, Siahkohian M. The Acute Effect of Resistance Exercise Training with Continuous and Intermittent Blood Flow Restriction on Growth Hormone, Insulin-Like Factor-1 and Lactate in Non- Athletic Young Men. Yafte. 2020; 21(4):44-57.
  • Article
    Heavy controlled loads of tendon with prolonged time under tension remains the treatment‐of‐choice in tendinopathy rehabilitation. The use of low‐load resistance exercise (LL, 20‐40% 1RM) in combination with blood flow restriction (BFR) has been advocated as a clinically important rehabilitation tool for persons not tolerating high muscle‐tendon loads. Similar or improved clinical outcomes have been reported after LL‐BFR compared to conventional rehabilitation following various types of knee injury, and also compared to load‐matched, free‐flow exercise. LL‐BFR augments muscular adaptations and is comparably effective for inducing muscle hypertrophy and strength gains compared to heavy‐load resistance training. The present study aimed to investigate the feasibility and effect of LL‐BFR as a rehabilitation tool in individuals with chronic unilateral patellar tendinopathy. The results demonstrated that (i) 3 wks LL‐BFR was well tolerated with moderate‐large pain improvements (Likert), (ii) pain scoring (NRS) was reduced by 50 % during single‐leg decline squat testing, and (iii) tendon vascularity diminished by 31 % following 3 weeks (9 sessions) of LL‐BFR. These novel data demonstrate substantial clinical and structural tendon improvements with short‐term (3 wks) LL‐BFR, which warrant further research into the potential efficacy of LL‐BFR as a clinical rehabilitation tool in patients with chronic tendinopathy.
Literature Review
  • Article
    Pope, ZK, Willardson, JM, and Schoenfeld, BJ. Exercise and blood flow restriction. J Strength Cond Res 27(10): 2914– 2926, 2013—A growing body of research has demonstrated the effectiveness of exercise (low-intensity resistance training , walking, cycling) combined with blood flow restriction (BFR) for increased muscular strength and hypertrophy. The BFR is achieved via the application of external pressure over the proximal portion of the upper or lower extremities. The external pressure applied is sufficient to maintain arterial inflow while occluding venous outflow of blood distal to the occlusion site. With specific reference to low-intensity resistance training, the ability to significantly increase muscle strength and hypertrophy when combined with BFR is different from the traditional paradigm, which suggests that lifting only higher intensity loads increases such characteristics. The purpose of this review was to discuss the relevant literature with regard to the type and magnitude of acute responses and chronic adaptations associated with BFR exercise protocols vs. traditional non-BFR exercise protocols. Furthermore, the mechanisms that stimulate such responses and adaptations will be discussed in the context of neural, endocrine, and metabolic pathways. Finally, recommendations will be discussed for the practitioner in the prescription of exercise with BFR.
  • Article
    Discrepancies exist whether blood flow restriction (BFR) exacerbates exercise-induced muscle damage (EIMD). This study compared low-intensity eccentric contractions of the elbow flexors with and without BFR for changes in indirect markers of muscle damage. Nine untrained young men (18-26 y) performed low-intensity (30% 1RM) eccentric contractions (2-s) of the elbow flexors with one arm assigned to BFR and the other arm without BFR. EIMD markers of maximum voluntary isometric contraction (MVC) torque, range of motion (ROM), upper arm circumference, muscle thickness and muscle soreness were measured before, immediately after, 1, 2, 3, and 4 days after exercise. Electromyography (EMG) amplitude of the biceps brachii and brachioradialis were recorded during exercise. EMG amplitude was not significantly different between arms and did not significantly change from set 1 to set 4 for the biceps brachii but increased for the brachioradialis (p ≤ 0.05, 12.0% to 14.5%) when the conditions were combined. No significant differences in the changes in any variables were found between arms. MVC torque decreased 7% immediately post-exercise (p ≤ 0.05), but no significant changes in ROM, circumference, muscle thickness and muscle soreness were found. These results show that BFR does not affect EIMD by low-intensity eccentric contractions.
  • Article
    Full-text available
    Low-intensity blood-flow restriction (BFR) resistance training significantly increases strength and muscle size, but some studies report it produces exercise-induced muscle damage (EIMD) in the lower body after exercise to failure. To investigate the effects of a pre-set number of repetitions of upper body concentric and eccentric exercise when combined with BFR on changes in EIMD. Ten young men had arms randomly assigned to either concentric BFR (CON-BFR) or eccentric BFR (ECC-BFR) dumbbell curl exercise (30% one-repetition maximum (1-RM), 1 set of 30 repetitions followed by 3 sets of 15 repetitions). Maximal isometric voluntary contraction force (MVC), muscle thickness (MTH), circumference, range of motion (ROM), ratings of perceived exertion (RPE), and muscle soreness were measured before, immediately after, and daily for 4 days post-exercise. MVC decreased by 36% for CON-BFR and 12% for ECC-BFR immediately after exercise but was not changed 1-4 days post-exercise (p > 0.05). Only CON-BFR had significant changes in MTH and circumference immediately after exercise (p < 0.05). Muscle soreness was observed in the ECC-BFR arm at 1 and 2 days after exercise. Low-intensity ECC-BFR produces significant muscle soreness at 24 h but neither ECC-BFR nor CON-BFR exercise produces significant changes in multiple indices of EIMD.
  • Article
    Full-text available
    Abstract The molecular mechanisms underlying skeletal muscle maintenance involve interplay between multiple signaling pathways. Under normal physiological conditions, a network of interconnected signals serves to control and coordinate hypertrophic and atrophic messages, culminating in a delicate balance between muscle protein synthesis and proteolysis. Loss of skeletal muscle mass, termed "atrophy", is a diagnostic feature of cachexia seen in settings of cancer, heart disease, chronic obstructive pulmonary disease, kidney disease, and burns. Cachexia increases the likelihood of death from these already serious diseases. Recent studies have further defined the pathways leading to gain and loss of skeletal muscle as well as the signaling events that induce differentiation and post-injury regeneration, which are also essential for the maintenance of skeletal muscle mass. In this review, we summarize and discuss the relevant recent literature demonstrating these previously undiscovered mediators governing anabolism and catabolism of skeletal muscle.
  • Article
    Full-text available
    To determine relationships between post-exercise changes in systemic [testosterone, growth hormone (GH), insulin like grow factor 1 (IGF-1) and interleukin 6 (IL-6)], or intramuscular [skeletal muscle androgen receptor (AR) protein content and p70S6K phosphorylation status] factors in a moderately-sized cohort of young men exhibiting divergent resistance training-mediated muscle hypertrophy. Twenty three adult males completed 4 sessions•wk(-1) of resistance training for 16 wk. Muscle biopsies were obtained before and after the training period and acutely 1 and 5 h after the first training session. Serum hormones and cytokines were measured immediately, 15, 30 and 60 minutes following the first and last training sessions of the study. Mean fiber area increased by 20% (range: -7 to 80%; P<0.001). Protein content of the AR was unchanged with training (fold change = 1.17 ± 0.61; P=0.19); however, there was a significant correlation between the changes in AR content and fiber area (r=0.60, P=0.023). Phosphorylation of p70S6K was elevated 5 hours following exercise, which was correlated with gains in mean fiber area (r=0.54, P=0.007). There was no relationship between the magnitude of the pre- or post-training exercise-induced changes in free testosterone, GH, or IGF-1 concentration and muscle fiber hypertrophy; however, the magnitude of the post exercise IL-6 response was correlated with muscle hypertrophy (r=0.48, P=0.019). Post-exercise increases in circulating hormones are not related to hypertrophy following training. Exercise-induced changes in IL-6 correlated with hypertrophy, but the mechanism for the role of IL-6 in hypertrophy is not known. Acute increases, in p70S6K phosphorylation and changes in muscle AR protein content correlated with muscle hypertrophy implicating intramuscular rather than systemic processes in mediating hypertrophy.
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    Full-text available
    To investigate hypertrophic signalling after a single bout of low-load resistance exercise with and without blood flow restriction (BFR). Seven subjects performed unilateral knee extensions at 30 % of their one repetition maximum. The subjects performed five sets to failure with BFR on one leg, and then repeated the same amount of work with the other leg without BFR. Biopsies were obtained from m. vastus lateralis before and 1, 24 and 48 h after exercise. At 1-h post-exercise, phosphorylation of p70S6K(Thr389) and p38MAPK(Thr180/Tyr182) was elevated in the BFR leg, but not in the free-flow leg. Phospho-p70S6K(Thr389) was elevated three- to fourfold in both legs at 24-h post-exercise, but back to baseline at 48 h. The number of visible satellite cells (SCs) per muscle fibre was increased for all post-exercise time points and in both legs (33-53 %). The proportion of SCs with cytoplasmic extensions was elevated at 1-h post in the BFR leg and the number of SCs positive for myogenin and/or MyoD was increased at 1- and 24-h post-exercise for both legs combined. Acute low-load resistance exercise with BFR resulted in early (1 h) and late (24 h) enhancement of phospho-p70S6K(Thr389), an early response of p38MAPK, and an increased number of SCs per muscle fibre. Enhanced phospho-p70S6K(Thr389) at 24-h post-exercise and increases in SC numbers were seen also in the free-flow leg. Implications of these findings for the hypertrophic effects of fatiguing low-load resistance exercise with and without BFR are discussed.