SAFETY CONSIDERATIONS WITH BLOOD FLOW RESTRICTED RESISTANCE TRAINING

Abstract

Blood flow restricted resistance (BFRR) training with pneumatic tourniquet has been suggested as an alternative for conventional weight training due to the proven benefits for muscle strength and hypertrophy using relatively low resistance, hence reducing the mechanical stress across a joint. As such, it has become an important part of rehabilitation programs used in either injured or operated athletes. Despite a general consensus on effectiveness of BFRR training for muscle conditioning, there are several uncertainties regarding the interplay of various extrinsic and intrinsic factors on its safety and efficiency, which have been reviewed from a clinical perspective. Among extrinsic factors tourniquet cuff pressure, size and shape have been identified as key for safety and efficiency. Among intrinsic factors, limb anthropometrics, patient history and presence of cardiac, vascular, metabolic or peripheral neurologic conditions have been recognized as most important. Though there are a few potential safety concerns connected to BFRR training, the following have been identified as the most probable and health-hazardous: (a) mechanical injury to the skin, muscle, and peripheral nerves, (b) venous thrombosis due to vascular damage and disturbed hemodynamics and (c) augmented arterial blood pressure responses due to combined high body exertion and increased peripheral vascular resistance. Based on reviewed literature and authors’ personal experience with use of BFRR training in injured athletes, guidelines have been given for its safe application. Also, a comprehensive risk assessment tool for screening of subjects prior to their inclusion in a BFRR training program has been introduced.

Full text

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SAFETY CONSIDERATIONS WITH BLOOD FLOW
RESTRICTED RESISTANCE TRAINING
Alan KACIN1, Benjamin ROSENBLATT2, Tina GRAPAR ŽARGI1, Anita BISWAS2
1 University of Ljubljana, Faculty of Health Sciences, Department of Physiotherapy Ljubljana,
Slovenia
2 English Institute of Sport, Bisham Abbey National Sports Centre, Marlow, SL7 1RR, United
Kingdom
Corresponding author:
Alan KACIN, RPT, PhD
University of Ljubljana, Faculty of Health Sciences, Department of Physiotherapy
Zdravstvena pot 5, 1000 Ljubljana, Slovenia
Phone: +386 1 300 11 43
Skype: alankacin
E-mail: alan.kacin@zf.uni-lj.si
ABSTRACT
Blood ow restricted resistance (BFRR) training with pneumatic tourniquet has
been suggested as an alternative for conventional weight training due to the proven
benets for muscle strength and hypertrophy using relatively low resistance, hence re-
ducing the mechanical stress across a joint. As such, it has become an important part of
rehabilitation programs used in either injured or operated athletes. Despite a general
consensus on effectiveness of BFRR training for muscle conditioning, there are several
uncertainties regarding the interplay of various extrinsic and intrinsic factors on its
safety and efciency, which are being reviewed from a clinical perspective. Among
extrinsic factors tourniquet cuff pressure, size and shape have been identied as key
for safety and efciency. Among intrinsic factors, limb anthropometrics, patient history
and presence of cardiac, vascular, metabolic or peripheral neurologic conditions have
been recognized as most important. Though there are a few potential safety concerns
connected to BFRR training, the following have been identied as the most proba-
ble and health-hazardous: (a) mechanical injury to the skin, muscle, and peripheral
nerves, (b) venous thrombosis due to vascular damage and disturbed hemodynamics
and (c) augmented arterial blood pressure responses due to combined high body exer-
tion and increased peripheral vascular resistance. Based on reviewed literature and
authors’ personal experience with the use of BFRR training in injured athletes, some
guidelines for its safe application are outlined. Also, a comprehensive risk assessment
review article UDC: 615.825:796.071.2
received: 2015-08-19

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tool for screening of subjects prior to their inclusion in a BFRR training program is
being introduced.
Keywords: blood ow restricted exercise, health risk assessment, tourniquet cuff
efciency, rehabilitation of athletes.
VARNA UPORABA VADBE Z ZMANJŠANIM
PRETOKOM KRVI
IZVLEČEK
Vadba proti majhnem uporu s sočasno zmanjšanim pretokom krvi v aktivnih mišicah
(ishemična vadba) dokazano spodbuja hipertrojo in izboljša mišično jakost primerlji-
vo s standardno vadbo proti velikem uporu, vendar ob znatno manjši mehanski obreme-
nitvi sklepa. Zato se ishemično vadbo pospešeno vključuje v zioterapevtske programe,
zlasti pri športnikih s poškodbami ali operativnimi posegi na sklepih spodnjih ali zgor-
njih udov. Kljub splošnem strinjanju glede pozitivnih učinkov na mišično zmogljivost
ostaja vrsta nejasnosti glede medsebojnega učinkovanja vrste intrinzičnih in ekstrinzič-
nih dejavnikov, ki se pojavijo med ishemično vadbo in zelo verjetno vplivajo na njeno
učinkovitost in varnost. Regulacija in velikost manšetnega tlaka ter oblika in velikost
manšete so bili prepoznani kot ključni ekstrinzični dejavniki varnosti in učinkovitosti.
Med intrinzičnimi dejavniki pa so bili v tem pogledu kot najbolj pomembni prepozna-
ni sledeči: antropometrija uda in prisotnost preteklih ali sedanjih srčnih, žilnih, pre-
snovnih ali perifernih živčnih okvar pacienta. Izmed vrste potencialnih zdravstvenih
problemov, povezanih z ishemično vadbo, so najbolj verjetni in zdravje ogrožajoči (a)
mehanske poškodbe kože, mišic in perifernih živcev, (b) globoka venska tromboza za-
radi poškodb ožilja in spremenjene hemodinamike in (c) povečan odziv arterijskega
krvnega tlaka zaradi povečanega občutka napora in upora perifernega ožilja zaradi
nameščene manšete. Na podlagi objavljenih podatkov v literaturi in osebnih izkušenj
avtorjev članka z uporabo ishemične vabe pri športnikih so podana priporočila za nje-
no varno uporabo. V članku je predstavljen tudi enostaven in razumljiv pripomoček
za presojanje dejavnikov zdravstvenega tveganja posameznika pred vključitvijo v pro-
gram ishemične vadbe.
Ključne besede: vadba z oviranim pretokom krvi, ocena dejavnikov tveganja, učin-
kovitost manšetnega sistema, zioterapija in rehabilitacija športnikov

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INTRODUCTION
Blood ow restricted resistance (BFRR) training, its most featured version also
known as kaatsu training, has long been suggested as an alternative for conventional
weight training due to the proven benets for muscle strength and hypertrophy using
relatively low resistance, hence reducing the mechanical stress across a joint. It has
been used in the elderly to maintain muscle mass (Fry et al., 2010) and in athletes
to improve performance (Takarada et al., 2002; Cook, Murphy & Labarbera, 2013)
or to accelerate post-surgical rehabilitation (Ohta et al., 2003). Increases in muscle
hypertrophy following low load BFRR training are well documented and are one of
the primary reasons behind utilizing this form of exercise (Wernbom, Augustsson &
Raastad, 2008). Interestingly, despite lower mechanical stress to the tissues, favourable
adaptations in bone turnover have also been demonstrated with BFRR training (Kara-
bulut et al., 2011).
However, the positive adaptation of muscle to BFRR training seems to extend bey-
ond mimicking hypertrophic effects of high-resistance training. Namely, improvements
in vascular function (Patterson & Ferguson, 2010; Hunt, Walton & Ferguson, 2012;
Hunt, Galea, Tufft, Bunce & Ferguson, 2013; Evans, Vance & Brown 2010), enhanced
oxygen delivery and muscle endurance (Takarada, Sato & Ishii, 2002; Kacin & Strazar,
2011) as well as cardiorespiratory endurance (Abe et al., 2010; Park et al., 2010) have
been also reported with BFRR training. A recent case study even reports of an increa-
sed rate of healing in patient with osteochondral fracture (Loenneke, Young, Wilson &
Andersen, 2013b).
An increasing number of published research supports the efcacy of the technique,
whereas its safety has not been extensively studied. Similar to the use of surgical tour-
niquets on limbs of resting patients (Fitzgibbons, DiGiovanni, Hares & Akelman, 2012;
Estebe, Davies & Richebe, 2011) the major concerns are due to (a) a mechanical injury
to the skin, muscle, and peripheral nerves and (b) venous thrombosis due to vascular
damage and disturbed hemodynamics, but also (c) augmented arterial blood pressure
(ABP) responses due to combined high body exertion and increased peripheral vascu-
lar resistance induced by the tourniquet. In addition, ischemic-reperfusion injury with
local or systemic effect may also play a role. The only epidemiological study available
has shown a surprisingly low occurrence of any adverse effects of BFRR training other
than skin bruising, in various populations in Japan (Nakajima et al., 2006). General and
specic health concerns with BFRR training in healthy people have been reviewed in
depth by Manini and Clark (2009), Loenneke, Wilson, Wilson, Pujol & Bemben (2011)
and Pope, Willardson & Schoenfeld (2013). The present review thus addresses safety
and efciency of BFRR training from clinical perspective, in regard to a complex in-
terplay of various extrinsic (tourniquet system and exercise) and intrinsic (anthropo-
metrics, medical history and life style) factors. Based on reviewed evidence and our
clinical experience with BFRR training in injured and operated athletes we set about
developing a risk assessment tool. The tool will allow physiotherapists and non-medi-

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cal staff such as strength and conditioning coaches, to manage the risk to the athletes
whilst allowing them to benet from an effective technique.
METHODS
Methods of literature review and clinical commentary were combined when prepa-
ring this manuscript. The search of scientic literature published in English language
was performed until March 2015 in various electronic databases (PubMed, WoS, ME-
DLINE, PEDro and ScienceDirect) by the following key words and phrases: blood ow
restricted exercise, ischemic training, reperfusion injury, safety and efciency of pneu-
matic tourniquets and health risk assessment for vascular occlusion. Initial search gave
1582 results which were rened by use of various key word combinations and addition
of new phrases most frequently associated with the topics of interest (rhabdomyolysis,
reperfusion injury, contour and cylindrical cuffs, nerve injury etc.). The second selec-
tion produced 133 publications, which were further reduced to 83 entries, based on
abstract content match with the topics, type of publication, research type and design,
sample size and full text availability. Case studies or reports and book chapters were
included only for the topics not studied by RCTs or other controlled cohort studies.
PROPOSED MECHANISMS OF MUSCLE ADAPTATION
TO BFRR TRAINING
How the positive training adaptations reviewed and discussed above are elicited
by muscle blood ow occlusion during exercise remains debatable. The proposed me-
chanisms were reviewed on several occasions, most recently and in-depth by Pope et
al. (2013) and Heitkamp (Heitkamp, 2015), who listed all hypothetical physiological
triggers identied so far: (a) hypoxia-induced additional or preferential recruitment of
fast-twitch muscle bers, (b) greater duration of metabolic acidosis via the trapping
and accumulation of intramuscular protons (H+ ions) and stimulation of metaborecep-
tors, possibly eliciting an exaggerated acute systemic hormonal response, (c) external
pressure-induced differences in contractile mechanics and sarcolemmal deformation,
resulting in enhanced growth factor expression and intracellular signalling, (d) me-
tabolic adaptations to the fast glycolytic system that stem from compromised oxygen
delivery, (e) production of reactive oxygen species (ROS) that promotes tissue growth,
(f) gradient-induced reactive hyperemia after removal of the external pressure, which
induces intracellular swelling and stretches cytoskeletal structures that may promote
tissue growth, and (g) activation of myogenic stem cells with subsequent myonuclear
fusion with mature muscle bers. Given that detailed review of all these mechanisms is
not the primary aim of the present review, only mechanisms most closely related to the
safety of tourniquet application will be discussed in the following.

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When performing BFRR exercise with a pneumatic tourniquet system, a tourniquet
cuff is applied to the proximal part of the upper or lower limb and inated to the set
pressure. With gradual mechanical compression of all soft tissues under the cuff, a
reduction in vascular diameter is achieved, resulting in occluded venous and reduced
or completely occluded arterial blood ow to the muscles at and distal to the cuff.
During muscle contraction, an increase in intra-muscular pressure is generated under
the pressurized cuff, further disturbing muscle blood ow. In case of isometric muscle
contraction, the contraction-induced muscular pressure is basically constant, whereas
during concentric/eccentric contractions it changes in a cyclical manner. If a rigid cuff
with no regulation of pressure is used, effective tourniquet pressure during contracti-
ons is ~50 % higher than the set value, with ~65−75 % variation between concentric
and eccentric phase of contraction (Figure 1). Depending on the cumulative degree of
blood ow reduction and exercise intensity, variable levels of muscle edema, ischemia
and hypoxia develop in the muscle during the exercise. Following deation of the tour-
niquet, reperfusion of the limb takes place.
Figure 1: Cyclic changes in rigid contour tourniquet cuff (13 cm wide) pressure during
ten concentric / eccentric knee-extension contractions performed at 20 % 1RM by a
representative subject. Set pressures were (A) 100 mmHg and (B) 150 mmHg, with no
pressure regulation provided during exercise (author’s unpublished data).

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There is a lack of a most optimal degree of venous and arterial blood ow reduc-
tion for muscle conditioning is. Although sound experimental evidence is still scarce,
it can be assumed that two distinct changes in muscle hemodynamics are achieved
during the dynamic leg exercise, by inducing either predominant venous-lymphatic oc-
clusion (tourniquet pressure of ~60 mmHg) or intermittent complete arterial occlusion
(≥150 mmHg). In the case of predominantly venous occlusion (VO), blood inow to
the muscle is not compromised, resulting in progressive rise in venous pressure (Iida
et al., 2007). Given that capillary pressure is four times more sensitive to increased ve-
nous pressure, the result is augmented capillary ltration. Fluid shift from vasculature
to extracellular compartments, combined with completely blocked lymphatic outow,
results in soft-tissue edema and increased interstitial uid pressure (Levick & Michel,
2010). Consequently, some of the uid is forced across the sarcolemma into the intra-
cellular compartment, along with non-selective transport of various smaller molecules.
Due to progressive congestion of blood in the muscle during the exercise, substantial
metabolite accumulation and tissue hypoxia are eventually developed. In contrast, the
resistance on both sides of the capillaries is equally reduced during complete arterial
occlusion (AO) hence no detectable muscle swelling occurs during dynamic exercise.
It does however substantially increase hypoxia and metabolic stress in the muscle and
hence post-ischemic hyperemia. As shown by near-infrared spectroscopy, a substantial
hypoxia of vastus lateralis muscle is induced after only a few initial contractions with
intermittent complete AO (tourniquet pressure ≥230 mmHg, width 13 cm) (Kacin &
Strazar, 2011). Upon the release of tourniquet, augmented reperfusion (active hyper-
emia) is driven by accumulated metabolites in the muscle cells which increases pres-
sure gradient across sarcolemma and further cell swelling. It is speculated that cell
swelling per se induces muscle protein synthesis (Loenneke, Fahs, Rossow, Abe &
Bemben, 2012a) as it is the case with other type of cells (Lang et al., 2000). Further-
more, signs of muscle damage and prolonged (up to 48 hrs.) sarcolemmal permeability
were demonstrated after only one bout of BFRR exercise (Wernbom, Paulsen, Nilsen,
Hisdal & Raastad, 2012), which suggests a thin line between hypertrophic stimulus and
potential muscle injury. A reduced muscle compliance to palpation can be noted after
BFRR exercise, and subjects describe muscle as “hard” or “pumped up” for a short
period after BFRR (authors’ unpublished observations). It was also demonstrated that
transient increase in sarcolemma permeability and cell swelling is an important trigger
of hypertrophy and augmented satellite cell activation (Nielsen et al., 2012). Also, mus-
cle hypertrophy and strength gains are shown to have a good correlation (r=0.60-0.88)
with metabolic stress (Takada et al., 2012; Sugaya, Yasuda, Suga, Okita & Abe, 2011).
Importantly, metabolic perturbation induced by disrupted hemodynamics increases
the magnitude of muscle activation, presumably of fast-twitch bers, during low load
BFRR training compared to free blood ow training of same intensity (Yasuda et al.,
2009; Yasuda et al., 2014; Yasuda, Loenneke, Ogasawara & Abe, 2013). This is seen as
one of the key acute adaptations which lead to strength gains following low load BFRR
training (Takarada et al., 2000).

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However, based on our clinical observations with preoperative conditioning of 23
athletes scheduled for ACL reconstruction, the same degree of blood ow restriction
does not have the same effect on muscle activation and performance of power or endu-
rance trained individuals of different build, even when tourniquet pressure is corrected
for resting arterial pressures and leg circumference by Graham’s formula (Graham,
Breault, McEwen & McGraw, 1993). The number of repetitions performed was up to
40 % higher in endurance compared to power athletes (authors’ unpublished observa-
tions). This may be due to different proportions of type I and type II muscle bers and,
hence, different effect of blood deprival on muscle fatigability. A similar observation
was recently reported by Downs et al. (2014), who noted a ~10-15% lower rate of fa-
tigue, calculated from the decrease in number of repetitions, for ankle plantar exors
compared to knee extensors at the same vascular occlusion, which was attributed to
profoundly different muscle composition between muscle groups (Gregory, Vanden-
borne & Dudley, 2001). To provide sufcient training stimulus of BFRR exercise re-
gardless of training status and muscle composition, our patients / athletes perform each
exercise set to volitional failure. This, however, substantially increases the whole body
exertion and cardiac load, thus patients with a history of cardiorespiratory disease must
be excluded. Optimization of exercise parameters for BFRR training in different patient
populations needs to be systematically addressed in further investigations.
POTENTIAL SAFETY AND EFFICIENCY ISSUES WITH BFRR TRAINING
Long-lasting (>30 min) AO induced by pneumatic tourniquets is routinely used dur-
ing limb surgery in order to prevent bleeding. Tourniquet pressure above 170 mm Hg
for upper and 270 mm Hg for lower limbs is usually used, which in combination with
prolonged constant compression poses a threat of mechanical and, upon the release of
tourniquet, ischemia-reperfusion injury of the vascular, neural, metabolic and musculo-
skeletal systems (Fitzgibbons et al., 2012). Ischemia is the reduction of blood supply to
a tissue which results in a lack of oxygen and substrates for cellular metabolism (Ames
& Nesbett, 1983). A prolonged complete ischemia and a rapid reperfusion of tissues
upon the release of blood ow are the causes of reperfusion injury (Estebe, Davies &
Richebe, 2011; Wakai et al., 2001; Hughes, Hendricks, Edwards & Middleton, 2010;
Hughes et al., 2007). It is well known that irreversible skeletal muscle damage occurs
after three hours of ischemia in normothermic conditions (Blaisdell, 2002; Pedowitz et
al., 1991) but adverse cellular events begin much earlier. Research shows that reperfu-
sion injury causes cell apoptosis, presumably by negative inuences on microcircula-
tion, subsequent local inammatory response and production of reactive oxygen spe-
cies (Blaisdell, 2002; Carden & Granger, 2000). In contrast, short episodes of ischemia
− reperfusion are speculated to be the trigger for cellular adaptation to BFRR training
(Wernbom et al., 2008; Manini & Clark, 2009) and were demonstrated to have both
a cardio-protective (Zhu et al., 2013) and a muscle performance enhancing effect (de
Groot, Thijssen, Sanchez, Ellenkamp & Hopman, 2010). However, an optimal protocol

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for effective and safe BFRR training remains elusive. Strength gains and hypertrophy
comparable to standard high load strength training were reported with various combi-
nations of exercise and tourniquet parameters (see (Wernbom et al., 2008; Loenneke,
Wilson, Marin, Zourdos & Bemben 2012c) for review). In addition, enhanced muscle
endurance capacity and hemodynamics were demonstrated with a combination of ei-
ther extremely low load (40 − 50 RM) exercise and high tourniquet pressures (150 −
230 mmHg, width 13-15 cm) with reperfusion between four sets for lower limbs (Kacin
& Strazar, 2011; Evans et al., 2010) or low to medium load (25 % and 50 % 1RM) ex-
ercise with low pressure (110 mmHg) without reperfusion between three sets for lower
and upper limbs (Patterson & Ferguson, 2010; Hunt et al., 2012; Hunt et al., 2013).
Morphologic adaptation occurred at all levels of the vascular tree with enhanced peak
reactive hyperemia and transient improvement in artery function preceding changes in
artery structural capacity (Hunt et al., 2013). Although tourniquet pressure is usually
regarded as a key extrinsic factor of blood ow reduction, other extrinsic and intrinsic
confounding factors like 1) tourniquet width and shape (Moore, Garn & Hargens,
1987; Crenshaw, Hargens, Gershuni & Rydevik, 1988; Pedowitz et al., 1993), 2) limb
circumference (Graham et al., 1993; Tuncali et al., 2006) and 3) individual’s arterial
blood pressures (ABP) (Newman & Muirhead, 1986; Graham et al., 1993) substantially
affect the nal degree of occlusion.
Inuence of Tourniquet Cuff Design and Pressure
Various combinations of tourniquet pressure (range 50 − 230 mmHg) and cuff width
(range 3.3 − 20.5 cm) were used in BFRR exercise studies. Although tourniquet pres-
sures and exposure times used are lower compared to the ones in surgery, the stretching
and shear forces in the tissue are most likely to be much higher due to muscle contrac-
tions under pressurized tourniquet cuff. As shown in Figure 1, the cuff pressure during
concentric phase of contraction peaks ≥ 50 % above the value set on the resting muscle
prior to the exercise, which reects a very high increase in intramuscular forces at the
site of cuff compression. Tourniquet system that provides a fast responsive and accu-
rate cuff pressure regulation during muscle contractions is thus essential for a safe and
efcient application of BFRR exercise.
In a resting limb, the same reduction of blood ow can be achieved using a wider
tourniquet cuff at much lower pressures (Moore et al., 1987; Crenshaw et al., 1988;
Pedowitz et al., 1993). Likewise, contoured (cone) cuffs induce arterial occlusion at
lower pressures than straight (cylindrical) ones (Younger, McEwen & Inkpen, 2004;
Pedowitz et al., 1993). Given that the shape and width of the cuff inuence pressure
distribution and sheer forces in the underlying muscle tissue (Pedowitz et al., 1991), us-
ing the lowest pressures possible to achieve the desired training effect should minimize
the risk of soft tissue damage. Cuff width, shape and pressure also have an important
inuence on pain provocation and, hence, patient comfort during the application. When
compared at the same ination pressure (SBP×1.3≈160 mm Hg), wide rigid cuffs (13.5

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cm) provoke somewhat higher pain levels (~2 points on Borg’s CR-10) and perception
of effort (~1.5 point on 6 − 20 Borg’s scale) during lower limb exercise than narrow
belt-like elastic cuffs (5 cm) (Rossow et al., 2012). Given that at the same pressure a
wider cuff induces more blood-ow restriction, such comparisons may be deceptive.
As demonstrated already by Estebe, Le Naoures, Chemaly and Ecoffey (2000) on
resting upper limbs, wider cuffs (14 cm) indeed provoke more pain than narrow cuffs
(7 cm) when compared at same absolute pressure (~260 mm Hg), but less pain when
compared at individual occlusion pressure. The latter was on average 55 mmHg lower
with wider cuffs (202 mmHg for narrow and 147 mmHg for wide cuffs) (Estebe et al.,
2000), suggesting that wider cuffs might in fact provoke less discomfort and pain for
the same occlusion stimulus also during the exercise. Given that different pressures and
conditions (exercise vs. rest) were scrutinized in these studies, more research is needed
in this regard.
In many published BFRR exercise studies, there is a lack of detailed technical char-
acteristics of the tourniquets and pressure systems used. The degree of blood ow re-
duction is, thus, difcult to estimate, but according to signicant differences in various
confounding factors listed above, vast variations between and within studies are likely.
Meta-analysis of well-designed and controlled BFRR studies (Loenneke et al., 2012c)
revealed a difculty in estimating the actual impact of various tourniquet pressures on
gains in muscle mass and strength, which is not surprising due to large variations in
tourniquet systems used. There is a clear need for a systematic study of differences in
intramuscular responses induced by various tourniquet systems used for BFRR training.
Impact of Limb Anthropometrics on Pressure Transmission
Transmission of pressure from a tourniquet to the underlying tissues showed to be
exponentially inverse to extremity circumference (Tuncali et al., 2006) and to the ratio
between circumference and tourniquet cuff width (Graham et al., 1993). Similarly, sig-
nicant negative correlations between tissue oxygenation and leg lean body mass, total
lean body mass, and thigh circumference were reported by Karabulut, McCarron, Abe,
Sato & Bemben (2011b). Furthermore, it was established that as much as ~80% of vari-
ability in the occlusion pressures with the use of rigid wide cuffs can be explained by
the ratio of muscle to subcutaneous fat cross-sectional areas and only ~20% by either
systolic (SAP) or diastolic (DAP) blood pressure (Loenneke et al., 2012d), which coun-
ters the previous reports (Newman & Muirhead, 1986; Graham et al., 1993). With an
application of elastic belt-like tourniquet cuffs, the total variance in occlusion pressures
explained by anthropometrics was much smaller, and was even non-signicant for SAP.
Taken together, the transmission of cuff pressure to the center of the limb, where the
majority of large blood vessels is located, seems to be negatively related to the limb
circumference and positively related to the cuff width.

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CONSIDERATIONS FOR CLINICAL SCREENING AND RISK
ASSESSMENT
The use of BFRR training for musculoskeletal rehabilitation is relatively new and
rapidly evolving. To improve our understanding of the risks associated with this form
of training, a thorough screening and regular auditing processes need to be established
by all users of the technique.
We consider that a high quality screening process, including a medical practitioner
is essential to safe guard against potential adverse reactions associated with this form of
exercise. The purpose of a screen is to lter out those patients that may be at increased
risk of injury for medical or other reasons. A further purpose is to identify the factors
which will reduce the risk of injury to potentially overstressed structures reviewed be-
low. Considering the safety aspects of BFRR training using these principles relies on a
comprehensive personal medical, social and family history. Particular attention needs
to be paid to any condition or lifestyle activity that may have impact on any of the
systems outlined below. In the development of a risk assessment tool we addressed the
following principles:
• identication of the structures affected by blood ow restriction;
• identication of which subjects / patients may be at higher risk from the potenti-
al negative effects of BFRR training and determination of the level of precaution
required;
• development of an easy-to-use risk assessment tool;
• review of any adverse reactions;
• review and update of the risk assessment tools as necessary.
In the process of identifying potential risks, the structures which may be affected by
the application of a tourniquet must be considered. We addressed each of these structu-
res individually when determining which medical conditions may increase the risk of
exposure to BFRR exercise.
Skin and subcutaneous tissues
Pressure necrosis and frictional burns can occur due to inadequate padding, poor
application of the tourniquet, and movement of the fully inated tourniquet over bare
skin. Soft wrinkle-free padding should be used below the cuff (Van der Spuy, 2012) to
avoid these issues. Stretch sleeves made of two-layer elastic material were shown to
provide the most effective protection against skin injury during application of surgical
tourniquets (Olivecrona, Tidermark, Hamberg, Ponzer & Cederfjäll, 2006). Frictional
burns and pinching are more likely to occur during BFRR exercise if no padding is
used.

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Alan KACIN, Benjamin ROSENBLATT, Tina GRAPAR ŽARGI, Anita BISWAS: SAFETY CONSIDERATIONS WITH BLOOD ..., 3–26
Musculoskeletal system
In the musculoskeletal system, consideration must be given to the effect of BFRR
on muscle and joints. Excessive and unaccustomed exercise may result in muscle dam-
age and delayed-onset soreness. Both of these have also been reported after a low load
BFRR training (Umbel et al., 2009), but this may be evidence of the adaptations nec-
essary for a training effect rather than an adverse response. It was shown that exces-
sive pressures combined with a wide tourniquet can provoke paraesthesia in the thighs
during the exercise. In addition, suppressed muscle hypertrophy in vastus intermedius
muscle with signs of atrophy at the site of tourniquet compression were observed after
four weeks of BFRR training (Kacin & Strazar, 2011).
Lack of blood perfusion to a limb and extreme physical exertion are both well-
known causes of rhabdomyolysis. This is a clinical syndrome resulting from skeletal
muscle damage and the release of potentially toxic substances into the circulation (Alli-
son & Bedsole, 2003). It may be caused by trauma or muscle hypoxia and manifests as
muscle pain and weakness. There was also a case report of rhabdomyolysis following
the initial exposure to BFRR training (Iversen & Rostad, 2010). Other potential causes
of rhabdomyolysis, which need to be excluded prior to BFRR training, are outlined in
Table 1.
Consideration must, therefore, be given in the case when other conditions associ-
ated with rhabdomyolysis are present. This includes restricted caloric intake (particu-
larly with low levels of potassium, phosphate and magnesium), a history of severe heat
illness / injury, a recent muscle trauma or a crush injury. Caution must, therefore, be
taken in individuals who lack any previous training history as unaccustomed exercise
can also be associated with an increased risk of rhabdomyolysis.
The personal experience of the authors is of the use of BFRR in the rehabilitation
of musculoskeletal injuries. When determining potential risk factors for the use of this
technique in patients after ACL reconstruction with or without partial menisectomy
(N=32), we were concerned about the potential negative effect on post-surgical patients
with a swollen joint, due to congestion of tissues or swelling that may result from the
external restriction of blood and lymphatic vessels. This may also have impact on those
with an inammatory arthropathy, synovitis, haemarthrosis or septic arthritis. Indeed,
in case of post-surgical synovitis (N=1) or haemarthrosis (N=1) exacerbation of symp-
toms were induced by BFRR (authors’ unpublished observations), hence, alternative
forms of training should be considered.

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ANNALES KINESIOLOGIAE • 6 • 2015 • 1
Table 1: Types and causes of rhabdomyolysis. (Allison & Bedsole, 2003)
Type Cause
Trauma or muscle
compression
Crush syndrome
Prolonged immobilization
Non-traumatic
exertional
rhabdomyolysis
Unaccustomed exertion in untrained individuals
Hyperthermia: malignant hyperthermia, neuroleptic malignant syn-
drome
Metabolic myopathies: mitochondrial myopathies, McArdles etc
Non-traumatic and
non-exertional
rhabdomyolysis
Drugs: alcohol, heroin, cocaine, amphetamines, methadone, and D-
-lysergic acid diethylamide (LSD), antipsychotics, statins, selective
serotonin reuptake inhibitors, zidovudine, colchicine, lithium, anti-
histamines, and several others
Toxins: metabolic poisons, such as carbon monoxide, snake venoms,
insect venoms, including wasp and bee stings, mushroom poisoning
Viral infections: acute viral infections (eg inuenza A and B),
coxsackievirus, Epstein-Barr, herpes simplex, parainuenza, adeno-
virus, echovirus, human immunodeciency virus, and cytomegalo-
virus
Bacterial infections: bacterial pyomyositis legionella, tularemia,
streptococcus and salmonella, E. coli, leptospirosis, coxiella burnetii
(Q fever), and staphylococcal infection
Electrolyte disorders: hypokalemia, hypophosphatemia,
diabetic ketoacidosis or nonketotic hyperglycemia, hypophosphate-
mia, hypocalcemia hyponatremia hypernatremia
Inammatory myopathies: inammatory myopathies, dermatomyo-
sitis, polymyositis
Endocrine disorders: diabetes, hyper and hypo-thyroidism
Cardiac function and arterial blood pressure
In healthy population, a substantially higher exercise-induced increase in SAP, DAP
and mean ABP and heart rate (HR) compared to free ow exercise were found after two
or more subsequent sets of BFRR exercise with no reperfusion between the sets (Renzi,
Tanaka & Sugawara 2010; Vieira, Chiappa, Umpierre, Stein & Ribeiro 2013; Takano
et al., 2005). As demonstrated by Renzi et al. (2010), increased HR during blood ow

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Alan KACIN, Benjamin ROSENBLATT, Tina GRAPAR ŽARGI, Anita BISWAS: SAFETY CONSIDERATIONS WITH BLOOD ..., 3–26
restricted walking exercise (cuff pressure 160 mmHg, width not reported) compensates
for a compromised venous return and, hence, reduced the stroke volume, which results
in a three-fold greater index of myocardial oxygen demand. A report by Vieira et al.
(2013) corroborates the exaggerated heart rate (HR) and ABP responses to single-arm
BFRR exercise (cuff pressure 120 mmHg, width not reported) performed at 30 % 1RM
in both young and older healthy men. Similar ndings were recently reported for uni-
lateral leg BFRR exercise with two different tourniquet cuff pressures (1.3×DAP and
1.3×SAP, width 6 cm), with the exception of an attenuated rather than augmented HR
response (Downs et al., 2014). It appears that BFRR exercise can either increase or
decrease a normal HR response, depending on the interplay between cardio accelera-
tion driven by increased sympathetic drive and reduced stroke volume and cardio de-
celeration driven by increased cardiac afterload and decreased preload. These ndings
show that a lack of reperfusion during the short rest between exercise sets progressively
exacerbates cardiac load and cardiovascular demand. However, if exercise protocols
are not matched for work and intensity, but performed until volitional failure, acute HR
and ABP responses are similar between BFRR and free ow exercise (Loenneke et al.,
2012b; Kacin, Strazar, Palma & Podobnik 2011; Kacin & Strazar, 2011). From clinical
perspective it is important that cardiac and blood pressure responses to low-load BFRR
exercise are still signicantly lower than during the standard high-load resistance ex-
ercise despite a higher perception of exertion (Poton & Doederlein Polito, 2014). The
latter is apparently driven predominantly by peripheral sensations from the occluded
limb. Given that a low load BFRR exercise does not induce post-exercise hypotension
comparable to a free ow high load resistance exercise (Rossow et al., 2011), it appears
that an overall level of exertion determines systemic cardiovascular responses, more
than blood ow restriction per se.
The safety of BFRR exercise in patient populations at increased risks for cardio-
vascular events has not been systematically studied so far. A recent pilot study of nine
patients with stabile ischemic cardiac disease (Madarame, Kurano, Fukumura, Fukuda
& Nakajima, 2013) also revealed an augmented exercise-induced increase in heart rate
and plasma noradrenaline concentration during the BFRR exercise, although the sub-
jects performed a xed number of repetitions per set rather than exercising to volitional
failure. Despite an increased body exertion, no warning signs of any cardiovascular
events were observed in these patients (Madarame et al., 2013). Thus, subjects with a
history of or an increased risk of cardiovascular disease should be thoroughly screened
prior to their inclusion to BFRR training program and closely monitored for excessive
HR and ABP responses during the exercise. Exercise is advised not to be performed to
volitional failure and should also allow longer and more frequent reperfusion during
multiple sets. In our experience, six sets of BFRR with 45 − 60s reperfusion between
two consecutive sets is better tolerated by ACL decient (N=32) patients or those with
knee osteoarthritis (N=12), than three or four sets without reperfusion. It can be assu-
med that such BFRR exercise protocol is also more appropriate for people with modera-
te risk for cardiovascular events. An alternating exercise for agonistic and antagonistic
muscles can further reduce the stress, but most likely reduces the BFRR exercise effect.

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ANNALES KINESIOLOGIAE • 6 • 2015 • 1
Little is known about the long-term effects of BFRR training on cardiovascular
regulation. A study of Kacin and Strazar (2011) revealed a small, but signicant in-
crease in pre-exercise resting diastolic arterial pressure after a 4-week BFRR training
program, which may indicate chronically elevated levels of stress hormones due to
repetitive high body exertion in healthy individuals. This observation warrants a further
investigation both in healthy individuals and cardiac patients.
Vascular considerations
Overall, there is evidence that there are vascular benets to the use of blood ow
restriction (Patterson & Ferguson, 2010; Hunt et al., 2012; Hunt et al., 2013), however,
blood ow through vessels is affected by a number of factors including the vessel diam-
eter and blood turgidity. Any condition that interferes with a ‘normal’ blood ow may
contribute to and compound these compressive effects by impacting on the turgidity of
the blood. It stands to reason that any condition affecting blood ow through the limb
to be trained and the wider cardiovascular system may show impact on the risk to the
patient. Nakajima estimated the risk of venous thrombus to be 0.055 % in their epide-
miological study in Japan (Nakajima et al., 2006), nonetheless it is very low, it is a real
risk. Consideration must therefore be given to a personal or family history of conditions
affecting blood ow through local vessels or the wider cardiovascular system. These
are outlined in Table 2.
Table 2: Medical and social factors which may affect limb muscle blood ow.
Lifestyle
Travel
Periods of immobilization
Medication
Smoking
Personal Medical
History
Clotting disorders
Connective tissue disorders
Thrombosis (deep vein, pulmonary embolus, stroke)
Traumatic injury to blood vessels or nerves, compartment syndrome,
fractures or surgery
Non traumatic injury etc. diabetes/ hypertension/ peripheral vascular
disease
Liver/ renal disease
Pregnancy
Family History
Clotting disorders
Connective tissue disorders
Sickle cell anemia

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Alan KACIN, Benjamin ROSENBLATT, Tina GRAPAR ŽARGI, Anita BISWAS: SAFETY CONSIDERATIONS WITH BLOOD ..., 3–26
Despite the potential risk, there is a growing body of evidence that BFRR exercise
does not increase risk of venous thrombosis, at least in healthy individuals. A single
bout of blood ow restriction exercise show to augment brinolytic potential (Clark et
al., 2011) without affecting coagulation (Clark et al., 2011; Madarame et al., 2010; Fry
et al., 2010) and inammatory responses (Clark et al., 2011). The question whether this
holds true also for patients with increased risk for cardiovascular events has not been
systematically studied yet. A recent pilot study of Madarame et al. (2013) showed that
hemostatic and inammatory responses are not signicantly increased by a single bout
(4 sets without reperfusion) of BFRR exercise performed at 20 % 1RM (5 cm wide
elastic cuff with pressure 200 mmHg) in patients with stabile ischemic heart disease.
However, these results should not be directly extrapolated to other patient populations
and the interpretation must be taken with caution; the number of subjects was rather
small and the degree of blood ow restriction must have been different between subject
at a given tourniquet pressure.
Neural Considerations
Disruptions in peripheral nerve function may be due to both compression and local
asphyxiation (Ochoa, Fowler & Gilliatt, 1972). Under lower levels of compression,
disruptions are usually due to local ischemia (Brown & Brenner, 1944) unless the dura-
tion of compression is prolonged, in which case disruption is due to the pressure ef-
fects alone. In experiments looking into the effects of tourniquet pressure on the tissues
beneath it, higher pressures have been shown to cause localized conduction block as a
result of mechanical deformation nerve bers (Ochoa, Fowler & Gilliatt, 1972), with
large nerve bers being affected more than those that are smaller (Bolton & McFarlane,
1978; Larsen & Hommelgaard, 1987). Lundborg, Gelberman, Minteer-Convery, Lee &
Hargens (1982) reported hand numbness resulting from tourniquet compression of arm
likely due to nerve ischemia and conduction block, with similar numbness reported also
in the thigh during the BFRR exercise by Kacin and Strazar (2011). Such acute nerve
compression, however, does not usually have a long-term negative effect on nerve con-
duction velocities, at least in healthy adults (Clark et al., 2011).
It is well known that peripheral nerve function (both sensory and motor) in diabetics
is reduced early in the disease and that this is also likely to be due to ischemia (Greger-
sen, Servo, Borsting & Theil, 1978) although the deterioration in nerve function can
be reduced by maintaining good control of blood sugars. Therefore, the relative risk of
nerve injury in diabetics using BFRR may be considered to be higher than in the gen-
eral population. In assessing risk, it also stands to reason that any history of previous
disruption to the peripheral nervous system particularly if due to compression, places a
patient at a higher risk of re-injury during BFRR training. Caution is particularly advi-
sed in paralympic athletes with a spinal cord injury, direct peripheral nerve injury (such
as post-traumatic joint dislocation) or a complex regional pain syndrome.

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ANNALES KINESIOLOGIAE • 6 • 2015 • 1
Metabolic and systemic conditions
There is good evidence that BFRR training is benecial in diabetics (Satoh, 2011).
However, besides the potential risk of adverse neural effects described above, there is a
well-documented increased risk of peripheral vascular disease with disordered regula-
tion of cutaneous blood ow and increased susceptibility to leg ulcers and limb loss
in this population (Sima, Thomas, Ishii & Vinik, 1997). There is an argument that any
method that restricts blood ow may compound these issues. In athletes with diabetes,
there is a likelihood of fewer other confounding risk factors than in non-athletic dia-
betic patients. We would, nevertheless, consider that, before using this form of training
in a diabetic athlete, a medical assessment of the overall risk versus benet for the
individual should be undertaken. In addition, based on the extensive Kaatsu work in
Japan (Nakajima et al., 2006) the risks of adverse effects are not as high as may be rst
considered, so this valuable method of training should not be automatically excluded.
In other diabetic populations the risk may be higher and each person should be assessed
individually as to their suitability.
Paralympic athletes may include those with Duchene muscular dystrophy. This is
a condition in which the protein, dystrophin, is absent and causes an increase in sarco-
lemma damage in response to the exercise (Markert, Ambrosio, Call & Grange, 2011).
Loenneke et al. (2013a) suggested that BFRR may be a good way to improve symptoms
in this group of patients for whom exercise may improve their condition, but may also
be associated with muscle damage, as discussed above. In considering the use of BFRR
training in paralympic athletes and other people with this condition, sound medical
reasoning was used in the authors’ clinical practice whilst acknowledging the absence
of strong medical evidence as to its risks or benets.
Other less common conditions for consideration and rarely seen in our popula-
tion, include genetic muscle diseases comprising familial paroxysmal rhabdomyolysis,
McArdles, myopathies, and severe hypothyroidism. The only published evidence on
these conditions is a case study in Inclusion Body Myositis in which a patient gained
improvements in strength and motor function after BFRR training with no adverse ef-
fects on his disease (Gualano et al., 2010). Certain medication such as statins and some
medications for Parkinson’s disease are also associated with this, which also increases
the risk of adverse effects (Table 1).
DEVELOPING A RISK ASSESSMENT TOOL
Considering the safety aspects of BFRR training using these principles relies on
a comprehensive personal, medical, social and family history. Particular attention
needs to be paid to any condition or lifestyle activity that may impact on any of the
systems outlined above. In recognition of this the following screening tool was de-
veloped (Figure 2).

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Alan KACIN, Benjamin ROSENBLATT, Tina GRAPAR ŽARGI, Anita BISWAS: SAFETY CONSIDERATIONS WITH BLOOD ..., 3–26
Figure 2: Clinical screening tool for risk assessment of subjects prior to their inclusion
in blood ow restricted resistance training program.
MAGNITU-
DE OF RISK MEDICAL HISTORY OR LIFESTYLE FACTOR PATIENT
RESPONSE DECISION
ABSOLUTE
Do you have a family history of clotting disorders
(e.g. SLE (lupus), haemophilia, high platelets)?
YES STOP
NO CONTINUE
Do you have level 1 hypertension (SAP ≥ 140
mmHg)?
YES STOP
NO CONTINUE
Do you have a past history of DVT or pulmona-
ry embolus?
YES STOP
NO CONTINUE
Have you suffered from a haemorrhagic or
thrombotic stroke?
YES STOP
NO CONTINUE
RELATIVE
Do you have a family history of clotting disorders
(e.g. SLE (lupus), haemophilia, high platelets)?
YES SEEK MEDICAL ADVICE
NO CONTINUE
Do you smoke? YES SEEK MEDICAL ADVICE
NO CONTINUE
Are you on any medication including the contra-
ceptive pill?
YES SEEK MEDICAL ADVICE
NO CONTINUE
Do you have a history of injury to your arteries
or veins?
YES SEEK MEDICAL ADVICE
NO CONTINUE
Do you have a history to any of your nerves
(including back or neck injury)?
YES SEEK MEDICAL ADVICE
NO CONTINUE
Do you have diabetes? YES SEEK MEDICAL ADVICE
NO CONTINUE
Does one of your parents or siblings have dia-
betes?
YES SEEK MEDICAL ADVICE
NO CONTINUE
Do you have hypertension (SAP 120-140
mmHg)?
YES SEEK MEDICAL ADVICE
NO CONTINUE
Do you have metal work in situ? YES SEEK MEDICAL ADVICE
NO CONTINUE
Do you have any undiagnosed groin/calf pain? YES SEEK MEDICAL ADVICE
NO CONTINUE
Do you have/have you suffered from compart-
ment syndrome?
YES SEEK MEDICAL ADVICE
NO CONTINUE
Have you had surgery in past 4 weeks? YES SEEK MEDICAL ADVICE
NO CONTINUE
Have you had a journey lasting more than 4
hours or a ight in the last 7 days?
YES SEEK MEDICAL ADVICE
NO CONTINUE
Do you have any other medical conditions inclu-
ding a history of synovitis?
YES SEEK MEDICAL ADVICE
NO CONTINUE

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ANNALES KINESIOLOGIAE • 6 • 2015 • 1
If it is considered that an athlete may benet from BFRR training, they ought to
be subjected to a series of questions to determine whether their medical history or
lifestyle may increase the risk of illness or injury when using BFRR training. The
purpose of the questions is to assess whether the athlete is at higher than normal risk
of adverse reactions or injury whilst using this form of training. The risk factors were
separated into ‘absolute’ and ‘relative’, where the following absolute risk factors were
recognized:
• history or presence of clothing disorders (including SLE, hemophilia and high
plateles count);
• history or presence of deep vein thrombosis (DVT) or pulmonary embolism;
• history of thrombotic or haemorrhagic stroke;
• presence of level 1 hypertension or higher.
If patients / athletes show an absolute risk factor then they are automatically
excluded from BFRR training. If they do not, then they are able to continue with the
assessment tool. If they showany relative risk factor, a referral is made to a medical
practitioner prior to progression with BFRR training. The tool was designed so it
can be used at the point of contact by a non-medical practitioner, but with a clear
understanding that the nal decision about the suitability of an athlete for BFRR is
ultimately a medical one.
The following precaution measures in different patient populations are suggested:
1. Where there may be an increased risk of thrombotic events screening should be
considered and at the very least, close monitoring is advised and a low threshold
maintained for using a different form of resistance training.
2. Subjects with a history or increased risk of cardiovascular disease should be
thoroughly screened prior to their inclusion to BFRR training program and clo-
sely monitored for excessive HR and ABP responses during the exercise. The
exercise not performed to volitional failure with longer and more frequent reper-
fusions allowed during multiple sets is also advised.
3. Those who may be at a higher risk of nerve injury such as diabetics should
be fully examined for evidence of current compromise and monitored for any
changes in sensation, or development of paraesthesia in the exercising limb.
In these subjects, monitoring blood glucose levels should be considered and in
those with poorly controlled diabetes, other forms of training may be advisable.
4. In all subjects, but particularly where factors that may contribute to the deve-
lopment of rhabdomyolysis exist, monitoring for excessive muscle pain and we-
akness, changes in urine color and systemic symptoms of malaise are essential
during BFRR training. Where there is a high level of suspicion, appropriate
medical advice should be sought early and training should be ceased.

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Alan KACIN, Benjamin ROSENBLATT, Tina GRAPAR ŽARGI, Anita BISWAS: SAFETY CONSIDERATIONS WITH BLOOD ..., 3–26
CONCLUSIONS
Tourniquet design and pressure and whether a patient / athlete is at a high risk of
adverse reactions are the two key considerations which can be managed to increase the
safety and efciency of BFRR training. A pneumatic tourniquet is very easy to use, but
is a rather crude method of blood ow restriction, hence, a safe and efcient applica-
tion can be provided only by well-controlled tourniquet pressure on tissues. The degree
of blood ow reduction and tissue compression induced by pneumatic cuffs during
dynamic exercise most likely varies greatly between subjects in published studies, thus,
precise parameters for a safe and efcient application cannot be established from avai-
lable data. Tourniquet pressure during BFRR training should be set individually, where
at least subject’s limb circumference and composition (skinfold), arterial blood pres-
sures and cuff design (width and shape) are to be taken into the account. We consider
that a high quality screening process including a medical practitioner is the best way to
safeguard against adverse reactions associated with this form of exercise. To improve
our understanding of the risks associated with BFRR training, a thorough and regular
auditing process needs to be established.
Conicts of interest
Authors declare no conict of interest or nancial benet connected with this
manuscript.
REFERENCES
Abe, T., Fujita, S., Nakajima, T., et al. (2010). Effects of low-intensity cycle training with
restricted leg blood ow on thigh muscle volume and VO2max in young men. Journal
of Sports Science and Medicine, 9(3), 452–458. VIEW ITEM
Allison, R. C., & Bedsole, D. L. (2003). The other medical causes of rhabdomyolysis.
American Journal of the Medical Sciences, 326(2), 79–88. VIEW ITEM
Ames, A., & Nesbett, F. B. (1983). Patho-physiology of ischemic cell-death. Time of onset
of irreversible damage - importance of the different components of the ischemic insult.
Stroke, 14(2), 219–26. VIEW ITEM
Blaisdell, F. W. (2002). The pathophysiology of skeletal muscle ischemia and the reperfu-
sion syndrome: a review. Vascular, 10(6), 620–630. VIEW ITEM
Bolton, C. F., & McFarlane, R. M. (1978). Human pneumatic tourniquet paralysis. Neuro-
logy, 28(8), 787–93. VIEW ITEM
Brown, D. D., & Brenner, C. (1944). Paralysis of nerve induced by direct pressure and by
tourniquet. Archives of Neurology and Psychiatry, 51(1), 1–26. VIEW ITEM
Carden, D. L., & Granger, D. N. (2000). Pathophysiology of ischaemia-reperfusion injury.
Journal of Pathology, 190(3), 255–266. VIEW ITEM

22
Alan KACIN, Benjamin ROSENBLATT, Tina GRAPAR ŽARGI, Anita BISWAS: SAFETY CONSIDERATIONS WITH BLOOD ..., 3–26
ANNALES KINESIOLOGIAE • 6 • 2015 • 1
Clark, B. C., Manini, T. M., Hoffman, R. L., et al. (2011). Relative safety of 4 weeks of
blood ow-restricted resistance exercise in young, healthy adults. Scandinavian Journal
of Medicine & Science in Sports, 21(5), 653–662. VIEW ITEM
Cook, S. B., Murphy, B. G., & Labarbera, K. E. (2013). Neuromuscular Function after
a Bout of Low-Load Blood Flow-Restricted Exercise. Medicine & Science in Sports &
Exercise, 45(1), 67–74. VIEW ITEM
Crenshaw, A. G., Hargens, A. R., Gershuni, D. H., & Rydevik, B. (1988). Wide tour-
niquet cuffs more effective at lower ination pressures. Acta orthopaedica Scandinavica,
59(4), 447–451. VIEW ITEM
de Groot, P. C. E., Thijssen, D. H. J., Sanchez, M., Ellenkamp, R., & Hopman, M. T. E.
(2010). Ischemic preconditioning improves maximal performance in humans. European
journal of applied physiology, 108(1), 141–146. VIEW ITEM
Downs, M. E., Hackney, K. J., Martin, D., et al. (2014). Acute Vascular and Cardio-
vascular Responses to Blood Flow-Restricted Exercise. Medicine & Science in Sports
& Exercise, 46(8), 1489–1497. VIEW ITEM
Estebe, J. P., Davies, J. M., & Richebe, P. (2011). The pneumatic tourniquet: mechani-
cal, ischaemia-reperfusion and systemic effects. European Journal of Anaesthesiology,
28(6), 404–411. VIEW ITEM
Estebe, J. P., Le Naoures, A., Chemaly, L., & Ecoffey, C. (2000). Tourniquet pain in a
volunteer study: effect of changes in cuff width and pressure. Anaesthesia, 55(1), 21–26.
VIEW ITEM
Evans, C., Vance, S., & Brown, M. (2010). Short-term resistance training with blood ow
restriction enhances microvascular ltration capacity of human calf muscles. Journal of
Sports Sciences, 28(9), 999–1007. VIEW ITEM
Fitzgibbons, P. G., DiGiovanni, C., Hares, S., & Akelman, E. (2012). Safe Tourniquet
Use: A Review of the Evidence. Journal of the American Academy of Orthopaedic Sur-
geons, 20(5), 310–319. VIEW ITEM
Fry, C. S., Glynn, E. L., Drummond, M. J., et al. (2010). Blood ow restriction exercise
stimulates mTORC1 signaling and muscle protein synthesis in older men. Journal of
applied physiology. 108(5), 1199–1209. VIEW ITEM
Graham, B., Breault, M. J., McEwen, J. A., & McGraw, R. W. (1993). Occlusion of ar-
terial ow in the extremities at subsystolic pressures through the use of wide tourniquet
cuffs. Clinical Orthopaedics & Related Research, 286, 257–261. VIEW ITEM
Gregersen, G., Servo, C., Borsting, H., & Theil, P. (1978). Myoinositol and function of
peripheral-nerves in human diabetics - controlled clinical-trial. Acta Neurologica Scan-
dinavica, 58(4), 241–248. VIEW ITEM
Gregory, C. M., Vandenborne, K., & Dudley, G. A. (2001). Metabolic enzymes and phe-
notypic expression among human locomotor muscles. Muscle and Nerve, 24(3), 387–
393. VIEW ITEM
Gualano, B., Neves, M., Jr., Lima, F. R., et al. (2010). Resistance Training with Vascular
Occlusion in Inclusion Body Myositis: A Case Study. Medicine & Science in Sports &
Exercise, 42(2), 250–254. VIEW ITEM
Heitkamp, H. C. (2015). Training with blood ow restriction - mechanisms, gain in stren-
gth and safety. The Journal of Sports Medicine and Physical Fitness, 55(5), 9–15. VIEW
ITEM

ANNALES KINESIOLOGIAE • 6 • 2015 • 1
23
Alan KACIN, Benjamin ROSENBLATT, Tina GRAPAR ŽARGI, Anita BISWAS: SAFETY CONSIDERATIONS WITH BLOOD ..., 3–26
Hughes, S. F., Hendricks, B. D., Edwards, D. R., Bastawrous, S. S., Roberts, G. E., &
Middleton, J. F. (2007). Mild episodes of tourniquet-induced forearm ischaemia-reper-
fusion injury results in leukocyte activation and changes in inammatory and coagula-
tion markers. Journal of Inammation (Lond), 4, 12. VIEW ITEM
Hughes, S. F., Hendricks, B. D., Edwards, D. R., & Middleton, J. F. (2010). Tourniquet-
-applied upper limb orthopaedic surgery results in increased inammation and changes
to leukocyte, coagulation and endothelial markers. PLoS One, 5, e11846. VIEW ITEM
Hunt, J., Galea, D., Tufft, G., Bunce, D., & Ferguson, R. (2013). Time course of regional
vascular adaptations to low load resistance training with blood ow restriction. Journal
of applied physiology, 115(3), 403–411. VIEW ITEM
Hunt, J., Walton, L., & Ferguson, R. (2012). Brachial artery modications to blood ow-
-restricted handgrip training and detraining. Journal of applied physiology, 112(6), 956–
961. VIEW ITEM
Iida, H., Kurano, M., Takano, H., et al. (2007). Hemodynamic and neurohumoral respon-
ses to the restriction of femoral blood ow by KAATSU in healthy subjects. European
journal of applied physiology, 100(3), 275–285. VIEW ITEM
Iversen, E., & Rostad, V. (2010). Low-Load Ischemic Exercise-Induced Rhabdomyolysis.
Clinical Journal of Sport Medicine, 20(3), 218–219. VIEW ITEM
Kacin, A., Strazar, K., Palma, P., & Podobnik, G. (2011). Effectiveness of low-load ische-
mic resistance exercise in treating chronic disuse atrophy of knee extensor muscles: a
case report. In 16th International WCPT Congress (p. eS575). Amsterdam: Elsevier, Phy-
siotherapy, 97(S1). VIEW ITEM
Kacin, A., & Strazar, K. (2011). Frequent low-load ischemic resistance exercise to failu-
re enhances muscle oxygen delivery and endurance capacity. Scandinavian Journal of
Medicine & Science in Sports, 21(6), e231–241. VIEW ITEM
Karabulut, M., Bemben, D. A., Sherk, V. D., Anderson, M. A., Abe, T., & Bemben,
M. G. (2011). Effects of high-intensity resistance training and low-intensity resistance
training with vascular restriction on bone markers in older men. European journal of
applied physiology, 111(8), 1659–1667. VIEW ITEM
Karabulut, M., McCarron, J., Abe, T., Sato, Y., & Bemben, M. (2011). The effects of
different initial restrictive pressures used to reduce blood ow and thigh composition
on tissue oxygenation of the quadriceps. Journal of Sports Sciences, 29(9), 951–958.
VIEW ITEM
Lang, F., Ritter, M., Gamper, N., et al. (2000). Cell volume in the regulation of cell proli-
feration and apoptotic cell death. Cellular Physiology and Biochemistry, 10(5-6), 417–
428. VIEW ITEM
Larsen, U. T., & Hommelgaard, P. (1987). Pneumatic tourniquet paralysis following intra-
venous regional analgesia. Anaesthesia, 42(5), 526–528. VIEW ITEM
Levick, J., & Michel, C. (2010). Microvascular uid exchange and the revised Starling
principle. Cardiovascular Research, 87(2), 198–210. VIEW ITEM
Loenneke, J., Fahs, C., Rossow, L., Abe, T., & Bemben, M. (2012). The anabolic benets
of venous blood ow restriction training may be induced by muscle cell swelling. Me-
dical Hypotheses, 78(1), 151–154. VIEW ITEM
Loenneke, J., Wilson, J., Balapur, A., Thrower, A., Barnes, J., & Pujol, T. (2012). Time
under tension decreased with blood ow-restricted exercise. Clinical Physiology and
Functional Imaging, 32(4), 268–273. VIEW ITEM

24
Alan KACIN, Benjamin ROSENBLATT, Tina GRAPAR ŽARGI, Anita BISWAS: SAFETY CONSIDERATIONS WITH BLOOD ..., 3–26
ANNALES KINESIOLOGIAE • 6 • 2015 • 1
Loenneke, J., Wilson, J., Marin, P., Zourdos, M., & Bemben, M. (2012). Low intensity
blood ow restriction training: a meta-analysis. European journal of applied physiology,
112(5), 1849–1859. VIEW ITEM
Loenneke, J. P., Fahs, C. A., Rossow, L. M., et al. (2012). Effects of cuff width on arterial
occlusion: implications for blood ow restricted exercise. European journal of applied
physiology, 112(8), 2903–2912. VIEW ITEM
Loenneke, J. P., Thiebaud, R. S., Abe, T., Manfro, I. G., & Marin, P. J. (2013). Acute
blood ow restricted exercise to treat Duchenne muscular dystrophy: would it be efca-
cious? Frontiers in physiology, 4(114), 1–3. VIEW ITEM
Loenneke, J. P., Wilson, J. M., Wilson, G. J., Pujol, T. J., & Bemben, M. G. (2011).
Potential safety issues with blood ow restriction training. Scandinavian Journal of Me-
dicine & Science in Sports, 21(4), 510–518. VIEW ITEM
Loenneke, J. P., Young, K. C., Wilson, J. M., & Andersen, J. C. (2013). Rehabilitation of
an osteochondral fracture using blood ow restricted exercise: a case review. Journal of
Bodywork and Movement Therapies, 17(1), 42–45. VIEW ITEM
Lundborg, G., Gelberman, R. H., Minteer-Convery, M., Lee Y. F., & Hargens, A. R.
(1982). Median nerve compression in the carpal tunnel-functional response to expe-
rimentally induced controlled pressure. The Journal of Hand Surgery, 7(3), 252–259.
VIEW ITEM
Madarame, H., Kurano, M., Fukumura, K., Fukuda, T., & Nakajima, T. (2013). Hae-
mostatic and inammatory responses to blood ow-restricted exercise in patients with
ischaemic heart disease: a pilot study. Clinical Physiology and Functional Imaging,
33(1), 11–17. VIEW ITEM
Madarame, H., Kurano, M., Takano, H., et al. (2010). Effects of low-intensity resistance
exercise with blood ow restriction on coagulation system in healthy subjects. Clinical
Physiology and Functional Imaging, 30(3), 210–213. VIEW ITEM
Manini, T. M., & Clark, B. C. (2009). Blood ow restricted exercise and skeletal muscle
health. Exercise & Sport Sciences Reviews, 37(2), 78–85. VIEW ITEM
Markert, C. D., Ambrosio, F., Call, J. A., & Grange, R. W. (2011). Exercise and du-
chenne muscular dystrophy: toward evidence-based exercise prescription. Muscle and
Nerve, 43(4), 464–478. VIEW ITEM
Moore, M. R., Garn, S. R., & Hargens, A. R. (1987). Wide tourniquets eliminate blood-
-ow at low ination pressures. The Journal of Hand Surgery, 12(6), 1006–1011. VIEW
ITEM
Nakajima, T., Iida, H., Kurano, M., et al. (2006). Use and safety of KAATSU training:
results of national survey. International Journal of KAATSU Training Research, 2(1),
5–13. VIEW ITEM
Newman, R. J., & Muirhead, A. (1986). A safe and effective low pressure tourniquet. A
prospective evaluation. The journal of bone and joint surgery Br, 68(4), 625–628. VIEW
ITEM
Nielsen, J., Aagaard, P., Bech, R., et al. (2012). Proliferation of myogenic stem cells in hu-
man skeletal muscle in response to low-load resistance training with blood ow restric-
tion. The Journal of Physiology (London), 590(17), 4351–4361. VIEW ITEM
Ochoa, J., Fowler, T. J., & Gilliatt, R. W. (1972). Anatomical changes in peripheral-nerves
compressed by a pneumatic tourniquet. Journal of Anatomy, 113(3), 433–455. VIEW
ITEM

ANNALES KINESIOLOGIAE • 6 • 2015 • 1
25
Alan KACIN, Benjamin ROSENBLATT, Tina GRAPAR ŽARGI, Anita BISWAS: SAFETY CONSIDERATIONS WITH BLOOD ..., 3–26
Ohta, H., Kurosawa, H., Ikeda, H., Iwase, Y., Satou, N., & Nakamura, S. (2003). Low-
-load resistance muscular training with moderate restriction of blood ow after anterior
cruciate ligament reconstruction. Acta orthopaedica Scandinavica, 74(1), 62–68. VIEW
ITEM
Olivecrona C., Tidermark, J., Hamberg, P., Ponzer, S., & Cederfjäll, C. (2006). Skin
protection underneath the pneumatic tourniquet during total knee arthroplasty: a rando-
mized controlled trial of 92 patients. Acta Orthopaedica, 77(3), 519–523. VIEW ITEM
Park, S., Kim, J. K., Choi, H. M., Kim, H. G., Beekley, M. D., & Nho, H. (2010). Increa-
se in maximal oxygen uptake following 2-week walk training with blood ow occlusion
in athletes. European journal of applied physiology, 109(4), 591–600. VIEW ITEM
Patterson, S., & Ferguson, R. (2010). Increase in calf post-occlusive blood ow and stren-
gth following short-term resistance exercise training with blood ow restriction in yo-
ung women. European journal of applied physiology, 108(5), 1025–1033. VIEW ITEM
Pedowitz, R. A., Gershuni, D. H., Botte, M. J., Kuiper, S., Rydevik, B. L, & Hargens,
A. R. (1993). The use of lower tourniquet ination pressures in extremity surgery faci-
litated by curved and wide tourniquets and an integrated cuff ination system. Clinical
Orthopaedics & Related Research, 287, 237–244. VIEW ITEM
Pedowitz, R. A., Gershuni, D. H., Schmidt, A. H., Fridén, J., Rydevik, B. L., & Har-
gens, A. R. (1991). Muscle injury induced beneath and distal to a pneumatic tourniquet:
A quantitative animal study of effects of tourniquet pressure and duration. The Journal
of Hand Surgery, 16(4), 610–621. VIEW ITEM
Pope, Z., Willardson, J., & Schoenfeld, B. (2013). Exercise and blood ow restriction.
Journal of Strength & Conditioning Research, 27(10), 2914–2926. VIEW ITEM
Poton, R., & Doederlein Polito, M. (2014). Hemodynamics responses during lower-limb
resistance exercise with blood ow restriction in healthy subjects. The Journal of Sports
Medicine and Physical Fitness. Ahead of print. VIEW ITEM
Renzi, C. P., Tanaka, H., & Sugawara, J. (2010). Effects of Leg Blood Flow Restriction
during Walking on Cardiovascular Function. Medicine & Science in Sports & Exercise,
42(2), 726–732. VIEW ITEM
Rossow, L., Fahs, C., Loenneke, J., et al. (2012). Cardiovascular and perceptual responses
to blood-ow-restricted resistance exercise with differing restrictive cuffs. Clinical Phy-
siology and Functional Imaging, 32(5), 331–337. VIEW ITEM
Rossow, L. M., Fahs, C. A., Sherk, V. D., Seo D-i, Bemben, D. A., & Bemben, M. G.
(2011). The effect of acute blood-ow-restricted resistance exercise on postexercise
blood pressure. Clinical Physiology and Functional Imaging, 31(6), 429–434. VIEW
ITEM
Satoh, I. (2011). Kaatsu Training: Application to Metabolic Syndrome. International Jour-
nal of KAATSU Training Research, 7(1), 7–12. VIEW ITEM
Sima, A. A. F., Thomas, P. K., Ishii, D., & Vinik, A. (1997). Diabetic neuropathies. Diabe-
tologia, 40(3), B74–B77. VIEW ITEM
Sugaya, M., Yasuda, T., Suga, T., Okita, K., & Abe, T. (2011). Change in intramuscular
inorganic phosphate during multiple sets of blood ow-restricted low-intensity exercise.
Clinical Physiology and Functional Imaging, 31(5), 411–413. VIEW ITEM
Takada, S., Okita, K., Suga, T., et al. (2012). Low-intensity exercise can increase muscle
mass and strength proportionally to enhanced metabolic stress under ischemic condi-
tions. Journal of applied physiology, 113(2), 199–205. VIEW ITEM

26
Alan KACIN, Benjamin ROSENBLATT, Tina GRAPAR ŽARGI, Anita BISWAS: SAFETY CONSIDERATIONS WITH BLOOD ..., 3–26
ANNALES KINESIOLOGIAE • 6 • 2015 • 1
Takano, H., Morita, T., Iida, H., et al. (2005). Hemodynamic and hormonal responses to
a short-term low-intensity resistance exercise with the reduction of muscle blood ow.
European journal of applied physiology, 95(1), 65–73. VIEW ITEM
Takarada, Y., Sato, Y., & Ishii, N. (2002). Effects of resistance exercise combined with
vascular occlusion on muscle function in athletes. European journal of applied physio-
logy, 86(4), 308–314. VIEW ITEM
Takarada, Y., Takazawa, H., Sato, Y., Takebayashi, S., Tanaka, Y., & Ishii, N. (2000).
Effects of resistance exercise combined with moderate vascular occlusion on muscular
function in humans. Journal of applied physiology, 88(6), 2097-2106. VIEW ITEM
Tuncali, B., Karci, A., Tuncali, B. E., et al. (2006). A New Method for Estimating Arterial
Occlusion Pressure in Optimizing Pneumatic Tourniquet Ination Pressure. Anesthesia
& Analgesia, 102(6), 1752–1757. VIEW ITEM
Umbel, J. D., Hoffman, R. L., Dearth, D. J., Chleboun, G. S., Manini, T. M., & Clark,
B. C. (2009). Delayed-onset muscle soreness induced by low-load blood ow-restricted
exercise. European journal of applied physiology, 107(6), 687–695. VIEW ITEM
Van der Spuy, L.-A. (2012). Complications of the arterial tourniquet. Southern African
journal of anaesthesia and analgesia, 18(1), 14–18. VIEW ITEM
Vieira, P. J. C., Chiappa, G. R., Umpierre, D., Stein, R., & Ribeiro, J. P. (2013). Hemo-
dynamic Responses to Resistance Exercise With Restricted Blood Flow in Young and
Older Men. Journal of Strength & Conditioning Research, 27(8), 2288–2294. VIEW
ITEM
Wakai A., Wang, J. H., Winter, D. C., Street, J. T., O’Sullivan, R. G., & Redmond, H. P.
(2001). Tourniquet-induced systemic inammatory response in extremity surgery. Jour-
nal of Trauma-Injury Infection & Critical Care, 51(5), 922–926. VIEW ITEM
Wernbom, M., Augustsson, J., & Raastad, T. (2008). Ischemic strength training: a low-
-load alternative to heavy resistance exercise? Scandinavian Journal of Medicine &
Science in Sports, 18(4), 401–416. VIEW ITEM
Wernbom, M., Paulsen, G., Nilsen, T. S., Hisdal, J., & Raastad, T. (2012). Contractile
function and sarcolemmal permeability after acute low-load resistance exercise with
blood ow restriction. European journal of applied physiology, 112(6), 2051–2063.
VIEW ITEM
Yasuda, T., Brechue, W. F., Fujita, T., Shirakawa, J., Sato, Y., & Abe, T. (2009). Muscle
activation during low-intensity muscle contractions with restricted blood ow. Journal
of Sports Sciences, 27(5), 479–489. VIEW ITEM
Yasuda, T., Fukumura, K., Fukuda, T., et al. (2014). Effects of low-intensity, elastic band
resistance exercise combined with blood ow restriction on muscle activation. Scandi-
navian Journal of Medicine & Science in Sports, 24(1), 55-61. VIEW ITEM
Yasuda, T., Loenneke, J. P., Ogasawara, R., & Abe, T. (2013). Inuence of continuous
or intermittent blood ow restriction on muscle activation during low-intensity multiple
sets of resistance exercise. Acta Physiologica Hungarica, 100(4), 419–426. VIEW ITEM
Younger, A. S., McEwen, J. A., & Inkpen, K. (2004). Wide contoured thigh cuffs and au-
tomated limb occlusion measurement allow lower tourniquet pressures. Clinical Ortho-
paedics & Related Research, 428, 286–293. VIEW ITEM
Zhu, S. B., Liu, Y., Zhu, Y., et al. (2013). Remote preconditioning, perconditioning, and
post-conditioning: a comparative study of their cardioprotective properties in rat mo-
dels. Clinics, 68(2), 263–268. VIEW ITEM