Fall

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PERSONALIZED BLOOD FLOW

RESTRICTION REHABILITATION
Johnny Owens

[Link]
 Table of Contents

Introduction 3

Strength and Hypertrophy 7

Lactate production 15

Neuromuscular 20

Growth Hormone 26

IGF-1 and Gene Expression 37

Myostatin 44

Protein Synthesis 53

Cell Swelling 61

Cycling and Walking 67

Bone 76

Proximal Gains 84

Muscle Damage 90

Safety 98

Clinical Studies 104

Exercise Prescription 109

Tourniquets 123

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 Paradigm Shift in Rehabilitation
Over the last decade I have had the opportunity to work with some true heroes, our
service members. More specifically, the Wounded Warriors injured in battle, training or
other mechanisms. I began my career with the military focusing on Sports Medicine
since this was my prior background. When I started with the military in 2004, no one
could fathom the length or toll Operation Iraqi and Enduring Freedom would take on
American service members.

I quickly transitioned to caring for limb salvage patients after our Chief of Trauma
Roman Hayda MD, approached me about bringing a Sports Medicine approach to blast
trauma patients. Restoring limb salvage patients to a higher functional level and
avoiding delayed amputations became my passion. I published my first paper on the
subject in 2010 describing the problem and potential solutions and a second paper
describing our successes. (Owens 2010, Owens 2011) From this, I became very
interested in any science or research available to help my patients. I was lucky enough
to collaborate with scientists at the Institute of Surgical Research (ISR), a military
research lab, to help tackle some of these tough problems. Our first project together
was the use of regenerative medicine and its application to rehabilitation. We published
a case study using a regenerative medicine application, an extracellular matrix scaffold,
to re-grow soft tissue injuries. (Mase 2010) This garnered national attention and even
made it onto 60 Minutes.

However, I realized that this science, although promising, was years away from realizing
its potential. The pressing problem was my limb salvage patients going on to amputate
their limbs because we could not get them out of pain or to higher level of functioning
like their amputee peers. I teamed up with the new Chief of Trauma, Joe Hsu MD, and
a prosthetist, Ryan Blanck CPO, to develop an exoskeleton that would act like a
prosthetic. This idea became much more successful than we could ever have imagined
and to date (2015) we have 10 peer reviewed publications related to this program,
multiple ongoing clinical trials and have treated over 700 service members. This
program also garnered national attention on the national and local stage including
National Public Radio and Time magazine.

Unfortunately we still had a problem. The exoskeleton that we built needed to be very
stiff. The device was so stiff it could potentially cause injury if you were weak in your
limb, and at best, it was not assured that it would perform properly. The majority of my
limb salvage patients had limb weakness, as severe trauma has this effect. To make
matters worse, the traditional methods to restore strength and hypertrophy were simply

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not applicable to most of my patients. Searching for a solution I kept coming across
blood flow restriction (BFR) training in the literature. It seemed that the application of a
tourniquet and reducing blood flow to an exercising limb would allow people to increase
strength and hypertrophy using light weights. After months of literature reviews and
intense discussions with my scientist colleagues and surgeons, I finally was given the
green light to attempt this modality on my patients. The anecdotal results were
amazing. We published a retrospective paper on the first cohort of our patients to
undergo this training in the Special Forces Journal and have since moved on to
prospective clinical trials. (Hylden 2015)

Over the last 4 plus years I have applied BFR extensively in the clinical setting. We
have moved on from trauma patients to sports medicine injuries and total joint
arthroplasties. To date, 100’s of patients have come through our clinic for this
treatment. Currently we are studying its effectiveness in the clinical setting after knee
arthroscopy, anterior cruciate ligament repair and fractures of the wrist and femur. We
hope to soon begin trials studying joint replacements, Achilles repairs and shoulder
pathologies. This is concurrent with many labs and clinics around the world looking at
mechanisms, physiologic changes and potential medical applications of BFR. This is a
modality with a very large amount of scientific literature to support it and its potential in
the clinical setting is tremendous.

Sincerely,

Johnny Owens, MPT

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 Bibliography

Mase, V, Hsu, J, Wolf, S, Wenke, J, Baer, D, Owens, J, Badylak, S, Walters, T. Clinical Application of an
ACellular Biologic Scaffold for Surgical Repair of a Large, Traumatic Muscle Defect of the
Quadriceps Femoris Muscle: A Case Report. Orthopedics. July 2010.

Hylden, C; Burns, T; Stinner, D; Owens, J. Blood Flow Strengthening as a Rehabilitation Modality: A

Case series. J Spec Oper Med. 2015 Spring;15(1):50-6.

Owens, J. Physical Therapy of the Patient with Foot and ankle Injuries Sustained in Combat. Foot and
Ankle Clinics. March 2010.

Johnny G. Owens, MPT, James A. Blair, MD, Jeanne C. Patzkowski, MD, Ryan V. Blanck, CPO, and
Joseph R. Hsu, MD. Return to Running and Sports Participation after Limb Salvage. Journal of
Trauma. Vol 71, 1 July Supplement 2011.

Jeanne C. Patzkowski, MD, Ryan V. Blanck, CPO, Johnny G. Owens, MPT, Jason M. Wilken, PhD, MPT,
James A. Blair, MD, and Joseph R. Hsu, MD. Can an Ankle-Foot Orthosis Change Hearts and
Minds? Journal of Surgical Orthopaedic Advances. Vol 20, #1, Spring 2011.

Jeanne C Patzkowski, Ryan V Blanck, Johnny G Owens, Jason M Wilken, Kevin L Kirk, Joseph C
Wenke, Joseph R Hsu and the Skeletal Trauma Research Consortium (STReC). Comparative
Effect of Orthosis Design on Functional Performance. Journal of Bone and Joint Surgery. 2012
Mar 21;94(6):507-15

Patzkowski JC, Owens JG, Blanck RV, Kirk KL, Hsu JR; Skeletal Trauma Research Consortium
(STReC). Deployment After Limb Salvage for High-Energy Lower Extremity Trauma. J Trauma
Acute Care Surg. 2012 Aug;73(2 Suppl 1):S112-5.

Patzkowski JC, Owens JG, Blanck RV, Kirk KL, Hsu JR; Skeletal Trauma Research Consortium.
Management of Posttraumatic Osteoarthritis with an Integrated Orthotic and Rehabilitation
Initiative. J Am Acad Orthop Surg. 2012;20 Suppl 1:S48-53. doi: 10.5435/JAAOS-20-08-S48.

Blair, J; Owens, J; Saucedo, J; Hsu, J. Functional rehabilitation with a foot plate modification for circular
external fixation. Foot and Ankle International. 34(6):890-897, June 2013. Presented Podium:
LLRS 2010.

Owens, JG; Hsu JR; Blanck RV. Wounded Warriors: Dedicated Professionals Give the Injured Another
Chance to Serve. Journal of Bone and Joint Surgery-Journal of Orthopaedic Sports Physical
Therapy Special Report: It Takes a Team. 2013 March

Katherine Bedigrew, Jeanne C Patzkowski, Ryan V Blanck, Johnny G Owens, Kevin L Kirk, Joseph R
Hsu, and Skeletal Trauma Research Consortium (STReC). Integrated Orthotic and rehabilitation
Initiative Results in Rapid Improvement. Clin Orth and Rel Research. 474(4). April 2014.

Sheean AJ, Owens J, Suttles S, Crossland BW, Stinner DJ. Return to duty after severe bilateral lower
extremity trauma. J Spec Oper Med. 2015 Spring;15(1):1-6.

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Mike M Crowell, Johnny G Owens, Gail D Deyle, Norma W Gill. Manual Physical Therapy Combined with
High-Intensity Functional Rehabilitation for Severe Lower Extremity Musculoskeletal Injuries: A
Case Series. J of Manual and Manip Therapy (In Press).

Ortiz D; Owens JG; Hsu JR; Pyo J; Deben S; Blanck RV; Dromsky DM. Collaborative Establishment of
an Integrated Orthotic and Rehabilitation Pathway. Jr of Surgical Orth Advances. (In Press)

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 Strength and Hypertrophy
According to the American College of Sports Medicine (ACSM), optimizing muscular
strength and hypertrophy can be achieved through moderate to high intensities of
resistance exercise that utilize 8∼10 upper and lower body exercises. These exercises
should target major muscle group’s 2∼3 dㆍwk-1 at a training intensity of more than
65% of the subject’s one-repetition maximum. (Donnelly 2009) This follows the
mechanical tension model of training in which sufficient load must be place on muscle to
induce adaptive changes. In fact, Dr. Meyer of Michigan State University states there is
one issue on which applied exercise physiologists and molecular biologists have
agreed: “to obtain substantial hypertrophy from a resistance training program, the target
muscles must be subjected to substantially increased load”. (Meyer 2006) Therefore,
the American College of Sports Medicine recommended that, during resistance training,
the load should exceed 70% of the one repetition maximum to achieve maximum
hypertrophy. Unfortunately, the elderly or people rehabilitating from injury may not be
able to tolerate these loads, which can limit their ability to have an adequate strength
and hypertrophy response.

Blood flow restriction (BFR) training in which a tourniquet is used on a proximal limb to
limit arterial inflow while blocking venous outflow has consistently demonstrated
strength and hypertrophy gains vs. controls and comparable gains to heavy load lifting.

For instance, in a study that compared low intensity exercise to low intensity exercise
with BFR, only the
group using a
tourniquet
demonstrated a
significant increase in
muscle cross
sectional area and
strength (thigh).
(Takarada 2004) The
cross sectional area
increase in size of
the knee extensors was 10.3 +/- 1.6% and the average increase in knee extension
strength was 9.3 +/1 2.2%. The study also demonstrated a significant rise in growth
hormone in the BFR group but not in the controls.

High intensity training (HIT 80% 1 RM), low intensity BFR (30% 1 RM) and low intensity
without BFR (30% 1 RM) demonstrated similar increases in strength between HIT and
BFR and both were significantly higher than the low intensity group. Additionally, the
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increases in muscle CSA were similar between HIT and BFR again, both were
significantly higher than the low intensity group. Furthermore, the triceps in the BFR
group hypertrophied significantly more than the HIT group. (Takarada 2000)

Additional studies that have demonstrated an increase in muscle strength using BFR
and exercise vs. exercise alone at low intensity are listed below.

• Abe T, Kearns CF, Sato Y. Muscle size and strength are increased following walk
training with restricted venous blood flow from the leg muscle, Kaatsu-walk
training. J Appl Physiol 100: 1460–1466, 2006.

• Abe T, Sakamaki M, Fujita S, Ozaki H, Sugaya M, Sato Y, Nakajima

T. Effects of low-intensity walk training with restricted leg blood flow on muscle
strength and aerobic capacity in older adults. J Geriatr Phys Ther 33: 34–40,
2010.

• Abe T, Sato Y, Inoue K, Midorikawa T, Yasuda T, Kearns CF, Koizumi K, Ishii N.

Muscle size and IGF-1 increased after two weeks of low-intensity “Kaatsu”
resistance training (Abstract). Med Sci Sports Exerc 36: S353, 2004.

• Evans C, Vance S, Brown M. Short-term resistance training with blood flow

restriction enhances microvascular filtration capacity of human calf muscles. J
Sports Sci 28: 999–1007, 2010.

• Drummond MJ, Fujita S, Takash A, Dreyer HC, Volpi E, Rasmussen BB. Human
muscle gene expression following resistance exercise and blood flow restriction.
Med Sci Sports Exerc 40: 691–698, 2008.

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• Madarame H, Neya M, Ochi E, Nakazato K, Sato Y, Ishii N. Crosstransfer effects
of resistance training with blood flow restriction. Med Sci Sports Exerc 40: 258–
263, 2008.

• Patterson SD, Ferguson RA. Increase in calf post-occlusive blood flow and
strength following short-term resistance exercise training with blood Flow
restriction in young women. Eur J Appl Physiol 108: 1025–1033, 2010.

• Takarada Y, Takazawa H, Sato Y, Takebayashi S, Tanaka Y, Ishii N. Effects of

resistance exercise combined with moderate vascular occlusion on muscular
function in humans. J Appl Physiol 88: 2097–2106, 2000.

• Yasuda T, Fujita S, Ogasawara R, Sato Y, Abe T. Effects of low intensity bench

press training with restricted arm muscle blood flow on chest muscle
hypertrophy: a pilot study. Clin Physiol Funct Imaging 30: 338–343, 2010.

In a recent meta-analysis the effect size (ES) for

strength between BFR vs. exercise at low load
was compared. The BFR and exercise ES was
0.58 compared to 0.00 (no effect) for the exercise
group. (Loenneke 2012) Additionally, there is a
significant increase in hypertrophy using a
tourniquet during low load exercise compared to
the same exercise without a tourniquet. Some of
the studies that have shown this effect:

• Abe T, Kearns CF, Sato Y. Muscle size and

strength are increased following walk training with restricted venous blood flow
from the leg
muscle, Kaatsu-walk training. J Appl Physiol 100: 1460–1466, 2006.

• Abe T, Sakamaki M, Fujita S, Ozaki H, Sugaya M, Sato Y, Nakajima

T. Effects of low-intensity walk training with restricted leg blood flow on
muscle strength and aerobic capacity in older adults. J Geriatr Phys Ther
33: 34–40, 2010.

• Abe T, Sato Y, Inoue K, Midorikawa T, Yasuda T, Kearns CF,

Koizumi K, Ishii N. Muscle size and IGF-1 increased after two weeks of
low-intensity “Kaatsu” resistance training (Abstract). Med Sci Sports
Exerc 36: S353, 2004.

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 • Madarame H, Neya M, Ochi E, Nakazato K, Sato Y, Ishii N. Crosstransfer
effects of resistance training with blood flow restriction. Med Sci
Sports Exerc 40: 258–263, 2008.

• Martin-Hernandez, J., Marin, P. J., Menendez, H., Loenneke, J. P., Coelho

-e-Silva, M. J., Garcia-Lopez, D., & Herrero, A. J. (2013). Changes in
muscle architecture induced by low load blood flow restricted training. Acta
Physiol Hung, 100(4), 411-418.

• Takarada Y, Takazawa H, Sato Y, Takebayashi S, Tanaka Y, Ishii N.

Effects of resistance exercise combined with moderate vascular occlusion
on muscular function in humans. J Appl Physiol 88: 2097–2106, 2000.

• Yasuda, T., Fukumura, K., Uchida, Y., Koshi, H., Iida, H., Masamune, K., . . .
Nakajima, T. (2014). Effects of Low-Load, Elastic Band Resistance Training
Combined With Blood Flow Restriction on Muscle Size and Arterial Stiffness in
Older Adults. J Gerontol A Biol Sci Med Sci.

• Wilson, J. M., Lowery, R. P., Joy, J. M., Loenneke, J. P., & Naimo, M. A. (2013).
Practical blood flow restriction training increases acute determinants of
hypertrophy without increasing indices of muscle damage. J Strength Cond Res,
27(11), 3068-3075.

The effect size between BFR + exercise vs low

intensity exercise vs HIT on muscle CSA
demonstrates a 0.39 ES for BFR, -0.01 for low
intensity exercise and 0.35 for HIT. As
mentioned, the results comparing BFR to HIT are
comparable. A list of some of the studies that
have demonstrated similar changes in strength
and hypertrophy between BFR and HIT are listed
below.

• Martin-Hernandez, J., P. J. Marin, H. Menendez, C. Ferrero, J. P. Loenneke, and A.

J. Herrero. 2013. Muscular adaptations after two different volumes of blood flow-
restricted training. Scand. J. Med. Sci. Sports 23:e114–e120.

• Vechin, F. C., C. A. Libardi, M. S. Conceicao, F. R. Damas, M. E. Lixandrao, R. P.

Berton, et al. 2015. Comparisons between low-intensity resistance training with

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 blood flow restriction and high-intensity resistance training on quadriceps muscle
mass and strength in elderly. J. Strength Cond. Res. 29:1071–1076.

• Laurentino, G. C., Ugrinowitsch, C., Roschel, H., Aoki, M. S., Soares, A. G.,
Neves, M., Jr., Tricoli, V. (2012). Strength training with blood flow restriction
diminishes myostatin gene expression. Med Sci Sports Exerc, 44(3), 406-412.

• Lowery, Ryan P., et al. "Practical blood flow restriction training increases muscle
hypertrophy during a periodized resistance training programme."Clinical
physiology and functional imaging 34.4 (2014): 317-321.

• 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. J Appl Physiol (1985), 88(6), 2097-
2106.

• Clark, B. C., et al. (2011). "Relative safety of 4 weeks of blood flow-restricted

resistance exercise in young, healthy adults." Scand J Med Sci Sports 21(5):
653-662.

• Kubo K, Komuro T, Ishiguro N, et al.. Effects of low-load resistance training with

vascular occlusion on the mechanical properties of muscle and tendon. J Appl
Biomech. 2006; 22 (2): 112–9.

• Karabulut M, Abe T, Sato Y, Bemben MG. The effects of low-intensity resistance

training with vascular restriction on leg muscle strength in older men. Eur J Appl
Physiol. 2010; 108 (1): 147–55.

The effect size for strength between BFR, low load exercise and HIT are 0.58, 0 and 0.8
respectively. (Loenneke 2012/Krieger 2010) Of
note, subjects that are untrained have a larger
effect size on strength in the BFR cohort. This
is also true for HIT training. The meta-analysis
that estimated the ES for BFR strength looked
at trained and untrained studies. The meta-
analysis for HIT was composed of almost all
untrained subjects. This may explain the
discrepancy between the ES for HIT and BFR.

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From this large body of evidence it becomes apparent that the combination of vascular
occlusion with low-level exercise can induce a strength and hypertrophy response. In
fact, the strength and hypertrophy responses from BFR are so predictable that scientists
now use it as a model to study muscle physiology. The exact mechanism for these
adaptations to BFR and exercise are not fully understood. One likely mechanism is the
metabolite theory of muscle strength and hypertrophy, which researchers are just
recently beginning to understand. The increase in metabolic byproducts from anaerobic
metabolism seems to play as powerful a role in muscle physiology as mechanical load.
In an invited editorial on BFR in the Journal of Applied Physiology Dr. Meyer’s states
“the recommendation that hypertrophy requires a load 70% of one repetition maximum
might just as well be recast as a recommendation that the training must result in
substantial anaerobic metabolism”. He concludes his editorial by stating that the
responses seen from BFR “deserves serious consideration from those interested in the
molecular biology of hypertrophy”. (Meyers 2006) Dr. Schoenfeld’s recent review on the
subject is an excellent source for further background on the metabolic adaptations to
hypertrophy. (Schoenfeld 2013)

What we do know is that BFR and low-level exercise has an effect on strength
and hypertrophy. What we don’t know is the exact mechanism. Current theories behind
the proposed mechanisms of BFR include increased fiber type recruitment, metabolic
accumulation, activation of muscle protein synthesis, and cell swelling, although it is
likely that many of the aforementioned mechanisms work together.

Understanding two of the prevailing mechanisms, metabolite accumulation and

cellular swelling, can aide the rehabilitation professional to develop personalized
protocols for a wide range of injuries. We will begin with metabolite accumulation.

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Additional Notes:

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 Bibliography

Donnelly JE, Blair SN, Jakicic JM, Manore MM, Rankin JW, Smith BK; American College of Sports
Medicine. American College of Sports Medicine Position Stand. Appropriate physical activity
intervention strategies for weight loss and prevention of weight regain for adults. Med Sci Sports
Exerc. 2009;41:459-471.

Kraemer WJ, Adams K, Cafarelli E, et al. American College of Sports Medicine position stand:progression
models in resistance training for healthy adults. Med Sci Sports Exerc. 2002;34(2): 364–80.

Loenneke, J. P., Wilson, J. M., Marin, P. J., Zourdos, M. C., & Bemben, M. G. (2012). Low intensity blood
flow restriction training: a meta-analysis. Eur J Appl Physiol, 112(5), 1849-1859. doi:
10.1007/s00421-011-2167-x

Meyer, R. A. (2006). Does blood flow restriction enhance hypertrophic signaling in skeletal muscle? J Appl
Physiol (1985), 100(5), 1443-1444.

Schoenfeld, B. J. (2013). Potential mechanisms for a role of metabolic stress in hypertrophic adaptations
to resistance training. Sports Med, 43(3), 179-194. doi: 10.1007/s40279-013-0017-1

Takarada, Y., Tsuruta, T., & Ishii, N. (2004). Cooperative effects of exercise and occlusive stimuli on
muscular function in low-intensity resistance exercise with moderate vascular occlusion. Jpn J.
Physiol, 54(6), 585-592.

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. J Appl
Physiol (1985), 88(6), 2097-2106.

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 Metabolite Theory
Lactate Production
Blood flow restriction (BFR) training follows many of the same physiological principles
as traditional high load strength training. However, there is a very important difference.
High load training uses the mechanical tension across the muscle to recruit higher order
motor units. This is the size principle of muscle fiber activation. Muscle is metabolically
expensive and our body has adapted to use the most efficient means to complete a
task. We always need to remember that although we are currently in a time of plentiful
food supplies, we evolved from a period of hunter gathering and more muscle means a
higher metabolism and the need for more food. We have multiple checks and balances
within our muscle metabolism to limit hypertrophy. Lifting heavy loads or doing powerful
activities such as sprinting forces our body to switch from slow twitch oxidative fibers to
fast twitch anaerobic fibers. Anaerobic metabolism produces very strong contractions,
is very short lived and creates subsequent byproducts. The byproduct of this action
lactate and hydrogen ions create the subsequent burn you feel in your muscle. This
burn you feel in the muscle is not muscle damage, it is simply the acidic environment
being created. However, during powerful contractions there is subsequent muscle
damage. This is why you cannot do heavy bench press every day in the gym (although
most guys try to). The mechanical tension theory was initially understood through lab
studies that simply attached a weight to a bird wing and allowed it to hang for several
days. The tension across the muscle and subsequent muscle damage created a
hypertrophy effect from growth factors released.

Blood flow restriction training also taps into the fast twitch fiber recruitment but it doesn’t
follow the mechanical tension model, the loads are very low. With blood flow restriction,
we limit the oxygen supply to a working muscle, which essentially forces it to switch
from aerobic to anaerobic metabolism. The same byproduct is lactate within the
muscle. When a person performs BFR exercises they will most definitely feel the
lactate “burn”.

The Kreb’s Cycle (or Citric Acid Cycle), utilizes oxygen to produce energy (ATP). While
we are doing sub-maximal or low intensity work the Kreb’s Cycle works completely fine
utilizing aerobic (using oxygen) metabolism. As long as we have sufficient oxygen then
pyruvate is fed into the Kreb’s Cycle and we can carry out work indefinitely (or at least
until we run out of food). For the metabolite theory of muscle strength and hypertrophy
we must build up lactate, which isn’t produced from the Kreb’s Cycle. To do this we
must activate the Cori Cycle.

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The Cori Cycle (or Lactic Acid Cycle) is the metabolic pathway where lactate is
produced by anaerobic metabolism; a byproduct of the Cori Cycle is lactate. The net
result is1 glucose molecule creating 2 lactate by-products. Lactate is moved out of the
muscle and to the liver where it undergoes gluconeogenesis, which is the conversion of
lactate to glucose, or it is used to replenish depleted glycogen stores. As mentioned,
heavy loads or powerful contractions utilize the Cori Cycle. If BFR truly activates this
cycle we should see a subsequent rise in lactate.

This is indeed what we see in the literature. Multiple studies that have measured blood
lactate after BFR have demonstrated a subsequent rise
in lactate. For instance, when comparing a load of 20%
1 RM low load exercise with and without a tourniquet
only the tourniquet group demonstrated a significant rise
in lactate. (Takarada 2000)

Additionally, Poton et al demonstrated that the levels of

blood lactate accumulation were similar between BFR
and exercise at
low load (20% 1RM) and High Intensity Training
(HIT 80% 1RM). A control group that performed
low load exercise (20%1RM) without BFR did not
have a significant rise in lactate. (Poton 2014) In
theory, the more hypoxic the muscle becomes
the more need for anaerobic metabolism.
Takarada et al supported this by demonstrating
that as tourniquet occlusive pressure is increased
(creating less oxygen within the muscle) limb
lactate concentration also increases. (Takararda
2000) This is a consequence of reduced oxygen supply and an increased need for
anaerobic metabolism. In the same study blood lactate was measured under varying
conditions, a control group that wore a tourniquet but did not exercise, a BFR group that
did 40% 1RM and a BFR group that did 80% 1RM. Only the BFR and exercise group
demonstrated a significant increase in lactate production. This tells us that it is not
simply the application of a tourniquet that activates the Cori Cycle and that exercise is
needed if a lactate response is desired.

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 What is interesting from this study is that the largest
lactate accumulation was the 40% 1RM group. The
authors speculated that the high intensity repetitions
(80% 1RM) were strong enough to cause a muscle
pumping effect and pushed out the metabolites. This
has also been observed in another study that
demonstrated no additional benefit of BFR during
moderate load (12 RM) and high load (6 RM) resistance
exercise on measures of muscle strength and size.
(Laurentino 2008) In fact, a recent meta-analysis found
that loads of 15-30% 1 RM had the largest effect on muscle size and strength when
employing BFR. (Loenneke 2012) This will be discussed in much more detail in the
Exercise Prescription chapter.

Unpublished literature from Dr. Jeremy Loenneke’s lab has demonstrated a significant
increase in lactate accumulation in the upper extremity using 50% limb occlusion
pressure. (Scott 2015) Although lactate wasn’t directly measured Sundberg et al in a
study dating back to 1994 found during ischaemic exercise (BFR) that there was a
higher degree of glycogen depletion, a greater depletion in type II vs. type I fibers, lower
ATP and higher nitrate content which are all byproducts of anaerobic metabolism.
(Sundberg 1994)

Loenneke et al did not demonstrate an increase in lactate after performing BFR and
exercise using knee wraps as a tourniquet. In this study, subjects performed knee
extension exercises with leg wraps and were compared to a work matched control that
did not use leg wraps. At the conclusion of the study there was no difference between
groups and the authors concluded with the statement that the “study does not support
the use of knee wraps as a mode of blood-flow restriction”. (Loenneke 2012) It is
possible that devices such as knee wraps either do not provide enough of an occlusive
effect or are unable to trap metabolites to build up a lactate response. This may re-
enforce the idea that a proper pneumatic tourniquet is needed to maintain a metabolite
build up.

In summary, utilizing BFR and doing low intensity exercise appears to augment lactate
production in the working muscle. The most obvious explanation for this is the hypoxic
state created by the tourniquet and the activation of fast glycolytic fibers (even though it
is light weight). However, other than demonstrating that we are in the Cori Cycle why
would we care about increasing lactate? One reason is the effect on motor unit
recruitment.

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Additional Notes:

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 Bibliography

Laurentino G, Ugrinowitsch C, Aihara AY, et al. Effects of strength training and vascular
occlusion. Int J Sports Med. 2008; 29(8): 664–7.

Loenneke JP, Wilson JM, Marin PJ, et al. Low intensity blood flow restriction training: a meta-
analysis. Eur J Appl Physiol.2012; 112(5):1849–59.

Loenneke, J. P., Kearney, M. L., Thrower, A. D., Collins, S., & Pujol, T. J. (2010). The acute
response of practical occlusion in the knee extensors. J Strength Cond Res, 24(10),
2831-2834.

Poton, R., & Polito, M. D. (2014). Hemodynamic response to resistance exercise with and without
blood flow restriction in healthy subjects. Clin Physiol Funct Imaging. doi:
10.1111/cpf.12218

Scott, B. R., Loenneke, J. P., Slattery, K. M., & Dascombe, B. J. (2014). Exercise with Blood Flow
Restriction: An Updated Evidence-Based Approach for Enhanced Muscular Development.
Sports Med. doi: 10.1007/s40279-014-0288-1

Sundberg, C. J. (1994). Exercise and training during graded leg ischaemia in healthy man with
special reference to effects on skeletal muscle. Acta Physiol Scand Suppl, 615, 1-50

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. J Appl Physiol (1985), 88(6), 2097-2106.

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 Metabolite Theory
Muscle Activation

Interestingly the increase in lactate may also drive an increase in muscle activation
(measured as iEMG activity). As lactate builds up in muscle, it inhibits the surrounding
contraction of working muscle fibers and consequently additional motor units need to be
recruited to maintain muscle force production. (Moritani 1992, Sundberg 1994, Miller
1996) This essentially follows the size principle in that as work under heavy load is
performed the muscle will recruit larger motor units (fast twitch) to complete the task.
Utilizing BFR to produce lactate also forces the muscle to use larger motor units. The
reduction in oxygen and subsequent metabolic accumulation during BFR increases fiber
recruitment through stimulation of the group III and IV afferents, which may cause an
inhibition of the alpha motor neuron, resulting in an increased fiber recruitment to
maintain force and protect against conduction failure. (Yasuda 2010)

In an older study (1992)

measuring blood lactate
under ischemic conditions
Moritani et al
demonstrated that
additional recruitment of
motor units must take
place to continue force
development. The
amount of muscle activity was correlated to the amount of
lactate production. Furthermore, as occlusion pressure is increased the resultant lack of
oxygen in the working muscle produces higher iEMG activity. (Sundberg 1994) As
mentioned in the previous chapter, the increase in occlusive pressure also increases
lactate production. So, as a muscle is forced to use more and more higher order fibers
(fast twitch) during anaerobic metabolism we not only see a rise in lactate but also
increased iEMG signal.

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 Support for iEMG and lactate hypothesis was
further explored by Yasuda et al who had
subjects exercise with elastic bands with BFR
and a control that exercised with the same
bands and same workload but did not use
BFR. The study found that blood lactate
concentration post training was significantly
higher under BFR than under CON (3.6 and
2.1 mmol/L, respectively).

Furthermore, during the triceps extension and

biceps flexion exercises, muscle activation
increased progressively under BFR (46% and 69%, respectively) but not under CON
(12% and 23%, respectively).

Blood lactate concentration at Post was significantly correlated with increased iEMG in
both triceps extension (r = 0.65, P < 0.01) and
biceps flexion exercises (r = 0.52, P < 0.05). Thus,
doing a typical “rehab” exercise using elastic
bands and BFR significantly increased blood
lactate vs. controls and subsequently increased
iEMG activity. (Yasuda 2014) This has also been
confirmed in lower extremity exercise that
compared iEMG activity between BFR at 20% 1
RM and work-matched controls. A significantly
higher muscular activity in the BFR group was
seen vs. controls. (Takarada 2000)

Further proof was seen in a study where subjects served as their own controls. iEMG
activity of the quadriceps was measured during three scenarios: One day subjects
muscle activity was measured doing nothing, one day it was measured just wearing a
tourniquet and 1 day wearing a tourniquet and performing low load exercise. As
expected, only the BFR and exercise day elicited a neuromuscular response. This
response was 217% higher than baseline measurements at 15% MVC. (Pierce 2006)

It also makes sense that the longer you can exercise in a hypoxic state the more fast
twitch fibers will need to be activated. If there is insufficient oxygen supply but the
exercise is still ongoing then the muscle is forced to recruit more motor units. Indeed,
Wilson et al found that after 4 sets of low resistance exercise (30% 1RM) there is not a
significant increase in iEMG without a tourniquet (still in the Kreb’s Cycle), however
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 there is with the addition of vascular occlusion.
Furthermore, the rise in muscle activity in the BFR
group was significantly higher by the final set
compared to the first set. (Wilson 2013)

Additional studies that have found higher muscle

activity with BFR include: Yasuda 2008, 2012,
Manini 2012, Labarbera 2013, Cook 2013,
Takarada 2013 and Yamada 2004.

In conclusion, using a tourniquet and performing low-level exercise can increase lactate
production. There is also increased motor unit recruitment as a muscle continues to
exercise under BFR. In the following chapters we will discuss the elaborate anabolic
responses created by this process beginning with growth hormone.

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Additional Notes:

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 Bibliography

Cook SB, Murphy BG, Labarbera KE. Neuromuscular function following a bout of Low-load blood flow
restricted exercise. Med Sci Sports Exerc 2013; 45:67–74.

Labarbera KE, Murphy BG, Laroche DP, Cook SB. Sex differences in blood flow restricted isotonic knee
extensions to fatigue. J Sports Med Phys Fitness 2013;53:444–52.

Manini TM, Vincent KR, Leeuwenburgh CL, et al. Myogenic and proteolytic mRNA expression following
blood flow restricted exercise. Acta Physiol (Oxf) 2011;201:255–63.

Miller, K. J., S. J. Garland, T. Ivanova, and T. Ohtsuki. Motor-unit behavior in humans during fatiguing
arm movements. J. Neurophysiol. 75: 1629–1636, 1996.

Moritani, T., W. Michael-Sherman, M. Shibata, T. Matsumoto, and M. Shinohara. Oxygen availability and
motor unit activity in humans. Eur. J. Appl. Physiol. 64: 552–556, 1992.

Pierce, J. R., Clark, B. C., Ploutz-Snyder, L. L., & Kanaley, J. A. (2006). Growth hormone and muscle
function responses to skeletal muscle ischemia. J Appl Physiol (1985), 101(6), 1588-1595. doi:
10.1152/japplphysiol.00585.2006

Sundberg, C. J. Exercise and training during graded leg ischaemia in healthy man with special reference
to effects on skeletal muscle. Acta Physiol. Scand. 615, Suppl.: 1–50, 1994.

Takarada Y, Nakamura Y, Aruga S, Onda T, Miyazaki S, Ishii N. Rapid increase in plasma growth
hormone after low-intensity resistance exercise with vascular occlusion. J Appl Physiol (1985).
2000;88:61-65.

Takarada Y, Takazawa H, Sato Y, Takebayashi S, Tanaka Y, Ishii N. Effects of

resistance exercise combined with moderate vascular occlusion on muscular function in humans.
J Appl Physiol 2000;88:2097–106.

Wernbom, M., Jarrebring, R., Andreasson, M. A., & Augustsson, J. (2009). Acute effects of blood flow
restriction on muscle activity and endurance during fatiguing dynamic knee extensions at low
load. J Strength Cond Res, 23(8), 2389-2395.

Wernbom, M, Augustsson, J, and Thomee<< , R. Effects of vascular occlusion on muscular endurance in

dynamic knee extension exercise at different submaximal loads. J Strength Cond Res 20: 372–
377, 2006.

Wilson JM, Lowery RP, Joy JM, Loenneke JP, Naimo MA. Practical blood flow restriction training
increases acute determinants of hypertrophy without increasing indices of muscle damage. J
Strength Cond Res 2013;27:3068–75.

Yamada E, Kusaka T, Tanaka S, Mori S, Norimatsu H, Itoh S. Effects of vascular occlusion on surface
electromyography and muscle oxygenation during isometric contraction. J Sport Rehabil
2004;13:287–99.

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Yasuda, T., Brechue, W. F., Fujita, T., Shirakawa, J., Sato, Y., & Abe, T. (2009). Muscle activation during
low-intensity muscle contractions with restricted blood flow. J Sports Sci, 27(5), 479-489. doi:
10.1080/02640410802626567

Yasuda, T., Fukumura, K., Fukuda, T., Iida, H., Imuta, H., Sato, Y. Nakajima, T. (2014). Effects of low-
intensity, elastic band resistance exercise combined with blood flow restriction on muscle
activation. Scand J Med Sci Sports, 24(1), 55-61.

Yasuda T, Loenneke JP, Thiebaud RS, Abe T. Effects of blood flow restricted low intensity concentric or
eccentric training on muscle size and strength. PLoS One 2012;7:e52843.

Yasuda T, Brechue WF, Fujita T, Sato Y, Abe T. Muscle activation during low intensity muscle
contractions with varying levels of external limb compression. J Sports Sci Med 2008;7:467–74.

Yasuda T, Abe T, Brechue WF, et al. Venous blood gas and metabolite response to low-intensity muscle
contractions with external limb compression. Metabolism 2010;59:1510–9

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 Metabolite Theory

Growth Hormone
An accumulation of lactate and hydrogen ions within the muscle results in an
augmented growth hormone release. (Goto 2005, Takarada 2000) This has been
confirmed in experiments where sodium bicarbonate, an alkaline product that can
neutralize acidity, ingested before exercise decreased GH release after intense cycle
sprinting compared to work matched controls. (Gordon 1994)
Further proof comes from individuals that lack the enzyme
myophosphorylase, McArdle’s Syndrome, which inhibits the
formation of lactate during exercise. These individuals display
a blunted GH response to exercise. (Godfrey 2009) As
lactate builds in the muscle, group III-IV afferents stimulate
the pituitary gland to release GH. (Gosselink 1998) So if we
can get a build up of lactate within the muscle there will be a
subsequent rise in growth hormone. Does the accumulation of
lactate from BFR translate into increased GH secretion as
well? From the available evidence it most certainly appears
that it does. Takarada et al found a large and significant rise in GH after performing low
intensity BFR for approximately 10 minutes of exercise. A second group performing low
intensity exercise without occlusion and a third group that simply wore a tourniquet did
not have a significant rise in growth hormone. (Takarada 2000) As noted, just wearing a
tourniquet but not exercising did not produce a GH response. This highlights the
combined effects of utilizing a tourniquet with low-level exercise to produce this
systemic response.

This finding was re-enforced in a separate study that measured GH between a BFR and
work matched control group. In this study the rise in GH
was 290% higher than baseline measurements. This is
1.7X higher than what has been reported for HIT training.
(Takarada 2000, Kraemer 1990) A control group that
performed the same exercise load without a tourniquet
did not demonstrate a significant change. This rise in
growth hormone was over twice as high in the BFR group
compared to the controls.

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The graphs comparing the rise in growth hormone and lactate production from this
study nearly mirror each other lending further support to the lactate and GH hypothesis.

Pierce et al demonstrated further proof for the need of exercise to be combined with the
occlusion. Subjects served as their own controls and had GH measurements taken
after BFR with exercise or just wearing a tourniquet. A significant rise in GH was found
only after performing exercise under occlusion.
(Pierce 2006)

Recently researchers compared growth hormone

levels after BFR and HIT in older and younger
men. They found increased levels of growth
hormone for both groups, however the elderly
population had a lower GH response than the
younger men. Interestingly, the younger patients
demonstrated a higher rise in GH after BFR than
HIT. (Manini 2012) It appears that manipulating
the rest period may have an effect on GH
secretions during traditional exercise. Kraemer et al demonstrated a 100 fold increase
in GH after HIT (80% 1RM) exercise with a 1 minute rest. The same exercise load and
volume with a 3-minute rest did not elicit the same spike in GH. (Kraemer 1990, 1991)
This lends credence to the theory that the build up of metabolites that accumulates
during short rest periods may play a role in the GH response. With BFR the rest
periods are relatively short 30-90 seconds and perhaps more importantly the cuff stays
inflated during the rest period, which prevents the removal of metabolites (lactate for
this purpose) by the blood stream.

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Lastly, a study that may be of interest in the rehabilitation setting is the application of
electrical stimulation with BFR (involuntary contraction). In this study subjects
performed isometric knee extension contractions to 20% MVC using electrical
stimulation. The subjects served as their own controls and performed the contractions
one day under BFR and one day without. Only the BFR condition was associated with
a significant rise in GH. (Inagaki 2011) This would allow a clinician to combine BFR
with electrical stimulation in the early phases of rehabilitation to induce a subsequent
GH response.

Many other studies measuring growth hormone responses to BFR and exercise have
found significant responses including; Fujita 2006, Madarame 2008, Madarame 2010,
Yasuda 2010, Reeves 2006 and Takano 2005. The totality of this evidence supports the
role of BFR to increase growth hormone levels even with low load exercises. But does
it really matter that you raise GH levels for your patients? Isn’t GH something athletes
use illegally to get stronger? Unfortunately, the media has hyped what growth hormone
truly does and its true role may be even more valuable for injury recovery.
Perhaps the name “growth” combined with “hormone” automatically leads to the
assumption that it is involved in muscle hypertrophy. This hormone has certainly caught
the attention of the athletic world and popular press. In fact, it is one of the most
frequent questions I am asked about BFR. From folks wanting to know if it “can really
increase my HGH” to professional teams worried that their athletes will test positive for
anabolics if they do BFR.

Contrary to popular opinion, exogenous administration of GH may not lead to an

increase in protein synthesis and subsequent muscle hypertrophy. (Yarasheski 1992)
In a double-blinded study in which 47 healthy elderly men and women received either
placebo or GH for a 12-week-period, no difference in muscle strength, muscle power
and muscle hypertrophy was observed (Lange et al., 2002a). Rennie confirmed this in a
follow up study in 2003 that also demonstrated no effect on human muscle size and
muscle protein synthesis with the administration of rhGH. (Rennie 2003) Even though it
is widely believed that GH plays a role in muscle anabolism and athletic performance, a
recent systematic review found no effect of HGH on athletic performance. (Liu 2008)

However, we know that exercise is one of the most potent physiological stimulators of
GH secretion. (Weltman et al., 1992; Pritzlaff et al., 1999) Thus growth hormone must
have a role in helping the body after exercise. We now understand that the role is
recovery, primarily through increased collagen synthesis.

Recently Doessing et al demonstrated that growth hormone played a direct role in

increased collagen synthesis after exercise. (Doessing 2010) In the study, subjects
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took exogenous GH for 14 days and demonstrated a 3.9 fold increase in tendon mRNA
expression and a 5.8 fold increase in muscle collagen synthesis. Muscle protein
synthesis did not change. It appears that the role of growth hormone is to protect our
tendon and muscle collagen structure after exercise. Thus, the correlation of increased
GH release as the exercise intensity increases may be the body’s protective response
to help our tendons and other collagen rich matrix recover.

Support for this is also seen in animal models.

Following Achilles tendon transection in rats,
treatment with local GH injection resulted in a
faster functional recovery compared with
controls (Kurtz et al., 1999). Furthermore,
decreased connective tissue deposition
observed in growth hormone individuals
seems to be reversible by GH
supplementation, again pointing toward a
close positive correlation between the level of
GH and collagen synthesis in connective
tissue. (Baroncelli 2000) Likewise, conditions
with excessive GH secretions such as acromegally, like Andre the Giant, are associated
with peri-articular soft-tissue hypertrophy and excess cartilage synthesis, causing
arthropathy (Colao et al., 1998, 1999b; Scarpa et al., 2004).

More evidence for the effect of GH on tendon structure was recently revealed in a study
that immobilized 1 leg of elderly men for 2 weeks then followed this up with 6 weeks of
rehabilitation. One group received GH supplementation and a control group received
placebo. The GH group exhibited increased tendon stiffness and improved collagen
synthesis compared to the control. The authors concluded “in elderly humans, GH
seems to have a matrix stabilizing effect during inactivity and rehabilitation by
stimulating collagen expression in the musculotendinous tissue and increasing tendon
CSA and stiffness”. (Boessen 2014)

Now that we know that GH has a response on tendon healing as well as the
ultrastructure supporting muscles we can see the benefits it can play in rehabilitation.
So why aren’t there more studies looking at GH to help recover from injuries? Doessing
et al in their meta-analysis concluded that the positive effects of GH on tendon structure
is well established, however “the lack of such studies can possibly be explained by
ethical concerns regarding possible side effects of high-dose rhGH administration or
because of concerns of increasing abuse of ergogenic substances”. (Doessing 2005)

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With BFR you can induce increased growth hormone production and potential healing
through collagen synthesis. It is clear that if we can increase lactate accumulation there
will be an accompanying rise in GH. By using a tourniquet and safe low loads we can
manipulate the healing environment around injured tendon, muscle and bone through
increased collagen synthesis. This is important not only for collagen, ligament and bone,
but also for the collagen matrix that supports muscle and is often disrupted after injury.
A recent review paper in its discussion on GH concluded that the large spikes in GH, up
to 300 times from baseline as seen in BFR studies, is to facilitate remodeling pursuant
to myotrauma.(Schoenfeld 2013) Additionally, we can reduce stress on injured soft
issues, joints and bone using low loads to produce lactate with the accompanying rise in
GH (to levels equal if not higher to HIT). The body’s reaction to more and more
strenuous exercise is to increase GH response in preparation for the subsequent
collagen breakdown. The low loads associated with BFR do not cause this breakdown
and you end with a positive collagen turnover.

Additional Notes:

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 Bibliography

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Boesen, A. P., Dideriksen, K., Couppe, C., Magnusson, S. P., Schjerling, P., Boesen, M., Langberg, H
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Additional Notes:

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 Metabolite Theory

IGF-1 and Satellite Cells

Insulin like growth factor or IGF-1 is a protein that in humans has been linked to muscle
growth. In fact a clear cause-effect relationship between IGF-1 and muscle hypertrophy
has been established and some feel that it is the regulator of muscle mass.(Haddad
2004, Stewart 2010) It is stimulated by growth hormone and may play a part in the
confusion about the hypertrophic effects of GH. However, as we saw with GH the effect
IGF-1 has on actual muscle hypertrophy may not be from simple increased protein
synthesis. It appears that IGF-1 does not play a significant role in post-exercise protein
accretion. (Velloso 2010) However, the anabolic effects of IGF-1 appear to be
increased with mechanical loading and increases in IGF-1 have been correlated with
subsequent strength gains. (Hammed 2004, Kostek 2005)

We now know that GH has a primary role in collagen synthesis. And the GH-IGF-1
pathways both play a critical part in improving tendon and bone health. However,
hypertrophy is associated with IGF-1, but muscle protein synthesis isn’t. At face value
this doesn’t make sense because protein accretion is needed for growth. Actually, it
appears that the primary hypertrophic role of IGF-1 is the fusion of satellite cells into
existing muscle fibers. What are satellite cells? They are precursors to skeletal muscle
cells. Essentially they are stem cells for our muscles. In fact, they are the oldest adult
stem cells that we are known to have. The load induced mechanical strain of traditional
high intensity lifting damages the muscle cell, which produces a “leakage” of growth
factors. Two important growth factors in this pathway are GH, which activates the
satellite cells, and IGF-1, which chaperones and fuses them into the muscle fiber.

Once in the muscle fiber the satellite cell can become a new myocyte and perform all
the functions needed for repair and growth. Since the muscles nuclear-content-to-fiber
mass ratio is the limiting factor in how much muscle protein synthesis can be performed,
the addition of new myocytes via satellite cell differentiation is believed to be essential
for realizing increases in muscle mass.(Timmons 2011) The myonucleus can only
express so much mRNA and to significantly increase fiber size (hypertrophy) there
needs to be an increase in the number of myocytes (activate satellite cells). This is
termed the relevance of myonuclear domain.(Petrella 2008, O’Connor 2007)

There is some confusion as to the increased muscle growth being from hyperplasia
(increased number of fibers), or hypertrophy (increased size). Hyperplasia has never

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been proven in a human model. This theory came from the bird model where a weight
was hung from its wing for an extended period of time. This massive stretch on the
muscle created damage and subsequent new formations of fibers. However, it is most
likely not true fiber addition but splitting of fibers from the excessive force. One limiting
factor to studying this in humans is the sheer number of fibers you would need to count
(in the hundreds of thousands) at the beginning of the study then go back to the same
area and try and re-count them.

With the adoption of the metabolite theory, through a lot of help from the BFR literature,
we are now understanding that muscle hypertrophy is possible with minimal mechanical
tension. Hypertrophy type training, which focuses on metabolite build up, has been
found to result in significantly more IGF-1 levels compared to high-intensity protocols.
(Kraemer 1990, Kraemer 1991, Rubin 2005) This is not surprising as we discussed
before increased lactate levels from metabolite build up activate growth hormone and
growth hormone activates IGF-1. It is also not surprising that BFR studies also show
significant increases in IGF-1 vs. controls. (Abe 2005, Takano 2005, Fujita 2007)

Abe et al demonstrated
a significant rise in IGF-
1 compared to work
matched controls. They
also found significant
changes in strength and
CSA in the BFR group,
including hypertrophy of
gluteus.

Again, the ability to increase metabolites is key for activating these pathways. By
increasing GH you activate your muscles stem cells, IGF-1 helps bring these cells to
your muscle fiber to create a new myocyte. Thus, we should see a rise in satellite cells
with BFR training.

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 To confirm this, a recent
report in The Journal of
Physiology demonstrated
that 3 weeks of training
with BFR at low loads for
the knee extensors
resulted in a significant
rise in the muscles
myogenic stem cells.
(Nielsen 2012) A work
matched control group
did not demonstrate any
changes in satellite cell proliferation. The graphs demonstrate the proliferation of cells
in the BFR group for both type I and type II fibers. Most notably, the number of cells
was still elevated after 10 days of detraining.

The authors also confirmed that the cells were

incorporated into the muscle fiber (chaperoned by IGF-1),
which translates into additional myonuclei.
The gains in the number of satellite cells were 280% at
mid-training, 250% 3 days after and 140% at 10 days
post. There were no gains in the control group. The
gains typically seen after high load training are 30-50%.
(Kadi 2000, Kadi 2004, Olsen 2006) This led the authors
to conclude, “Active muscle contractions and vascular
occlusion are required to obtain highly amplified
elevations in MSC proliferation and differentiation”.

The same study examined muscle fiber size via biopsy.

The BFR group demonstrated a significant gain at mid
training and this persisted even after 10 days of
detraining. The control group had a significant increase at
mid-training, but this quickly went back to baseline after 3
days of detraining. The increase in muscle fiber area in
the BFR group was 30-40% during and after training. To
put this into perspective 12-16 weeks of heavy resistance
training has demonstrated a 15-20% increase in muscle
fiber area in untrained men. (Aagaard 2001, Kadi 2004, Olsen 2006) For even more
perspective, Petralla et al found a 37% increase in muscle fiber area after 16 weeks of
heavy lifting in individuals identified as hypertrophy responders. (Petrella 2008)

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In contrast, 12 weeks of low load training without BFR did not result in any change in
muscle fiber area. (Mackey 2010) The increase in muscle fiber area for the control
group at mid training in the current study was felt to be an effect of swelling which can
last up to 3 days after training. The prolonged increase in size in the BFR group 10
days after training was felt to be due to muscle protein synthesis. The addition of more
myonuclei represents an important mechanism for the maintenance of muscle mass
during detraining. In support of this, Jepersen et al found significant atrophy of type II
fibers after 10 days of detraining after a 90-day resistance protocol. A lack of myofibre
addition was found in the Jesperesen study, which is in contrast to this study and lends
further support to the need of additional myonuclei to maintain gains. (Jesperesen 2004)

Lastly, the addition of more myonuclei translated into a

significant increase in strength in the BFR group. The
control group did not demonstrate similar changes.

A second study a year later demonstrated an increase in

satellite cell proliferation immediately after exercise.
(Wernbom 2013) In this study subjects performed knee
extensions at 20% 1 RM under BFR, then waited 10
minutes and performed the same load and volume on
their opposite leg without BFR. The increase in satellite
cell proliferation in both legs 1 hour, 24 hours and 48
hours post exercise increased by 33-53%

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Additional Notes:

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 Bibliography

Aagaard P, Andersen JL, Dyhre-Poulsen P, Leffers AM,Wagner A, Magnusson SP, Halkjaer-Kristensen J

& Simonsen EB (2001). A mechanism for increased contractile strength of human pennate
muscle in response to strength training: changes in muscle architecture. J Physiol 534, 613–623.

Abe T, Yasuda T, Midorikawa T, et al. Skeletal muscle size and circulating IGF-1 are increased after two
weeks of twice daily KAATSU resistance training. Int J Kaatsu Train Res. 2005;1: 6–12.

Fujita S, Abe T, Drummond MJ, et al. Blood flow restriction during low-intensity resistance exercise
increases S6K1 phosphorylation and muscle protein synthesis. J Appl Physiol. 2007;103(3):903–
10.

Haddad F, Adams GR. Inhibition of MAP/ERK kinase prevents IGF-I-induced hypertrophy in rat muscles.
J Appl Physiol. 2004;96(1):203–10.

Hameed M, Lange KH, Andersen JL, et al. The effect of recombinant human growth hormone and
resistance training on IGF-I mRNA expression in the muscles of elderly men. J Physiol.
2004;555(Pt 1):231–40.

Jespersen JG, Nedergaard A, Andersen LL, Schjerling P & Andersen JL (2011). Myostatin expression
during human muscle hypertrophy and subsequent atrophy: increased myostatin with detraining.
Scand J Med Sci Sports 21,215–223.

Kadi F, Schjerling P, Andersen LL, Charifi N, Madsen JL, Christensen LR & Andersen JL (2004). The
effects of heavy resistance training and detraining on satellite cells in human skeletal muscles. J
Physiol 558, 1005–1012.

Kadi F & Thornell LE (2000). Concomitant increases in myonuclear and satellite cell content in female
trapezius muscle following strength training. Histochem Cell Biol 113, 99–103.

Kostek MC, Delmonico MJ, Reichel JB, et al. Muscle strength response to strength training is influenced
by insulin-like growth factor 1 genotype in older adults. J Appl Physiol. 2005;98(6): 2147–54

Kraemer WJ, Marchitelli L, Gordon SE, et al. Hormonal and growth factor responses to heavy resistance
exercise protocols. J Appl Physiol. 1990;69(4):1442–50.

Kraemer WJ, Gordon SE, Fleck SJ, et al. Endogenous anabolic hormonal and growth factor responses to
heavy resistance exercise in males and females. Int J Sports Med. 1991;12(2): 228–35.

Mackey AL, Holm L, Reitelseder S, Pedersen TG, Doessing S, Kadi F & Kjaer M (2010). Myogenic
response of human skeletal muscle to 12 weeks of resistance training at light loading intensity.
Scand J Med Sci Sports 21,

Nielsen, J. L., Aagaard, P., Bech, R. D., Nygaard, T., Hvid, L. G., Wernbom, M., . Frandsen, U. (2012).
Proliferation of myogenic stem cells in human skeletal muscle in response to low-load resistance
training with blood flow restriction. J Physiol, 590(Pt 17), 4351-4361. 773–782.

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O’Connor RS, Pavlath GK. Point:counterpoint: satellite cell addition is/is not obligatory for skeletal muscle
hypertrophy. J Appl Physiol. 2007;103(3):1099–100.

Olsen S, Aagaard P, Kadi F, Tufekovic G, Verney J, Olesen JL, Suetta C & Kjaer M (2006). Creatine
supplementation augments the increase in satellite cell and myonuclei number in human skeletal
muscle induced by strength training. J Physiol 573, 525–534.

Petrella JK, Kim JS, Mayhew DL, Cross JM & Bamman MM (2008). Potent myofiber hypertrophy during
resistance training in humans is associated with satellite cell-mediated myonuclear addition: a
cluster analysis. J Appl Physiol 104, 1736–1742.

Rubin MR, Kraemer WJ, Maresh CM, et al. High-affinity growth hormone binding protein and acute heavy
resistance exercise. Med Sci Sports Exerc. 2005;37(3):395–403.

Stewart CE, Pell JM. Point:Counterpoint: IGF is/is not the major physiological regulator of muscle mass.
Point: IGF is the major physiological regulator of muscle mass. J Appl Physiol.
2010;108(6):1820,1; discussion 1823-4; author reply 1832.

Takano H, Morita T, Iida H, et al. Hemodynamic and hormonal responses to a short-term low-intensity
resistance exercise with the reduction of muscle blood flow. Eur J Appl Physiol. 2005;95(1):65–
73.

Timmons JA. Variability in training-induced skeletal muscle adaptation. J Appl Physiol. 2011;110(3):846–
53.

Velloso CP, Harridge SD. Insulin-like growth factor-I E peptides: implications for aging skeletal muscle.
Scand J Med Sci Sports. 2010;20(1):20–7.

Wernbom, M., Apro, W., Paulsen, G., Nilsen, T. S., Blomstrand, E., & Raastad, T. (2013). Acute low-load
resistance exercise with and without blood flow restriction increased protein signalling and
number of satellite cells in human skeletal muscle. Eur J Appl Physiol, 113(12), 2953-2965.

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 Metabolite Theory
Myostatin

(Image Courtesy of the Wall Street Journal)

In 1997 scientists at Johns Hopkins University were studying proteins involved in

muscle growth. One they thought was important was isolated and “knocked out” in a
mouse model. They expected the mouse to whither and die. To their surprise, the
mouse lived. At first the researchers were disappointed because the protein they
isolated looked like it didn’t work. Fortunately, the mouse wasn’t sacrificed after the
study and it went back in its cage. Over the ensuing days and weeks the researchers
began to notice that the mouse looked more and more swollen. Perplexed the
researchers dissected the mouse and found it had an extreme amount of muscle
hypertrophy.

Removing this protein made a very muscled

mouse. The team named the protein myostatin
and the enthusiasm of researchers, drug
companies and body-builders was at a fever pitch
to develop a myostatin-blocking drug.
Researchers could not find any evidence of this
deficient gene in humans. They did find a breed of
cattle known for it’s massive muscle, the Belgian

Blue, was deficient in myostatin. This explains not only the animal’s massive size but
also its low fat content and not surprisingly lack of people clamoring to eat its steaks.

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Still, the team was coming up short finding a human surrogate to these animals. Then
several years ago word got out about a German baby born with an inordinate amount of
muscle. Upon testing the child it was discovered that he was deficient of the myostatin
gene. The child is doing very well today and is still very muscular.

Fast forward 18 years and we still don’t have a commercial myostatin-blocking drug. It
is not from lack of trying. In fact many drug companies feel that it could be one of the
greatest discoveries not only for muscle wasting diseases, sarcopenia, cachexia and
possibly black market abuse but also for their bank accounts. J.P. Morgan estimated
$3.4 billion in annual sales for a potential Novartis myostatin-blocking drug.

Myostatins role is to block myogenesis, or muscle cell growth and differentiation. Think
of it as the bodies switch to shut muscle development off. We would want this because
muscle is extremely costly metabolically. If we were hunter-gatherers and a saber tooth
tiger was chasing us, we would recruit fast twitch fibers build up metabolites and kick off
the cascade we have discussed in previous chapters. For a while myostatin would
down regulate because our body knows we need to get a little bit stronger and faster to
run away from the tiger next time. However, it would bring myostatin back up to slow or
stop this muscle growth because it knows we might also starve to death if we have too
much muscle and the associated need to feed it.

But for our purposes, we want to down regulate myostatin for our patients so that they
can benefit from their resistance training. How do we do this?

For starters, patients can lift heavy. Roth et al demonstrated a down regulation of
myostatin after 9 weeks of heavy (up to 85% 1 RM) lifting. This also correlated to an
increase is muscle strength and hypertrophy. (Roth 2003) This has been confirmed by
other studies. (Forbes 2006, Hill 2003, Saremi 2010 and Willoghby 2004) This makes
sense because a stressful event such as running for your life or lifting very heavy weight
(your body doesn’t know the difference) should be enough of a signal to allow us to put
on some muscle (i.e…. shut myostatin off for a brief bit). It would also make sense that
BFR would down regulate myostatin since we have learned it makes your body believe
it has gone through a stressful situation similar to heavy lifting.

To confirm this, Laurentino et al measured myostatin markers between 3 groups. One

group performed low intensity resistance training (20% 1 RM) a second group
performed low intensity resistance training (20% 1 RM) under blood flow restriction and
a third group performed high intensity resistance training (80% 1RM). This was carried
out over 8 weeks. They also measured muscle strength and muscle cross sectional
area. (Laurentino 2012)

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 At the conclusion of the experiment only the BFR and HIT
groups demonstrated a significant reduction in myostatin.

Additionally muscle cross sectional area was increased in

the BFR and HIT groups, but not in the controls. (Fig 31)
The muscle strength increased proportionately between the
BFR and HIT groups (36.2% and 40.1%) the low intensity
group did not have a significant change. The authors
concluded, that these findings suggest that both BFR and
HIT resulted in a diminished proteolysis rate (protein
breakdown), which may at least partially explain the significant muscle mass increment
observed in these groups.

The study mentioned above confirmed what we knew about high intensity training, it
could down regulate myostatin, which correlates to an increase in muscle size and
strength. It also told us that BFR has the same effect and that exercise using the same
load and same volume without occlusion does not have an effect. In fact the decrease
in myostatin was slightly higher (45%) in the BFR group than the HIT group (41%)
although statistical significance was not met.

Novartis is leading the race in a myostatin-blocking drug named BYM338. Their current
trial is on a rare muscle-wasting disease called inclusion-body myositis. They have
demonstrated a small increase in thigh size and the ability to walk farther by taking their
drug, although the effects wore off after the treatment was stopped.

Severe muscle wasting is a symptom of inclusion-body myositis. It is believed that this

is from an exaggerated inflammatory response. The disease process is unfortunately
unresponsive to anti-inflammatory treatments. Until recently, exercise was
contraindicated in these patents because it was believed to increase the inflammatory
response. However, new evidence revealed that these patients tolerated low intensity
exercise. Unfortunately, as we have seen low intensity low load exercise is not a good
option if you are seeking to diminish atrophy and develop hypertrophy. Traditional
heavy load exercise does result in an increased inflammatory response and again was
not an option for this patient population.

BFR has the potential to block the myostatin gene to the same levels as HIT.
Additionally, the Novartis drug trial demonstrated improvements in this patient
population by blocking myostatin. So, recently researchers attempted BFR on a 65-
year-old male with an 8-year history of idiopathic myositis. He had muscle wasting most

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pronounced in his quadriceps and a significant history of falls. Of note, he had been
attending Physical Therapy for over a year, however he noted a decline in his
improvement. Most notably he was now dependent on an assistive device to ambulate
and his muscle strength and size (tape measurement) had diminished by 5% and 7%
respectively.

He underwent BFR at 20%, 1 RM 2x a week for 12 weeks.

The exercises included
leg press, 1/2 squat and
leg extensions. At the
conclusion of his
program he
demonstrated a 15.9%
improvement in leg
press 1RM. His timed
up and go test improved
60% and thigh CSA as
measured by MRI
increased 4.7%. All SF-36 subscales indicated the
patient’s progress. The specific changes were 150%
for physical functioning, 7400% for role–physical, 57% for bodily pain, 18% for general
health, 267% for vitality, 600% for social functioning, 200% for role–emotional, and 43%
for the mental health scales. Just as important markers of muscle damage or
inflammation stayed within normal limits. Additionally, the measurement of IGF-1
(through mechanogrowth factor) increased 3.97 fold, which may explain the increase in
muscle CSA. To support this after 10 weeks of detraining the patient’s leg press 1 RM
only decreased by 0.5%. (Gualano 2010)

To follow up on this, researchers last year measured

myostatin levels in a patient with inclusion body
myositis. He performed BFR exercises on his lower
extremities 2 days a week for 12 weeks. After the
training the researchers found a 25% reduction in
myostatin levels. They also found increases in IGF-1
related growth factors. (Santos 2014)

So, mysostatin is the switch that allows proliferation

of myogenic stem cells to proliferate and allow

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muscle hypertrophy. Decreased myostatin is key for muscular hypertrophy. Two ways
shown to do this are heavy resistance training or light resistance training with BFR.
However, myostatin also has another role, which is to help induce fibrosis.

Myoststatin and TGF-Beta

One-way mysostatin blocks muscle growth is through inhibiting satellite cell

proliferation. (McCroskery 2003, Mendias 2012) This in turn limits the protein synthesis
potential as well as regeneration capability of muscle after injury. Why would our body
have a protein that blocks muscle regeneration after injury?

Myostatin belongs to the TGF-Beta superfamily. These proteins are found in many cells
and are released upon damage to the cell. In some cases, the injured tissue
regenerates to native tissue (gut, bladder) In other cases, such as skeletal tissue there
is often a large increase in fibrosis. (Branton 1999) Why would we evolve to this state?
One theory is that our organs simply will not function if they had significant scarring after
injury and some regeneration capacity is necessary for survival. However, if we were
again running from the proverbial saber tooth lion and we injured a muscle we do not
have time to allow full muscle regeneration. The bodies response to an injury to muscle
tissue is fibrosis which can occur very quickly and fill in the gap of the injured tissue
(much like filling in a pot hole on the street). Thus, quickly scarring down the damaged
tissue with collagen may not make us better, but it will allow us to keep moving over the
ensuing days and weeks.

One approach to treating fibrosis in skeletal tissue

is gene specific targeting to block these pathways.
Recently, Johnny Huard, PhD and colleagues at
UPMC discovered that blocking the TGF-Beta
pathway with a drug, an ace inhibitor, improved
the regeneration of injured tissue in an animal
model. (Terada 2013)

Myostatin, a member of the TGF-Beta family, is

found almost exclusively in the muscle. It has
been demonstrated in animal models that
inhibiting myostatin after injury reduces the
fibrosis seen in the muscle. (Wagner 2005) And even more impressively researchers at
Johns Hopkins found that lowering myostatin reversed muscle fibrosis. (Bo 2012)

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As mentioned before we still do not have a commercially available myostatin-blocking
drug in humans. Also, blocking complete pathways in the human body can lead to
bigger problems such as bleeding gums. Furthermore, a recent study found that
completely blocking TGF-Beta helps in early recovery but leads to worse changes long
term in animals.(Gumucio 2013)

However, we do have a mechanism to reduce myostatin naturally with light loads.

Blood flow restriction. After a muscle injury you would never advise your patient to lift
weights in excess of 80% 1RM to reduce the ensuing fibrosis from myostatin. This can
make BFR with low loads a means to help with the regenerative process by down
regulating myostatin and allowing satellite cell differentiation.

BFR can increase GH, IGF-1 and cause a subsequent proliferation and differentiation of
the muscles stem cells. The fact that this happens acutely and is maintained even after
detraining can explain the fact that we typically see hypertrophy and strength gains in
our patients within a few weeks. Traditionally, strength training follows an increase in
neuromuscular recruitment early on and gains in hypertrophy after a prolonged period of
training (>12 weeks). BFR flips this paradigm to an early hypertrophy model through its
metabolite build up pathway. However, the actual gain in muscle size and strength
needs protein synthesis. Up to this point we have not identified the pathway that is
responsible for muscle protein synthesis (MPS) with BFR. Furthermore, to make a
conclusive case that BFR actually increases fiber size through protein accretion we
would need evidence that BFR is intimately involved in MPS. The next chapter will
provide a conclusive case for this.

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Additional Notes:

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 Bibliography

Bo Li Z1, Zhang J, Wagner KR. Inhibition of myostatin reverses muscle fibrosis through apoptosis. J
Cell Sci. 2012 Sep 1;125(Pt 17):3957-65. doi: 10.1242/jcs.090365. Epub 2012 Jun 8.

Branton, M. H., & Kopp, J. B. (1999). TGF-beta and fibrosis. Microbes Infect, 1(15), 1349-1365.

Forbes D, Jackman M, Bishop A, Thomas M, Kambadur R, Sharma M. Myostatin

auto-regulates its expression by feedback loop through Smad7 dependent mechanism. J Cell
Physiol. 2006; 206(1). 264–72.

Gualano, B., Neves, M., Jr., Lima, F. R., Pinto, A. L., Laurentino, G., Borges, C. Ugrinowitsch, C. (2010).
Resistance training with vascular occlusion in inclusion body myositis: a case study. Med Sci
Sports Exerc, 42(2), 250-254.

Gumucio, J. P., Flood, M. D., Phan, A. C., Brooks, S. V., & Mendias, C. L. (2013). Targeted inhibition of
TGF-beta results in an initial improvement but long-term deficit in force production after
contraction-induced skeletal muscle injury. J Appl Physiol (1985), 115(4), 539-545.

Gumucio, J. P., Flood, M. D., Phan, A. C., Brooks, S. V., & Mendias, C. L. (2013). Targeted inhibition of
TGF-beta results in an initial improvement but long-term deficit in force production after
contraction-induced skeletal muscle injury. J Appl Physiol (1985), 115(4), 539-545.

Hill JJ, Qiu Y, Hewick RM, Wolfman NM. Regulation of myostatin in vivo by growth and differentiation
factor–associated serum protein-1: a novel protein with protease inhibitor and follistatin domains.
Mol Endocrinol. 2003;17(6):1144–54.

Laurentino, G. C., Ugrinowitsch, C., Roschel, H., Aoki, M. S., Soares, A. G., Neves, M., Jr., Tricoli, V.
(2012). Strength training with blood flow restriction diminishes myostatin gene expression. Med
Sci Sports Exerc, 44(3), 406-412.

McCroskery, S., Thomas, M., Maxwell, L., Sharma, M., & Kambadur, R. (2003). Myostatin negatively
regulates satellite cell activation and self-renewal. J Cell Biol, 162(6), 1135-1147.

Mendias, C. L., Gumucio, J. P., Davis, M. E., Bromley, C. W., Davis, C. S., & Brooks, S. V. (2012).
Transforming growth factor-beta induces skeletal muscle atrophy and fibrosis through the
induction of atrogin-1 and scleraxis. Muscle Nerve, 45(1), 55-59.

Roth SM, Martel GF, Ferrell RE, Metter EJ, Hurley BF, Rogers MA. Myostatin gene expression is reduced
in humans with heavy-resistance strength training: a brief communication. Exp Biol
Med(Maywood). 2003;228(6):706–9.

Santos, A. R., Neves, M. T., Jr., Gualano, B., Laurentino, G. C., Lancha, A. H., Jr., Ugrinowitsch, C., Aoki,
M. S. (2014). Blood flow restricted resistance training attenuates myostatin gene expression in a
patient with inclusion body myositis. Biol Sport, 31(2), 121-124.

Saremi A, Gharakhanloo R, Sharghi S, Gharaati MR, Larijani B, Omidfar K. Effects of oral creatine and
resistance training on serum myostatin and GASP-1. Mol Cell Endocrinol. 2010;317(1–2):25–30.

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Spector SA, Lemmer JT, Koffman BM, et al. Safety and efficacy of strength training in patients with
sporadic inclusion body myositis. Muscle Nerve. 1997;20:12428.

Terada, S., Ota, S., Kobayashi, M., Kobayashi, T., Mifune, Y., Takayama, K., Huard, J. (2013). Use of an
antifibrotic agent improves the effect of platelet-rich plasma on muscle healing after injury. J Bone
Joint Surg Am, 95(11), 980-988.

Wagner, K. R. (2005). Muscle regeneration through myostatin inhibition. Curr. Opin. Rheumatol. 17, 720-
724.

Willoughby DS. Effects of heavy resistance training on myostatin mRNA and protein expression. Med Sci
Sports Exerc. 2004;36(4):574–82.

Photo courtesy: [Link]

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 Metabolite Theory
Mammalian Target of Rapamycin Complex 1
(MTORC1)

The formula for muscle hypertrophy is Net Protein Balance=Muscle Protein Synthesis-
Muscle Protein Breakdown, or NPB=MPS-MPB. To increase muscle size the equation
needs to be positive. MPS is seen within 24 hours after a heavy bout of resistance
exercise. (Bickel 2005) The signaling pathway responsible for protein synthesis is
known as mechanistic/mammalian target of rapamycin complex or MTORC1. It is the
pathway necessary for protein accretion and ultimately hypertrophy. How scientists
discovered this pathway and the unique name it was given is an interesting story.

Scientists from Wyeth

pharmaceuticals were
searching the remote
Easter Islands in the
Pacific Ocean looking for
a bacterial strain that was
known to have anti-fungal
properties. They isolated
a bacteria and gave it the
name Rapamycin after
the native name of the
island Rapa Nui. They
soon discovered that the
bacteria secreted a
compound that bound to a protein in our bodies. It was later discovered that binding to
this protein became a potent immunosuppressant and a drug was created out of the
bacteria to aid in organ transplants. What were not known was what this proteins real
role was and why these bacteria bind to it. The protein was given the name Mammalian
Target of Rapamycin. Over time the true function of MTORC1 became understood. It
serves as a switch to turn cell growth on or off. Where does the signal come from to
activate it? From the growth factors we mentioned earlier, from the energy status of the
cell, exercise (specifically heavy mechanical load) and the supply of amino acids.
Currently, Rapamycin is a drug used to stop protein synthesis and cell growth in tumors
and is still used as an immunosuppressant.

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Taking a muscle to failure will activate MTORC1. (Mitchell 2012) As the muscle recruits
more and more fibers either under increasing loads or repetitions the level of MTORC1
activation rises concurrently. If there is adequate protein supply the muscle protein
synthesis is augmented. MTORC1 is dependent on heavy load or exercises to failure,
but does blood flow restriction training activate it
as well?

To explore this, Fujita et al measured the acute

effects of BFR at 20% 1RM vs work matched
controls. At the completion of the session only
the BFR group demonstrated a significant rise
in S6K1 levels (ribosomal kinase) a
downstream marker of the MTOR pathway.
(Fujita 2007)

Increased levels of S6K1 (MTORC1) to this

magnitude
should also translate in increased muscle protein
synthesis. In the BFR group MPS increased by
46% 3 hours post training. In the control group
there was no change.

As we age there is a gradual loss of muscle mass,

strength and fiber size, termed sarcopenia.
(Aniansson 1980, Nair 2005) To compound this
problem, many elderly individuals are unable to lift
the required load to induce a hypertrophy
response. Furthermore, aging muscle looses its ability to process protein.(Sheffield
2005, Kumar 2009) A recent study examined the effects of BFR on muscle protein
synthesis in older men. The authors found the same result as the previous study. Both
MTORC1 (measured through S6K1) and protein synthesis increased in the BFR group
but not in the controls. The average increase in MPS for the elderly BFR subjects was
56% 3 hours post training. (Fry 2010)

In an elegant study published last year Drummond et al demonstrated that the muscle
protein synthesis associated with BFR and exercise is directly tied to the MTORC1
pathway. (Gunderman 2014) Up until this study there was still some debate as to the
actual mechanism increasing MPS after BFR. This was partly due to the fact that
MTORC1 activation was linked to mechanical load and the very low load associated
with BFR should not induce this pathway. In their study, two groups of patients

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performed BFR exercise at 20% 1RM, however the experimental group took the drug
Rapamycin to block the MTORC1 pathway. The same authors have previously
demonstrated that Rapamycin blocks MTORC1/protein synthesis after exercise and
after amino acid ingestion. (Drummond 2009) They hypothesized that the Rapamycin
group would not demonstrate an increase in
muscle protein synthesis.

At the conclusion of the training session,

muscle protein synthesis increased 41.5% in
the BFR group without Rapamycin and 69.4%
24 hours post-training. The BFR group taking
Rapamycin did not show any significant
changes. It is interesting to note that 24 hours
post training there was still significant MPS
occurring after low load BFR training.

As expected markers of MTORC1 activation

were also significantly elevated in the BFR group
but not in the BFR and Rapamycin cohort.

This is convincing evidence that to produce muscle

protein synthesis after exercise at low loads the
addition of BFR is key. This is a paradigm shift in
our understanding of a pathway that was previously
dependent on load. In a commentary on this
phenomenon Dr. Ronald Meyer, a Physiologist from
Michigan State University, states “the
recommendation that hypertrophy requires a load
70% of one repetition maximum might just as well be recast as a recommendation that
the training must result in substantial anaerobic metabolism”. He further eluded to the
fact that the recruitment of fast twitch fibers and subsequent increase in EMG activity
seen with BFR training may play a key role; “it is likely that exercise with flow restriction
requires recruitment of the larger, fast motor units, which are normally only recruited
during stronger efforts. In fact, greater integrated electromyograph amplitudes were
recorded during exercise with flow restriction compared with the same exercise without
restriction”. (Meyer 2006)

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 Nutrition

Muscle mass takes up approximately 45% of body mass. It is one of the most
metabolically active tissues in the body. In fact, 25% of cellular energy is used when
protein synthesis is occurring. During our hunter-gatherer days we had periods of time
where we did not have an abundance of available energy sources. To protect our body
from going into an energy deficit the MTORC1 pathway will not activate to its full
potential if there is insufficient nutrient availability. If you are in an energy rich state
(available nutrients) MTORC1 is turned on. In an energy poor state MTORC1 is turned
off. Luckily, we almost all live in an energy rich state and we need our patients to
enhance the MTORC1 pathway that they just activated through BFR.

If you combine load and amino acids together you are compounding the protein
synthesis potential. After a session of BFR you must ingest all of the essential amino
acids to support protein synthesis. (Tipton 1999) In fact, ingestion of essential amino
acids “results in a change from net muscle protein degradation to net muscle protein
synthesis after heavy resistance exercise”. (Tipton 1999) The body’s main storage for
protein is muscle and if sufficient amino acids are not readily available your body must
breakdown muscle to activate protein synthesis. Furthermore, leucine is the key amino
acid needed to turn on MTORC1. (Churchward-Venne 2012) Without leucine a blunted
response to muscle protein synthesis occurs. I was lucky enough to spend some time
working with the Seal Team 6 group. While I was there I had lunch with their sports
nutritionist. I asked him what the most important supplement or nutrient was that he
recommended to his operators. He quickly replied “leucine”. It appears that there is an
intracellular sensor that is sensitive to Leucine. This sensor, leucyl-tRNA syntheses
(LRS) triggers MTORC1 and the subsequent protein synthesis cascade within the cell.
(Han 2012)

So what is the best source of protein to quickly get it into your system, get all the
essential amino acids especially leucine? Dairy, particularly whey protein. The fact that
whey protein is available in liquid form helps your body quickly get protein to the proper
source. Van Loon et al, who demonstrated that hamburger meat increased protein
synthetic rate more than eating a steak, recently explored support for the readily
available protein hypothesis.

How much protein needs to be ingested? For young healthy males, 20 grams of protein
is sufficient. For older adults, a higher dose of 40 grams is needed to maximally
stimulate protein synthesis. Typically, 1 scoop of whey is 20 grams or protein, however
this can vary based on serving sizes between manufacturers. Ideally, you would ingest
this dose every 4 hours to maximize the response except during the overnight fast while

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sleeping. As noted, even 24 hours post -training MPS is still significantly occurring so
the ingestion of protein should occur at least through this time period. Although it is
probably wise to get it in quickly, the exact window of time needed for protein digestion
has not been established.

What about other protein sources such as soy?

Although these alternative sources can work they do
not have the same effect on MPS as whey. Work
from Dr.
Stuart Phillips
lab has
repeatedly
demonstrated
that the net
balance of
amino acids
delivered to the muscle is lower in soy protein as
is the leucine content and the muscle protein
synthesis (fractional synthetic rate) is diminished
as well. (Wilkinson 2007)

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Additional Notes:

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 Bibliography

Aniansson A, Grimby G, Rundgren [Link] and isokinetic quadriceps muscle strength in 70-yearold
men and women. Scand J Rehabil Med12: 161–168, 1980.

Bickel CS, Slade J, Mahoney E, Haddad F, Dudley GA, Adams GR. Time course of molecular responses
of human skeletal muscle to acute bouts of resistance exercise. J Appl Physiol (1985).
2005;98:482-488.

Chew smaller chunks. [Link]

Drummond MJ, Fry CS, Glynn EL, Dreyer HC, Dhanani S, Timmerman KL, Volpi E, Rasmussen BB.
Rapamycin administration in humans blocks the contraction-induced increase in skeletal muscle
protein synthesis. J Physiol 587: 1535–1546, 2009.

Churchward-Venne, NA Burd, CJ Mitchell, DWD West, A Philp. Supplementation of a suboptimal protein

dose with leucine or essential amino acids: effects on myofibrillar protein synthesis at rest and
following resistance exercise in men The Journal of Physiology 590 (11), 2751-2765

Fry, C. S., Glynn, E. L., Drummond, M. J., Timmerman, K. L., Fujita, S., Abe, T., Rasmussen, B. B. (2010).
Blood flow restriction exercise stimulates mTORC1 signaling and muscle protein synthesis in
older men. J Appl Physiol (1985), 108(5), 1199-1209.

Gundermann, D. M., Walker, D. K., Reidy, P. T., Borack, M. S., Dickinson, J. M., Volpi, E., & Rasmussen,
B. B. (2014). Activation of mTORC1 signaling and protein synthesis in human muscle following
blood flow restriction exercise is inhibited by rapamycin. Am J Physiol Endocrinol Metab, 306(10),
E1198-1204.

Han, Jung Min, et al. "Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-
signaling pathway." Cell 149.2 (2012): 410-424.

Kumar V, Selby A, Rankin D, Patel R, Atherton P, Hildebrandt W, Williams J, Smith K, Seynnes O,

Hiscock N, Rennie [Link]-related differences in the dose-response relationship of muscle
protein synthesis to resistance exercise in young and old men. J Physiol587: 211–217, 2009.

Meyer, R. A. (2006). Does blood flow restriction enhance hypertrophic signaling in skeletal muscle? J Appl
Physiol (1985), 100(5), 1443-1444

Mitchell CJ, Churchward-Venne TA, West DWD, et al. Resistance exercise load does not determine
training-mediated hypertrophic gains in young men. Journal of Applied Physiology.
2012;113(1):71-77. doi:10.1152/japplphysiol.00307.2012.

Nair [Link] muscle. Am J Clin Nutr81: 953–963, 2005.

Sheffield-Moore M, Paddon-Jones D, Sanford AP, Rosenblatt JI, Matlock AG, Cree MG, Wolfe [Link]
muscle and hepatic derived plasma protein metabolism is differentially regulated in older and
younger men following resistance exercise. Am J Physiol Endocrinol Metab288: E922–E929,
2005.

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Tipton, K. D., Ferrando, A. A., Phillips, S. M., Doyle, D., Jr., & Wolfe, R. R. (1999). Postexercise net
protein synthesis in human muscle from orally administered amino acids. Am J Physiol, 276(4 Pt
1),

Van Loon LJ, Boirie Y, Gijsen AP, Fauquant J, de Roos AL, Kies AK, Lemosquet S, Saris WH, Koopman
R. The production of intrinsically labeled milk protein provides a functional tool for human nutrition
research. J Dairy Sci. 2009;92:4812–4822.

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 Cell Swelling
Thus far, build up of metabolites has demonstrated positive effects after performing BFR
with exercise. However, some studies have demonstrated changes by simply using a
tourniquet without exercise. A current prevailing hypothesis is that cellular swelling can
play a role in these adaptive gains. A myocycte that is dehydrated does not undergo
protein synthesis, however acute cell swelling has been shown to increase protein
synthesis and suppress proteolysis.(Haussinger 1993, 1996) Dr Haussinger’s landmark
paper in the journal Lancet first described the cell swelling phenomenon. Schliess et al
further linked cellular hydration to MTORC1. (Schliess 2006) Besides potentially
activating MPS cellular swelling may also shift metabolism to a lipolysis state and spare
protein. (Berneis 1999, Keller 2003) It appears that similar to a water balloon that
continues to fill with water and is at risk of bursting cells may behave the same way to
reinforce their structure to avoid apoptosis (cell death).

So does BFR induce cell swelling or is it just

blood pooling from venous congestion? If it were
simply venous congestion then the fluid should
quickly leave the limb after the tourniquet is
released. Researchers recently measured plasma
fluid shift after wearing a tourniquet without
exercise. In the study participants wore a
tourniquet on their proximal thigh which was
inflated and held for 5 minute bouts for 5 times
with a 3 minute rest period between sets. The
authors found a significant increase in muscle
thickness in the vastus laterals (6% p=0.027) and
rectus femurs (22% p-0.001). Additionally they found a decrease in plasma volume of
15% (p=0.001). The authors concluded that the increased acute swelling in the muscle
was from a plasma fluid shift into the muscle. (Loenneke 2012)

To support this, multiple papers have demonstrated increased limb swelling after
application of BFR including Ogawa 2012, Yasuda 2012, Fry 2010, Thiebaud 2013,
Wilson 2013 and Yasuda 2008.

However, if a fluid shift induces hypertrophy then studies of BFR with no exercise
should demonstrate a response. To study this Takarada et al. observed that applying
BFR (238 mmHg, 9 cm wide cuff) to patients following anterior cruciate ligament
reconstruction surgery without exercise effectively diminished the post operation disuse

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atrophy (measured by MRI) of the knee extensors.
The subjects used the tourniquet daily for 2 sessions
from the 3rd to the 14th post-op day. The control group
demonstrated a 20% decrease in the cross sectional
area (CSA) of the knee extensors vs. only a 9%
decrease in the tourniquet group. (Takarada 2000) In
this case, the BFR without exercise did not cause
hypertrophy but it significantly reduced atrophy
compared to the control.

Similarly, Kubota et al immobilized subjects and kept

them non-weight bearing (NWB) for 2 weeks. For this
study they wanted to assess the preservation of strength through cell swelling. The
subjects were split into a control group or a group that wore a tourniquet for 25 minutes
(5 sets of 5 minutes with 3 minutes rest 2x day) at a very low pressure (50 mmHG). No
exercises were performed during the 2 weeks of NWB. At the conclusion of the 2-week
period the subjects in the BFR group had less loss of strength in the knee extensors,
flexors and ankle plantar flexors vs. control. (Kubota 2011)

The same authors also compared BFR without exercise at a higher pressure (200
mmHG) to a group that performed isometric thigh and ankle exercises and a control
group that did not exercise or wear a tourniquet. All 3 groups were immobilized and
NWB for 2 weeks. At the conclusion of the study the authors found that
immobilization/unloading resulted in significant decreases in muscle strength of knee
extensor and flexor muscles and thigh and leg circumferences in the CON group, and
significant decreases in muscle strength of the knee flexor muscles, ankle plantar flexor
muscles, and leg circumference in the IMT group. RBF protected against these changes
in muscle strength and thigh/leg circumference. (Kubota 2008) The authors also found
no significant rise in growth hormone in either group lending credence to the cell-
swelling hypothesis.

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From this, it appears that multiple pathways can affect muscle strength and hypertrophy
including but not limited to mechanical tension, metabolite accumulation and a volume
sensor to cell swelling.

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Additional Notes:

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 Bibliography

Berneis K, Ninnis R, Haussinger D, Keller U. Effects of hyper- and Hypo-osmolality on whole body protein
and glucose kinetics in humans. Am J Physiol 1999;276:E188–95.

Fry CS, Glynn EL, Drummond MJ, et al. Blood flow restriction exercise stimulates mTORC1 signaling and
muscle protein synthesis in older men. J Appl Physiol 2010;108:1199–209.

Haussinger D, Roth E, Lang F, Gerok W. Cellular hydration state: an important determinant of protein
catabolism in health and disease. Lancet (1993); 341: 1330–1332.

Haussinger D. The role of cellular hydration in the regulation of cell function. Biochem J 1996;313(Pt
3):697–710.

Keller U, Szinnai G, Bilz S, Berneis K. Effects of changes in hydration on protein, glucose and lipid
metabolism in man: impact on health. Eur J Clin Nutr 2003;57(Suppl. 2):S69–74.

Kubota, Atsushi, et al. "Blood flow restriction by low compressive force prevents disuse muscular
weakness." Journal of Science and Medicine in Sport 14.2 (2011): 95-99.

Kubota, Atsushi, et al. "Prevention of disuse muscular weakness by restriction of blood flow." Medicine
and science in sports and exercise 40.3 (2008): 529-534.

Loenneke JP, Fahs CA, Thiebaud RS, et al. The acute muscle swelling effects of
blood flow restriction. Acta Physiol Hung 2012;99:400–10.

Schliess, F., Richter, L.,vom Dahl, S., & Haussinger, D. (2006). Cell hydration and mTOR-dependent
signalling. Acta Physiol (Oxf), 187(1-2), 223-229.

Takarada, Yudai, Haruo Takazawa, Ishii Naokota. "Applications of vascular occlusions diminish disuse
atrophy of knee extensor muscles."Medicine and science in sports and exercise 32.12 (2000):
2035-2039.

Ogawa M, Loenneke JP, Yasuda T, et al. Time course changes in muscle size and fatigue during walking
with restricted leg blood flow in young men. JPESM 2012;3:14–9.

Yasuda T, Loenneke JP, Thiebaud RS, Abe T. Effects of blood flow restricted low-intensity concentric or
eccentric training on muscle size and strength. PLoS One 2012;7:e52843.

Thiebaud RS, Yasuda T, Loenneke JP, Abe T. Effects of low-intensity concentric and eccentric exercise
combined with blood flow restriction on indices of exercise-induced muscle damage. Interv Med
Appl Sci 2013;5:53–9.

Wilson JM, Lowery RP, Joy JM, Loenneke JP, Naimo MA. Practical blood flow restriction training
increases acute determinants of hypertrophy without increasing indices of muscle damage. J
Strength Cond Res 2013;27:3068 75.

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Yasuda T, Brechue WF, Fujita T, Sato Y, Abe T. Muscle activation during low intensity muscle
contractions with varying levels of external limb compression. J Sports Sci Med 2008;7:467–74.

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 Endurance
Cycling

Up to this point we have seen impressive effects with BFR combined with low load
exercise. But, there are also several effects that occur with lower load activities such as
cycling and walking. Historically, cycling at a low intensity and walking are not enough
stimuli to induce hypertrophy and strength changes.

Traditionally, endurance exercises such as walking or cycling have shown

improvements in maximum oxygen uptake. Some studies show interference in strength
training when aerobic conditioning is added. (Bell 200, Kraemer 1995)

Abe et al tested the hypothesis that cycling at a

low intensity could increase not only endurance
but also muscle strength and size. (Abe 2010)
Their study examined BFR cycling at 40% VO2
Max for 15 minutes compared to a control group
that cycled for 45 minutes at 40% VO2 max
without BFR. The study was carried out 3 days a
week for 8 weeks. At the conclusion of the
training thigh and quadriceps muscle volumes
increased (p< 0.01) by 3.8 and 5.1%,
respectively, for the BFR- training group as
measured on MRI. The control group did not
demonstrate any muscle size changes.

Maximal isometric knee extension strength tended to increase (p < 0.10) in the BFR-
training group (7.7%) but not in the CON-training group (1.4%). There was no change
in flexion strength for either group.

Absolute and relative VO2max increased in the BFR-training group by 6.4% (p < 0.05)
but did not change in the CON-training group. Additionally, an increase in exercise time
until exhaustion was observed in the BFR- training group (15.4%, p < 0.01) but not in
the CON- training group.

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There are various interesting takeaways from this study. Previously improved
hypertrophy and aerobic capacity from a single modality have been seen in only a few
studies and they involved long duration (40 minutes at 75% Max HR) or very intense
training sessions. (Hass 2001, Tabata 1990) However, none of these studies
demonstrated concurrent gains in muscle size, which suggests the strength adaptations
were neuromuscular. The magnitude of change in VO2max increases as exercise
intensity increases from 50-100% of VO2max. (Gaesser 1984, Wenger 1986) The
minimum stimulus thought to be needed for change is 50% VO2max and the lower the
stimulus the longer the duration of exercise needed (>35 minutes) and longer duration
may be more effective than short duration at higher intensities. (Wenger 1986) The
current study used a very short duration (15 minutes) and very low intensity (40%
VO2max) and demonstrated changes in VO2max, hypertrophy, strength (although not
statistically significant (p=0.10) and time to exhaustion. The authors explained the
change in VO2max to be related to a decrease in stroke volume (SV) secondary to the
tourniquets and an increase in heart rate (HR) to maintain cardiac output (CO). This
has already been confirmed in prior BFR exercise studies. (Ozaki 2010, Takano 2005)
From the maximum HR the authors were able to average the intensity of the BFR group
to be 59% VO2max which is within the effective training window for aerobic adaptations.
Sundberg reported similar changes in aerobic endurance comparing supine cycling with
and without BFR. In the study subjects cycled with one leg while in the supine position
under BFR then trained with the contralateral leg at the exact same power output
without BFR. The sessions lasted 45 minutes per leg 4 days a week over 4 weeks.
Peak oxygen uptake and total time to fatigue improved in the BFR leg but not in the
control leg. The BFR condition also increased total capillary per fiber and glycogen
content. Strength and hypertrophy were not increased in the BFR condition but this
may be related to the very low pressures used (50 mmHG) not being able to build a
sufficient metabolic build up. (Sundberg 1994) The authors in the current study also
speculated that the increase in VO2max after BFR cycling might be related to the

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increased hypertrophy seen in the BFR group. A decrease in muscle mass has long
been known to play a significant role in VO2max as the shift from metabolical active
muscle tissue moves to inactive adipose tissue. (Paffenberger 1970, Goodpaster 2000)
In fact, 50% of the decline in VO2max as a result of aging is attributed to the age-
induced decreases in muscle mass and the concomitant increase in fat mass. (Proctor
1997) With increased muscle volume comes increased mitochondria (from satellite cell
proliferation and new myocyte incorporation), which increases peripheral aerobic
capacity.

Ozaki et al compared upright cycling with BFR vs

a work matched control and measure the
difference in VO2max. At 40% maximal O2
uptake the difference between the groups was
6% at 60% VO2 uptake the difference was 10%.
This confirms the assumption that BFR requires
greater energy demand vs. work-matched
controls during endurance events. (Ozaki 2010)

Recently the effect of BFR cycling on endurance

was repeated however this time the authors used
a severe intensity cycling testing protocol to
assess improvements. (Corvino 2014) In the
study subjects were divided into a BFR and
non-BFR condition (free flow). Both groups
cycled for 2 minutes for 2 sets of 5 repetitions
(10 minutes) the first 2 weeks and 2 sets of 8
(16 minutes) the second 2 weeks. There was a
1-minute rest between sets. Both groups
cycled at 30% of P (peak). Pre and post testing
consisted of an exhausting incremental test
which increased resistive work every 3 minutes
until exhaustion and a severe cycling time to
exhaustion at 110% P(peak). At completion of
the study the BFR cycling group improved their
time to exhaustion by 53% (Pre: 227 ± 44s vs. Post: 338 ± 76s) while the control grip
did not (Pre: 236 ± 24s vs. Post: 212 ± 26s). The authors concluded that the
physiological strain induced by BFR, not the intensity (30% Peak), were responsible for
the changes seen on the severe intensity cycling tests.

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Walking

Studies examining walking with BFR have also

demonstrated impressive results. Recently a study
reported increases in VO2max after 6 days a week (2
weeks) of 2x/day walking. (Park 2010) The study
involved highly trained athletes, college basketball
players, who walked for 3 minutes with both legs
under BFR for 5 sets with a 1-minute rest between
sets. The overall improvement in VO2max was 11.6%
for the BFR group; controls did not exhibit a
statistically significant improvement. The authors
concluded that BFR walk training might be used as a
low intensity alternative for athletes to maintain or improve endurance.

Recently, Ozaki et al demonstrated that elderly adults

who walked for 20 minutes 4 days a week for 10 weeks
at a low intensity (45% heart rate reserve) increased
their maximum knee joint strength (15%) and thigh
muscle CSA (3%)
under BFR conditions.
The control group did
not demonstrate
significant changes.
(Ozaki 2011)

Similarly, in the Journal of Geriatric Physical Therapy

Abe et al demonstrated in older adults that walking 5
days a week for 20 minutes at a normal walking pace
over 6 weeks. At the conclusion of the study only the BFR group demonstrated
improvements in knee strength 7% and 16% (extension and flexion) and muscle cross
sectional area increased 5.8% for the thigh and 5.1% for the lower leg. The control
group did not demonstrate changes. Additionally functional improvements were seen in
the BFR group on the Timed Up and Go and chair sit to stand test. (Abe 2010)

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This confirmed previous work by the same group published in the Journal of Physiology
that demonstrated a significant increase in knee strength, thigh CSA and growth
hormone response after walking with BFR. Similarly to the previous studies the control
group did not demonstrate changes. (Abe 2006)

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 It should be pointed out that although growth
hormone increased in the walking with BFR group it
peaked out at 13 ng/ml which is well below previous
reported levels reported with BFR after exercise
which reach 40 ng/ml and higher. (Takarada 2000)

Sakamaki et al examined the effects of BFR walk

training on muscle hypertrophy distal to the
tourniquet as well as muscles proximal to include the
gluteus maximus, iliopsoas and lumbar L4-5 region.
(Sakamaki 2011) They chose this study design based on recent literature that has
demonstrated increased muscle CSA on the trunk musculature after performing BFR.
(Discussed Below) Subjects were split into 2 groups, 1 BFR and 1 work matched
control. Both groups walked 6 days a week for 3 weeks. The walking protocol was 5
sets of 2-minute bouts of walking at a normal pace with 1-minute rest between sets. At
the conclusion of the training only the BFR group demonstrated significant increases in
CSA. However, only the thigh and lower leg significantly changed. The iliopsoas
trended towards significance (p=0.07). The gluteus and lumbar musculature did not
increase.

A possible explanation for the lack of hypertrophy in the previous study may be the
limited amount of metabolite build up from walking under BFR conditions. Impressive
strength and hypertrophy changes have been seen with BFR and exercise and proximal
improvements have also been noted. In studies that have measured metabolite
accumulation after BFR and exercise there is conclusive evidence to suggest a
substantial increase. The downstream effects of a sufficient metabolite build up,
appears to be muscle hypertrophy. (Loenneke 2011, Schoenfeld 2013)

To test this theory researchers measured blood lactate levels after walk training with
BFR vs. work matched controls. (Loenneke 2011) At the conclusion of the walk
training, there was not a significant change in the whole blood lactate between the BFR
and control group. One limitation of the study was that the subjects wore elastic knee
wraps instead of surgical tourniquets, which may have not been able to maintain the
lactate accumulation. A previous study by the same group comparing exercise with
BFR, using knee wraps, vs controls did not show a difference between groups. The
authors concluded, “The current protocol in the study did not increase metabolic stress
more than normal low-intensity exercise. This study does not support the use of knee
wraps as a mode of blood-flow restriction”. (Loenneke 2010)

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Additional Notes

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Abe, T., Sakamaki, M., Fujita, S., Ozaki, H., Sugaya, M., Sato, Y., & Nakajima, T. (2010). Effects of low-
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Abe, T., Yasuda, T., Midorikawa, T., Sato, Y,, Kearns, C,F,, Inoue, K, Koizumi, K, and Ishii, N. (2005)
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Abe, T., Kearns, C,F, and Sato, Y. (2006) Muscle size and strength are increased following walk training
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Bell, G.J., Syrotuik, D., Martin, T.P., Burnham, R. and Quinney, H.A. (2000) Effect of concurrent strength
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(2010) Matabolic and cardiovascular responses to upright cycle exercise with leg blood flow
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Ozaki H, Miyachi M, Nakajima T, et al. Effects of 10 weeks walk training with leg blood flow reduction on
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Proctor, D. N., & Joyner, M. J. (1997). Skeletal muscle mass and the reduction of VO2max in trained older
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Sakamaki, Mikako, Michael G. Bemben, and Takashi Abe. "Legs and trunk muscle hypertrophy following
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isokinetic muscle power. European Journal of Applied Physiology and Occupational Physiology
60, 254-258.

Takano, H., Morita, T., Iida, H., Asada, K., Kato, M., Uno, K., Hirose, K., Matsumoto, A., Takenaka, K.,
Hirata, Y., Eto, F., Nagai, R., Sato, Y. and Nakajima, T. (2005) Hemodynamic and hormonal
responses to a short-term low intensity resistance exercise with the reduction of muscle blood
flow. European Journal of Applied Physiology 95, 65–73.

Takarada Y, Nakamura Y, Aruga S, Onda T, Miyazaki S, Ishii N. Rapid increase in plasma growth
hormone after low-intensity resistance exercise with vascular occlusion. J Appl Physiol
2000;88:61–5.

Wenger, H.A. and Bell, G.J. (1986) The interactions of intensity, frequency and duration of exercise
training in altering cardiorespiratory fitness. Sports Medicine 3, 346-356.

Bone
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As demonstrated, an increase in growth factors such as GH has a positive effect on
tendon and muscle structure. Is there an effect on bone? From the available evidence
it appears that GH plays a role in collagen synthesis within bone. This makes sense
from a mechanistic standpoint that the harder the intensity of exercise the more growth
hormone is released fro bone remodeling.

As mentioned earlier the NEJM study that supplemented elderly males with GH
demonstrated as 1.6% increase in vertebral density. The control group did not
demonstrate any change. They also found increases in other collagen-based
substances such as skin, increase of 7.1 % in the GH group none in the controls.
(Rudman 1990) It is important to note that this study did not involve exercise; it was
simply supplementation with GH.

The administration of GH in animals treated with maximal doses of IGF-1 stimulated

growth further as seen in both the tibia and the femur. (Fielder 1996) Furthermore, the
lack of GH secretion and consequently low level of IGF-1 results in osteopenia and
reduced cortical bone in an animal model. (Sims 2000) Osteoblasts have receptors for
GH and the administration of GH exerts a direct effect, stimulating cell proliferation and
differentiation. (Ohlsson 1998, Kassem 1993) Once the osteoblasts arrive at the bone
surface they produce bone matrix that becomes mineralized. Improved bone resorption
and new bone formation has also been demonstrated with the addition of GH in healthy
subjects (Brixen 1990) in post-menopausal osteoporosis (Clemmesen 1993, Erdtsieck
1995) and men with idiopathic osteoporosis (Gillberg 2002).

So do increasing levels of growth hormone have an effect on fracture healing? In tibiae

of micropigs it has been demonstrated that callus area, bone area, cartilage area, and
bone perimeter were regenerated after GH administration and that GH promotes bone
formation and maturation of the regenerate without disturbing the callus structure. (Bail
1998) Several studies have indicated improved healing and bone formation with GH
supplementation after hip fracture (Van der Lely 2004, Yeo 2003, Boonen 2002 and
Hedstrom 2004) as well as total hip replacement (Weissberger 2003) and tibia fractures
(Krusenstjerna-Hafstrom 2011).

A trial of 406 patients with closed tibia fractures treated with GH vs placedo controls
demonstrated significantly shorter time to healing. (Raschke 2007) In the study,
patients were administered GH for 16 weeks (or until fracture healing) after surgery. Of
note, 3 different doses of GH were administered with the highest dose 60 ug/kg
corresponding to the most significant benefit. The estimated median number of days
from surgery to fracture healing in closed fractures was 95 days in the 60 μg/kg GH

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 group versus 129 days in the placebo group
corresponding to a 26% decrease in healing time. (The
authors concluded “in closed tibial fractures comprising
the vast majority of tibial fractures, GH accelerated
healing significantly during the 12-month study period.
The GH-induced enhancement of healing may be of
potential benefit in patients with closed tibial fractures”.

Thus the increased GH response after BFR may be used as an adjunctive treatment
during the patient’s rehabilitation from bone or cartilage injury. Of course, clinical trails
need to be performed to validate this statement.

Bone is adaptable to mechanical loading, Wolf’s Law. However, recent research

suggests that bone adapts to peak monetary loads and that these loads are applied to
bone through muscle contractions as well as gravitational forces. (Frost 2001, Turner
1998) Currently the tissue strain that bone cells perceive is known as the interstitial
fluid flow (IFF) hypothesis. During loading strain a pressure gradient is created that
causes fluid sheer stress on the osteocyte membrane. (Fritton 2009) This pressure
gradient is influenced by mechanical loading, vascular blood pressure and fluid shifts
due to bed rest and changes in gravity (space flight). (Stephens 2006)

Studies measuring unloading have found that intramedullary pressure (a marker of IFF)
is decreased by up to 77%. (Stevens 2006) The importance of blood flow to regulate
IFF and its potential on bone health has long been understood. In a dog and goat
model, venous occlusion resulted in increased bone density and new bone formation vs
controls. (Kelly 1990, Welch 1993) This was observed in animals that were allowed to
ambulate normally and was not under weight bearing restrictions. The use of venous
occlusion to reduce the effects of non-weight bearing on bone loss in a hind limb
suspension model has also been demonstrated. (Bergula 1999) More impressively, the
use of intermittent venous occlusion in an animal model has demonstrated improved
fracture healing vs. controls. (Hewitt 2005, Park 2003)

A third mechanism where BFR may compliment

bone factors is through a protein called vascular

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endothelial growth factor or VEGF. Interestingly, an acute hypoxic state leads to
increased expression of VEGF and subsequent blood vessel formation into damaged
bone after fractures. (Schipani 2009)

Increasing VEGF during fracture healing increases healing time in an animal model.
The figure below illustrates increased bone formation after fracture in a saline vs VEGF
(DFO) comparison. (Wan 2008)

Up regulation of VEGF is stimulated

by hypoxia and lactate, which both
occur during BFR and exercise.
(Hunt 2008, Constant 2000)
Takano et al demonstrated that
BFR significantly increased
VEGF as well as lactate; a work
matched control group did not
demonstrate these changes.
(Takano 2005)

The efficacy of BFR on bone markers has also been studied. Three weeks of walking
with intermittent BFR vs. walking without BFR found that bone specific alkaline
phosphate (BAP) a marker of osteoblastic activity was elevated in the BFR group but
not the control. This study also found significant increases in strength and hypertrophy
in the thigh muscles of the BFR group. (Beekley 2005) Bemben et al found that a
marker for bone reabsorption was significantly lower in a BFR group performing 20% 1
RM knee extensions vs. controls. (Bemben 2007) Lastly a study that compared 6
weeks of BFR leg exercises (knee extension and leg press) at 20% 1 RM to the same
exercises at 80% 1 RM demonstrated positive blood bone markers in similar amounts in
both groups. (Karabulut 2011)

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Because of the low load nature of BFR it could be assumed that there would be no
effect on bone. However, there may be several mechanisms that it positively affects
bone. These include, but are not limited to increased GH and IGF1 release, increased
IFF and increased VEGF.

Additional Notes:

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 Bibliography

Bail H, Raschke MJ, Kolbeck SF, Weiler A, Haahr PM, Haas NP. Recombinant growth hormone
increasus callus maturation time in distraction osteogenesis—a histomorphometric study.
Langenbecks Archiv für Chirurgie. 1998;115(supplement I):675–680.

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Beekley MD, Sato Y, Abe T. KAATSU-walk training increases serum bone specific alkaline phosphatase
in young men. Int J KAATSU Training Res 2005;1:77–81.

Bemben DA, Palmer IJ, Abe T, Sato Y, Bemben MG. Effects of a single bout of low intensity KAATSU
resistance training on markers of bone turnover in young men. Int J KAATSU Training Res
2007;3:21–6.

Bergula AP, Huang W, Frangos JA. Femoral vein ligation increases bone mass in the hind limb
suspended rat. Bone 1999;24:171–7.

Brixen K, Nielsen HK, Mosekilde L, Flyvbjerg A. A short course of recombinant human growth hormone
treatment stimulates osteoblasts and activates bone remodeling in normal human
[Link] of Bone and Mineral Research. 1990;5(6):609–618.

Clemmesen B, Overgaard K, Riis B, Christiansen C. Human growth hormone and growth hormone
releasing hormone: a double-masked, placebo-controlled study of their effects on bone
metabolism in elderly women. Osteoporosis International. 1993;3(6):330–336.

Constant, James S., et al. "Lactate elicits vascular endothelial growth factor from macrophages: a
possible alternative to hypoxia." Wound Repair and Regeneration 8.5 (2000): 353-360.

Erdtsieck RJ, Pols HAP, Valk NK, et al. Treatment of post-menopausal osteoporosis with a combination
of growth hormone and pamidronate: a placebo controlled trial. Clinical
Endocrinology.1995;43(5):557–565.

Fielder PJ, Mortensen DL, Mallet P, Carlsson B, Baxter RC, Clark [Link] long-term effects of
insulin-like growth factor-I (IGF-I), growth hormone (GH), and IGF-I plus GH on body growth and
IGF binding proteins in hypophysectomized rats. Endocrinology. 1996;137(5):1913–1920.

Fritton SP, Weinbaum S. Fluid and solute transport in bone: flow-induced mechanotransduction. Annu
Rev Fluid Mech 2009;41:347–74.

Frost HM. From Wolff’s law to the Utah paradigm: insights about bone physiology and its clinical
applications. Anat Rec 2001;262:398–419.

Gillberg P, Mallmin H, Petrén-Mallmin M, Ljunghall S, Nilsson AG. Two years of treatment with
recombinant human growth hormone increases bone mineral density in men with idiopathic
[Link] of Clinical Endocrinology & Metabolism. 2002;87(11):4900–4906.

Hedström M, Sääf M, Brosjö E, et al. Positive effects of short-term growth hormone treatment on lean
body mass and BMC after a hip fracture: a double blind placebo-controlled pilot study in 20
patients. Acta Orthopaedica Scandinavica. 2004;75(4):394–401.

Hewitt JD, Harrelson JM, Dailiana Z, Guilak F, Fink C. The effect of intermittent pneumatic compression
on fracture healing. J Orthop Trauma 2005;19:371–6.

Hunt TK, Aslam R, Hussain Z, Beckert S. Lactate, with oxygen,incites angiogenesis. Adv Exp Med Biol.
2008;614:73-80.

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Kassem M, Blum W, Ristelli J, Mosekilde L, Eriksen EF. Growth hormone stimulates proliferation and
differentiation of normal human osteoblast-like cells in vitro. Calcified Tissue
International.1993;52(3):222–226.

Kelly PJ, Bronk JT. Venous pressure and bone formation. Microvasc Res1990;39:364–75.

Krusenstjerna-Hafstrøm T, Rasmussen MH, Raschke M, Govender S, Madsen J, Christiansen JS.

Biochemical markers of bone turnover in tibia fracture patients randomly assigned to growth
hormone (GH) or placebo injections. Implications for detection of GH abuse. Growth Hormone
and IGF Research.2011;21(6):331–335.

Loenneke, J. P., Young, K. C., Fahs, C. A., Rossow, L. M., Bemben, D. A., & Bemben, M. G. (2012). Blood
flow restriction: rationale for improving bone. Med Hypotheses, 78(4), 523-527. doi:
10.1016/[Link].2012.01.024

Park SH, Silva M. Effect of intermittent pneumatic soft-tissue compression onfracture–healing in an

animal model. J Bone Joint Surg Am 2003;85:1446 53.

Ohlsson C, Bengtsson B, Isaksson OGP, Andreassen TT, Slootweg MC. Growth hormone and
[Link] Reviews. 1998;19(1):55–79.

Raschke M, Rasmussen MH, Govender S, Segal D, Suntum M & Christiansen JS (2007). Effects of
growth hormone in patients with tibial fracture: a randomised, double blind, placebo-controlled
clinical trial. Eur J Endocrinol 156, 341–351.

Rudman, D., Feller, A. G., Nagraj, H. S., Gergans, G. A., Lalitha, P. Y., Goldberg, A. F., Mattson, D. E.
(1990). Effects of human growth hormone in men over 60 years old. N Engl J Med, 323(1), 1-6.
doi: 10.1056/NEJM199007053230101

Schipani E, Maes C, Carmeliet G, Semenza GL. Regulation of osteogenesis

angiogenesis coupling by HIFs and VEGF. J Bone Miner Res 2009;24:1347– 53.

Sims NA, Clément-Lacroix P, da Ponte F, et al. Bone homeostasis in growth hormone receptor-null mice
is restored by IGF-I but independent of Stat5. The Journal of Clinical
Investigation.2000;106(9):1095–1103.

Stevens HY, Meays DR, Frangos JA. Pressure gradients and transport in the murine femur upon hindlimb
suspension. Bone 2006;39:565–72

Takano, H., Morita, T., Iida, H., Asada, K., Kato, M., Uno, K., Nakajima, T. (2005). Hemodynamic and
hormonal responses to a short-term low-intensity resistance exercise with the reduction of muscle
blood flow. Eur J Appl Physiol, 95(1), 65-73.

Turner CH. Three rules for bone adaptation to mechanical stimuli. Bone 1998;23:399–407.

Van der Lely AJ, Lamberts SW, Jauch KW, et al. Use of human GH in elderly patients with accidental hip
fracture. European Journal of Endocrinology. 2000;143(5):585–592.

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Wan C, Gilbert SR, Wang Y, Cao X, Shen X, Ramaswamy G, et al. Activation of the hypoxia-inducible
factor-1alpha pathway accelerates bone regeneration. Proc Natl Acad Sci USA 2008;105:686–91.

Weissberger AJ, Anastasiadis AD, Sturgess I, Martin FC, Smith MA, Sönksen PH. Recombinant human
growth hormone treatment in elderly patients undergoing elective total hip replacement. Clinical
Endocrinology. 2003;58(1):99–107.

Welch RD, Johnston 2nd CE, Waldron MJ, Poteet B. Bone changes associated with intraosseous
hypertension in the caprine tibia. J Bone Joint Surg Am1993;75:53–60.

Yeo A-L, Levy D, Martin FC, et al. Frailty and the biochemical effects of recombinant human growth
hormone in women after surgery for hip fracture. Growth Hormone and IGF Research.
2003;13(6):361–370.

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 Proximal Gains
One limiting factor to BFR training is the inability to occlude blood flow of the trunk
musculature. This could be limiting for rehabilitating proximal injuries to the shoulders
and hips.

However, several studies have measured proximal effects of BFR training. Abe et al
investigated the effects of low load (20% 1RM) squat and leg curl exercises with and
without BFR on thigh and gluteus muscle volume
and strength.(Abe 2005) In the study both groups
exercised for 3 sets of 15 repetitions 2xday, 6
days a week for 2 weeks. The subjects had a 4-
hour rest between sessions. At the conclusion of
2 weeks the subjects in the BFR group
demonstrated a 17% increase in squat strength
and a 23% increase in leg curl strength. The
control group had a 9% and 2% increase; the
difference between the groups was statistically
significant (p<0.05).

Additionally, an increase in quadriceps, biceps

femurs and gluteus maximus muscle volume of
7.7%, 10.1% and 9.1% for the BFR group
(p<0.01) and 1.4%, 1.9% and -0.6% for the
control group (p<0.05) was measured on MRI.

Yasuda et al investigated the effects of low load

(30% 1RM) bench press training with and
without BFR on strength and muscle CSA.
(Yasuda 2010) The pectorals and triceps
muscles volume was measured using MRI.
They utilized the standard 30/15/15/15 protocol
and performed exercises 2x day (separated by
4 hours) for 6 days over 2 weeks (12 sessions). At the conclusion of the 2 weeks only
the BFR group demonstrated significant increases in bench press 1 RM (6% BFR vs -
2% Con p<0.05) and triceps and pectorals major size (8% and 16% p<0.01 BFR vs -1%
and 2% Con). (Yasuda 2010)

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In a second study the same authors compared muscle size and strength changes
between HIT (80% 1RM) and BFR with low load (30% 1RM). Subjects performed the
exercises 3 days a week for 6 weeks. At the conclusion of the study both the HIT and
BFR group increased their muscle size and strength. Triceps brachii and pectoralis
major muscle CSA increased 8.8% and 15.8% (P < 0.01), respectively, in the HIT group
and 4.9% (P < 0.05) and 8.3% (P < 0.01), respectively, in the LI-BFR group. Bench
press 1RM strength increased 19.9% in the HIT group
and 8.7% in the BFR
group. (Yasuda 2011) It
is interesting to note that
the increases in strength
and hypertrophy after
BFR were similar in this
study as well as the
authors’ previous study.
However, the training duration and sessions differed
between the two studies. In the previous study subjects trained 2x day for 2 weeks in
the current study subjects trained 3x week for 6 weeks.

The same authors conducted a third bench press study, however this time they
combined BFR and HIT. A similar training design was implemented where subjects
trained 3x week for 6 weeks. However, in this study the combined (BFR-HIT) group did
BFR at 30% 1RM 2x week (Mon-Wed) and HIT 1 day a week (Fri). At the conclusion of
the study all 3 groups demonstrated improvements in strength and muscle CSA.
However, the improvements were larger and very similar between the HIT and
Combined HIT-BFR groups. (Yasuda 2011)

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An interesting study in the Medicine and Science in Sport and Exercise (the ACSM
journal) examined the potential systemic effects of BFR on strength and hypertrophy.
(Madarame 2008) Subjects were divided into a BFR and control group. Both groups
performed bicep curls on 1 arm at 50% 1RM and
did not exercise the
contralateral arm. Then
both groups performed
leg extension and flexion
exercises at 30% 1RM,
however the BFR group
did their LE exercises
under occlusion while the
Control group did the
same exercises under free flow. At the conclusion
of the study only the bicep that exercised at 50%
1RM in conjunction with LE BFR exercise demonstrated a significant change in strength
and hypertrophy.

Additionally, the authors found levels of the anabolic factors noradrenaline and growth
hormone had significantly increased in the BFR group vs controls. Testosterone also
increased in the BFR group, but did not reach statistical significance.

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More evidence to support the systemic response of BFR on proximal strength was
provided by Cook et al. (Cook 2014) In their study semi-professional rugby players
exercised for 3 weeks performing squats, bench press,
and weighted pull-ups
at 70 % 1 RM. The
players were divided
into 2 groups, 1 group
wore tourniquets on
bilateral lower
extremities during the
entire session while the
control group exercised
at free flow. At the
conclusion of the
training block the BFR subjects demonstrated significant improvements in squat and
bench 1RM as well as sprint time and counter-jump movement. Additionally, the
subjects were tested for increased cortisol and
testosterone levels after the training. Again, only the
BFR subjects demonstrated a significant change in
these measures. The authors suggested that the
improvements seen in the BFR group were related to
a systemic hormone response.

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Additional Notes:

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 Bibliography

Abe T. Effects of short-term low-intensity KAATSU training on strength and skeletal muscle size in young
men. J Train Sci Exerc Sports (2004); 16: 199–207.

Cook, Christian J., Liam P. Kilduff, and C. Martyn Beaven. "Improving strength and power in trained
athletes with 3 weeks of occlusion training." Int J Sports Physiol Perform 9.1 (2014): 166-172.

Madarame, H., Neya, M., Ochi, E., Nakazato, K., Sato, Y., & Ishii, N. (2008). Cross-transfer effects of
resistance training with blood flow restriction. Med Sci Sports Exerc, 40(2), 258-263.

Yasuda T, Fujita S, Ogasawara R, Sato Y, Abe T. Effects of low-intensity bench press training with
restricted arm muscle blood flow on chest muscle hypertrophy: a pilot study. Clin Physiol Funct
Imaging (2010); 30: 338–343.

Yasuda T, Ogasawara R, Sakamami M, Bemben MG, Abe T. Relationship between limb and trunk
muscle hypertrophy following high-intensity resistance training and blood flow restricted low-
intensity resistance training. Clin Physiol Funct Imaging (2011); 31: 347–351.

Yasuda, Tomohiro, et al. "Combined effects of low-intensity blood flow restriction training and high-
intensity resistance training on muscle strength and size." European journal of applied physiology
111.10 (2011): 2525-2533.

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 Muscle Damage
You will recall this equation from previous chapters: Net Protein Balance=Muscle
Protein Synthesis-Muscle Protein Breakdown, or NPB=MPS-MPB. The goal in
resistance training is to be on the positive side of the equation. Blood flow restriction
increases MTORC1 and there is a concomitant rise in MPS. In theory, the low loads
seen with BFR should lead to less protein breakdown. This could prove especially
beneficial in injured populations.

Even though muscle damage sounds bad, it is quite common after strenuous
exercise. Several factors play a role including contraction type; with eccentric
contractions producing significantly more damage than concentric (Nosaka 2002).
Additionally, the mechanical load and peak force produced during exercise plays a
role. (Lieber 1993, McCully 1986) As the number of eccentric contractions increases
muscle damage increases, likewise as the intensity of the contractions increases so
does muscle damage. When the sarcomere is stretched during moderate to heavy
resistance training eventual disruption of the cytoskeletal matrix occurs. This sets off
an inflammatory cascade that can lead to more damage as the muscle tries to repair.
(Tidball 2010) The timing of muscle soreness that corresponds to these changes is
typically 24-72 hours post-exercise. (Loenneke 2014)

As stated, the low load nature of BFR exercise leads us to believe that there is
minimal muscle damage. This is supported by the literature. One concern is potential
ischemia-reperfusion injuries. This is injury to the muscle from prolonged tourniquet
time, typically seen in surgery, and is associated with full occlusion of the limb and
tourniquet times of 4-6 hours. Prolonged hypoxia results in cell death and the
subsequent reperfusion from the release of the tourniquet pressure further damages
the cell structure through the release of reactive oxygen species (ROS). (Wang
2011) Increased measurements of ROS have not been demonstrated in the BFR
literature. (Loenneke 2011)

Umbel et al measured DOMS (patient reported),

prolonged swelling, MVC and and pain-pressure
threshold after BFR at 35% 1RM on one leg and the
same load and work on the contralateral limb without
BFR. (Umbel 2009) It should be pointed out that the
BFR leg did exercise to failure and the contralateral
leg did work matched, which would not be to failure
without BFR. After the training, DOMS was

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significantly higher in the BFR group 24 and 48 hours after exercise, however
returned to non-significant levels 96 hours after training. However, both groups did
increase (again, the work in the control leg was considered sub-maximal compared
tot he BFR leg). Chronic swelling, changes in MVC and PPT were not altered
compared to the control group.

In contrast, Wernbom et al compared exercise to

failure in one leg under BFR and exercise to failure in
the contralateral leg without BFR. The authors found
that DOMS as well as rating of perceived exertion
were both higher in the control leg. It also took
significantly more repetitions to reach failure under the
non-BFR condition. (Wenbom 2009)

Loenneke et al used a sub-maximal protocol (very similar to what is used in the

clinic) to determine muscle damage. In this study, subjects completed 4 sets of
30/15/15/15 exercises with one leg under BFR
and the contralateral leg without. The authors
measured decreases in torque at set times points
after exercise. It can be argued that decrements
in torque over time, especially after exercise is
the best independent predictor of muscle
damage. (Warren 1999) At completion of the
experiment there was a large decrease in torque
for both groups immediately after exercise. The
drop was larger in the BFR group. However, at 1
hour and 24 hours after exercise the torque had
rapidly returned to baseline. The immediate drop in torque in both groups was most
likely related to fatigue and not muscle damage since levels quickly returned to
baseline. (Loenneke 2013)

A second part of their study measured the effects of a tourniquet alone on torque
decrement. Subjects rested for 4 minutes with BFR on one leg (4 minutes is about
the time it takes to complete the 30/15/15/15 protocol and should allow for venous
pooling) and rested for 4 minutes without a tourniquet on. There were no changes in
MVC at any time point for either group. The authors concluded that the exercise, not
occlusion explains the initial decline in muscle torque.

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Wilson et al investigated swelling, decrements in power and DOMS under BFR and free
flow training. In a crossover design subjects performed
30/15/15/15 reps at 30% 1RM. At completion of the study
the BFR condition had a significant increase in swelling
through 5 minutes post workout but returned to baseline at
24 hours. There were no differences between conditions
for DOMS or changes in power. (Wilson 2013)

The effects of eccentric vs. concentric contractions under

BFR on indirect markers of muscle damage have also
been studied. Subjects completed 30/15/15/15 repetitions at 30% 1RM with 1 arm
doing concentric only and the contralateral arm, performing eccentric only. After 24
hours muscle soreness was the only variable still slightly elevated (eccentric group).
It returned to baseline at 72 hours. MVC and swelling were decreased acutely after
exercise, but returned to baseline at 24 hours. (Thiebaud 2013)

Taken in whole, there are no prolonged signs of muscle damage via indirect markers
in the studies listed above. There are acute changes in torque, which would be
expected from fatigue. Additionally, there are increases in swelling but this may be a
critical factor in the mechanism behind BFR as we will discuss in the next section and
this is only an acute change. Lastly, DOMS is elevated but it appears to be relatively
equal between BFR and low load exercise when the volume is equal between
groups. Although indirect markers serve as a very good surrogate of muscle damage
it is worth looking at studies that have measured direct markers of muscle damage.

In their study examining the role of Rapamycin in limiting muscle protein synthesis
the authors also measured the rate of muscle protein
breakdown at 6 and 24 hours after exercise. In
theory, if BFR induced MPB then the Rapamycin
group would demonstrate a net decrease in MPS
since the MTORC1 pathway was blocked by the
drug. The authors found no change in MPB after
training in the BFR Rapamycin group. The control
group (performing BFR without Rapamycin) also did
not demonstrate a change in MPB. (Gunderman
2014)

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Direct muscle damage markers such as creatine kinase and lipid peroxides have also
been examined after BFR
training. Creatine kinase is
used in clinical labs to detect
inflammation in muscles. It
is a common test used for
rhabdmmyolysis, a severe
form of muscle damage.
Lipid peroxides are a sign of
muscle or vascular damage
via free radicals. Neither of these muscle damage
markers were increased significantly from baseline or between groups post treatment.
(Takarada 2000)

In this study, the concentration of interleukin-6 (IL-6) did increase significantly after BFR
training with the largest rise occurring at 120 minutes post training and a rapid decrease
towards baseline at 24 hours. Although IL-6 has traditionally been thought of as a
marker of muscle damage recent evidence suggests that this may not be the case.
(Pederson 2011) It appears the main source of IL-6 is not from macrophages but from
the muscle contraction itself. (Pedersen 2007) The rise in IL-6 from BFR after 90
minutes was close to 1 pg/ml. After strenuous eccentric exercise the rise in IL-6 has
been reported to exceed 4 pg/ml, 4x higher than the BFR study. Again, the large
mechanical tension associated with traditional heavy eccentric exercise would explain
such a rise.

Low-level activities such as walking and its potential effects on muscle damage have
also been studied. Abe et al
found no increase in creatine
kinase or myoglobin (both
markers of damage) after walking
with BFR. (Abe 2005)

Additionally, signs of muscle

damage after BFR in the elderly
have not been found. Karabulut et al examined creatine kinase levels and IL-6 in older
men and compared them to low intensity exercise with BFR at 20% 1 RM, high intensity
training (HIT) at 80% 1RM or no exercise. At the completion of 6 weeks of training there
was no significant increase in CK or IL-6 from baseline levels and no group differences.
(Karabulut 2013)

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An intriguing study to support the lack of muscle damage during BFR was published this
year. In it researchers used an animal model (rat) and electrical stimulation to force a
maximal eccentric contraction. There were 4 groups: an eccentric only group, and
eccentric with BFR at 140, 160 and 200 torr (pressure). After completion of 40 maximal
contractions the animals were biopsied for analysis. Not surprisingly, the eccentric
exercises caused significant muscle damage, which peaked at 3 days post-training.
However, the BFR group at 200 torr showed no muscle damage and the other BFR
groups had minimal damage. (Sudo 2015) The authors could only speculate why BFR
had a protective effect for the muscle after eccentric exercise. It was their feeling that
the increase in CA from stretch activation, which normally damages the cell membrane,
did not occur in the BFR condition. Further studies are warranted to tease out the true
mechanism.

From the totality of the evidence it appears that there are no direct or indirect measures
of muscle damage associated with blood flow restriction exercise. Again, the goal is to
be on the positive side of the muscle protein synthesis equation. The large increase in
MPS after BFR and the limited MPB may explain the relatively quick (usually in the first
2 weeks) hypertrophic effects that we see. This also explains the ability to perform BFR
more frequently than traditional resistance training. For instance, Nielsen et al
performed BFR 2x day for 3 weeks and demonstrated an increase in muscle size,
strength and gene expression vs. work matched controls. (Nielsen 2012)

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Additional Notes:

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 Bibliography

Abe, T., Kearns, C. F., & Sato, Y. (2006). Muscle size and strength are increased following walk training
with restricted venous blood flow from the leg muscle, Kaatsu-walk training. J Appl Physiol
(1985), 100(5), 1460-1466.

Gundermann, D. M., Walker, D. K., Reidy, P. T., Borack, M. S., Dickinson, J. M., Volpi, E., & Rasmussen,
B. B. (2014). Activation of mTORC1 signaling and protein synthesis in human muscle following
blood flow restriction exercise is inhibited by rapamycin. Am J Physiol Endocrinol Metab, 306(10),
E1198-1204.

Karabulut, M., Sherk, V. D., Bemben, D. A., & Bemben, M. G. (2013). Inflammation marker, damage
marker and anabolic hormone responses to resistance training with vascular restriction in older
males. Clin Physiol Funct Imaging, 33(5), 393-399.

Lieber RL, Friden J. Muscle damage is not a function of muscle force but active muscle strain. J Appl
Physiol 1993: 74: 520–526.

Loenneke, J. P., Thiebaud, R. S., & Abe, T. (2014). Does blood flow restriction result in skeletal muscle
damage? A critical review of available evidence. Scand J Med Sci Sports, 24(6), e415-422.

Loenneke JP, Thiebaud RS, Fahs CA, Rossow LM, Abe T, Bemben MG. Blood flow restriction does not
result in prolonged decrements in torque. Eur J Appl Physiol 2[Link] 923–931.

Loenneke JP, Balapur A, Thrower AD, Barnes JT, Pujol TJ. Blood flow restriction reduces time to
muscular failure. Eur J Sport Sci 2012a: 238–243.

Loenneke, J. P., Wilson, J. M., Wilson, G. J., Pujol, T. J., & Bemben, M. G. (2011). Potential safety issues
with blood flow restriction training. Scand J Med Sci Sports, 21(4), 510-518.

McCully KK, Faulkner JA. Characteristics of lengthening contractions associated with injury to skeletal
muscle fibers. J Appl Physiol 1986: 61: 293–299.

Nielsen, J. L., Aagaard, P., Bech, R. D., Nygaard, T., Hvid, L. G., Wernbom, M. Frandsen, U. (2012).
Proliferation of myogenic stem cells in human skeletal muscle in response to low-load resistance
training with blood flow restriction. J Physiol, 590(Pt 17), 4351-4361.

Nosaka K, Sakamoto K, Newton M,Sacco P. The repeated bout effect of reduced-load eccentric exercise
on elbow flexor muscle damage. Eur JAppl Physiol 2001: 85: 34–40.

Pedersen BK. Muscles and their myokines. J Exp Biol 2011: 214:337–346. Pedersen BK, Fischer CP.
Beneficial health effects of exercise – the role of IL-6 as a myokine. Trends Pharmacol Sci 2007:
28: 152–156.

Mikuki Sudo, Soichi Ando, David C. Poole, Yutaka Kano Blood flow restriction prevents muscle damage
but not protein synthesis signaling following eccentric contractions Physiological Reports Jul
2015, 3 (7)

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Takarada Y, Nakamura Y, Aruga S, Onda T, Miyazaki S, Ishii N. Rapid increase in plasma growth
hormone after low-intensity resistance exercise with vascular occlusion. J Appl Physiol (1985).
2000;88:61-65.

Thiebaud, R. S., Yasuda, T., Loenneke, J. P., & Abe, T. (2013). Effects of low-intensity concentric and
eccentric exercise combined with blood flow restriction on indices of exercise-induced muscle
damage. Interv Med Appl Sci, 5(2), 53-59.

Tidball JG, Villalta SA. Regulatory interactions between muscle and the immune system during muscle
regeneration. Am J Physiol Regul Integr Comp Physiol 2010: 298:

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 flow-restricted exercise. Eur J Appl
Physiol, 107(6), 687-695.

Wang WZ, Baynosa RC, Zamboni WA. Update on ischemia-reperfusion injury for the plastic surgeon:
2011. Plast Reconstr Surg 2011: 128: 685e–692e.

Warren GL, Lowe DA, Armstrong RB. Measurement tools used in the study of eccentric contraction-
induced injury. Sports Med 1999: 27: 43–59

Wernbom, M., Jarrebring, R., Andreasson, M. A., & Augustsson, J. (2009). Acute effects of blood flow
restriction on muscle activity and endurance during fatiguing dynamic knee extensions at low
load. J Strength Cond Res, 23(8), 2389-2395.

Wilson, J. M., Lowery, R. P., Joy, J. M., Loenneke, J. P., & Naimo, M. A. (2013). Practical blood flow
restriction training increases acute determinants of hypertrophy without increasing indices of
muscle damage. J Strength Cond Res, 27(11), 3068-3075.

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 Safety
Undoubtedly concerns about safety will come up from your peers, patients and
physicians. Blood flow restriction training is a new and novel modality and is not
common in clinical practice. Exercise is one of the most stressful events placed on the
body. It is not surprising that “Consult your Physician before starting an exercise
program” is attached to every piece of exercise equipment. Fortunately, there is quite a
bit of research exploring the safety of BFR. However, sound clinical judgment is key
and it is up to the clinician and physician to determine if their patient is an appropriate
candidate.

Thrombus

Contrary to most peoples beliefs tourniquets in and of themselves used for a short
duration do not seem to pose an increased thrombus risk. (Noordin 2009) In fact,
despite the substantial risk of postoperative deep venous thrombosis in orthopaedic
extremity surgery, use of a pneumatic tourniquet does not appear to be an independent
risk factor and tourniquet deflation is associated with anti-thrombolytic factors and
(Jarrett 2004) it is well established that acute bouts of tourniquet use have fibrinolytic
potential. (Holemans, 1963; Hozknecht et al., 1969; Robertson et al., 1972; Shaper et
al., 1975; Stegnar & Pentek, 1993). Furthermore, resistance exercise has also been
shown to stimulate the fibrinolytic system (deJong et al., 2006).

BFR studies that look specifically at potential markers of thrombus formation have not
found any. Madarame et al. (2010) found no increase in markers of thrombin
generation or intravascular clot formation after BFR with exercise. Likewise, Clark et al
did not show any changes in fibrinogen, d-dimer or CRP acutely after 1 bout or after 4
weeks of BFR and HIT training. (Clark 2011) Additionally, they found that tPA (a
fibrinolytic protein) was significantly increased after BFR
and HIT training. (Fig 77)

The authors stated “ Regarding the theoretical risk

associated with blood clotting, we observed that both
BFRE and HLE acutely increased tPA antigen
immediately following a single bout of exercise,
suggesting that an acute bout of these exercises
enhances fibrinolytic potential without elevating the

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thrombolytic potential (based on no changes in fibrinogen or D-dimer).” This is
consistent with Nakajima et al who reported that an acute bout of BFR significantly
increased tPA without any subsequent increase in thrombus markers. (Nakajima 2007)
In elderly subjects Fry et al did not find any changes in D-dimer after acute bouts of
BFR and exercise. (Fry 2010) In a recent study utilizing BFR after knee arthroscopy
Hylden et al found no changes in thrombus formation measured through venous doppler
after 4 weeks of training. (Hylden 2014)

Central Cardiac Responses

Exercise is a stressful event on the body. For all of the health benefits that come from
adaptations to chronic exercise the risks both actually and chronically cannot be
ignored. As mentioned previously, ACSM guidelines suggest loads of 75-85% of an
individual’s 1RM are needed to induce a strength and hypertrophy response.
MacDougal et al have reported elevations in BP as high as 480/350 mmHg when
exercising at 80-100% 1RM. Additionally, heart rate reached values of 170 BPM. It was
concluded that the mechanical pressure on the blood vessels while lifting heavy loads
elicits a potent pressure and Valsalva response to produce extreme elevations in blood
pressure. They further demonstrated that single-arm curls elevated BP to a mean group
average of 255/190. (McDougall 1985)

In contrast, comparing BFR

at 20% 1RM to a free flow
work-matched group
(bilateral leg extension)
found slightly higher values
in the BFR group vs control
for HR (109 vs 96 BPM)
and BP (182/105 v 155/99
mmHg).

The authors concluded that these values are all well below changes seen with
traditional HIT training.
(Takano 2005)

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Because of the decreased venous return from the tourniquet during BFR there is a
slight decrease in stroke volume, 12% (Takano 2005), however cardiac output is
maintained through the slight elevation in HR. Iida et al measured the effects of BFR in
supine and compared them to standing measures of HR, SV and TPR (total peripheral
resistance). They found that supine BFR had similar hemodynamic and neurohumeral
measurements as upright standing. This may make BFR a useful modality for
prolonged bed bound patients, patients suffering from orthostatic hypotension or after
spaceflight. (Iida 2007)

Peripheral Vascular Changes

The effects of exercise on peripheral vascular changes are somewhat mixed. As we

age there is a decreased arterial compliance (Celermajer 1994, Hamilton 2001) and
resistance exercise may increase arterial stiffness in the elderly. (Cortex 2005, Kawano
2008, Miyachi 2004) Due to the varying methods, ages and conditions of subjects
studied using BFR and vascular function a consensus is difficult to find. Below is a list
of some of the studies. Horiuchi et al 2011 and Loenneke et al 2011 both provide
excellent reviews.

• Fahs et al reported an improved arterial compliance acutely after LE exercise

with BFR. (Fahs 2011)

• Fans et al extended the study to 6 weeks and observed no change in arterial

compliance. (Fans 2012)

• Kim et al reported no change in arterial compliance after 3 weeks of BFR

training. (Kim 2009)

• Clark et al found no change in arterial stiffness after 4 weeks of BFR training.

(Clark 2011)

• Ozaki et al found no change in carotid artery compliance after bench press with
BFR, but did find a decreased arterial compliance after HIT (Ozaki 2013)

• Ozaki et al found significantly improved arterial compliance after 10 weeks of

BFR walking in elderly subjects. (Ozaki 2011)

Horiuchi et al in their review of these studies in the International Jr of Vascular Medicine

concluded that “what we can say is that BFR training including resistance exercise and
walking may not worsen arterial compliance”. (Horiuchi 2011)
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Additional Notes:

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 Bibliography

Clark, B. C., Manini, T. M., Hoffman, R. L., Williams, P. S., Guiler, M. K., Knutson, M. J., Kushnick, M. R.
(2011). Relative safety of 4 weeks of blood flow-restricted resistance exercise in young, healthy
adults. Scand J Med Sci Sports, 21(5), 653-662.

Celermajer DS, Sorensen KE, Spiegelhalter DJ, Georgakopoulos D, Robinson J. Deanfield JE. Aging is
associated with endothelial dysfunction in healthy men years before the age-related decline in
women. J Am Coll Cardiol. 1994;24:471-476.

Cortez-Cooper MY, DeVan AE, Anton MM, Farrar RP, Beckwith KA, Todd JS, Tanaka H. Effects of high
intensity resistance training on arterial stiffness and wave reflection in women. Am J Hypertens.
2005;18:930-934.

DeJong AT, Womack CJ, Perrine JA, Franklin BA. Hemostatic responses to resistance training in patients
with coronary artery disease. J Cardiopulm Rehabil 2006: 26: 80–83.

C. A. Fahs, L. M. Rossow, D. I. Seo et al., “Effect of different types of resistance exercise on arterial
compliance and calf blood flow,” European Journal of Applied Physiology, vol. 111, no. 12, pp.
2969–2975, 2011.

Fry, Christopher S., et al. "Blood flow restriction exercise stimulates mTORC1 signaling and muscle
protein synthesis in older men." Journal of Applied Physiology 108.5 (2010): 1199-1209.

Hamilton CA, Brosnan MJ, McIntyre M, Graham D, Dominiczak AF. Superoxide excess in hypertension
and aging: a common cause of endothelial dysfunction. Hypertension. 2001;37:529-534.

Holemans R. Increase in fibrinolytic activity by venous occlusion. J Appl Physiol

1963: 18: 1123–1129.

Horiuchi, M., & Okita, K. (2012). Blood flow restricted exercise and vascular function. Int J Vasc Med,
2012, 543218. doi: 10.1155/2012/543218

Hozknecht F, Spottl F, Braunsteiner H. Enhancement of fibrinolysis by venous occlusion. Results of long-

term thrombelastography and activator determination. Thromb Diath Haemorrh 1969: 21: 304–
310.

Hylden, C., et al. "Blood Flow Restriction Rehabilitation for Extremity Weakness: A Case Series." Journal
of special operations medicine: a peer reviewed journal for SOF medical professionals 15.1
(2014): 50-56.

Iida, Haruko, et al. "Hemodynamic and neurohumoral responses to the restriction of femoral blood flow by
KAATSU in healthy subjects." European journal of applied physiology 100.3 (2007): 275-285.

Kawano H, Tanimoto M, Yamamoto K, Sanada K, Gando Y, Tabata I, Higuchi M, Miyachi M. Resistance

training in men is associated with increased arterial stiffness and blood pressure but does not
adversely affect endothelial function as measured by arterial reactivity to the cold pressor test.
Exp Physiol. 2008;93:296-302.

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S. J. Kim, V. D. Sherk, M. G. Bemben, and D. A. Bemben, “Effects of short-term, low-intensity resistance
training with vascular restriction on arterial compliance in untrained young men,” International
Journal of KAATSU Training Research, vol. 5, no. 1, pp. 1–8, 2009.

Loenneke, J. P., Wilson, J. M., Wilson, G. J., Pujol, T. J., & Bemben, M. G. (2011). Potential safety issues
with blood flow restriction training. Scand J Med Sci Sports, 21(4), 510-518. doi: 10.1111/j.1600-
0838.2010.01290.x

MacDougall, J. D., et al. "Arterial blood pressure response to heavy resistance exercise." Journal of
Applied Physiology 58.3 (1985): 785-790.

Madarame, Haruhiko, et al. "Effects of low‐intensity resistance exercise with blood flow restriction on
coagulation system in healthy subjects." Clinical physiology and functional imaging 30.3 (2010):
210-213.

Madarame, H., Sasaki, K., & Ishii, N. (2010). Endocrine responses to upper- and lower-limb resistance
exercises with blood flow restriction. Acta Physiol Hung, 97(2), 192-200.

Miyachi M, Kawano H, Sugawara J, Takahashi K, Hayashi K, Yamazaki K, Tabata I, Tanaka H.

Unfavorable effects of resistance training on central arterial compliance: a randomized
intervention study. Circulation. 2004;110:2858-2863.
Noordin, Shahryar, et al. "Surgical tourniquets in orthopaedics." The Journal of Bone & Joint Surgery
91.12 (2009): 2958-2967.

Robertson BR, Pandolfi M, Nilsson IM. ‘‘Fibrinolytic capacity’’ in healthy volunteers as estimated from
effect of venous occlusion of arms. Acta Chir Scand 1972: 138: 429–436.

Shaper AG, Marsh NA, Patel I, Kater F. Response of fibrinolytic activity to

venous occlusion. Br Med J 1975: 3: 571–573.

Stegnar M, Pentek M. Fibrinolytic response to venous occlusion in healthy subjects: relationship to age,
gender, body weight, blood lipids and insulin. Thromb Res 1993: 69: 81–92.

Takano, Haruhito, et al. "Hemodynamic and hormonal responses to a short-term low-intensity resistance
exercise with the reduction of muscle blood flow."European journal of applied physiology 95.1
(2005): 65-73.

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 Clinical Studies
From the previous chapters one can see that there is a large amount of scientific
literature that has studied blood flow restriction. However, the majority of these studies
have examined healthy subjects, both young and old. Nonetheless, there are some
studies that have examined BFR on injured populations.

Persistent thigh weakness is a concern after anterior cruciate ligament surgery. (Tegner
1984, 1986) In fact at 1 year follow up over 65% of patients demonstrate quadriceps
weakness >20% of the uninvolved limb. (Sachs 1989) With this in mind, Ohta et al
examined the
effects of BFR on
thigh strength and
hypertrophy after
ACL surgery. (Ohta
2003) The study
took place over 16
weeks after surgery
BFR beginning at
week 2. The
exercises were
identical for both groups except the experimental group (BFR) performed the exercises
utilizing blood flow restriction. After 16 weeks of training post-op KT measurements did
not show any difference between groups. Thigh strength improved significantly in the
BFR group compared to controls in all tests.

Additionally, quadriceps CSA improved significantly in the BFR group vs controls (as
measured on MRI). Hamstring muscle CSA did not
differ between the groups. The authors concluded that
the significant effect seen in muscle hypertrophy and
strength in the experimental group was related to BFR
since both groups performed the exact same exercise
protocol and the only added variable was BFR.

Loenneke et al presented a case report of a body

builder who suffered an osteochondral fracture.
Radiographs confirmed the diagnosis and he was
scheduled to have surgery 2 weeks after his injury.
(Loenneke 2013) The surgeon agreed to allow the patient participate in low load BFR

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training to maintain his thigh mass and strength for an upcoming body building
competition. After approximately 2 weeks the patient returned for his follow up visit to
pre-op for surgery. At this time, the patient was pain free and repeat radiographs
demonstrated significant healing of his OCD. The patient and surgeon agreed to cancel
surgery and the patient was instructed to continue BFR training for 6 additional weeks
before engaging in HIT. The authors suggested that the potential for BFR to improve
bone healing may have played a role in the patients rapid improvement. This is not
uncommon from the results we have seen with BFR for cartilage defects in my clinic
practice. We routinely use BFR after cartilage surgery with excellent results.

Segal et al examined BFR vs. free flow strength training in women with risk factors for
knee osteoarthritis. (Segal 2014) Subjects completed low load resistance training (30%
1RM) 3x week for 4 weeks randomized to a free flow or BFR group. After 4 weeks,
isotonic 1RM improved
significantly more in the BFR
group (28.3 ± 4.8 kg) than in
the control group (15.6 ± 4.5
kg) (P = .0385). Isokinetic
knee extensor strength
scaled to body mass
increased significantly more
in the BFR group (0.07 ±
0.03 nm/kg) than in the control group (-0.05 ± 0.03 nm/kg) (P = .0048). The authors
concluded that the “addition of BFR to a 30% 1RM resistance training program was
effective in increasing leg press and knee extensor strength in women at risk for knee
OA, in comparison with the same program without BFR”.

We recently published a paper in the

Journal of Special Operations Medicine on
the results of our first cohort to utilize BFR.
The patients were post trauma and had
thigh weakness that ranged from 35%-75%
of the uninvolved limb. After 2 weeks of
training all patients demonstrated
improvement in thigh strength with average
power improving 42% to 81% respectively.
More importantly, these severely
compromised cases all tolerated the treatment well without incident or adverse side
effects. (Hylden 2015)

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 Additionally, we just completed a study exploring the effects of BFR after knee
arthroscopy surgery. (Unpublished Results) In the study we randomized patients to
post-operative rehabilitation with BFR or a free flow condition. We measured thigh girth;
strength, functional measures and patient self reported outcome measures.
Additionally, all patients underwent pre and post training venous ultrasound scans to
rule out clot formations.

At the completion of 4 weeks of training the BFR group demonstrated significant

improvements is thigh girth and strength. The
work matched
control group did
not demonstrate
significant
changes.

Both groups
demonstrated
significant
improvement in functional outcomes including sit-to-stand, self-selected walking velocity
and 4-square step test and there was no difference
between groups. However, our functional test for
power, timed stair ascent, demonstrated a significant
difference between the BFR and controls.

The self reported

outcome, Knee
Injury and Osteoarthritis Outcome Score (KOOS),
revealed a greater improvement in all sub scales
for the BFR group.

Lastly, there were no signs of thrombus on full bilateral leg

ultrasounds for any subjects.

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Additional Notes:

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 Bibliography

Gualano, B., Neves, M., Jr., Lima, F. R., Pinto, A. L., Laurentino, G., Borges, C. , Ugrinowitsch, C. (2010).
Resistance training with vascular occlusion in inclusion body myositis: a case study. Med Sci
Sports Exerc, 42(2), 250-254.

Hylden, C., et al. "Blood Flow Restriction Rehabilitation for Extremity Weakness: A Case Series." Journal
of special operations medicine: a peer reviewed journal for SOF medical professionals 15.1
(2014): 50-56.

Kubota, Atsushi, et al. "Prevention of disuse muscular weakness by restriction of blood flow." Medicine
and science in sports and exercise 40.3 (2008): 529-534.

Ohta, Haruyasu, et al. "Low-load resistance muscular training with moderate restriction of blood flow after
anterior cruciate ligament reconstruction." Acta Orthopaedica 74.1 (2003): 62-68.

Sachs, Raymond A., et al. "Patellofemoral problems after anterior cruciate ligament reconstruction." The
American journal of sports medicine 17.6 (1989): 760-765.

Santos, A. R., Neves, M. T., Jr., Gualano, B., Laurentino, G. C., Lancha, A. H., Jr., Ugrinowitsch, C., Aoki,
M. S. (2014). Blood flow restricted resistance training attenuates myostatin gene expression in a
patient with inclusion body myositis. Biol Sport, 31(2), 121-124.

Segal, Neil A., et al. "Efficacy of Blood Flow–Restricted, Low-Load Resistance Training in Women with
Risk Factors for Symptomatic Knee Osteoarthritis."PM&R 7.4 (2015): 376-384.

Tegner Y, Lysholm J, Gillquist J, Oberg B. Two-yearsʼ follow-up of conservative treatment of knee

ligament injuries. Acta Orthop Scand 1984; 55: 176-80.

Tegner Y, Lysholm J, Lysholm M, Gillquist J. Strengthening exercises for old cruciate ligament tears. Acta
Orthop Scand 1986; 57: 130-4.

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 Exercise Prescription
There is a very large amount of literature studying BFR, >160 articles. Determining the
optimal exercise prescription with this modality is difficult secondary to different
methodologies used in all of these studies. The following recommendations are based
off of the best evidence, anecdotal clinical information and a recent meta-analysis on
BFR.

Training Frequency

Traditional strength training using high loads typically

produces muscle damage that requires a recovery
period that can take days to weeks. The low loads
associated with BFR do not produce lasting muscle
damage or decrements in torque. In theory, it can be
done daily and in some very well done studies (Nielsen
et al) it has been done 2x day. The effects size for BFR
training frequency is listed below. The largest effect is
seen with 2-3 days a week.

Endurance training and BFR may not follow the same rules as strength training when it
comes to frequency. Several studies looking at endurance have shown effects with 4-6
days of training. At my clinic, if we have patients come in daily we alternate BFR days
between strength and endurance work.

Training Duration

The effect’s size for training duration demonstrates that longer durations up to 10 weeks
have the largest effect
size. This is not unlike
traditional HIT. What is
different between the
groups is the early
hypertrophy seen with
BFR. This may be from
the increased satellite
cell fusion and resultant
muscle protein

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synthesis. Do not be surprised if you patient notices hypertrophy within the first 2
weeks of BFR training. This is very common in my practice.

Rest Periods

Rest periods are being explored 30-second rest

more when it comes to muscle periods between
physiology. With BFR the rest sets have the
periods are relatively short. The largest effect size.
largest effect size is seen with The tourniquet
rest periods of 30 seconds. It is stays inflated
important to keep the cuff
during the rest to
inflated during the rest periods
trap metabolites!
to capture metabolites.

Tourniquet Cuff Pressure

Cuff pressure is a very difficult measure to assess fro the

literature because it is probably themes variable. The
amount of pressure needed to occlude blood flow in a limb
depends on the limb size, underlying soft tissue, cuff width
and device used. Many studies do not report al lot these
variables. Some studies don’t use a tourniquet or cuff;
some examples include wraps and blood pressure cuffs.
Furthermore, studies use varying means to determine
pressure including systolic pressure, an arbitrary number
and a sliding scale. The effect size for different pressures
is listed below. There is considerable overlap because of the variability on the literature.

Limb Occlusion Pressure (LOP)

Limb occlusion pressure, which is the minimal amount of pressure needed to occlude
arterial blood flow, is the gold standard in the tourniquet literature. It is now the
standard being used by many of my colleagues conducting
rd
3 Generation BFR research. At my clinic we initially used a handheld
Tourniquet Systems Doppler and a distal pulse to determine LOP. This was not
feature built in LOP only time consuming, but also added additional cost to
measurement purchase a Doppler and significant human error. The
capabilities. advent of new 3rd generation tourniquet systems features a

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built in system to measure vascular flow. This allows a personalized tourniquet
pressure for each individual patient and eliminates the need to account for cuff width,
limb size or blood pressure.

BFR training requires the reduction of arterial inflow and the elimination of venous
outflow. The pressure to stop venous outflow is lower than the pressure to stop arterial
inflow. If the occlusion pressure is too high the blood supply to the exercising limb can
be eliminated. If the pressure is too low then there may be to much arterial inflow and
subsequent venous congestion in the limb. This can cause a painful condition for your
patients.

Using LOP we currently recommend a pressure of 80% occlusion for the lower
extremities and 50% for the upper extremities. These are starting points and may need
to be altered based on your patient’s tolerance and results.

Training Intensity

The intensity needed to

produce a maximal strength For BFR &
and hypertrophy response resistance training
aim for a 15-30%
has been calculated from
load.
the available literature. A
load of 15-30% 1 RM or
MVC has the largest effect size. As mentioned
previously higher loads may actually have a pumping
effect to eliminate metabolite accumulation and blunt
the response. Lower intensities such as cycling,
walking and isometrics have a response but it is much lower than a 15-30% load.
However, the response with cycling, walking and simply wearing a tourniquet is
significantly higher than controls at the same intensities.

Determining 1RM

The traditional method for determining a 1RM is to lift a weight with an increasing load
until you reach muscle failure. Unfortunately this kind of testing is often difficult to
perform on injured populations. Rep max calculators have been developed however the
validations of these are questionable especially in inured populations. Furthermore, rep
max testing can be tedious and time consuming.

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If you are in the acute stages of rehabilitation rep max testing is probably not needed.
The goal is to mitigate atrophy and increase neuromuscular activity. As mentioned in
previous chapters just the application of a tourniquet can mitigate the effects of atrophy.
However, when strength and hypertrophy is desired finding an estimated 20-30% load
will be needed.
The adult Omnibus Resistance Exercise Scale (OMNI-
RPE has a high RES) has been validated and shown effective in
correlation to percent
evaluating exercise intensity during resistance exercise.
MVC.
Morshita 2013 (Robertson
2003,
Robertson
2004) It has been shown to be a valid metric
to track absolute and relative strength
changes over a 12-week resistance program.
(Andrews 2007, Gearhart 2008, 2009)
Recently it was found to be a safe modality to
determine 1RM in older adults. (Gerhard
2011) The OMNI-RES has been adapted to
use pictures and a scale to help subjects
assess exercise intensity. To use the OMNI-
RES you instruct the patient to imagine the easiest lightest weight they could lift (0).
Next you ask them to imagine the heaviest possible weight that they can lift (10). Then
for our purposes you have them attempt to lift a weight that corresponds to a 2-3 (20-
30% 1RM) on the OMNI-RES scale. This will be the load that is used as your RM for
BFR training. The scale will be ineffective during the BFR exercise session because of
the build up of lactate that is associated with BFR. Hetzler et al determined that RPE is
more strongly associated with the accumulation of lactate than with heart rate or blood
pressure. (Hetzler 1991) Tracking of the patients 1RM using the OMNI-RES can be
done on a by session, weekly or bi-weekly basis. Strength training studies have
demonstrated improved results using regular tracking of RPE and 1RM. (Gerhard 2011)

Exercise Selection

BFR is typically a single joint exercise modality for strength training or a low-level cardio
exercise. The purpose is to increase strength and hypertrophy in a muscle after injury
or surgery. Additionally, the systemic actions mentioned earlier can be beneficial for
collagen synthesis, protein synthesis, etc. Any exercise that is performed for the
extremities in a typical rehabilitation scenario is reasonable to use with BFR. These
include but are not limited to:

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 Lower Body

Walking, Cycling, Isometrics, Leg Extension, Hamstring Curl, Straight Leg Raises, Short
Arc Quad, Terminal Knee Extension, Hip Abd/Clam, Hip Extension, Hip Adduction, Hip
External/Internal Rotation, Bridge, Hip Thruster, Leg Press, Hack Squat, Squat, Split
Squat, Lunge, Ankle Dorsiflexion, Plantarflexion, Inversion, Eversion and all Foot
Exercises.

Upper Body

Upper Body Ergometer, UBE, Isometrics, Scapular Rows, Serratus Punches, Shoulder
Abduction, Shoulder Scaption, Shoulder Extension, Shoulder Adduction, Shoulder
External Rotation, Shoulder Internal Rotation, Prone T, Prone Y, Prone I, PNF Patterns,
Bench Press, Push-up, Elbow Flexion, Elbow Extension, Elbow Supination, Elbow
Pronation, Wrist Flexion, Wrist Extension, Flexion, Abduction, Adduction and all Hand
Gripping Exercises.

Additionally, electrical stimulation and or biofeedback can be applied for a

potential enhanced response in the early stages of rehabilitation. Make sure that
the pads are not touching or under the tourniquet cuff.

As mentioned before, the tourniquet cuff should be on the most proximal portion of the
upper leg or arm even during lower leg and arm exercises. NEVER PUT THE CUFF
OVER A JOINT OR SUPERFICIAL NERVE.
Hitting the Target Exercise Volume

Because we are trying to develop a metabolite response in the muscle and take
advantage of the downstream systemic effects volume during the exercise session is
the focus. The standard repetition scheme used in
Use 4 sets of
BFR is a set of 30 repetitions followed by a 30 second
30/15/15/15 with a 30 rest followed by 3 more sets of 15 with 30 second rests
second rest between in between (30/15/15/15). This gives us the target 75
sets and a 2-second repetitions. The first set of 30 can be seen as the
concentric and 2- priming load to begin the Cori cycle. This first set is
second eccentric typically tolerated well by the patient and they often feel
contraction for a like it is too easy. We leave the tourniquet inflated
metabolite response. during the rest period, this is very important because
we are trying to trap metabolites. The following 3 sets
and rest periods will feel very difficult because of the subsequent lactate build up.

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Remember RPE is closely related to lactate accumulation. Also, the patients may feel
their heart rate raise somewhat during the exercise. This is normal because of the
reduced venous return, subsequent decreased stroke volume and increased HR to
maintain cardiac output. If at anytime your patient becomes faint, dizzy, has moderate
to severe pain under the tourniquet cuff or begins to feel numbness or paresthesia in
the limb stop the exercise session.

Once the patient finishes the exercise session the reperfusion of blood into the limb
flushes out the lactate and the lactate “burn” in the limb generally goes away relatively
quickly. They do often feel very fatigued I the limb and studies measuring force
production immediately after BFR even at low loads have demonstrated significantly
reduced force. Because of this high intensity
Volume and a light load
exercises such as olympic lifts, plyometrics, agility
work should not be done immediately after BFR. is the key for a
These same exercises should also not be done metabolite response.
while using BFR. Manipulate rest periods
first if the patient is
However, there will be times when your patient is missing the target.
unable to hit the target volume. Remember volume
is key for strength and hypertrophy in our BFR training.

Below are guidelines to follow concerning exercise progression and difficulties with
volume achievement:

Load: 20-30% 1RM (Determined, Estimated or OMNI-RES)

Patient Achieves:

75 Repetitions =Continue with training, re-assess 1RM within 1-3 sessions. Re-
establish new 20-30% range as strength improves.

60-74 Repetitions=Continue with training, but extend rest period between sets 3 and 4
to 45 seconds. Until 75 repetitions is completed.

45-59 Repetitions=Continue with training, but extend rest period between all sets to 45-
60 seconds.

<44 Repetitions=Reduce load by approximately 10% until 75 repetitions is achieved.

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Forced to stop before 75 repetitions because of undue pain, soreness or general
uncomfortable feeling underneath the tourniquet cuff=Reduce tourniquet
pressure by 10mmHg at each training session until cuff tolerance is achieved.
Ramp cuff pressure back up 10 mmHg to target limb occlusion pressure if patient
can tolerate.

Rehabilitation Guidelines

In the very early phases of rehab after injury or surgery the goal is to mitigate atrophy
and promote a healing environment. During this phase simply performing BFR with low-
level exercise such as isometrics with or without electrical-stimulation, mat exercises
(SLR/4-way hip) or no exercise can achieve this. For example, researchers in the UK
are beginning a study using BFR in the ICU to decrease muscle atrophy.

Once the patient moves into a more sub-acute stage BFR can be used for slightly
higher loads such as walking and cycling. This has been shown to increase strength,
hypertrophy and endurance.

As the patient can tolerate additional load, he can move into isotonic exercises with a
15-30% load. This will produce even more substantial gains.

As the patient transitions into the later phases of rehab we typically transition to BFR
and HIT training on alternating days. This has demonstrated even larger gains than
BFR alone. This also acts as a bridge for the patient to discharge to a home
strengthening program consisting of just HIT training. Remember all the work they did
early on with BFR has made permanent anatomical changes through increased
myocyte incorporation and improved your patients muscle protein synthesis potential.

We also use BFR as a form of strength and endurance training to supplement the
patient while they are working on a higher-level program such as plyometrics, running
and agility into the late phases of rehab.

We have had the occasion where the patient has returned to work (military duty in my
case) or sports and have suffered a set back such as an effused joint or tendonitis.
BFR is a great modality to start back up during these times to diminish the losses they
might have during this setback. My patients really appreciate the fact that they are
maintaining or increasing their strength while they are recovering instead of meds and
RICE while they watch their gains atrophy daily.

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Sample Protocols

Below are sample protocols for BFR and some common injuries. These are simply
suggestions and the clinician must determine the appropriateness of their application.

Anterior Cruciate Ligament Reconstruction

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Knee Arthroscopy

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Non-Weight Bearing Lower Extremity

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Shoulder Rehabilitation

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Wrist Injuries/Fractures

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Additional Notes:

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 Bibliography

Andrews, R. D., MacLean, D. A., & Riechman, S. E. (2006) Protein intake for skeletal muscle
hypertrophy with resistance training in seniors. International Journal of Sport Nutrition and
Exercise Metabolism 16, 362-372.

Gearhart, R. F., Lagally, K. M., Riechman, S. E., Andrews, R. D., & Robertson, R. J. (2008) RPE at
relative intensities following 12 weeks of resistance exercise training in older adults. Perceptual
and Motor Skills, 106, 893-903.

Gearhart, R. F., Lagally, K. M., Riechman, S. E., Andrews, R. D., & Robertson, R. J. (2009) Strength
tracking using the OMNI resistance exercise scale in older men and women. Journal of Strength
and Conditioning Research, 23, 1011-1015.

Gearhart Jr, Randall F., et al. "Safety of using the adult Omni Resistance Exercise Scale to determine 1-
RM in older men and women." Perceptual and motor skills 113.2 (2011): 671-676.

Hetzler RK, Seip RL, Boutcher SH, Pierce E, Snead D, Weltman A. Effect of exercise modality on ratings
of perceived exertion at various lactate concentrations. Medicine Med Sci Sports Exerc, 1991;
23(1): 88-92.

Loenneke, J. P., Wilson, J. M., Marin, P. J., Zourdos, M. C., & Bemben, M. G. (2012). Low intensity blood
flow restriction training: a meta-analysis. Eur J Appl Physiol, 112(5), 1849-1859. doi:
10.1007/s00421-011-2167-x

Morishita S, Yamauchi S, Fujisawa C, Domen K (2013) Rating of Perceived Exertion for Quantification of
the Intensity of Resistance Exercise. Int J Phys Med Rehabil 1: 172.

Robertson, R. J. (2004) Perceived exertion for practitioners: rating effort with the OMNI picture system.
Champaign, IL: Human Kinetics.

Robertson, R. J., Goss, F., Rutkowski, J., Lenz, B., Dixon, C., Timmer, J., Frazee, K., Dube, J., &
Andreacci, J. (2003) Concurrent validation of the OMNI perceived exertion scale for resistance
exercise. Medicine & Science in Sports & Exercise, 35, 333-341.

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 Tourniquets
There are many different tourniquet systems available not the market. Take a quick
glance at the BFR literature and you will find that almost no two studies use the same
device for vascular occlusion. Some researchers don’t use a tourniquet system.
Tourniquets are medical devices and the clinician should always follow the Hippocratic
oath to “First Do No Harm”. The technological advances of 3rd generation tourniquets
and cuffs have made tourniquet use very safe if performed by experienced medical
professionals.

Tourniquet History

A tourniquet controls arterial and venous circulation by applying circumferential pressure

around limb. From this, occlusion of veins and arteries occur beneath the tourniquet.
(AORN Conf 2015)

Tourniquets have been in use since 4th century BC. The early systems were crude and
simply used mechanical force to apply pressure to the limb. Jean Louis Petit coined the
term “tourniquet” which in French means to “turn”.

By 1904 Harvey Cushing developed the first

pneumatic tourniquet. This allowed rapid application
and removal, which decreased the incidence of
nerve paralysis. This is considered the 1st
generation of tourniquet systems. The first electronic
tourniquet system was invented by James McEwan,
PhD, [Link] in the early 1980’s. These second
generation systems significantly improved tourniquet
safety by allowing precise pressure control and
additional safety features such as self cheeks and calibrations, audio visual alarms,
monitoring of tourniquet time and rapid inflation/deflation. These were considered 2nd
generation tourniquet systems. ([Link])

More recently tourniquet system advances include patient personalization. Features

such as automatically measuring the minimum pressure required for limb occlusion and
recommendations of a personalized minimal pressure needed for occlusion.
Additionally they utilize specifically designed tourniquet cuffs and limb protection
sleeves that conform to the limb and shape of the individual. The advancements in

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these 3rd generation tourniquet systems further improve patient safety while under
tourniquet use. ([Link])

It is estimated that these modern pneumatic tourniquets are used in over 1 million
surgical cases annually. By utilizing a 3rd generation system the risk of tourniquet
complication is very low, ranging from 0.04% to 0.8%. (Odinsson 2006, Kalla 2003)
However, there are inherent risks to tourniquet use. Some of the more common
complication includes:

• Nerve Injury
• Skin Injury
• Pain
• Chemical Burns
• Respiratory, cardiovascular, cerebral circulatory and hematological effects
caused by prolonged ischemia
• Temp. Changes
• Prolonged postoperative swelling of the affected limb
• Arterial Injury

The underlying causes for these complications include high cuff pressures, high-
pressure gradients under the tourniquet, and long durations of use.
An area of particular concern for clinicians is potential nerve damage from
tourniquet use. In fact, it has been suggested that tourniquet related nerve injuries are
under reported. (McEwan 1981, Middleton
1974) The mechanism of nerve injury is now
well understood and appears limited to the
portion of the nerve under and near the edges
of the cuff. (Ochoa 1971, Ochoa 1972)
Higher-pressure gradients beneath the cuff
can result in the stretching of the underlying
nerve structures. The figure to the left
compares the difference in pressure gradients
between a modern pneumatic tourniquet, a
non-pneumatic battlefield type tourniquet and
a non-pneumatic ring made of elastic material.

The FDA regulates tourniquets as Class I medical devices. This is the lowest regulatory
classification for medical devices issued by the FDA. This can be explained in part by
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the inherent safety features and evidence based adaptations in 2 nd and 3rd generation
tourniquet systems. Utilization of these systems and the guidelines adopted by
organization such as AORN (Association of periOperative Registered Nurses) can help
provide the safest possible use of a tourniquet on a patient. An excellent review is
provided in the JBJS 2009 article “Surgical Tourniquets in Orthopedics”.

The use of emergency tourniquets in the clinical setting should be avoided. These are
reserved for austere environments and typically for life saving measures. What is even
more dangerous is the multitude of blood flow restriction products appearing on the
market. These obviously do not follow any of the proposed guidelines and should
never be used in a clinical setting.

[Link]

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Tourniquet Cuff

The purpose of the tourniquet cuff is to stop blood flow through the application of
pressure. There are generally 3 types of cuff shapes: cylindrical, fixed-contour and
variable-contour. Due to the tapered anatomy of limbs variable-contour cuffs provide
the most intimate fit and reduce potential safety concerns. Cylindrical and fixed-contour
cuffs may result in distal gaps on the limb and require more or place excessive pressure
to the underlying limb.
Variable contour cuffs can be adjusted to the shape of the
limb. This not only enhances comfort but it further
decreases the risk of mechanical shearing, and can occlude
blood flow at lower pressures due to the improved fit.
(AORN conference 2015)
Wider and variable
Cuffs should come in different
contour cuffs can
lengths to accommodate
significantly
varying limb sizes. They
should be long enough to reduce pressure
ensure full close, but not too long that there is excessive gradients and
overlap which may result in unwanted cuff movement potential nerve
during inflation. A wider cuff can minimize the risk of injury.
injury to the underlying soft tissue by dispersing pressure
over a greater surface area. Wider cuffs also reduce the amount of occlusive pressure
needed, which significantly reduces pressure gradients.

Crenshaw et al demonstrated that the wider the cuff, the lower the pressure required
occluding circulation (e.g., for an 18-cm-wide cuff, ~140 mm Hg was needed to occlude
blood flow, whereas a 4.5-cm cuff required more than 360 mm Hg of pressure).
(Crenshaw 1988)
Estelle et al compared a 14 cm cuff to a 7 cm cuff to
measure how much pressure is needed to occlude arterial
flow. The wide cuff group needed significantly less
pressure to occlude blood flow compared to the narrow cuff
group. Additionally, the narrow cuff caused significantly
more pain after reaching arterial occlusion compared to the
wide cuff. (Estelle 2000)
Graham et al found that using a wider cuff (80 cm) vs
narrow cuff (4.5 cm) allowed significantly less pressure, in
the sub systolic range. The authors concluded that a wide cuff might reduce the risk of
tourniquet-induced injury to underlying soft tissues by lowering inflation pressures.

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(Graham 1993) In addition to achieving full occlusion at lower pressures than narrow
cuffs, wide cuffs reduce the variability in full occlusion pressures and make these less
dependent on limb circumference (Crenshaw et al. 1988; Graham et al. 1993).
Furthermore, Rossow et al. demonstrated that wider (13.5 cm) BFR cuffs are required
to induce greater tissue hypoxia, which is a stimulator of muscular hypertrophy.
(Rossow 2012)

Tourniquet Instrument

Considered the brain of the tourniquet system, the

instrument provides a digital display of pressure, inflation
time, and allows the user an interface to control the
tourniquet system. 3rd generation systems not only provide
alarms that monitor the pressure, self calibration, rapid
inflation and deflation and a user interface they also
provide a means to determine the minimal occlusive
pressure personalized to each patient. Furthermore, the
pressure is regulated and monitored continuously to
compensate for changing levels in the cuff during movement.

Below is a list of the safety features built into a 3rd generation tourniquet system:

• Self-calibration to establish correct pressure readings

• Self-check to make sure the system is operational prior to use
• Ability to set the maximum tourniquet pressure and inflation time limits
• Automatic timer to provide an accurate record of tourniquet inflation time
• Back-up battery to allow the instrument to continue operating in case of a power
interruption
• Automatic measurement of Limp Occlusion Pressure (LOP) allowing individual
setting of safer tourniquet pressures
• Audio-visual alarms for:
▪ Reaching the maximum pressure
▪ Reaching the maximum inflation time
▪ Low cuff pressure
▪ High cuff pressure
▪ Occlusion in the pneumatic system
▪ Leakage in the pneumatic system
▪ Low battery
▪ Failure of the cuff to depressurize when deflation is intended

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 Limb Occlusion Pressure

Measurement of limb occlusion pressure (LOP) can help minimize tourniquet pressures
and pressure gradients. (Nordic 2009) LOP is defined as the minimum pressure
required, at a specific time by a specific tourniquet cuff applied to a specific patient’s
limb at a specific location. LOP inherently accounts for variables such as systolic blood
pressure, tourniquet cuff design, cuff application method, limb circumference and shape,
and tissue characteristics at the cuff site.

Criteria for Tourniquet Cuff Selection and Application

All patients should be assessed for risks and contraindications to tourniquet use prior to
application in the clinic.

Risks

◆ Patients with poor circulatory systems:

Indicators of poor circulatory nutrition include shining or scaly skin; brittle, dry nails;
and extremity hair loss. Other indicators for circulatory considerations include
capillary filling time and the presence of varicose veins. (AORN 2014)
◆ Patients who are obese or with limb tissue that is loose (The risk of tourniquet
shifting may be increased)
◆ Patients who have:
⁃ Arterial calcification
⁃ Abnormal clotting times
⁃ Diabetes
⁃ Sickle cell trait
⁃ Tumor
⁃ General Infection
⁃ Hypertension
⁃ Cardiopulmonary conditions
⁃ Renal Compromise
⁃ Clinically significant acid-base imbalance
⁃ Atherosclerotic vessels (McEwan 2014, Wakai 2001)
◆ Patients who are taking
⁃ Anti-hypertensive
⁃ Creatine supplements (Gupta 2008, Sheth 2006)

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 Contraindications

Possible contraindications for tourniquet use include:

◆ Venous thromboembolism
◆ Impaired circulation or peripheral vascular compromise
◆ Previous revascularization of the extremity
◆ Extremities with dialysis access
◆ Acidosis
◆ Sickle cell anemia
◆ Extremity infection
◆ Tumor distal to the tourniquet
◆ Medications and supplements known to increase clotting risk
◆ Open fracture
◆ Increased intracranial pressure
◆ Open soft tissue injuries
◆ Post-traumatic lengthy hand reconstructions
◆ Severe crushing injuries
◆ Severe hypertension
◆ Elbow surgery (where there is concomitant excess swelling)
◆ Skin grafts in which all bleeding points must be readily distinguished
◆ Secondary or delayed procedures after immobilization
◆ Vascular grafting
◆ Lymphectomies
◆ Cancer

A list of potential conditions and the resultant

risks for DVT potential is listed below. As with
exercise in general, a Physician should clear
patients with these presenting conditions
before initiating BFR.

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 Limb Protection
The use of wider cuffs, variable cuffs and LOP can help minimize
tourniquet risk. However, frictional burns from cuff shifting
especially on patients with significant adipose tissue or loose skin
may occur. Too minimize the risk of tissue damage under the
cuff the following guidelines should be followed. Avoid placing
the cuff directly over clothing. However, padding should always
be used directly under the cuff. Olivecrona et al studies the
effects on skin protection while using a tourniquet between a 2-
layer stockinet, cast padding or no padding after total knee
surgery. At the conclusion of the trial there were 10 patients with
skin blisters, 3 in the cast padding group and 7 in the no
protection group. (Olivecrona 2012)

Based on a total of
55 trials of 5 different
limb protection types,
stretched sleeves
made of two-layer
tubular elastic
material and
matched to specific
tourniquet cuffs
produced
significantly fewer and less severe pinches and
wrinkles in the skin surface than all other padding types.

Procedures for Tourniquet Cuff Application include:

Step 1: Equipment Inspection:

• Before use, inspect and test the tourniquet instrument, cuff and connecting
tubing.
• Verify cleanliness and examine for defects, such as cracks or holes in the tubing

Step 2: Limb Protection:

• The limb protection and the tourniquet cuff should be applied to the most
proximal portion of the thigh or upper arm. This is the application of the
cuff for all BFR training.

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 • Make sure that the cuff does not lie to close to any joints of the extremity
(i.e.…knee, elbow)
• Place a soft, non-shedding material (2 layers of stockinette) or a matching limb-
protection sleeve around the limb at the planned location.

Step 3: Tourniquet cuff application:

• Wrap the tourniquet cuff around the protection material
• Grasp the application handle and p port connector in the desired position on the
limb.
⁃ The cuff port connector should always be placed on the lateral aspect of
the limb to avoid hose kinking or
undue pressure on the nerves
• Slide the fastening strap under the
application handle.
• Tension the cuff and secure the strap for a
snug application of the cuff on the limb.

Delfi Personalized Tourniquet

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System for BFR

The Delfi PTS for BFR is the unit that I highly recommend
clinicians use for BFR training. It has all the features of a 3rd
generation tourniquet and makes performing BFR in the clinic
standardized, personalized and intuitive.

Below is a list of some of the key features for this course. For a
more detailed explanation or further questions please contact at
[Link].

Once the system is powered on the unit will go through a brief Self Test and Calibration
Check.

After this, the main user interface will appear with options at the
bottom.

The first option is the Pressure Set

Point. This allows the user to adjust
the pressure up or down by
increments of 1 mmHg manually. The
pressure can be adjusted while the

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unit is inflated by pressing the Pressure Adjustment button and choosing to adjust up or
down by pressing the button under the arrows.

The second button is the time inflation and rest button. Pressing this will show you the
set inflation and required rest period. This is defaulted at 5
minutes inflation and 1-minute rest. The default setting can be
changed in the Settings screen. If you would like to change the
work/rest time for a particular exercise simply push the Time Limit
button the main screen and toggle up or
down to the inflation or rest section and
adjust. The default setting of 5 minutes
follows the estimated amount of time it
takes to complete the standard
30/15/15/15 strength session. If
patients are doing this at a 2 second concentric and 2-second
eccentric tempo (recommended) than the total time is 5
minutes. If you factor in 3 rest periods at 30 seconds then the
total time under tourniquet is 6 minutes and 30 seconds. The
1-minute deflation allows for rest and recovery after a
particular exercise session. The cuff cannot be re-inflated during the rest period.

4 sets of 30/15/15/15 (at 2

seconds concentric and 2
seconds eccentric) with a 30
second rest period equals 6
minutes and 30 seconds
under tourniquet time. Plan
your time accordingly.

The third heart shaped button with PTP in it is the Personalized Tourniquet Pressure.
By pressing this button you are measuring the patient’s LOP.

This measurement should be done with the patient lying supine

and still. Once the cuff is in the proper position and tubing
connected to the cuff this measurement can be taken. The
default setting for LOP is 80% which is the most common
pressure used for the lower extremities. This value can be
changed in the settings screen (discussed below).

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Once you push the PTP button the LOP measurement
begins. You can always stop this measurement by
pressing Stop at the bottom of the screen. I typically warn
patients that the pressure they feel under the cuff during the
LOP measurement is higher than the actual pressure that they
will feel and use while working out. Remember, the
system is measuring how much pressure is needed for full
occlusion; we exercise at 80% and below his number.

Once LOP is determined you will see two numbers, PTP and LOP both within a heart.
The LOP is the amount of pressure needed for full occlusion on this particular patient at
this moment in time. PTP is the
LOP should
percentage of that pressure chosen
always be tested
for this BFR session. If you agree
with these numbers hit the Pressure supine with the
Set Point key at the bottom left which patient as still as
will lock in that pressure followed by possible.
the back button, this will return you to
the main screen. You can also make
adjustments to the pressure before
accepting it. If you wait longer than 5 seconds a brief alarm will sound and the unit will
automatically accept the PTP and take you back to the main screen. Press the stop
button to reject the PTP setting, the default setting will be maintained.

Various error readings may occur during PTP. If an error message comes up that states
LOP Stopped, No Signal or Noisy Signal check the hose connections, reapply the
tourniquet cuff (snuggly) and remind the patient to refrain from movement during testing.
In my experience, talking or moving patients are the most common reason for errors
followed by the cuff being too loose or the cuff being placed over loose or thick clothing.

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If you get the reading LOP high than the reading was higher than the allowable upper
limit of the unit (350 mmHg). A reading of LOP Low is below the lower limit (90 mmHg).
Follow the same procedures as above and re-
check. If the same reading returns a manual
setting may need to be chosen. Ideally this
would be done through a handheld Doppler.

After the completion of an exercise session or stoppage of the unit a Stats Option will
appear at the far right on the screen. Pressing this button will allow you to see the
relevant stats from the session including LOP, PTP, Max Pressure,
Min Pressure, Inflation Time, Rest Time, Cycles, Total Time.
Pressing the far right button with two blue arrows on the right of the
stats screen will clear the stats and return you to the main screen.

At the main screen, pressing the far right Settings

button will allow you to make adjustments to the
default settings and run calibrations.
This includes changing the PTP percentage,
adjusting the default time, adjusting the default
pressure adjustment, changing the volume of the alarms and running a
cuff test to check for leaks.

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Additional Notes:

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 Bibliography

AORN. Recommended Practices for Use of the Pneumatic Tourniquet in the Preoperative Practice
Setting. In: Preoperative Standards and Recommended Practices for Inpatient and Ambulatory
Settings. 2014 ed. Denver, CO AORN Inc, 2014:183-208.

Crenshaw AG, Hargens AR, Gershuni DH, Rydevik B (1988) Wide tourniquet cuffs more effective at lower
inflation pressures. Acta Orthop Scand 59:447–451

Estebe, J‐P., et al. "Tourniquet pain in a volunteer study: effect of changes in cuff width and pressure."
Anaesthesia 55.1 (2000): 21-26.

Graham, B., Breault, M. J., McEwan, J. A., & McGraw, R. W. (1993). Occlusion of arterial flow in the
extremities at subsystolic pressures through the use of wide tourniquet cuffs. Clinical
orthopaedics and related research, 286, 257-261.

Gupta, K., et al. "Re‐emphasizing the importance of tourniquet time: severe myocardial depression
following tourniquet deflation." Acta Anaesthesiologica Scandinavica 52.6 (2008): 873-873.

Kalla, Timothy P., et al. "Survey of tourniquet use in podiatric surgery." The Journal of foot and ankle
surgery 42.2 (2003): 68-76.

McEwan, JA. Tourniquet use and care. [Link]/use_care. Accessed 2014

McEwen, James A. "Complications of and improvements in pneumatic tourniquets used in surgery." Med
Instrum 15.4 (1981): 253-7.

Middleton, K. W. D., and J. P. Varian. "Tourniquet Paralysis1." Australian and New Zealand Journal of
Surgery 44.2 (1974): 124-128.

Noordin, Shahryar, et al. "Surgical tourniquets in orthopaedics." The Journal of Bone & Joint Surgery
91.12 (2009): 2958-2967.

Ochoa, J., et al. "Nature of the nerve lesion caused by a pneumatic tourniquet." (1971): 265-266.

Ochoa, J., T. J. Fowler, and R. W. Gilliatt. "Anatomical changes in peripheral nerves compressed by a
pneumatic tourniquet." Journal of Anatomy [Link] 3 (1972): 433.

Odinsson, A., and V. Finsen. "Tourniquet use and its complications in Norway."Journal of Bone & Joint
Surgery, British Volume 88.8 (2006): 1090-1092.

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