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Zac Dunkle Prezi Part 1

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johnny owens

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Transcript of Zac Dunkle Prezi Part 1

The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense. All patients have given their expressed written consent to be filmed and photographed for this presentation.

Personal Disclosure: Medical Consultant,Delfi Medical
Seige of Turin 1537
World War II 1939
World War II
WW I
WW II
Alignment and stiffness adjustability

Which one better engages the quadriceps?

Considerations During Loading Response

Knee Moment at Loading Response

Loading Response Considerations
ACSM guidelines Recommend Novice and Intermediate Lifters Use 75-85% 1 Rep Max for Strength and Hypertrophy 12-16 weeks.





ACSM Position Stand. Progression Models in Resistance Training for Healthy Adults. Med Sci Sports Exerc. 2009;41(3):687-708.

Courtesy: Military Times
Blood Flow Restriction Training
Hylden, C., Burns, T., Owens, J., "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.


Funded/Ongoing
Knee Arthroscopy (completed and submitted)
ACL/Chronic Weakness (AMMTI $215,000)
Femur Fractures (CDMRP/PRORP $4 Million)
Regenerative Medicine (AFFIRM $1.43 Million)
Distal Radius Fractures
West Point Meniscus Repair (AMMTI $225,000)
Ft Bragg Achilles Tendinopathy (AMMTI $250,000)
Beaumont ACL Fatty Infiltrate (Internal $)
Total Knee Arthroplasty
Neurorecovery agent post stroke
Feasibility in iSCI

Future
Achilles Repairs
Rotator Cuff Repairs
Stress Fractures
Strength and Hypertrophy
Improved Strength vs Controls

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.

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

0.0
0.58
Muscle Hypertrophy

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.

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.

0.35
0.39
-0.01
Metabolite Theory
Size Principal=under normal conditions Slow Twitch (ST) before fast (FT).

Dependant on load and intensity=Mechanical Tension
Krebs Cycle (aerobic) vs Cori (anaerobic)
Does BFR activate the Cori Cycle?
Cori=Lactic Acid Cycle
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.
O2
LACTATE
Moritani in 1992 demonstrated that during occlusion an additional recruitment of motor units must take place to continue force development.
O2
iEMG
Increased Peripheral Muscle Activation Changes:
Moritani 1992
Takarada 2000
Yasuda 2006
Yasuda 2008,
Manini 2012,
Labarbera 2013,
Cook 2013,
Takarada 2013
Yamada 2004.


BFR can increase lactate

Increasing pressures have a higher effect

Exercise needs to be involved

Don't need heavy loads if doing BFR

Need a good device that can trap the lactate

Correlates to increased motor unit recruitment

Early physiology studies used tourniquets to study this effect.
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)
BFR GROWTH HORMONE?



BFR LACTATE



The rise in growth hormone in the BFR and exercise group was significantly higher than what has been reported after heavy resistance training (1.7x higher). (Kraemer 1990)
Subjects Serving as their own Controls
Involuntary Contraction
Growth Hormone
Additional GH and BFR Studies:

Fujita 2006
Madarame 2008, 2010
Yasuda 2010
Reeves 2006
Takano 2005
The rise in lactate causes a subsequent rise in GH when using BFR.

BFR needs to be combined with exercise to augment the GH response.

GH levels after BFR have measured higher than what has historically been measured with HIT.

Young and old can see a benefit, but young have a higher response in GH release with BFR vs HIT.

Involuntary contractions with e-stim combined with BFR produce a GH response.

Lower Extremities have a larger effect than Upper.
Exogenous administration of GH does 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).
This was confirmed in a follow up study by Rennie, 2003 that also demonstrated no effect on human muscle size and muscle protein synthesis with the administration of rhGH. (Rennie 2003)
BUT.....

Exercise has a potent effect on growth hormone secretion???

(Weltman et al., 1992; Pritzlaff et al., 1999)
Collagen Synthesis
Animal Studies:

Following Achilles tendon transection in rats, treatment with local GH injection resulted in a faster functional recovery compared with controls (Kurtz et al., 1999).






Studies of GH-deficient dwarf rats showed a significant increase in collagen turn-over in knee tendon and ligaments following 14 days of GH supplementation (Kyparos et al., 2002).
Recently Doessing et al demonstrated that growth hormone played a direct role in increased collagen synthesis after exercise. (Doessing 2010)
MPS did not change.
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 with 1 group receiving GH supplementation and a control group receiving placebo.
..."it is possible to use the relationship (BFR and GH) as a basis for developing exercise protocols to evoke a GH response"...Pierce 2006 J App Phys
Growth hormones primary role is most likely collagen synthesis.

Combining BFR and exercise can create a very large and significant endogenous GH spike.

The low load on the joint, tendon and bone during BFR exercise combined with increased collagen synthesis can be a very powerful tool during rehabilitation.


IGF-1 is a protein in humans linked to muscle growth.

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)

Abe et al demonstrated a significant rise in IGF-1 in a BFR group vs controls.


This corresponded to a significant increase in strength and hypertrophy.
Heavy resistance training, endurance training, injury
GH=Proliferation
IGF-1=Chaperone and incorporate
Nielsen 2012
The gains in the number of satellite cells were 280% at mid-training, 250% at 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)
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)
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%.


BFR= Lactate GH IGF-1 Myogenic Stem Cells

Increased satellite cells create more myonuclei

Muscle has more potential for growth and repair with more myonuclei
NPB=MPS-MPB.
Fujita et al measured the acute effects of BFR at 20% 1RM vs work matched controls.

Only the BFR group demonstrated a significant rise in S6K1 levels (ribosomal kinase) a downstream marker of the MTOR pathway.
MTORC1 increased 41.5% at 3 hours and 69.4% 24 hours post-training.

MTORC1 needs Protein
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)
Furthermore, leucine is the key amino acid needed to turn on MTORC1. (Churchward-Venne 2012) Without leucine there is a blunted response to muscle protein synthesis.
Young=20 grams
Older=40 grams

Every 4 hours for at least 24 hours
BFR?
56% Increase in MPS
3 Hours Post Training
MTORC1 is the switch to start the entire muscle protein synthesis cascade

It typically requires moderate to heavy loads, however BFR has consistently demonstrated an increase activation vs controls

You should augment the pathway with protein (preferably liquid and dairy)
Researchers recently measured for a 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 femoris (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.
Kubota et al immobilized subjects and kept them non-weight bearing (NWB) for 2 weeks.

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)
.


No exercises were performed during the 2 weeks of NWB.

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.

All 3 groups were immobilized and NWB for 2 weeks.


Schliess et al further linked cellular hydration to MTORC1. (Schliess 2006)
Cell Swelling
“Resource Utilization and Disability Outcomes Assessment of Combat Casualties from Operation Iraqi Freedom and Operation Enduring Freedom”
Masini, BD; Waterman, SM; Wenke, JW;
Owens, BD; Hsu, JM; Ficke, JR;
Journal of Orthopaedic Trauma. 2009 Apr;23(4):261-6

...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.

...the phenomenon deserves serious consideration from those interested in the molecular biology of hypertrophy.
Biceps= 69%
Triceps=46%
p<0.05
Biceps=23%
Triceps=12%

Importantly, research suggests that low load resistance exercise (20-30% 1RM) and low load aerobic exercise (<70 m/min walking), which would not be expected to cause considerable increases in muscular quantity or quality under normal circumstances, when combined with BFR produced an exaggerated response for maximizing muscle strength and hypertrophy.
University of Tokyo
16 weeks 43% stronger
1 year 60% stronger
Combining Clinically Available Rehabilitative and Regenerative Strategies To Improve Functional Outcomes After Severe Extremity Trauma.

CRMRP Awarded $1.43 mill
Muscle Physiology
Low Load
Low Load
BFR
0.35
0.39
-0.01
Muscle Protein Synthesis
MTORC1

217% Increase from baseline at 15% MVC.
(Pierce 2006)
After 4 sets of low resistance exercise (30% 1RM) there is not a significant increase in iEMG, however there is with the addition of vascular occlusion.
290% Higher than Baseline
46% Increase
BFR in the elderly and MPS

MTORC1 (measured through S6K1) increased in the BFR group but not in the controls.


Exercise in and of itself is one of the most stressful events you can apply to your body.
Does BFR increase Vascular or Cardiac Risk Factors?
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.
.
They further demonstrated that small muscle groups (single-arm curls) elevated BP to a mean group average of 255/190. (McDougall 1985)
BFR
Because of the decreased venous return from the tourniquet during BFR there is a slight decrease in stroke volume, 12% (Takano 2005)

Cardiac output is maintained through the slight elevation in HR.
Tourniquets in and of themselves used for a short duration do not seem to pose an increased thrombus risk.

"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".
(Jarrett 2004)
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).
No changes in fibrinogen, d-dimer or CRP acutely after 1 bout or after 4 weeks.

tPA (a fibrinolytic protein) was significantly increased after BFR and HIT training.
The authors concluded
“ Regarding the theoretical risk associated with blood clotting...an acute bout of these exercises enhances fibrinolytic potential without elevating the thrombolytic potential."

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)
Hylden et al found no changes in thrombus formation measured through venous doppler after 4 weeks of training (knee arthroscopy) (Hylden 2014)
Capillarity improved x14% in the BFR group vs no change in work matched controls. (Hunt 2013)
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)


Fahs et al reported an improved arterial compliance acutely after LE exercise with BFR. (Fahs 2011)

Fahs et al extended the study to 6 weeks and observed no change in arterial compliance. (Fans 2012)
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)

The same authors found significantly improved arterial compliance after 10 weeks of BFR walking in elderly subjects. (Ozaki 2011)
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)
Calf Blood Flow
Strength
True Failure Model

Free-flow=increased DOMS
Direct=
NPB=MPS-MPB
Measures of Creatine Kinase and Lipid Peroxides


Sarcomere Stretching and Eventual Disruption of the Cytoskeletal Matrix


Load

Contraction Type
Muscle Damage
Intensity

TUT
MECHANICAL TENSION
BFR at 35% 1RM vs work matched controls.

Chronic Swelling
Pain-Pressure Threshold
MVC
DOMS
Does a tourniquet have any effect on indirect markers of muscle damage.

The authors concluded that the exercise, not occlusion explains the initial decline in muscle torque.

Indirect Markers of Muscle Damage

Prolonged Swelling
Decreased MVC
Loss of ROM
Prolonged Soreness
Summary:
Indirect Markers

Mild Doms (comparable to work matched controls)

Short Term Swelling (Pump)
Direct Markers

Increased Muscle Protein Breakdown

Creatine Kinase
Creatine kinase is used in clinical labs to detect inflammation in muscles. It is the common test used for rhabdomyolysis.

Lipid Peroxides
Sign of muscle or vascular damage through free radicals.

Rapamycin and the rate of muscle protein breakdown at 6 and 24 hours after exercise.

There was no change in MPB after training in the BFR Rapamycin group.


Creatine Kinase or Myoglobin Breakdown Endurance Model/Chronic Changes
(Walking)
Animal model (rat) and electrical stimulation to force a maximal eccentric contraction (Plantarflexors).

4 groups. Eccentric only, and Eccentric BFR at 140, 160 and 200 torr (pressure).

After completion of 40 maximal contractions the animals were biopsied for analysis.

Sudo 2015
MTORC1
"The present findings suggest that ECC combined with BFR, even at high exercise intensities, may enhance muscle protein synthesis without appreciable muscle fiber damage." Sudo 2015
Non-failure 30/15/15/15

MVC decreased immediately after, but returned to baseline by 24 hours.

Crossover 30/15/15/15 reps at 30% 1RM BFR v Free Flow.

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.
Neither of these were increased significantly from baseline or between groups post treatment.
NPB=MPS-MPB
69.4%
Tourniquet Risks


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.
Tourniquets are regulated as Class I medical devices by the FDA.

FDA Defines FULL or PARTIAL Vascular Occlusion Falling Under This Guideline.
The use of emergency tourniquets in the clinical setting should be avoided.

These are reserved for austere environments and typically for life saving measures.
"if it causes the loss of a limb it may save a life."
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.

Measurement of limb occlusion pressure (LOP) can help minimize tourniquet pressures and pressure gradients. (Nordic 2009)

Measuring LOP with specialized sensors in the tourniquet cuff is just as accurate as using a doppler (Masri et al, 2016)

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. (
www.tourniquets.org
)

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
.
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.
Self Regulated and Calibrated System
Personalized Limb Occlusion Pressure
Wide and Contoured Cuffs
Limb Protection Sleeves
Rapid Inflation and Deflation
Battery Back Up System
Safety Shut-Off Feature**
The Delfi PTS Personalized Tourniquet System for Blood Flow Restriction (BFR) device when used according to the device’s Intended Use and Indications for Use statements in the Operator and Maintenance Manual is cleared for market under Delfi Medical Innovations Inc’s FDA Device Listing for Pneumatic Tourniquets E127474 as a Class I device exempt from premarket notification procedures. Delfi Medical Innovations Inc is a registered establishment with the FDA under registration number 9681444.
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 with known clotting risks
◆ 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
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
⁃ Infection
⁃ Hypertension
⁃ Cardiopulmonary conditions
⁃ Clinically significant acid-base imbalance
⁃ Atherosclerotic vessels (McEwan 2014, Wakai 2001)

Patients who are taking
⁃ Anti-hypertensive
⁃ Creatine supplements (Gupta 2008, Sheth 2006)


E-stim at 10% MVC (involuntary contractions)
Slow Twitch
Fast Twitch

Elderly & Protein Synthesis
What is the problem?
350 grams
10%
30%
ANABOLIC RESISTANCE
MPS
27-31%
310 grams
Cell Swelling MPS
How Do I Know I Activated Fast Twitch Fibers?
How Do I Know I Increased Muscle Activity?
Great, My Patient is Full of Lactate!?
Am I Causing Muscle Damage?
Collagen Synthesis Huh?

What About Tendons?

Tendinopathies Just Need Eccentrics!!
Very Complex
It is a Cellular Problem
Risk Factors (Cholesterol, Adipose Tissue, DM)
Eccentrics Aren't the End All Be All (Compliance)
Tendons Like Load, But Not Drastic Changes!
Blood Flow Restriction Rehabilitation
Update
Morita 2010
Biceps curls, NIRS, Cerebral Blood Flow
HL, LL, LL BFRC, LL BFRI
The main findings of the present study were;

(i) overall, the increase in MEP (motor evoked potential) amplitude of the biceps brachii was greater following BFR-C compared with all other trials, and remained so
for up to 60 minutes post-exercise

(ii) both BFR trials rapidly increased corticomotor
excitability

(iii) MEP amplitude was unaffected by traditional heavy-load resistance
exercise;
Transcranial magnetic stimulation
Therefore, the net increase in corticomotor excitability seen in the present study not only provides support for benefits of BFR resistance exercise in healthy populations, but may also be important for clinical populations that require increased motor
function such as the elderly, stroke patients, and following musculoskeletal injury.
Update
12 cm cuff required significantly less pressure than 5 cm, 10 cm
1) Arm circumference
2) Males > Females
3) Black>White/Hispanic
4) Time of day

*Systolic blood pressure does not explain any additional variance
Update
The primary finding of this study was that the pronounced
muscle hypertrophy (10 cm above the elbow joint) and
strength gain following 6 weeks of CON-BFR training
were retained after 6 weeks of detraining.
12 wks train 24 wks detrain
NFL, MLB, NBA, NHL, MLS
Workers Comp
CHUBB - Global Sports
Memorial Hermann Healthcare System
Methodist Healthcare System Houston
Beaumont Healthcare Detroit
Carolinas Medical Center
MetroHealth Medical Center
University of Alabama
Florida State University
Ohio State University
University of Florida
University of Nebraska
University of Arkansas
UCLA
USC
Tulane University
University of Memphis
Washington University
University of Pittsburgh
University of Maryland
University of Michigan
University of Missouri
Indiana University
DOD
Kaiser Permanente NORCAL (July)
No Alternative ACSM Lift Light-Weight Guideline!
Multi-lig knee
Acute Ankle Sprain
NFL Training Room
Chronic Knee Pain
College Training Room
J.P. Morgan estimated $3.4 billion in annual sales for the Novartis myostatin blocking drug.
For one you 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 in muscle strength and hypertrophy. (Roth 2003) and has been confirmed by many other studies. (Forbes 2006, Hill 2003, Saremi 2010 and Willoghby 2004)
Inclusion-body myositis, myostatin and BFR.

65 year old male with an 8 year history of idiopathic myositis.

Muscle wasting most pronounced in his quadriceps and a significant history of falls.

Physical Therapy for over a year, however he noted a decline in his improvement
.


Dependent on an AD 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.
To follow up on this, researchers last year measured myostatin levels in a patient with inclusion body myositis.

Used the same protocol.

25% reduction in Myostatin levels.

Increases in IGF-1 related growth factors.
Mysostatin is the switch that blocks proliferation of myogenic stem cells and limits hypertrophy. So, the less myostatin the better if you want to build muscle. Two ways shown to do this are
heavy resistance training
or
light resistance training with BFR.
Laurentino compared 8 weeks of HIT v BFR 20% v Exer 20% on Myostatin levels.
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.
Leg Press 15.9%
Up & Go 60%
CSA Thigh 4.7% (MRI)
10 Weeks of De-Training
Only 0.5% Decrease Press
Growth Factors
Detraining
Tissue Re-Growing Business
Beating the Bully
Maximal horizontal gait speed increased by 19%, which was accompanied by 38-92% improvements in mechanical muscle function (maximal isometric strength, rate of force development and muscle power). In conclusion, BFR training was well tolerated by the patient with sIBM and led to substantial improvements in mechanical muscle function and gait speed.

A primary role of mysostatin is 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?

Myostatin and TGF-Beta
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)

Again, why?
One theory is that our organs simply will not function if they had significant scarring after injury.

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.

Thus, quickly scarring down the damaged tissue with collagen will allow us to keep moving over the ensuing days.
Future approaches to treating fibrosis in skeletal tissue is gene specific targeting to block these pathways.

Recently, Johnny Huard PhD and his colleagues at UPMC have discovered that blocking the TGF-Beta pathway with a drug, an ace inhibitor, improves the regeneration of injured tissue in an animal model. (Terada 2013)
Myostatin, again 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 in a recent study demonstrated a reversal of muscle fibrosis. (Li 2012)
BFR Myostatin Fibrosis Improved Soft Tissue Recovery ?


Regenerative Medicine Study


Myostatin, again 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 in a recent study demonstrated a reversal of muscle fibrosis. (Li 2012)
"We estimated the athlete would
return to play in four to six weeks.
However, by adding BFR into the regimen, we
were able to return the athlete to full competition
after only three weeks. This eye-opening result
was backed up by systematic diagnostic ultrasound
imaging (US)".
"In our previous biceps femoris tears, US revealed
slow integral changes (about 10 to 20 percent
improvement) in the area of injury when examined
on a weekly basis. With the UF athlete using
BFR, we were able to document approximately
30 percent improvement in muscle tissue repair
using the same parameters".
IGF-1 is a protein in humans linked to muscle growth.

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)

Abe et al demonstrated a significant rise in IGF-1 in a BFR group vs controls.


Post-op ACL weeks 2-16

The exercises were identical for both groups except the experimental group (BFR) performed the exercises utilizing blood flow restriction.
Very dense protein source with all the AA's and a Leucine bolus.
Bone?
Moreover, the Myostatin inhibitor boosted the concentration of bone specific alkaline phosphatase
Early vs Delayed Weight Bearing: A Randomized Prospective Trial
Carolinas Medical Center
Washington University, Methodist Hospital
University of Maryland Shock Trauma Center
Wake Forest University
MetroHealth Medical Center
Washington University/Barnes Jewish Hospital
University of Texas at Houston
JBSA/Center for the Intrepid
Currently the tissue strain that bone cells perceive is known as the interstitial fluid flow hypothesis (IFF)

A pressure gradient is created that causes fluid sheer stress on the osteocyte membrane. (Fritton 2009, Stevens 2006)
IFF
Studies measuring unloading have found that intramedullary pressure (a marker of IFF) is decreased by up to 77%. (Stevens 2006)
More impressively, the use of intermittent venous occlusion, similar to BFR, in an animal model has demonstrated improved fracture healing vs controls. (Hewitt 2005, Park 2003)
Control
Occlusion
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.
GH and Fractures=Improved healing and bone formation

Hip Fracture (Van der Lely 2004, Yeo 2003, Boonen 2002 Hedstrom 2004)

Total Hip Replacement (Weissberger 2003)

Tibia Fractures (Krusenstjerna-Hafstrom 2011).
The most convincing effect of growth hormone on closed fractures is given in a placebo-controlled trial of 406 patients with tibia fractures who had a significantly shorter time to healing after GH supplementation. (Raschke 2007)
Upregulation of VEGF is stimulated by hypoxia as is lactate, which both occur during BFR and exercise. (Hunt 2008)

Takano et al supported this when they demonstrated that BFR significantly increased VEGF as well as lactate, a work matched control group did not demonstrate these changes. (Takano 2005)
For Bone:
Applied to the limb with the fracture
30/15/15/15 same LOP guidelines
Downregulation of Myostatin
Upregulation of GH
Increased IFF
Increased VEGF
Plus, increased muscle strength/CSA
Safe low load

Stress Rxn/Fx's??
VMO stO2
p<0.0001
HbR (deoxygenated Hb)
p<0.0001
Hiemstra LA, Webber S, MacDonald PB, et al. 2000. Knee
strength deficits after hamstring tendon and patellar tendon
anterior cruciate ligament reconstruction. Med Sci Sports
Exer 32:1472–1479.

DeVita P, Hortobagyi T, Barrier J. 1998. Gait biomechanics
are not normal after anterior cruciate ligament reconstruction
and accelerated rehabilitation. Med Sci Sports Exer
30:1481–1488.

Paterno MV, Ford KR, Myer GD, et al. 2007. Limb
asymmetries in landing and jumping 2 years following
anterior cruciate ligament reconstruction. Clin J Sport Med
17:258–262.

Bryant AL, Kelly J, Hohmann E. 2008. Neuromuscular
adaptations and correlates of knee functionality following
ACL reconstruction. J Orthop Res 26:126–135.

Webster KE, Feller JA. 2011. Alterations in joint kinematics
during walking following hamstring and patellar tendon
anterior cruciate ligament reconstruction surgery. Clin Biomech
26:175–180.

Feller JA, Webster KE. 2003. A randomized comparison of
patellar tendon and hamstring tendon anterior cruciate
ligament reconstruction. Am J Sports Med 31:564–573.


Jansson KA, Linko E, Sandelin J, et al. 2003. A prospective
randomized study of patellar versus hamstring tendon
autografts for anterior cruciate ligament reconstruction. Am
J Sports Med 31:12–18.

Maletis GB, Cameron SL, Tengan JJ, et al. 2007.
A prospective randomized study of anterior cruciate ligament
reconstruction: a comparison of patellar tendon and
quadruple-strand semitendinosus/gracilis tendons fixed
with bioabsorbable interference screws. Am J Sports Med
35:384–394.

Natri A, Jarvinen M, Latvala K, et al. 1996. Isokinetic
muscle performance after anterior cruciate ligament surgery.
Long-term results and outcome predicting factors after
primary surgery and late-phase reconstruction. Int J Sports
Med 17:223–228.

Palmieri-Smith RM, Thomas AC, Wojtys EM. 2008. Maximizing
quadriceps strength after ACL reconstruction. Clin
Sports Med 27:405–424. vii-ix.

Snyder-Mackler L, Delitto A, Bailey SL, et al. 1995.
Strength of the quadriceps femoris muscle and functional
recovery after reconstruction of the anterior cruciate ligament.
A prospective, randomized clinical trial of electrical
stimulation. J Bone Joint Surg Am 77:1166–1173.
Persistent Weakness
When the cuff remains inflated throughout the exercise, the conversion of ATP to ADP is similar between BFR and HIT; as is the change in phosphocreatine
Suga et al, 2012
BFR Effect on Knee Pain
Anterior Knee Pain (Korkakis et al, 2016)
Significantly reduced pain during bilateral squat, step down and single leg squat 45 minutes post exercise
"Interestingly, we found
no non-responders to BFR
bout in any case of symptom duration, type of pathology, or symptom severity"

Patellofemoral Knee Pain (Giles et al, 2017)
93% greater pain reduction during ADL's than training at 70% 1RM
49% greater increase in knee extensor torque with BFR training
2 Weeks of Reduced Activity Decreases Lean mass and Induces Anabolic Resistance
Daily step count decreased 76% to 1,413 steps/day
Leg fat free mass decreased 3.9%
Insulin sensitivity decreased 43%
MPS decreased 26%
Visceral fat increased 7%
Absolute VO2max decreased 7%

Healthy adults who reduce their ambulation status demonstrate anabolic resistance
Sarcopenia, The Hallmark of Aging
Decreased MPS
Decreased response to a bolus of protein
Decreased response to resistance training

Decreased perfusion

Decreased Satellite cell quantity

As a result of the above, the elderly have a decreased anabolic response to the same resistance training episode compared to young adults
Kumar et al, 2013
Impaired MPS
Local insulin resistance
Peaks within the first 20 days of decreased weightbearing
Clinical Significance
Low Intensity
HIT
BFR
What About Pain
The Added Effect of Combining Cell Swelling with NMES
Natsume et al, 2015
8 untrained individuals serving as their own controls received 23 minutes of NMES with or without cell swelling

5 days/week for 2 weeks with a 2 week follow up
Muscle thickness increased 3.9% in the BFR +NMES after 2 weeks and decreased 3% following detraining; no change noted in the NMES alone.
Isokinetic strength improved 7% and 8.3% at 90*/s and 180*/s respectively with no significant decrease after detraining. NMES alone did not significantly increase isokinetic strength
Slysz and Burr, 2017
20 individuals completed 6 weeks of 4d/week training in either cell swelling only, cell swelling+NMES, NMES alone or a control
Strength in cell swelling+NMES increased 32kg, cell swelling 18, NMES 16, Control 3kg
Ace -031
Novartis and BYM338.
Activin receptor blocker
Early animal results were successful, but stopped due to gum and nose bleeding
Myo-029
Antibody designed to bind to and inhibit myostatin
Safety study showed the drug was safe, but no functional or strength improvements were found in those with adult MD
4 cycles of 5 minutes of ischemia followed by 1 minute of reperfusion
Cell swelling consisted of 3 cycles of 4 minutes of ischemia followed by 4 minutes of reperfusion
Bench press 1RM strength was maintained after 6 weeks of training followed by 3 weeks of detraining
Leg extension and leg press strength was significantly greater after 12 weeks and after 24 weeks of detraining compared to pre-training
Ischemic Conditioning
What is Ischemic Conditining
A stimulus capable of causing injury or death to tissue can produce a protective mechanism when delivered just below the threshold of damage
This stimulus can be delivered pre ischemia, per ischemia, and post ischemia
Ischemic Conditioning Protocol
3 cycles of 5 minutes of ischemia (100% LOP)/5 minutes reperfusion
No exercise is performed during Ischemic Conditioning

If using to improve post workout recovery, can use pre workout or post
Ischemic Injury
Shift to anaerobic metabolism leading to glycolytic substrate exhaustion, failure of ATP dependant ion channels, leading to an uncontrolled influx of Ca2+, increased cellular inflammation and ultimately tissue necrosis
Musculoskeletal
Damage to the sarcoplasmic reticulum and T-Tubules contributes to impaired Ca2+ reuptake
Disruption at the Z line leads to an immediate neutrophil response and an increase in adhesion proteins contributing to a prolonged increase in ROS
Adenosine inhibits excitatory amino acids and inhibits the influx of Ca2+ via upregulation of Adenosine A1 receptors
K+ ATP Channels promote an increase in the electron transport chain rate, providing prolonged aerobic ATP production
Ischemic PreConditioning
19 participants were randomized into either eccentric biceps curls only or eccentric biceps curls preceded by Ischemic Preconditioning
Eccentric protocol: 80% 1RM 3x10
IPC protocol: 3 cycles 5 minutes occlusion/5 minutes reperfusion
Ischemic Post Conditioning
16 healthy males
8 received IPostC (200mmHg 14.5 cm wide cuff)
8 received sham (20mmHg)

Protocol
Eccentric Exercise: 5x20 depth jumps from .6m box
IPC: 3 cycles 5 minute inflation/5 minute reperfusion
University of Florida wide receiver underwent a microfracture surgery following a grade IV OCD. The athlete returned to football activities by 6 months, and full participation in 7 months. Typical recovery is 7-12 months
Kruithof E, et al, 2018
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