Skeletal Muscle as an Endocrine Organ: Myokine Optimization

Skeletal Muscle as an Endocrine Organ: Myokine Optimization

Practical Blood Flow Restriction (pBFR) Applications Skeletal Muscle as an Endocrine Organ: Myokine Optimization Chris Deck, PT, MA, MBA Nils Hakansson, Ph.D. Copyright, Howard Christopher Deck. All rights reserved. Balance Scores vs. PT Treatments 60 50 40 Berg TUG 30 Sec PT Rx

30 20 10 0 Nov-16 Dec-16 Jan-17 Feb-17 Mar-17 Apr-17 May-17 Jun-17 Jul-17

Aug-17 Sep-17 Copyright, Howard Christopher Deck. All rights reserved. Oct-17 Nov-17 Dec-17 Jan-18 Participant Participant 1 Participant 2 Participant 3 Participant 4 Participant 5 Participant 6 Participant 7 Participant 8

30 sec sit to stand Change 25% 41.7% 50% 62.5% 37.5% 54.5% 129% 37.5% TUG Change -27% -31.3% -23% -11.1% -100.0% -50.0% -26% -25.0% Percent Changes in Balance Scores among First Three Months of BFR Implementation Berg Change

4% 12.5% 6% 10.2% 10.4% 1.8% 18% 4.1% Copyright, Howard Christopher Deck. All rights reserved. Participant with COPD Current Smoker 45 40 35 30 25 20 Sum of FirstRep Sum of NuStep 15 10

5 0 7 7 7 7 7 7 7 7 7 7 7 8 8 8 8 8 8 8 8 8 8 8 8

8 8 8 8 8 8 8 8 8 8 8 8 01 201 201 201 201 201 201 201 201 201 201 201 201 201 201 201 201 201 201 201 201 201 201 201 201 201 201 201 201 201 201 201 201 201 201 2 / / / / / / / / / / /

/ / 9/ 6 8 2/ 8/ 9/ /2/ /5/ /8/ 10 12 16 18 23/ 25/ 30 9 2 /4 14/ 17/ 21/ 30/ 31 1/ 4/ 1/ 3/ 0/ 1/ /5/ 16 21 1/ /5/ /2 12/ 12/ 12/ 12/ 2/1 2/1 2/2 2/2 2/2 2/2 1 1 1 1/ 2/ 2 2/ 3/ 3/1 5 5/

6/ 6 1/ 1/ 1/ 1/ 1/ 1/ 2/ 5/ 5/ 5/ 5/ 11 1 1 1 1 1 1 Copyright, Howard Christopher Deck. All rights reserved. Falls and Fallers per Member per Month

29% 28% 28% f(x) = 0.01 x + 0.29 R = 0.5 f(x) = 0.02 x + 0.26 R = 0.74 20% 21% 21% 20% 19% 19% 16% 16% 12%

12% 10% 10% 9% Nov Dec Jan Falls PMPM Feb Linear (Falls PMPM) Mar Apr Fallers PMPM May Linear (Fallers PMPM) Copyright, Howard Christopher Deck. All rights reserved.

Jun Jul BFR: Demonstration Shoulder Press (Modified Push-Up) Sit to Stand Sets: 30/15/15/15 Rest: 30 seconds between sets. Cuff from axilla to proximal elbow Light weight Cuff from inguinal crease to proximal knee Thirty second sit to stand rate with BFR applied (1st set) Next three sets are half the first number. Thirty second rest between sets. If fatiguing fast, then first increase time between sets and second

decrease weight. If not fatigued at last set of 15, then increase weight slightly. Copyright, Howard Christopher Deck. All rights reserved. Methinks that the moment my legs begin to move, my thoughts begin to flow Henry David Thoreau from: Thoreaus Journal August 19, 1851 Copyright, Howard Christopher Deck. All rights reserved. Sarcopenia: Objectives Students will be able to describe the principle mechanism for sarcopenia including muscle fiber, action of Myostatin (MSTN), and involvement of Satellite Cells (SC). Students will be able to describe Myonuclear Domain and how it relates to sarcopenia. Students will be able to list three disease

states or conditions in which sarcopenia is more prevalent. Students will list three metabolites linked to sarcopenia. Copyright, Howard Christopher Deck. All rights reserved. Sarcopenia and aging It has been estimated that between onequarter to one-half of all individuals over age 65 are sarcopenic, and obesity is one of the better predictors of sarcopenia (Iannuzzi-Sucich 2002) Older men and women have 25-35% smaller muscles with significantly more fat and connective tissue (Evans 1995) Muscle area reduced an average of 40% between the ages of 20 and 80 years old with reduction beginning as early as 25 years old. By 50 years 10% of muscle area was lost and accelerated reduction afterwards (Evans 1995) Copyright, Howard Christopher Deck. All rights reserved. Decreasing

Muscle Cross Sectional Area as Age Increases (Evans 1995) Copyright, Howard Christopher Deck. All rights reserved. Sarcopenia and bed rest The present study demonstrates that the (3.9 0.6%) loss of quadriceps cross-sectional area induced by 5 days of muscle disuse is accompanied by an approximate halving of postabsorptive myofibrillar protein synthesis rates when compared with the nonimmobilized control leg. (Wall 2015) Copyright, Howard Christopher Deck. All rights reserved. Sarcopenia

and Type II Muscle Fibers Sarcopenia is primarily related to a decrease in the number of and the cross-sectional area (CSA) of Type II muscle fibers (29% reduction in fiber size in elderly males compared to younger males). (Nilwik 2013) Verdijk (2007) found Type II muscle fiber content was less in the elderly versus the young (47% vs. 57%) and the percentage of total muscle area with Type II muscle fibers was less in the elderly than the young (42% vs. 59%). Copyright, Howard Christopher Deck. All rights reserved. Sarcopenia and Fewer Type II Satellite Cells Sarcopenia in the elderly is likely

due to a lack of satellite cells on Type II muscle fibers resulting in fewer as well as smaller Type II muscle fibers. (Verdijk 2007) Satellite cells represent the principal reservoir of stem cells in skeletal muscle. (Ceccarelli 2017) Copyright, Howard Christopher Deck. All rights reserved. Sarcopenia and Type II Muscle Satellite Cells (Verdijk 2007) Copyright, Howard Christopher Deck. All rights reserved. Sarcopenia: Satellite Cells & Exercise in Older Men

Type II fiber satellite cells did not respond to resistance exercise in older men; whereas, there was a 46% increase among young men to the same exercise (McKay 2012). Copyright, Howard Christopher Deck. All rights reserved. Sarcopenia and Myofibers McKay found that sarcopenia is primarily related to a decrease in myonuclei. Myonuclei control a certain amount of cytoplasm, and this is termed Myonucelar Domain. The limited myonuclei is directly proportional to the amount of satellite cells (2012). Copyright, Howard Christopher Deck. All rights reserved. Sarcopenia: Satellite

Cell Picture (Petrella 2008) Copyright, Howard Christopher Deck. All rights reserved. Conditions Sarcopenia Copyright, Howard Christopher Deck. All rights reserved. Sarcopenia and Disease Certain disease conditions such as Cancer, Chronic Obstructive Pulmonary Disease, and severe trauma activate metabolites in the Muscle Protein Breakdown (MPB) chain. (Loenneke 2011) Copyright, Howard Christopher Deck. All rights reserved.

Sarcopenia and Ligamento us Injury with Subsequen t Surgical Repair Type II muscle fiber atrophy was noted in a study of 44 males and females aged 18-52 who had undergone Anterior Cruciate Ligament (ACL) reconstruction (Ohta 2003) Copyright, Howard Christopher Deck. All rights reserved. Sarcopenia and Fractures The size of Type II muscle fibers in elderly women who had a femur fracture was 30% smaller

than age matched controls (Kramer 2017). Copyright, Howard Christopher Deck. All rights reserved. Metabolites Sarcopenia Copyright, Howard Christopher Deck. All rights reserved. Sarcopenia and mTOR (Reduced Muscle Protein Synthesis) Mammalian Target of Rapamycin (mTORC), a metabolite that increases Muscle Protein Synthesis (MPS), attenuates with men over 70 years old. (Fry 2011)

Copyright, Howard Christopher Deck. All rights reserved. Sarcopenia and Myostatin We confirm that older adult individuals (6575 years old) have a lower Satellite Cell (SC) pool size, mainly due to a reduction in Type II fiberassociated SCs. In response to the same relative physiological stimulus (acute exercise at 75% one repetition maximum (1-RM), older men demonstrated a markedly blunted myogenic response, isolated to the Type II fibers compared with younger controls. Notably, this coincided with a significantly higher percentage of Type II SCs expressing Myostatin protein in the older men throughout the post-exercise time course. (McKay 2012) Copyright, Howard Christopher Deck. All rights reserved. mTORC1 & Myostatin

Copyright, Howard Christopher Deck. All rights reserved. Sarcopenia and PGE2 (Increased Muscle Protein Breakdown ) Prostaglandin E2 (PGE2), a metabolite that decreases Muscle Protein Synthesis (MPS) and increases Muscle Protein Breakdown (MPB), is increased in the elderly (Lui 2015) Copyright, Howard Christopher Deck. All rights reserved. COX Inhibitor Pathway Copyright, Howard Christopher Deck. All rights reserved. Sarcopenia:

Objectives Students will be able to describe the principle mechanism for sarcopenia including muscle fiber, action of Myostatin (MSTN), and involvement of Satellite Cells (SC). Students will be able to describe Myonuclear Domain and how it relates to sarcopenia. Students will be able to list three disease states or conditions in which sarcopenia is more prevalent. Students will list three metabolites linked to sarcopenia. Copyright, Howard Christopher Deck. All rights reserved. Break for Lab! Repeat Sit to Stand Copyright, Howard Christopher Deck. All rights reserved. Blood Flow Restriction (BFR): Objectives

Describe potential mechanisms of action for why Blood Flow Restriction (BFR) may work Delineate the effects of BFR on Muscle Protein Breakdown (MPB) vs. Muscle Protein Synthesis (MPS) Compare and contrast flow reduction based on cuff width and pressure Describe safety considerations of BFR Describe the optimal BFR exercise prescription Copyright, Howard Christopher Deck. All rights reserved. BFR Mechanism s: Metabolite Theory: Hypoxia BFR creates hypoxia then hyperoxia with release of pressure; specifically, BFR decreases partial pressure of Oxygen (PO2) to 74.5% in the

affected limb during exercise in elderly men (Kawada 2005; Fry 2010) Copyright, Howard Christopher Deck. All rights reserved. BFR Mechanism s: Metabolite Theory: Hypoxia Lactic Acid Lactic Acid increases because of Adenosine Triphosphate (ATP) production through anaerobic glycolysis; in other words, metabolic overload (i.e., depletion of phosphocreatine stores and decreases in muscle pH) normally associated with higher muscle activations observed during high intensity resistance exercise (Schoenfeld 2013; Gundermann 2012) BFR doubles Lactic Acid compared to exercise without occlusion while another study found blood lactate concentration after exercise was higher (P < 0.05) under BFR than with the

control (3.6 and 2.1 mmol/L, respectively). (Takarada 2000; Yasuda 2014) BFR lowers pH (Suga 2010, Fujita 2007) Copyright, Howard Christopher Deck. All rights reserved. 2.5 Blood Lactate BFR / Control / HIT Lactate mmol 2 1.5 1 (Poton 2014) 0.5 0

BFR Copyright, Howard Christopher Deck. All rights reserved. CON HIT 35 30.9 30 Lactate BFR / Control (Takano 2005) Lactate (mg / mL) 25 24.1

20 16.8 15 15.2 12.6 11.2 9.7 108.6 5 0 Supine Exer 10m BFR Copyright, Howard Christopher Deck. All rights reserved. CON

30 min BFR Mechanisms: Metabolite Theory: Hypoxia Lactic Acid Growth Hormone Increases in Lactate and H+ elevates Growth Hormone (Suga 2010) 290-fold increase in Growth Hormone (GH), which was up to 40 g/l with low intensity g /l with low intensity exercise in young males after low-load training at 20% 1RM. In another study, GH increased nine-fold in elderly under BFR; still another study saw an increase 41 times more than resting levels to ~8 g/l, (Takarada 2000; Ohta 2003; Fry 2011; Reeves 2006) GH causes enhanced muscular electrical activity and endocrine responses (Takarada 2000) Copyright, Howard Christopher Deck. All rights reserved.

0.5 0.45 Lactate Response BFR / Control (Takarada 2000) Whole Blood Lactate (mg/ml) 0.4 0.35 0.3 0.25 0.2 0.15 0.1 0.05 0 e Pr st

o P 15 m in 30 in m CON Copyright, Howard Christopher Deck. All rights reserved. in m 45 BFR 60 m

in 90 in m 0 2 1 in m 24 rs u Ho 40 35 30 GH Response

BFR / Control (Takarada 2000) Plasma GH (ng/ml) 25 20 15 10 5 0 e Pr 0m in 15 m in 30

m in 45 CON Copyright, Howard Christopher Deck. All rights reserved. m in 60 BFR m in 90 m in rs

in u m 0 Ho 2 1 24 BFR Mechanisms: Metabolite Theory: Hypoxia Lactic Acid Growth Hormone Endocrine Response (Decrease MPB) Decreased Muscle Protein Breakdown (MPB) from a lack of microtrauma may play a partial role in the hypertrophic response with BFR (Gundermann 2012) mRNA expression of MuRF-1, Atrogin-1 and FOXO-3A were downregulated 8 hrs postexercise (~2-fold decrease) (Manini 2011)

Decrease in the mRNA gene expression of MURF-1, atrogin, and myostatin; myostatin mRNA expression has been shown to reduce by 45% with BFR compared to 41% for high intensity group (Gundermann 2012, Sudo 2015, Schoenfeld 2013) Copyright, Howard Christopher Deck. All rights reserved. The Physiology of Strengtheni ng: Summary (Schoenfel d 2013) Copyright, Howard Christopher Deck. All rights reserved. BFR Mechanisms: Metabolite Theory: Hypoxia Lactic Acid Growth

Hormone Decreased Myostatin # P < 0.05 for within group comparisons (PRE vs. POST) ! P < 0.05 when compared with LI group Copyright, Howard Christopher Deck. All rights reserved. BFR Mechanisms: Metabolite Theory: Hypoxia Lactic Acid Growth Hormone Endocrine Response (Increase MPS) Increases in Insulin-like Growth Factor 1 (IGF-1) (Schoenfeld 2013), which increases Muscle Protein Synthesis (MPS) mTORC1 is enhanced by BFR in in older men and this has a direct relationship with MPS (Fry 2010 & Gundermann 2012)

Testosterone: BFR does not increase testosterone (Schoenfeld 2013) Copyright, Howard Christopher Deck. All rights reserved. BFR Mechanisms: Metabolite Theory: Hypoxia Lactic Acid Growth Hormone Endocrine Response (Increase MPS) S6K1: Increased in Type II over Type I muscle fibers by three-fold including in studies focusing on the elderly (Fujita 2007; Koopman 2006; Fry 2010) BFR has biphasic response over 24 hours; BFR increases Muscle Protein Synthesis (MPS) 56% in elderly (Gundermann 2012; Fry 2010) BFR increases MPS as evidences by Fractional Synthetic Rate (FSR) three

hours post exercise (Fujita 2007; Fry 2010) Copyright, Howard Christopher Deck. All rights reserved. 0.09 0.08 0.07 Protein Synthesis BFR / Control (Fujita 2007) FSR (%/hr) 0.06 0.05 0.04 0.03 0.02 0.01 0 Baseline

3 hour - Post p < 0.05 BFR Copyright, Howard Christopher Deck. All rights reserved. CON BFR / Control (Fujita 2007) S 6 K 1 P h o sp h o ry la ti o n (% B a se li mTORC1 (via S6K1) 350 300 250 200 150 100 50

0 Baseline 3 hour - Post p < 0.05 BFR Copyright, Howard Christopher Deck. All rights reserved. CON 450 400 350 IGF-1 BFR / Control (Abe 2005) IGF (ng/ml) 300

250 200 150 100 50 0 Baseline 2 weeks BFR Copyright, Howard Christopher Deck. All rights reserved. CON 7 5.8 6 GH and Collagen Synthesis

(Doessing 2010) Fold Increase 5 3.9 4 3 2 1 0 0.1 0.2 Baseline 14 days Collagen Synthesis Tendon mRNA Expression Copyright, Howard Christopher Deck. All rights reserved.

Muscle Collagen Synthesis Blood Flow Restriction: Benefit Summary Abbreviation Definition Lactic Acid Growth Hormone Growth Hormone IGF collagen healing The area under the curve Proximal muscle of a rectified EMG signal hypertrophy muscles responsiveness Muscle fires with less to calcium stimulus Increase SC Inhibits MPS Muscle Protein Synthesis iEMG Post Activation Potential

Cellular Swelling Myostatin MPS Affects Copyright, Howard Christopher Deck. All rights reserved. BFR (Resistance) ~200% 290% nine-fold 40% (EMG) 1.8 times 51% Initiates mTORC1 45% 56% BFR Results: Increased Hypertroph y and

Strength The percent increase in CSA of knee extensors was 10.3 1.6%, and the average percent increases in isometric and isokinetic strengths at all velocities examined was 9.2% 2.2% after an 8-wk training exercise in Light Intensity Obstructed limb (Takarada 2004) Maximal isometric torque per unit CSA was unchanged (in N m-1): pretraining = 3.3 0.2; posttraining = 3.2 0.2. Thus, the increases in isometric and isokinetic strengths could be considered to be mainly caused by muscular hypertrophy (Takarada 2004) Leg press (HRT: 54%, p , 0.001; LRT-BFR: 17%, p = 0.067) and quadriceps CSA (HRT: 7.9%, p , 0.001; LRT-BFR: 6.6%, p , 0.001); (Vechin 2015) Copyright, Howard Christopher Deck. All rights reserved. 7 6 Thigh Cross Section Area BFR / Control

(Abe 2006) % Change (from Baseline) 5 4 3 2 1 0 -1 -2 BFR CON p < 0.05 Copyright, Howard Christopher Deck. All rights reserved. 12 10.3 10

CSA Knee Extensors BFR / Control % Change 8 6 4 (Takarada 2004) 2 0 0 CON BFR p < 0.01 Copyright, Howard Christopher Deck. All rights reserved. 12 10.1

10 Cross Section Area BFR / Control (Abe 2005) % Change 8 9.1 7.7 6 4 2 1.9 1.4

0 -0.6 -2 Quadriceps Biceps Femoris p < 0.01 BFR Copyright, Howard Christopher Deck. All rights reserved. CON Gluteus Maximus Cross Section Area of Triceps, Brachialis, and Biceps Control / HIT / BFR

CSA CON / HIT / BFR Takarada 2000 25 20.3 20 18.4 17.8 BFR 30% HIT CON 15 13.7 11.8 10 6.9 6.6

5 3.8 (Takarada 2000) 1.5 0 Biceps Brachialis Copyright, Howard Christopher Deck. All rights reserved. Triceps Blood Flow Restriction: Muscle hypertrophy that results in increased strength

BFR increases strength (LI = 20.7%, LIR = 40.1%, and HI = 36.2%) (Laurentino 2012) BFR increases CSA - 6.3% LIR and 6.1% HI (Laurentino 2012) BFR increases strength and hypertrophy of proximal muscles (Dankel 2015) Untrained patients gained more muscle strength than recreationally active groups (Loenneke 2012) Copyright, Howard Christopher Deck. All rights reserved. 10 9.2 9 8 Strength BFR / Control (Takarada 2004) % Change

7 6 5 4 3.1 3 2 1 0 BFR CON p < 0.05 Copyright, Howard Christopher Deck. All rights reserved. 18 16 14 BFR / Control

(Abe 2010) % Change Knee Extension & Flexion Strength 12 10 8 6 4 2 0 Knee Ext Knee Flex p < 0.05 BFR Copyright, Howard Christopher Deck. All rights reserved.

CON 25 23 20 Strength BFR / Control % Change 17 15 10 9 (Abe 2005) 5 2 0

Squat Leg Curl p < 0.05 BFR Copyright, Howard Christopher Deck. All rights reserved. CON 305 300 295 BFR / Control (Nielsen 2012) Isometric MVC (nm) Strength (Days after exercise)

290 285 280 275 270 265 260 255 Pre Post 5 BFR Copyright, Howard Christopher Deck. All rights reserved. CON Post 12 0.9 0.8 0.8 0.7

BFR / Control / HIT (Loenneke 2012) Effect Size Effect Size Strength 0.6 0.58 0.5 0.4 0.3 0.2 0.1 0 BFR CON

0 p < 0.05 Copyright, Howard Christopher Deck. All rights reserved. HIT BFR Results: Improved Bone Health BFR increases bone alkaline phosphatase (ALP) by 21% in elderly men; this may be an indication that BFR stimulates bone formation. (Karabulut 2011) BFR for 6 weeks increased bone turnover which indicates improved bone health (Hughes 2017) Copyright, Howard Christopher Deck. All rights reserved. 120 104

103 49 48 47 Exer 10 min 30 min 100 86 VEGF BFR / Control (Takano 2005) VEGF (pg/mL)

80 60 41 40 33 20 0 Supine BFR Copyright, Howard Christopher Deck. All rights reserved. CON BFR Results: Increased Satellite Cell Activity Satellite cell activity increases

after BFR. BFR increases myonuclei through Satellite Cell proliferation of both Type I and II muscle fibers, Satellite Cell /myoblast fusion which results in substantial gains in muscle fiber area (Drummond 2008; Nielsen 2012) Copyright, Howard Christopher Deck. All rights reserved. 90 80 Type I Fiber (Nielsen 2012) Pax 7 + Cell per mm Muscle Satellite Cell Proliferatio n

70 60 50 40 30 20 10 0 Pre Mid 8 Post 3 Time (Days) BFR Copyright, Howard Christopher Deck. All rights reserved. CON Post 10 70

60 Type II Fiber (Nielsen 2012) 50 Pax 7 + Cell per mm Muscle Satellite Cell Proliferatio n 40 30 20 10 0 Pre Mid 8

Post 3 Time (Days) BFR Copyright, Howard Christopher Deck. All rights reserved. CON Post 10 0.45 0.4 Muscle Satellite Cell Fusion Type I and II Fibers (Nielsen 2012) Pax 7 + Cell per mm 0.35

0.3 0.25 0.2 0.15 0.1 0.05 0 Pre mid 8 BFR Copyright, Howard Christopher Deck. All rights reserved. post 3 CON post 10 BFR Results: Benefits to the freeflow limb

Non-Occluded Limb increased strength and hypertrophy, the increases in SCs with extensions were not significant, although a trend was observed at 24-h postexercise (46 % increase, p = 0.03 with a t-test, effect size = 0.97). (Wernbom 2013) Copyright, Howard Christopher Deck. All rights reserved. BFR Results: Increased EMG Activity BFR increases EMG activity - suggest that normally inactive muscle fibers are recruited (Fujita 2007) Increased EMG activity from 47.6 13.6% (1st set) to 66.8 18.9% (4th set) (p = 0.002) of maximal voluntary contraction in the BFR exercise group with no change in the control exercise group (53.5 13.5% (1st set) to 58.9 13.7% (4th set), p =0.084). Further

analyses showed the BFR exercise group had higher EMG levels at the 4th set than the control group (66.8 18.9% vs. 58.9 13.7%, p < 0.05). (Manini 2011) Copyright, Howard Christopher Deck. All rights reserved. BFR Results: Increased EMG Activity EMG in the low-intensity exercise with occlusion equaled that of the high-intensity exercise (Takarada 2000) In one study, EMG signal increased by 40%, while in another study EMG activity increased 1.8 times (Takarada 2000) BFR increases post-activation potential (PAP) (Moore 2004) Copyright, Howard Christopher Deck. All rights reserved. BFR

Results: Benefits to proximal muscles Dankel found in his meta-analysis (2015) that muscles proximal to occlusion consistently increased in strength and hypertrophy. He proposed that this is due to EMG activity of Type II recruitment, and this increased EMG activity occurs primarily during the final set of traditional BFR exercises. Copyright, Howard Christopher Deck. All rights reserved. 18 16 BFR / Control (Yasuda 2010) 12 % Change

Cross Section Area of Pectoralis and Triceps 14 10 8 6 4 2 0 Pectoralis Triceps p < 0.05 BFR Copyright, Howard Christopher Deck. All rights reserved. CON

BFR Results: Functional Benefits In my practice, it is common to see the rate of 30 second sit to stand double among elderly patients in two weeks of BFR treatment In my practice, it is also common to see a 15-point increase in the Berg balance test after two weeks of BFR treatment. Copyright, Howard Christopher Deck. All rights reserved. 14 12 Timed UpGo BFR / Control (Abe 2010)

% Change 10 8 6 4 2 0 BFR CON p < 0.01 Copyright, Howard Christopher Deck. All rights reserved. 14 12 10 Sit-Stand BFR / Control (Abe 2010)

% Change 8 6 4 2 0 -2 -4 BFR CON p < 0.01 Copyright, Howard Christopher Deck. All rights reserved. Break for Lab! Modified Push-Ups Copyright, Howard Christopher Deck. All rights reserved. BFR Safety: General Comments

KAATSU training is a safe method of training (Nakajima 2006) BFR is a suitable substitute to High Intensity Training (HIT) (Meyer 2006; Hughes 2017) No greater risk than traditional exercise (Hughes 2017) When used in a controlled environment by trained and experienced personnel, provides a safe training alternative for most individuals regardless of age and training status (Loenneke 2010) BFR may be applicable for other clinical populations who suffer from MSK weakness and bone degradation (e.g. patients with osteoporosis, rheumatoid arthritis, multiple myeloma and lymphoma). In premature situations when individuals suffering from muscle weakness are not able to begin even low-load exercise (e.g. postoperative immobilization), BFR alone can be used as an early rehabilitation intervention. (Hughes 2017) Copyright, Howard Christopher Deck. All rights reserved. BFR Safety: Prevents Muscle Damage

Joint Health: BFR is a safe method for strengthening with osteoarthritis (OA) among women and men (Segal 2015) Neural Health: BFR is safe with Nerve Conduction Velocity (NCV) however wider cuffs may impede NCV (Loenneke 2011) Pain: BFR decreases pain from knee OA (Bryk 2017) Prevention of muscle damage: BFR with eccentric strengthening demonstrated no muscle damage (Sudo 2015) Copyright, Howard Christopher Deck. All rights reserved. BFR Safety: Thrombus BFR does not increase risk of Deep Vein Thrombosis (DVT) in elderly men (Fry 2010) The incidence of side effects was as follows; venous thrombus (0.055%), pulmonary embolism (0.008%) and rhabdomyolysis (0.008%). (Nakajima 2006) Only 0.06% out of 300,000 training sessions resulted in an incidence of venous

thrombosis, which is lower rate than that reported for the general Asian population ( 0.20.26%) BFR does not cause DVT and may decrease the risk for DVT (Loenneke 2011) Copyright, Howard Christopher Deck. All rights reserved. BFR Safety: Vascular Function BFR increased strength without altering nerve or vascular function (Clark 2009) BFR improves arterial compliance (Ozaki 2011) BFR improves vascular and peripheral nerve health (Shimizu 2016) BFR increases post occlusive blood flow (Patterson 2011) BFR is safe with peripheral blood flow (Loenneke 2011) BFR is safer than High Intensity Training with blood pressure and heart rate (Loenneke 2011) Copyright, Howard Christopher Deck. All rights reserved.

Precautions: 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 Arterial calcification Arterial calcification abnormal clotting times abnormal clotting times Arterial calcification abnormal clotting times Diabetes Arterial calcification abnormal clotting times Sickle cell trait Arterial calcification abnormal clotting times Tumor Arterial calcification abnormal clotting times General Infection Arterial calcification abnormal clotting times hypertension Arterial calcification abnormal clotting times Cardiopulmonary conditions Arterial calcification abnormal clotting times Renal Compromise Arterial calcification abnormal clotting times Clinically significant acid--base imbalance Atherosclerotic vessels base imbalance Arterial calcification abnormal clotting times Atherosclerotic vessels (McEwan 2014, Wakai 2001) Patients who are taking Arterial calcification abnormal clotting times Anti--base imbalance Atherosclerotic vessels hypertensive Arterial calcification abnormal clotting times Creatine supplements (Gupta 2008, Sheth 2006) 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--base imbalance Atherosclerotic vessels 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 BFR Safety: Contraindicati ons & Precautions BFR should be approved by referring physician before proceeding. Copyright, Howard Christopher Deck. All rights reserved. BFR Treatment: Device BFR Devices include pneumatic cuffs, hand-pumped blood pressure cuffs, or elastic wraps (Hughes 2017) A recent study found no differences between elastic and nylon cuffs in resting arterial

occlusion pressure or repetitions to volitional failure (an indirect marker of blood flow) between cuffs. (Mattocks 2018) Copyright, Howard Christopher Deck. All rights reserved. BFR Treatment: Devices Copyright, Howard Christopher Deck. All rights reserved. BFR Treatment: Pressure Low pressures 40% limb occlusion pressure (LOP) produced similar results to that of higher pressures (90% LOP) with less discomfort reported; one study showed significant adaptations demonstrated at 50 mm Hg (Hughes 2017; Pope 2013) Cuff Pressure should be individualized with larger limbs requiring more

pressure than smaller limbs (Fatela 2016; Mattocks 2019) Copyright, Howard Christopher Deck. All rights reserved. BFR Treatment: Cuff Width Large cuff width means less pressure needed; (Wernbom 2013; Loenneke 2012; Brandner 2015; Laurentino 2016; Pope 2013) large cuff width reduces variability and is less dependent on limb circumference (Wernbom 2013) Large cuff width can place more pressure on deeper tissues, which means less pressure needed in comparison to a smaller cuff (Crenshaw 1988) No difference in hypertrophy and strength using a narrow vs. wide cuff (Laurentino 2015) Copyright, Howard Christopher Deck. All rights reserved. Sym. Definition

BFR Treatment: Cuff Width: HaganPoiseuille Equation Q P r l Flow Rate Pressure Radius Fluid Viscosity Length of tubing Type Narrow Wide Cuff Constant Constant Variable 1 unit

Constant Variable 5cm 1.41 units 20cm Q = PrPr4/8l Qa=Qb PrPra4/8la = PrPrb4/8lb ra4/5cm = rb4/20cm 4 = rb4/ ra4 4^0.25 = (rb4/ ra4) ^0.25 1.414 = rb/ ra Copyright, Howard Christopher Deck. All rights reserved. Wide Cuff can achieve the same reduction in flow as a narrow cuff if the radius of the vein being occluded is 41% wider than with the narrow cuff Practical

Blood Flow Restriction (pBFR): Benefits Practical BFR (pBFR) increases muscle activation and thickness without damage (Wilson 2013) pBFR strengthens like High Intensity Training (HIT) (Lowery 2013; Luebbers 2014) pBFR is safe: elicits muscle hypertrophy without the muscle damage incurred by heavier weight (Lowery 2013) Copyright, Howard Christopher Deck. All rights reserved. BFR Exercise Prescription : Frequency & Duration Frequency: 2-3x/wk (Hughes

2017; Loenneke 2012) Duration: At least 10 weeks of duration is optimal (Loenneke 2012); BFR had the greatest result after 8 weeks of treatment (Slysz 2016) Copyright, Howard Christopher Deck. All rights reserved. 1.2 1 0.8 (Loenneke 2012) 0.6 Effect Size Exercise Intensity: Best Practices 0.4 0.2

0 0% 3 15 60 50 in m / (m Copyright, Howard Christopher Deck. All rights reserved. n la ki )w g 5% 4 / 40

V O2 (c g) n li yc 0.5 0.44 0.45 0.4 (Loenneke 2012) 0.35 0.35 Rest Periods

Rest Periods Effect Size 0.37 0.3 0.25 0.2 0.15 0.1 0.05 0 0 sec Copyright, Howard Christopher Deck. All rights reserved. 30 sec 60 sec 1.6 1.4 1.2

Duration (Loenneke 2012) Effect Size 1 0.8 0.6 0.4 0.2 0 <4 5 to 8 Weeks Copyright, Howard Christopher Deck. All rights reserved. 9 to 10 BFR Exercise

Prescription : Basics Category Recommendation Weight 15-30% 1RM Frequency 30/15/15/15 Rest Days per week 30 seconds between repetitions 2-3 days per week Duration

Over 10 weeks Closed Chain Exercises Open Chain Exercises Seated weighted Swiss ball kicks (e.g. 5 lbs on ankles with 65 cm ball) Copyright, Howard Christopher Deck. All rights reserved. Squats Heel Raises (balance) Arm Presses Arm Pulls (Rows) BFR Exercise Prescription

: Calculating Appropriate Resistance One can calculate 15-30% 1RM by telling the patient that they should imagine the heaviest weight for a particular exercise this is 10 out of 10. Then have the patient lift what they think 2 out of 10 should be. For repeat sit-to-stand exercises, have the patient stand up as many times as possible in 30 seconds. This would be the first number of repetitions, the three following reps would be half that number. If the patient is having difficultly making it through their exercises, then increase the time they rest to up to one minute before reducing weight or reps. Copyright, Howard Christopher Deck. All rights reserved. Clinical Application s: Repeat sit-to-stand

Complete a 30 second sit-to-stand test. Round result up to an even number, which becomes the number of the first set. Divide that number in half for the three last sets. Example: 30 sit-to-stand = 15 reps. BFR: 16/8/8/8 with 30 seconds rest Copyright, Howard Christopher Deck. All rights reserved. Clinical Application s: Resisted Long Arc Quads (LAQs) With BFR, apply 3-pound cuff weights to both ankles. Have the patient kick a 65 cm ball for 1-3 minutes Copyright, Howard Christopher Deck. All rights reserved.

Practical Blood Flow Restriction (pBFR): Lessons Learned 1 When applying the cuff, the practitioner should position themselves to the side of the leg rather than in front of the patient. Ask the patient to help you bring the wrap as close to the groin as possible. Creating a small slit at the end of each wrap will enable the wrap to become a slip knot. This often facilitates wrapping around the arm. Copyright, Howard Christopher Deck. All rights reserved. Practical Blood Flow Restriction (pBFR):

Lessons Learned 2 With pBFR, it is not uncommon for patients with sciatic nerve sensitivity or IT band tightness to have increased discomfort. Rolling the leg with a foam massage roller often reduces this discomfort. Sciatic nerve mobilizations may also reduce discomfort with wrapping. Wrapping lightly on the affected limb is sometimes needed. Copyright, Howard Christopher Deck. All rights reserved. Practical Blood Flow Restriction (pBFR): Lessons Learned 3 Wraps may be a substitute for T-Band Best research will

describe cuff width Tourniquet vs. Compression What about Cancer? Copyright, Howard Christopher Deck. All rights reserved. Guide patients in home BFR program through free app that also provides nudges to improve health outcomes. Next Steps Biomarker-based exercise prescription for expanded conditions (depression, CF, COPD, DM, etc.) Copyright, Howard Christopher Deck. All rights reserved. Sarcopenia: References

Evans, W. J., & Lexell, J. (1995). Human Aging, Muscle Mass, and Fiber Type Composition. Fry, C. S., Drummond, M. J., Glynn, E. L., Dickinson, J. M., Gundermann, D. M., Timmerman, K. L., & ... & Rasmussen, B. B. (2011). Aging impairs contraction-induced human skeletal muscle mTORC1 signaling and protein synthesis. Iannuzzi-Sucich M, P. K. (2002). Prevalence of sarcopenia and predictors of skeletal muscle mass in healthy, older men and women. Kramer, I. F. (2017). Extensive Type II Muscle Fiber Atrophy in Elderly Female Hip Fracture Patients. Copyright, Howard Christopher Deck. All rights reserved. Liu, S. Z. (2015). Prostaglandin E2-cyclooxygenase pathway in human skeletal muscle - influence of muscle fiber type and age. Loenneke, J. P. (2011). Sarcopenia: An emphasis on occlusion training and dietary protein. McKay, B. R. (2012). Myostatin is associated with age-related human muscle stem cell dysfunction. Sarcopenia:

References Nilwik, R. S. (2013). The decline in skeletal muscle mass with aging is mainly attributed to a reduction in Type II muscle fiber size . Ohta, H. K. (2003). Low-load resistance muscular training with moderate restriction of blood flow after anterior cruciate ligament reconstruction. Verdijk, L. B. (2007). Satellite cell content is specifically reduced in Type II skeletal muscle fibers in the elderly. Wall, B. T., Dirks, M. L., Snijders, T., van Dijk, J. W., Fritsch, M., Verdijk, L. B., & van Loon, L. J. (2015). Short-term muscle disuse lowers myofibrillar protein synthesis rates and induces anabolic resistance to protein ingestion. American Journal of Physiology-Endocrinology and Metabolism, 310(2), E137-E147. Copyright, Howard Christopher Deck. All rights reserved. The Physiology of Strengtheni ng: References Drummond, M. J. (2009). Rapamycin administration in humans blocks the contraction-induced increase in skeletal muscle protein synthesis.

Fujita, S. A. (2007). Blood flow restriction during low-intensity resistance exercise increases S6K1 phosphorylation and muscle protein synthesis. Gonzalez, A. M. (2016). Intramuscular Anabolic Signaling and Endocrine Response Following Resistance Exercise. McCall, G. E. (1996). Muscle fiber hypertrophy, hyperplasia, and capillary density in college men after resistance training. Ohta, H. K. (2003). Low-load resistance muscular training with moderate restriction of blood flow after anterior cruciate ligament reconstruction. Petrella, J. K. (2008). Potent myofiber hypertrophy during resistance training in humans is associated with satellite cell-mediated myonuclear addition. Rnnestad, B. R. (2011). Physiological elevation of endogenous hormones results in superior strength training adaptation. Schoenfeld, B. J. (2013). Potential Mechanisms for a Role of Metabolic Stress in Hypertrophic Adaptations to Resistance Training. Seynnes, O. R. (2007). Early skeletal muscle hypertrophy and architectural changes in response to high-intensity resistance training. Verdijk, L. B. (2009). Skeletal Muscle Hypertrophy Following Resistance Training Is Accompanied by a Fiber Type Specific Increase in Satellite Cell Content in Elderly Men. Copyright, Howard Christopher Deck. All rights reserved. Fry, C. S. (2010). Blood flow restriction exercise stimulates mTORC1 signaling and muscle protein synthesis in older men.

Blood Flow Restriction: Metabolite Theory References Fry, C. S., Drummond, M. J., Glynn, E. L., Dickinson, J. M., Gundermann, D. M., Timmerman, K. L., & ... & Rasmussen, B. B. (2011). Aging impairs contraction-induced human skeletal muscle mTORC1 signaling and protein synthesis. Fujita, S. A. (2007). Blood flow restriction during low-intensity resistance exercise increases S6K1 phosphorylation and muscle protein synthesis. Gundermann, D. M. (2012). Reactive hyperemia is not responsible for stimulating muscle protein synthesis following blood flow restriction exercise. Gundermann, D. M. (2014). Activation of mTORC1 signaling and protein synthesis in human muscle following blood flow restriction exercise is inhibited by rapamycin. Kawada, S. (2005). What phenomena do occur in blood flowrestricted muscle? Copyright, Howard Christopher Deck. All rights reserved. Blood Flow Restriction:

Metabolite Theory References Koopman, R. Z.-S. (2006). Increase in S6K1 phosphorylation in human skeletal muscle following resistance exercise occurs mainly in Type II muscle fibers. Manini, T. M. (2011). Myogenic and proteolytic mRNA expression following blood flow restricted exercise. Nielsen, J. L. (2012). Proliferation of myogenic stem cells in human skeletal muscle in response to low-load resistance training with blood flow restriction. Ohta, H. K. (2003). Low-load resistance muscular training with moderate restriction of blood flow after anterior cruciate ligament reconstruction. Reeves, G. V. (2006). Comparison of hormone responses following light resistance exercise with partial vascular occlusion and moderately difficult resistance exercise without occlusion. Copyright, Howard Christopher Deck. All rights reserved. Schoenfeld, B. J. (2013). Potential Mechanisms for a Role of Metabolic Stress in Hypertrophic Adaptations to Resistance Training.

Blood Flow Restriction: Metabolite Theory References Sudo, M. A. (2015). Blood flow restriction prevents muscle damage but not protein synthesis signaling following eccentric contractions. Suga, T. O. (2010). Dose effect on intramuscular metabolic stress during low-intensity resistance exercise with blood flow restriction. Takarada, Y. N. (2000). Rapid increase in plasma growth hormone after low-intensity resistance exercise with vascular occlusion. Takarada, Y. T. (2000). Applications of vascular occlusion diminish disuse atrophy of knee extensor muscle fibers. Takarada, Y. T. (2004). Cooperative effects of exercise and occlusive stimuli on muscular function in low-intensity resistance exercise with moderate vascular occlusion. . Wernbom, M. A. (2013). Acute lowload resistance exercise with load resistance exercise with and without blood flow restriction increased protein signalling and number of satellite cells in human skeletal muscle. Yasuda, T. F. (2014). Effects of low-intensity elastic band resistance exercise combined with blood flow restriction on muscle

activation. Copyright, Howard Christopher Deck. All rights reserved. Blood Flow Restriction: References Gundermann, D. M. (2012). Reactive hyperemia is not responsible for stimulating muscle protein synthesis following blood flow restriction exercise. Hughes, L. P. (2017). Blood flow restriction training in clinical musculoskeletal rehabilitation - a systematic review and meta-analysis. Loenneke, J. W. (2010). Potential safety issues with blood flow restriction training. Copyright, Howard Christopher Deck. All rights reserved. Practical Blood Flow Restriction (pBFR):

References Lowery, R. P. (2013). Practical blood flow restriction training increases muscle hypertrophy during a periodized resistance training programme. Luebbers, P. F. (2014). The effects of a 7week practical blood flow restriction program on well-trained collegiate athletes. Wilson, J. L. (2013). Practical Blood Flow Restriction Training Increases Acute Determinants of Hypertrophy Without Increasing Indices of Muscle Damage Copyright, Howard Christopher Deck. All rights reserved. Blood Flow Restriction: Treatment References Brandner, C. K. (2015). Unilateral bicep curl hemodynamics: Lowpressure continuous vshigh-pressure intermittent blood flow restriction. Crenshaw, A. G. (1988). Wide tourniquet cuffs more effective at lower inflation pressures. Fatela, P. R.-H. (2016). Acute effects of exercise under different

levels of blood-flow restriction on muscle activation and fatigue. Hughes, L. P. (2017). Blood flow restriction training in clinical musculoskeletal rehabilitation - a systematic review and metaanalysis. Laurentino, G. C. (2016). The Effect of Cuff Width on Muscle Adaptations after Blood Flow Restriction Training. Laurentino, G. L. (2015). The Effect of Cuff Width on Muscle Adaptations after Blood Flow Restriction Training. Loenneke, J. P. (2012). Blood Flow Restriction: How Does it work? Pope, Z. K. (2013). Exercise and Blood Flow Restriction. Wernbom, M. A. (2013). Acute lowload resistance exercise with load resistance exercise with and without blood flow restriction increased protein signalling and number of satellite cells in human skeletal muscle. Copyright, Howard Christopher Deck. All rights reserved. BFR Exercise Prescription : References Brandner, C. K. (2015). Unilateral bicep curl hemodynamics: Low-pressure continuous vshighpressure intermittent blood flow restriction. Brandner, C. R. (2015). Unilateral bicep curl hemodynamics - Low-pressure continuous vs highpressure intermittent blood flow restriction.

Hughes, L. P. (2017). Blood flow restriction training in clinical musculoskeletal rehabilitation - a systematic review and meta-analysis. Loenneke, J. P. (2012). Blood Flow Restriction: How Does it work? Slysz, J. S. (2016). The efficacy of blood flow restricted exercise - A systematic review & meta-analysis. Wernbom, M. A. (2013). Acute lowload resistance exercise with load resistance exercise with and without blood flow restriction increased protein signalling and number of satellite cells in human skeletal muscle. Yasuda, T. F. (2014). Effects of low-intensity elastic band resistance exercise combined with blood flow restriction on muscle activation. Copyright, Howard Christopher Deck. All rights reserved. Blood Flow Restriction: Safety References Bryk, F. F. (2017). Exercises with partial vascular occlusion in patients with knee osteoarthritis: a randomized clinical trial.

Clark, B. M. (2009). Relative safety of 4 weeks of blood flow-restricted resistance exercise in young, healthy adults. Fry, C. S. (2010). Blood flow restriction exercise stimulates mTORC1 signaling and muscle protein synthesis in older men. Hughes, L. P. (2017). Blood flow restriction training in clinical musculoskeletal rehabilitation - a systematic review and meta-analysis. Loenneke, J. P. (2011). Sarcopenia: An emphasis on occlusion training and dietary protein. Loenneke, J. W. (2010). Potential safety issues with blood flow restriction training. Copyright, Howard Christopher Deck. All rights reserved. Blood Flow Restriction: Safety References Meyer, R. A. (2006). Does blood flow restriction enhance hypertrophic signaling in skeletal muscle? Nakajima, T. K. (2006). Use and Safety of KAATSU Training: Results of a National Survey. Ozaki, H. S. (2010). Increases in Thigh Muscle Volume and Strength

by Walk Training with Leg Blood Flow Reduction in Older Participants. Patterson, S. D. (2011). Enhancing Strength and Postocclusive Calf Blood Flow in Older People With Training With Blood-Flow Restriction. Segal, N. A. (2015). Efficacy of Blood Flow Restricted, Low-Load Resistance Training in Women with Risk Factors for Symptomatic Knee Osteoarthritis. Shimizu, R. H. (2016). Low-intensity resistance training with blood flow restriction improves vascular endothelial function and peripheral blood circulation in healthy elderly people. Sudo, M. A. (2015). Blood flow restriction prevents muscle damage but not protein synthesis signaling following eccentric contractions. Copyright, Howard Christopher Deck. All rights reserved. Blood Flow Restriction: Walking and Aquatic References Abe, T. K. (2006). Muscle size and strength are increased following walk training with

restricted venous blood flow from the leg muscle, Kaatsu-walk training. Arajo, J. P. (2015). The effects of water-based exercise in combination with blood flow restriction on strength and functional capacity in post-menopausal women. Ozaki, H. S. (2010). Increases in Thigh Muscle Volume and Strength by Walk Training with Leg Blood Flow Reduction in Older Participants. Pope, Z. K. (2013). Exercise and Blood Flow Restriction. Copyright, Howard Christopher Deck. All rights reserved. BFR Results: References Dankel, S. J. (2015). The Effects of Blood Flow Restriction on Upper-BodyMusculature Located Distal and Proximal to Applied Pressure. Drummond, M. J. (2008). Human muscle gene expression following resistance exercise and blood flow restriction. Fujita, S. A. (2007). Blood flow restriction during low-intensity resistance exercise increases S6K1

phosphorylation and muscle protein synthesis. Hughes, L. P. (2017). Blood flow restriction training in clinical musculoskeletal rehabilitation - a systematic review and meta-analysis. Iida, H. N. (2011). Effects of walking with blood flow restriction on limb venous compliance in elderly subjects. Karabulut, M. A. (2010). The effects of lowintensity resistance training with vascular restriction on leg muscle strength in older men. Copyright, Howard Christopher Deck. All rights reserved. Blood Flow Restriction: Results References Karabulut, M. B. (2011). Effects of high-intensity resistance training and low-intensity resistance training with vascular restriction on bone markers in older men. Kubo, K. K. (2006). Effects of Low-Load Resistance Training With Vascular Occlusion on the Mechanical Properties of Muscle and Tendon. Laurentino, G. U. (2012). Strength Training with Blood Flow Restriction Diminishes Myostatin Gene

Expression. Loenneke, J. P. (2011). Sarcopenia: An emphasis on occlusion training and dietary protein. Manini, T. M. (2011). Myogenic and proteolytic mRNA expression following blood flow restricted exercise. Moore, D. R. (2004). Neuromuscular adaptations in human muscle following low intensity resistance training with vascular occlusion. Copyright, Howard Christopher Deck. All rights reserved. Blood Flow Restriction: Results References Nielsen, J. L. (2012). Proliferation of myogenic stem cells in human skeletal muscle in response to low-load resistance training with blood flow restriction. Takarada, Y. N. (2000). Rapid increase in plasma growth hormone after low-intensity resistance exercise with vascular occlusion. Takarada, Y. T. (2000). Effects of resistance exercise combined with moderate vascular occlusion on muscular function in humans. Takarada, Y. T. (2004). Cooperative effects of exercise and

occlusive stimuli on muscular function in low-intensity resistance exercise with moderate vascular occlusion. . Vechin, F. C. (2015). Comparisons between low-intensity resistance training with blood flow restriction and high-intensity resistance training on quadriceps muscle mass and strength in elderly. . Wernbom, M. A. (2013). Acute lowload resistance exercise with load resistance exercise with and without blood flow restriction increased protein signalling and number of satellite cells in human skeletal muscle. Copyright, Howard Christopher Deck. All rights reserved. References: Kubota, A. S. (2011). Blood flow restriction by low compressive force prevents disuse muscular weakness. Takarada, Y. T. (2000). Applications of vascular occlusion diminish disuse atrophy of knee extensor muscles. Copyright, Howard Christopher Deck. All rights reserved. Aerobic Interval

Training (AIT): References Tan, R. N. (2018). Skeletal muscle fibertype-specific changes in markers of capillary and mitochondrial content after low-volume interval training in overweight women. Weston, K. S. (2014). High-intensity interval training in patients with lifestyleinduced cardiometabolic disease: a systematic review and meta-analysis. Copyright, Howard Christopher Deck. All rights reserved. Protein Supplementat ion: References Liao, C. D. (2017). Effects of protein supplementation combined with resistance exercise on body composition and physical function in older adults. Loenneke, J. P. (2011). Sarcopenia: An emphasis on occlusion training and

dietary protein. Reidy, P. T. (2017). Postexercise essential amino acid supplementation amplifies skeletal muscle satellite cell proliferation in older men 24 hours postexercise. Copyright, Howard Christopher Deck. All rights reserved. COX Inhibitors: References Trappe, T. A. (2012). Prostaglandin and myokine involvement in the cyclooxygenase-inhibiting drug enhancement of skeletal muscle adaptations to resistance exercise in older adults. Trappe, T. A. (2013). Effects of prostaglandins and COX-inhibiting drugs on skeletal muscle adaptations to exercise. Copyright, Howard Christopher Deck. All rights reserved.

Skeletal Muscle as an Endocrine Organ : References Gamas, L., Matafome, P., Seica, R. (2015). Irsin and Myonectin Regulation in the Insulin Resistant Muscle: Implications to Adipose Tissue: Muscle Crosstalk. Journal of Diabetes Research 2015. Gorgens, S.W., Eckardt, K., Jensen, J., Drevon, C.A., Eckel, J. (2015). Exercise and Regulation of Adipokine and Myokine Production. Progress in Molecular Biology and Translational Science 135:313-336. Eckardt, K., Gorgens, S.W., Raschke, S., Eckel, J. (2014). Myokines in insulin resistance and Type 2 diabetes. Diabeologia 57: 1087-1099.

Hiscock, N., Chan, H.S., Bisucci, T., Darby, I.A., Febbraio, M.A. (2004). Skeletal myocytes are a source of interleukin-6 mRNA expression and protein release during contraction: evidence of fiber type specificity. The FASEB Journal: 1-12. Steensberg, A., Febbraio, M.A., Osada, T., Schjerling, P., van Hall, G., Saltin, B., Pederson, B.K. (2001). Interleukin-6 production in contracting human skeletal muscle is influenced by pre-exercise muscle glycogen content. Journal of Physiology 537(2): 633-639. Steensberg, A., van Hall, G., Osada, T., Sacchetti, M., Saltin, Bengt, Pederson, B. K. (2000). Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6. Journal of Physiology 529(1): 237-242. Cox, A.A., Sagot, Y., Hedou, G., Grek, C., Wilkes, T., Vinik, A.I., Ghatnekar, G. (2017). Low-Dose Pulsatile Interleukin-6 as a Treatment Option for Diabetic Peripheral Neuropathy. Frontiers in Endocrinology 8(89). Copyright, Howard Christopher Deck. All rights reserved. Blood Flow Restriction: Benefit Comparison Abbreviation Definition CSA Affects Cross Strength

Section Area COX HIT AIT Inhibitors 12.5% 28% (Ace) Strength 26.7% Capillary per Fiber Ratio 24% Satellite Cell VO2Max Muscle stem myonuclei cell Protein Occlusion

Only 45.4% less than control 18.9 41.5% % less than control BFR BFR (Resistance) (Endurance) 10.3% 4-7% 9.2% 8-10% T-I: 23% T-II: 21% 75% 46% 24%

Copyright, Howard Christopher Deck. All rights reserved. 14% Glossary Term Abbv Definition The principle molecule in the body for Adenosine storing and releasing energy to power Triphospate ATP movement and other cellular functions. Brain Derived Myokine that increases growth in Neurotrophic Factor BDNF hippocampus Cells in the pancreas that create insulin. Degeneration of these cells causes Type I Beta Cell -cell Diabetes Mellitus Cross Sectional Area CSA The cross sectional area of a muscle Cytoplasm --The jelly-like substance in a cell.

Copyright, Howard Christopher Deck. All rights reserved. Glossary Term Abbv Definition Fatty Acid Transport An insulin-sensitive fatty acid transporter Protein 1 FATP-1 involved in diet-induced obesity A hormone, secreted by the pituitary gland, that assists with the healing of Growth Hormone GH collagen A hormone similar to the molecular Insulin-like Growth structure of insulin that is synthesized in Factor - I IGF-1 the liver and has anabolic effects in adults Copyright, Howard Christopher Deck. All rights reserved. Term

Abbv Definition Mamallian Target of A metabolite that functions to increase Rapamycin mTOR MPS MicroRNA Muscle Protein Breakdown Approximately 22 Nucleotides along a miRNA non-coding RNA molecule MPB The body's process for reabsorbing muscle Copyright, Howard Christopher Deck. All rights reserved. Glossary Term Muscle Protein Synthesis

Abbv Definition The body's process for creating new MPS muscle The amount of cytoplasm a myonuclei is Myonuclear Domain --- able to control Myonuclei --- The nucleus of the muscle fiber Metabolite that plays a key role in the MPB Myostatin MSTN process Copyright, Howard Christopher Deck. All rights reserved. Term Abbv Definition Regulates MPS through satellite cell Paired Box Protein 7 PAX7+ proliferation (assoc. with BDNF) Peroxisome proliferatoractivated receptor Metabolite that stimulates mitochondrial gamma biogenesis and promotes remodeling of coactivator 1-alpha PGC-1muscle tissue from Type II to Type I

Metabolite affected by Acetaminophen Prostaglandin E2 PGE2 that contributes to MPB Prostaglandin F2 Metabolite affected by Acetaminophen alpha PGF2 that contributes to MPS Copyright, Howard Christopher Deck. All rights reserved. Term Abbv Definition Oxygen radicals (superoxide) and nonReactive Oxygen radical oxidizing agents (hydrogen Species ROS peroxide) S6 kinase beta-1 S6K1 Part of the signalling pathway for MPS A stem cell that is on a Type I or Type II Satellite Cell SC muscle fiber Slow-twich muscle cell that relies on the Type I Muscle Fiber Type I aerobic process to create ATP

Copyright, Howard Christopher Deck. All rights reserved. Term Abbv Definition Type Fast-twitch muscle cell that relies on the Type II Muscle Fiber II anaerobic process to create ATP Vascular Endothelial A protein that promotes the growth of new Growth Factor VEGF blood vessels The measurement of the maximal amount of oxygen that an individual can utilize VO2 Max VO2 during peak exercise. Copyright, Howard Christopher Deck. All rights reserved.

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