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BLOOD FLOW

RESTRICTION TRAINING

OPBYGNING OG VEDLIGEHOLDELSE AF MUSKELMASSE MED LAV-INTENSIV STYRKETRÆNING Per Aagaard, Maj Lund Jepsen, Mads Brink Hansen, Jarl Pors Jakobsen,

Institut for Idræt og Biomekanik, Syddansk Universitet Dansk Vandski Forbund · Team Danmark

Team Danmark Formidlingsseminar · Brøndby 12. Maj 2015

Velkommen til workshop: BFRE/okklusionstræning

13:30-14:00: Okklusionstræning: videnskabelig baggrund

mekanismer, anvendelsesområder - v. Per Aagaard

14:00-14:10: Spørgsmål og diskussion

14:10-14:20: Kaffe og fortsat snak og diskussion

14:20-14:50: Vandskihop og okklusionstræning - v. Maj Lund

Jepsen, Jarl Pors Jakobsen og Mads Brink Hansen

14:50-15:00: Spørgsmål og diskussion

• Resistance training performed with concurrent partial blood flow occlusion, and using low

• external loads (20-50% 1RM)

picture courtsey Ben Rosenblatt, UK Sports

blood flow restricted exercise (BFRE)

OKKLUSIONSTRÆNING

(2)

Free-flow low-load strength training:

No or only minor increases in muscle size

Holm, Aagaard et al, J Appl Physiol 2008 Heavy: training loads 70% 1RM, Light: training loads 20% 1RM,

12 weeks, 36 sessions, isolated knee extension, matched for total work load

Quadriceps Muscle Cross-sectional Area

*

(P<0.05) (P<0.01) VL VM RF VI

pre training, distal site post training, distal site

pre training, proximal site post training, proximal site

Abe et al, 2005 % Change in mid-thigh Muscle-Bone CSA Subjects: Young men (n=16) age 23.9 ± 8.4 yrs Occlusion pressure: 160  240 mm Hg Loading intensity/volume: 20% 1RM 2 weeks (minus sunday) 2 sessions/day 3 sets, 15 reps Squat and leg curls Occlusion pressure maintained in breaks (30-s) Total session duration

10 min

blood flow restricted exercise (BFRE)

OKKLUSIONSTRÆNING

Changes in elbow flexor CSA and MVC with 16 wks BFRE

* LI-BFRE, HI > LI (p<0.05)

Muscle CSA Muscle strength

Subjects: Elderly women (n=19) age 58.2 ± 6.6 yrs (range 47-67) Occlusion pressure: 110 mm Hg Loading intensity/volume: ~ 80% 1RM (HI) ~ 50% 1RM (LI, LI-BFRE) 16 wks, 2 sessions/wk LI-BFRE and HI: reps performed until failure LI: reps performed to ensure equal work matched to LI-BFRE Cross-over design

(3)

Knee extensor exercise with partial blodflow occlusion (Rugby players): 4 sets to failure, ~50% 1RM training loads, 2 sessions per week, 8 wks 12% increase in quadriceps CSA

Takarada et al, Eur J Appl Physiol 2002

PRE TRAINING POST TRAINING

Blood flow restricted resistance exercise (BFRE) can

induce hypertrophy in highly strength trained athletes

Blood flow restricted resistance exercise can improve

muscle strength/power in highly strength trained athletes

Cook et al, J Sports Physiol Perform 2014

Blood flow restricted resistance exercise can improve

muscle strength/power in highly strength trained athletes

(4)

Blood flow restricted resistance exercise can improve

muscle strength/power in highly strength trained athletes

Cook et al, J Sports Physiol Perform 2014

Semiprofessional rugby union athletes Randomized to lower-body BFR training (occlusion cuff inflated to 180 mmHg intermittently on the proximal thighs) or control intervention training without BFR 9 sessions in 3 wks

5 sets of 5 repetitions: bench press, leg squat, pull-ups 70% of 1-RM

Blood flow restricted resistance exercise can improve

muscle strength/power in highly strength trained athletes

Cook et al, J Sports Physiol Perform 2014 BFR training

Control

Substantial muscular hypertrophy

can be elicited by use of low-resistance

blood flow restricted (BFR) strength training!

(5)

Substantial muscular hypertrophy

can be elicited by use of low-resistance

blood flow restricted (BFR) strength training!

PROPOSED

ADAPTIVE MECHANISMS

- Enhanced cellular net protein synthesis ... YES!

-

Growth hormone secretion?

... evidence exists

-

Autocrine/paracrine IGF-1 production

... maybe

- Reduced myostatin expression? ... evidence exists

- Activation of muscle stem cells

(satellite cells)

???

Effects of resistance exercise on

skeletal muscle satellite cell activity

Picture courtsey Abigail MacKey ISMC, Bispebjerg Hospital, University of Copenhagen

Myonucleus Satellite cell Cell membrane Ba s al la m in a Sa rc o le m m a Myofibre Vierck et al., Cell Biol. Int. 24, 2000

NCAM/D56 antibody staining haematoxylin counterstaining Satellite cells = dormant myogenic

cells situated between the basal lamina and the muscle cell

membrane

Satellite

Satellite

cells

cells

in human skeletal muscle

in human skeletal muscle

Myogenic satellite cells mediate muscle cell repair and growth in response to overloading Kadi 2000 Myonucleus Satellite cell Cell membrane Bas a l la m in a Sar co le m m a Myofibre Vierck et al, Cell Biol Int 24, 2000

(6)

Satellite cells in human skeletal muscle

Myonucleus Satellite cell Cell membrane Ba s al la m in a Sa rc o le m m a Myofibre Vierck et al., Cell Biol. Int. 24, 2000

NCAM/D56 antibody staining haematoxylin counterstaining Satellite cells = dormant myogenic

cells situated between the basal lamina and the muscle cell

membrane

Satellite

Satellite

cells

cells

in human skeletal muscle

in human skeletal muscle

Myonucleus Satellite cell Cell membrane Bas a l la m in a Sar co le m m a Myofibre Vierck et al, Cell Biol Int 24, 2000

Kadi et al, J Physiol 2004

NCAM/CD56 antibody staining Haematoxylin counterstaining

Satellite cells in human skeletal muscle

Resistance training, satellite cells and

skeletal muscle hypertrophy

Responders vs non-responders

Picture courtsey Abigail MacKey ISMC, Bispebjerg Hospital, University of Copenhagen

(7)

S at el li te ce ll s (S C p e r 1 0 0 f ib e rs ) R el at ive sa tel li te ce ll s (% a ll n u c le i) M ea n f ib er ar ea (  m 2)

Changes in muscle fiber area and satellite cell content in response to 16 wks of heavy-resistance strength training

(young, old, men, women)

Petrella, Bamman et al, J Appl Physiol 2008

Resistance training, satellite cells and

skeletal muscle hypertrophy

Responders vs non-responders

F ib er C S A p er m y o n u cl eu s (  m 2) M y o n u cl ea r n u m b er (n u c le i p e r f ib e r) M ea n f ib er ar ea (  m 2)

Changes in muscle fiber area and myonuclei content in response to 16 wks of heavy-resistance strength training

(young, old, men, women)

Petrella, Bamman et al, J Appl Physiol 2008

Resistance training, satellite cells and

skeletal muscle hypertrophy

Responders vs non-responders

Resistance training, satellite cells and

skeletal muscle hypertrophy

14 days lower limb immobilization → 4 wks strength training:

Hypertrophy response associated with upregulated satellite cell activity

Suetta, Frandsen, Aagaard, Kjaer et al. J Physiol 591, 2013

Young (24 yrs) Old (67 yrs)

(8)

Modified from MacKey et al, Scand J Med Sci Sports 2007

Exercise induced self renewal of SC’s

exercise, tissue injury

1

2

3

Pool of myogenic stem cells (satellite cells: CS)

Snijders et al, Ageing Research Reviews 8, 2009

 cell volume / nuclei sustained cell volume / nuclei 

INCREASE IN MYONUCLEI NUMBER

WITH SATELLITE CELL ACTIVATION

Satellite cell activation/proliferation

 SC fusion with myofibers

Effects of blood-flow restricted muscle exercise

(BFRE

)

on myofiber size and myogenic satellite cells?

(9)

M o n d a y T u e sd a y W e d n e sd a y T h u rsd a y F ri d a y M o n d a y T u e sd a y W e d n e sd a y T h u rsd a y F ri d a y T u e sd a y W e d n e sd a y T h u rsd a y F ri d a y

Nielsen, Aagaard, Suetta, Wernbom, Frandsen et al, J Physiol 590, 2012 23 TRAINING SESSIONS performed in 3 wks (19 days) Low-resistance BFR-ST (n=22) or load/work matched RE (n=8) 4 sets at 20% 1RM performed to failure, rest periods 45 sec - total duration of occlusion: 6-8 minutes

Cuff-pressure: 100 mmHg, no cuff release between sets 15-cm cuff width

pneumatic cuff

TRAINING and TEST PROTOCOL

pneumatic cuff Str en g th T esti n g M u scl e b io p sy sam p li n g M u scl e b io p sy sam p li n g M u scl e b io p sy sam p li n g M u scl e b io p sy sam p li n g Str en g th T esti n g Str en g th T esti n g

PRE MID8 POST 3 days POST 10 days

MUSCLE BIOPSY SAMPLING (VL muscle)

PRE, MID8 (5 days BFR-ST + 2 days rest), POST3, POST 10 (3,10 days post training)

M o n d a y T u e sd a y W e d n e sd a y T h u rsd a y F ri d a y M o n d a y T u e sd a y W e d n e sd a y T h u rsd a y F ri d a y T u e sd a y W e d n e sd a y T h u rsd a y F ri d a y

Nielsen, Aagaard, Suetta, Wernbom, Frandsen et al, J Physiol 590, 2012

TRAINING and TEST PROTOCOL

(10)

Immunohistochemical tripple staining marking MHC I (blue), MHC I IA (red) and MHC IIX (black) isoforms while laminin (green) marks the basal membrane. Scale bar: 100 m Assessment of fibertype composition

Tripple immunohistochemical MHC-antibody stainings performed to determine fiber type distribution Kosek et al 2006

Assessment of fiber area Laminin antibody stainings performed to visualize the fiber membrane

MUSCLE BIOPSY ANALYSIS

Nielsen, Aagaard, Suetta, Wernbom, Frandsen et al, J Physiol 590, 2012

IIA

IIA

IIA

Assessment of fibertype composition Tripple immunohistochemical MHC-antibody stainings performed to determine fiber type distribution Kosek et al 2006

Assessment of fiber area Laminin antibody stainings performed to visualize the fiber membrane

Satellite cells Myogenic satellite cells (SC) stained for Pax-7, with verified sub-sarcolemmal position

MUSCLE BIOPSY ANALYSIS

Nielsen, Aagaard, Suetta, Wernbom, Frandsen et al, J Physiol 590, 2012 Boldrin et al, J Histochem Cytochem 2012

Assessment of fibertype composition Tripple immunohistochemical MHC-antibody stainings performed to determine fiber type distribution Kosek et al 2006

Assessment of fiber area Laminin antibody stainings performed to visualize the fiber membrane

Satellite cells Myogenic satellite cells (SC) stained for Pax-7, with verified sub-sarcolemmal position Myonuclei

Myonuclei stained with DAPI

(11)

TRAINING VOLUME & PAIN SCORING

TRAINING SESSIONS T o ta l tr a in in g r e p e ti ti o n s

Week 1 Week 2 Week 3

V A S s co re (m a x = 1 0 0 ) +13%

Type I fibers Type II fibers

BFRE CON BFRE CON

BFRE CON BFRE CON

Satellite cells per muscle fiber

Type I fibers Type II fibers

different from PRE (p<0.01) *,**

different from CON (p<0.05) † different from mid8 (p<0.05) ‡

Nielsen, Aagaard, Suetta, Wernbom, Frandsen et al, J Physiol 590, 2012

Satellite cells per muscle fiber

+301% +160% +284% +147%

different from PRE (p<0.01) *,**

different from CON (p<0.05) † different from mid8 (p<0.05) ‡

Nielsen, Aagaard, Suetta, Wernbom, Frandsen et al, J Physiol 590, 2012

BFRE CON BFRE CON

Type I fibers Type II fibers

Myonuclei per muscle fiber

Myonuclei per muscle fiber

(12)

different from PRE (p<0.01) *,** different from CON (p<0.05) † different from mid8 (p<0.05) ‡

Nielsen, Aagaard, Suetta, Wernbom, Frandsen et al, J Physiol 590, 2012

Type I fibers Type II fibers

BFRE CON BFRE CON

BFRE CON BFRE CON

Myofiber CSA

Type I fibers Type II fibers

Type I fibers Type II fibers

BFRE CON BFRE CON

BFRE CON BFRE CON

Myofiber CSA

Type I fibers Type II fibers

Type I fibers Type II fibers

BFRE CON BFRE CON

BFRE CON BFRE CON

Myofiber CSA

Type I fibers Type II fibers

Myofiber cross-sectional area

+37% +39%

+28% +31% +30%

+28%

different from PRE (p<0.01) *,**

different from CON (p<0.05) † different from mid8 (p<0.05) ‡

Nielsen, Aagaard, Suetta, Wernbom, Frandsen et al, J Physiol 590, 2012

Maximal muscle strength (MVC)

+6% +13%

Effects of blood flow restricted low-intensity resistance training (BFRE) on myogenic satellite cells

CONCLUSIONS

BFR-ST can be used to induce marked increases (+30-40%) in myofiber size of both type I and II fibers within a very short period of time (3 weeks)

BFR-ST results in a markedly upregulated (1½-2 fold increased) myogenic satellite cell (SC) content in the trained muscles

The hyperactivation of SC’s with BFR-ST is accompanied by elevated myonuclei number - reflecting an increased transcriptional capacity (elevated myogenic capacity)

(13)

PERSPECTIVES

Short-term BFRE

marked increases in SC content (150-200%) and myonuclear number (30-35%)

‘myogenic priming’ of human skeletal muscle

important potential implications - for instance: TRAINING OF ATHLETES

(1) Rapid and amplified increases in muscle mass with conventional strength training when preconditioned by BFRE? (2) Increased myonuclei number in BFRE trained myofibers  exploiting ‘muscle memory’ Bruusgaard, Gundersen et al, PNAS 2010

Effects of blood flow restricted low-intensity resistance training (BFRE) on myogenic satellite cells

PERSPECTIVES

Short-term BFRE

marked increases in SC content (150-200%) and myonuclear number (30-35%)

‘myogenic priming’ of human skeletal muscle

important potential implications - for instance: TRAINING IN PATIENTS

Unable to perform heavy-load RT due to musculo-skeletal-tendinous injury, with primary or secondary loss in muscle mass, i.e. neuromuscular myopathology (MS, ALS), sarcopenic elderly, ACL injury, etc Effects of blood flow restricted low-intensity resistance training (BFRE) on myogenic satellite cells

PERSPECTIVES

Short-term BFRE

marked increases in SC content (150-200%) and myonuclear number (30-35%)

‘myogenic priming’ of human skeletal muscle

important potential implications - for instance: TRAINING IN PATIENTS

Unable to perform heavy-load RT due to musculo-skeletal-tendinous injury, with primary or secondary loss in muscle mass, i.e. neuromuscular myopathology (MS, ALS), sarcopenic elderly, ACL injury, etc Potentially allows

accelerated rehabilitation i.e. following ACL

reconstruction

May similarly allow accelerated rehabilitation

in non-reconstructed ACL injured subjects

Effects of blood flow restricted low-intensity resistance training (BFRE) on myogenic satellite cells

(14)

Loenneke, Abe, Bemben et al, 2012

Use of BFRE versus general progression training

From bed rest to walking to training following limb immobilizing injury

Jakob L. Nielsen

Phd-student, Cand.Scient Institute of Sports Science and Clinical Biomechanics

University of Southern Denmark

Accelerated rehabilitation in ACL reconstructed

patients via hyper-activation of myogenic stem

cells by use of kaatsu exercise (BFRE)

(15)

TV2 Sporten (SportsLAB) - 24. marts 2014

TV2 Sporten (SportsLAB) - 24. marts 2014

(16)

TV2 Sporten (SportsLAB) - 24. marts 2014

TV2 Sporten (SportsLAB) - 24. marts 2014

(17)

TV2 Sporten (SportsLAB) - 24. marts 2014

THANKS for your attention !

Acknowledgements

Jakob L. Nielsen Anders Jørgensen Ulrik Frandsen Charlotte Suetta Nis Nissen Lars Grøndahl Hvid Mathias Wernbom Rune Dueholm Bech Tobias Nygaard Ben Rosenblatt Abigail Mackey Fawzi Kadi Michael Kjær

References

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