5/12/2015. OKKLUSIONSTRÆNING blood flow restricted exercise (BFRE) BLOOD FLOW RESTRICTION TRAINING. Velkommen til workshop: BFRE/okklusionstræning

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1 Team Danmark Formidlingsseminar Brøndby 12. Maj 2015 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 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 OKKLUSIONSTRÆNING blood flow restricted exercise (BFRE) Resistance training performed with concurrent partial blood flow occlusion, and using low external loads (20-50% 1RM) picture courtsey Ben Rosenblatt, UK Sports 1

2 Free-flow low-load strength training: No or only minor increases in muscle size Quadriceps Muscle Cross-sectional Area VI RF VM VL pre training, distal site post training, distal site * pre training, proximal site post training, proximal site (P<0.05) (P<0.01) Heavy: training loads 70% 1RM, Light: training loads 20% 1RM, 12 weeks, 36 sessions, isolated knee extension, matched for total work load Holm, Aagaard et al, J Appl Physiol 2008 OKKLUSIONSTRÆNING blood flow restricted exercise (BFRE) Subjects: Young men (n=16) age 23.9 ± 8.4 yrs % Change in mid-thigh Muscle-Bone CSA Occlusion pressure: 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 Abe et al, 2005 OKKLUSIONSTRÆNING blood flow restricted exercise (BFRE) Subjects: Elderly women (n=19) age 58.2 ± 6.6 yrs (range 47-67) Changes in elbow flexor CSA and MVC with 16 wks BFRE 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-BFRE, HI > LI (p<0.05) LI: reps performed to ensure equal work matched to LI-BFRE Cross-over design Muscle CSA Muscle strength Takarada et al, J Appl Physiol 2000; in Manini & Clark, ESSR

3 Blood flow restricted resistance exercise (BFRE) can induce hypertrophy in highly strength trained athletes PRE TRAINING POST TRAINING 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 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 Cook et al, J Sports Physiol Perform

4 Blood flow restricted resistance exercise can improve muscle strength/power in highly strength trained athletes 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 Cook et al, J Sports Physiol Perform 2014 Blood flow restricted resistance exercise can improve muscle strength/power in highly strength trained athletes BFR training Control Cook et al, J Sports Physiol Perform 2014 Substantial muscular hypertrophy can be elicited by use of low-resistance blood flow restricted (BFR) strength training! WHAT ARE THE ADAPTIVE MECHANISMS? 4

5 Sarcolemma Sarcolemma Basal lamina Basal lamina 5/12/2015 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 Satellite cells in human skeletal muscle Satellite cells in human skeletal muscle Satellite cells = dormant myogenic cells situated between the basal lamina and the muscle cell membrane Myogenic satellite cells mediate muscle cell repair and growth in response to overloading Cell membrane Satellite cell Myonucleus Myofibre Vierck et al, Vierck et al., Cell Biol Int Cell 24, Biol Int. 24, 2000 NCAM/D56 antibody staining haematoxylin counterstaining Kadi

6 Sarcolemma Sarcolemma Basal lamina Basal lamina 5/12/2015 Satellite cells in human skeletal muscle Satellite cells in human skeletal muscle Satellite cells in human skeletal muscle Satellite cells = dormant myogenic cells situated between the basal lamina and the muscle cell membrane Kadi et al, J Physiol 2004 Cell membrane Satellite cell Myonucleus Myofibre Vierck et al, Vierck et al., Cell Biol Int Cell 24, Biol Int. 24, 2000 NCAM/D56 NCAM/CD56 antibody antibody staining staining haematoxylin Haematoxylin counterstaining counterstaining Resistance training, satellite cells and skeletal muscle hypertrophy Responders vs non-responders Picture courtsey Abigail MacKey ISMC, Bispebjerg Hospital, University of Copenhagen 6

7 Resistance training, satellite cells and skeletal muscle hypertrophy Responders vs non-responders Mean fiber area (m 2 ) Satellite cells (SC per 100 fibers) Relative satellite cells (% all nuclei) 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 Mean fiber area (m 2 ) Myonuclear number (nuclei per fiber) Fiber CSA per myonucleus (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 14 days lower limb immobilization 4 wks strength training: Hypertrophy response associated with upregulated satellite cell activity Young (24 yrs) Old (67 yrs) Suetta, Frandsen, Aagaard, Kjaer et al. J Physiol 591,

8 exercise, tissue injury Exercise induced self renewal of SC s Pool of myogenic stem cells (satellite cells: CS) Modified from MacKey et al, Scand J Med Sci Sports 2007 INCREASE IN MYONUCLEI NUMBER WITH SATELLITE CELL ACTIVATION Satellite cell activation/proliferation SC fusion with myofibers cell volume / nuclei sustained cell volume / nuclei Snijders et al, Ageing Research Reviews 8, 2009 Effects of blood-flow restricted muscle exercise (BFRE) on myofiber size and myogenic satellite cells? satellite cell 8

9 Strength Testing Muscle biopsy sampling Monday Tuesday Monday Tuesday Wednesday Thursday Friday Wednesday Thursday Friday Muscle biopsy sampling Tuesday Tuesday Wednesday Thursday Friday Wednesday Thursday Friday Monday Tuesday Monday Tuesday Wednesday Thursday Friday Wednesday Thursday Friday Muscle biopsy sampling Strength Testing Muscle biopsy sampling Strength Testing 5/12/2015 TRAINING and TEST PROTOCOL pneumatic cuff 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 TRAINING and TEST PROTOCOL pneumatic cuff 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) 9

10 MUSCLE BIOPSY ANALYSIS Assessment of fibertype composition Tripple immunohistochemical MHC-antibody stainings performed to determine fiber type distribution Kosek et al 2006 IIA Assessment of fiber area Laminin antibody stainings performed to visualize the fiber membrane IIA IIA 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 MUSCLE BIOPSY ANALYSIS 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 Boldrin et al, J Histochem Cytochem 2012 MUSCLE BIOPSY ANALYSIS 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 10

11 Total training repetitions 5/12/2015 TRAINING VOLUME & PAIN SCORING Week 1 Week 2 Week 3 +13% VAS score (max = 100) TRAINING SESSIONS Satellite cells per muscle fiber Satellite cells per muscle fiber +301% Type I fibers +160% Type II fibers+284% +147% Type I BFRE fibers CON Type BFRE II fibers CON BFRE CON BFRE CON different from PRE (p<0.01) *,** different from CON (p<0.05) different from mid8 (p<0.05) Myonuclei per muscle fiber +35% Myonuclei per muscle fiber +30% +30% +27% Type I fibers Type II fibers BFRE CON BFRE CON different from PRE (p<0.01) *,** different from CON (p<0.05) different from mid8 (p<0.05) 11

12 Myofiber cross-sectional area Myofiber CSA Myofiber CSA Type I fibers Type Type I fibers II fibers Type II fibers Type I Myofiber CSA BFRE fibers CON +37% Type Type I BFRE fibers II fibers CON CON Type BFRE II fibers CON +30% +39% Type I fibers Type II fibers +31% Type I BFRE fibers CON +28% Type BFRE II fibers +28% CON BFRE CON BFRE BFRE CON CON BFRE CON BFRE CON BFRE CON different from PRE (p<0.01) *,** different from CON (p<0.05) different from mid8 (p<0.05) Maximal muscle strength (MVC) +6% +13% different from PRE (p<0.01) *,** different from CON (p<0.05) different from mid8 (p<0.05) 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) 12

13 Effects of blood flow restricted low-intensity resistance training (BFRE) on myogenic satellite cells PERSPECTIVES Short-term BFRE marked increases in SC content ( %) 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 ( %) 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 Potentially allows accelerated rehabilitation i.e. following ACL reconstruction Short-term BFRE marked increases in SC content ( %) and myonuclear number (30-35%) myogenic priming of human skeletal muscle important potential implications - for instance: May similarly allow accelerated rehabilitation in non-reconstructed ACL injured subjects 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 13

14 Use of BFRE versus general progression training From bed rest to walking to training following limb immobilizing injury Loenneke, Abe, Bemben et al, 2012 Accelerated rehabilitation in ACL reconstructed patients via hyper-activation of myogenic stem cells by use of kaatsu exercise (BFRE) Jakob L. Nielsen Phd-student, Cand.Scient Institute of Sports Science and Clinical Biomechanics University of Southern Denmark Jørgensen et al, accepted for publication Clinical Physiology and Functional Imaging

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17 TV2 Sporten (SportsLAB) 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 17