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Skeletal Muscle Injury

Skeletal Muscle Injury. Contraction-induced Muscle Injury. Initiation of an exercise program Novel or intense physical activity Spaceflight Prolonged bed rest Limb immobilization. Non-contraction-induced Muscle Injury. Passive stretch Trauma Crushed Punctured Surgery

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Skeletal Muscle Injury

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  1. Skeletal Muscle Injury

  2. Contraction-induced Muscle Injury • Initiation of an exercise program • Novel or intense physical activity • Spaceflight • Prolonged bed rest • Limb immobilization

  3. Non-contraction-induced Muscle Injury • Passive stretch • Trauma • Crushed • Punctured • Surgery • Ischemia - reperfusion • Transplantation • Local anesthetics

  4. Experimental Models:Contraction-induced • Repetitive eccentric contractions • Downhill running • Forced-lengthened contractions • Muscle unloading - reloading • Spaceflight • Bed rest

  5. Contraction-Induced Muscle Injury • Initial Injury • Within 5-10 minutes post contraction • Focal ultra-structural disruptions • Sarcomeres • myofilaments • Secondary Injury (hours to days post-injury) • More extensive ultra-structural disruptions

  6. Secondary Injury • Extensive ultra-structural disruptions • Muscle edema • Sarcolemma disruption or altered permeability • Increased muscle concentrations of inflammatory cells • neutrophils and macrophages

  7. MUSCLE INFLAMMATORY CELLS NEUTROPHILS MACROPHAGES 0 2 4 6 12 24 48 HOURS OF RECOVERY

  8. Functional Changes • Reduced force production • Muscle soreness • Delayed onset muscle soreness (DOMS) • Loss of joint range of motion

  9. Isometric strength

  10. Significance of Contraction-induced Muscle Injury • Applied • Decreases exercise adherence • May increase the risk of more severe injury • Impairs performance

  11. The Problem of Contraction-induced Muscle Injury • Basic • Mechanisms for muscle injury? • Relationship to muscle growth?

  12. Proposed Mechanisms • Mechanical • skeletal muscle proteases • Lysosomal • Ubiquitin-proteasome pathway • Calcium-sensitive (calpains)

  13. Proposed Mechanisms • Free radicals • Oxygen • Nitrogen • Inflammatory cells • Neutrophils • Macrophages

  14. Proposed Means of Prevention • Warm-up • Stretching • Low-intensity  higher intensity • Anti-inflammatory drugs • Anti-oxidants (Vitamin E and C)

  15. Treatment • Anti-inflammatory drugs • Cryotherapy • Electrical stimulation? • Ultrasound • Massage • Injurious exercise

  16. Mechanism for Adaptation? • Mechanical • Sarcomere length homogeneity • Increased sarcomere number • Increased connective tissue • Increased cytoskeletal strength • Other mechanisms?

  17. Events of Muscle Regeneration • Removal of injured or necrotic muscle • Stimulation, proliferation, and migration of satellite cells • Formation of myotubes • Myotube fusion with myofiber (injured fiber) or myotube development into a muscle fiber (necrotic fiber)

  18. Satellite Cells and Regeneration • Satellite Cells • Resident “stem” cells • Present outside of sarcolemma • Primarily composed of quiescent nucleus • No other organelles such as mitochondria

  19. Embryonic Myogenesis Myoblasts Myogenic cell proliferation, differentation and fusion Muscle fibre Satellite cell

  20. Satellite Cells Quiescent Membrane Injury Mitotically active Migration Fusion: Myotubes Necrosis Injured Develop:Myofiber Fusion: myofiber

  21. Proliferation and Fusion • Proliferation of satellite cells evident within hours of injury and persists for days • Once proliferation has ceased, fusion ensues • Myoblast + Myoblast  Myotube • 2-5 days post-injury • Myotubes + Myofiber  repaired Fiber • 6-10 days post-injury

  22. Cell Signals: Proliferation & Migration • Where does the signal for satellite cell recruitment come from???? • Injured Muscle • Inflammatory cells? • Candidates: • Growth factors • Platelet derived growth factor (PDGF) • Cytokines • Interleukin-6 (IL-6)

  23. Secondary Injury Good or Bad • Is the secondary injury good or bad? • Are the events associated with secondary injury good or bad?

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