Download Document

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
– Ischemia - reperfusion
– Transplantation
– Local anesthetics
Experimental Models:Contraction-induced
• Repetitive eccentric contractions
– Downhill running
– Forced-lengthened contractions
• Muscle unloading - reloading
– Spaceflight
– Bed rest
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
Secondary Injury
• Extensive ultra-structural disruptions
• Muscle edema
• Sarcolemma disruption or altered
permeability
• Increased muscle concentrations of
inflammatory cells
– neutrophils and macrophages
MUSCLE INFLAMMATORY CELLS
NEUTROPHILS
MACROPHAGES
0
2
4
6
12
24
HOURS OF RECOVERY
48
Functional Changes
• Reduced force production
• Muscle soreness
– Delayed onset muscle soreness (DOMS)
• Loss of joint range of motion
Isometric strength
Significance of Contractioninduced Muscle Injury
• Applied
– Decreases exercise adherence
– May increase the risk of more severe injury
– Impairs performance
The Problem of Contractioninduced Muscle Injury
• Basic
– Mechanisms for muscle injury?
– Relationship to muscle growth?
Proposed Mechanisms
• Mechanical
• skeletal muscle proteases
– Lysosomal
– Ubiquitin-proteasome pathway
– Calcium-sensitive (calpains)
Proposed Mechanisms
• Free radicals
– Oxygen
– Nitrogen
• Inflammatory cells
– Neutrophils
– Macrophages
Proposed Means of Prevention
•
•
•
•
•
Warm-up
Stretching
Low-intensity  higher intensity
Anti-inflammatory drugs
Anti-oxidants (Vitamin E and C)
Treatment
•
•
•
•
•
•
Anti-inflammatory drugs
Cryotherapy
Electrical stimulation?
Ultrasound
Massage
Injurious exercise
Mechanism for Adaptation?
• Mechanical
–
–
–
–
Sarcomere length homogeneity
Increased sarcomere number
Increased connective tissue
Increased cytoskeletal strength
• Other mechanisms?
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)
Satellite Cells and Regeneration
• Satellite Cells
– Resident “stem” cells
– Present outside of sarcolemma
– Primarily composed of quiescent nucleus
• No other organelles such as mitochondria
Embryonic Myogenesis
Myoblasts
Myogenic cell
proliferation,
differentation
and fusion
Muscle fibre
Satellite cell
Satellite Cells
Quiescent
Membrane Injury
Mitotically active
Migration
Fusion: Myotubes
Necrosis
Develop:Myofiber
Injured
Fusion: myofiber
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
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)
Secondary Injury Good or Bad
• Is the secondary injury good or bad?
• Are the events associated with secondary
injury good or bad?