Muscle 1 Flashcards
When does the DMD gait become lordotic and waddling?
3-6
What muscles enlarge in DMD and what muscles are affected first?
Calf, gluteal, lateral vastus, deltoid and infraspinatus muscles
Limb and trunk muscles affected first
What is DMD caused by?
Mutation in dystrophin on gene Xp21 (x-linked recessive)
Are DMD muscles more susceptible to injury, why?
Yes, more fragile sarcolemmas
What are the characteristic features of mdx mice?
Larger muscles but reduced force producing capacity
What is the vertical hang test?
Time how long an animal can hold on to measure endurance and strength
What are the pros of the vertical hang test?
Natural, simple, can assess motivation
What are the cons of the vertical hang test?
Cant assess specific muscles, crude
What is the running wheel test?
Latency to fall indicates ability, coordination and speed
What are the pros of the running wheel?
Simple, can track performance regularly, provides many assessments
What are the cons of the running wheel?
Difficult to identify specific muscle effects
What is the grip strength test?
Non invasive measure of body strength
What are the pros of grip strength?
Simple, can assess regularly and track performance
What are the cons of grip strength?
Crude, requires motivation, considerable variation between assessors, biomechanical advantages can affect reliability
What is functional assay in vitro and what are the pros and cons?
- Assess force for isometric or shortening lengthening contractions
- Pros: assess functional parameters directly in the absence of nerve or blood supply
- Cons: less physiological, need to ensure all motor units activated for accuracy of force measures
What is functional assay in situ and what are the pros and cons?
- Shorten, lengthen or contract a muscle whilst keeping nerve and blood supply intact
- Pros: preserve nerve and blood supply, assess properties of a single muscle and its specific adaptations to interventions
- Cons: technically challenging, time consuming
What is functional assay in vivo and what are the pros and cons?
- Foot pressing on plate, activating whole muscle group to produce force
- Pros: minimally invasive, able to assess muscle groups, can use for training programs
- Cons: technically difficult, equipment can be very expensive, cannot isolate effects to a specific muscle
What are cellular functional assays (mechanical and chemical)?
- Mechanically skinned fibres: study excitation contraction coupling, SR calcium release and uptake
- Chemically permeabilized fibres: contractile apparatus, force per calcium and SR, velocity of shortening, contraction induced injury
What are the pros and cons of cellular functional assays?
- Pros: can study cellular level for mechanistic understanding
- Cons: technically difficult and requires expensive equipment
What does overexpression of Hsp72 cause?
Amelioration of dystrophic pathophysiology in mdx mice, reduced CK, increased calcium uptake, SERCA pump improvement
What is the mechanical hypothesis?
Loss of DGC leads to contraction induced rupture of muscle cell membranes, noted by cytoplasmic accumulation of serum proteins in muscle fibre. Exercise in DMD patients and mdx mice causes greater muscle damage than in unaffected controls
What is the calcium hypothesis?
Influx of calcium into cytosol overwhelms muscle cells ability to maintain physiologic calcium levels, elevated calcium causes programmed cell death via activation of proteases such as calpains
What mediates dystrophin interaction with the cytoskeleton?
F-actin
What is the significance of muscle branch points?
More susceptible to injury and prone to stretching
What is the prevalence of DMD?
1 in 3500-6000 males
What is the role of dystrophin and what happens when it is gone?
Anchors sarcolemma to costamere and stabilises the sarcolemma
If missing the costamere is disorganised and there is membrane leak (influx of calcium and evans blue dye)
What is the timeline of injury events?
- Injury
- Vesicle clumping at day 1
- Secondary injury day 2-5
- Regeneration
- Myotube formation (1-2 weeks)
- Recovered by 1 month
