Volumetric Muscle Loss

muscle injury

loss of muscle function caused by physical disruption of muscle structures involved in producing/transmitting force

muscle

bundle of fascicles

fascicle

bundle of muscle fibers

muscle cells/fibers

bundle of myofibrils; multinucleated cells

myofibril

bundle of sarcomeres

sarcomere

contains a lattice of thick myosin and thin actin protein filaments

neuromuscular junction

synapse formed by contact between motor neuron and muscle fiber; site of signal exchange

muscle contraction

1. neurotransmitter causes release of calcium

2. calcium binds to actin

3. mysosin attaches to actin and pulls toward M-line

3 types of contractions

concentric, eccentric, isometric

most common type of contraction-induced injury

eccentric

concentric contraction

muscle contracts

eccentric contraction

muscle elongates

isometric contraction

muscle contraction

delayed-onset muscle soreness

exercise damages sarcomeres and sarcoplasmic reticulum -> Ca+ leaks out of sarcoplasmic reticulum and collects in mitochondria -> reduced ability of muscles to produce ATP and contract -> membrane damage -> inflammation and pain

neutrophils

immune cells that promote inflammation and degrade and phagocytize damaged myofibers

macrophages

immune cells that

- phagocytize hematoma and damaged tissue

- assist with ECM modeling

fibroblasts

promote ECM modeling and provide scaffold for muscle regeneration

satellite cells

muscle stem cells that

- differentiate into myoblasts

- fuse to form myotubes

- regenerate damaged muscle fibers

chemotaxis

migration of cells toward or away from a concentration gradient of a soluble chemical attractant

volumetric muscle loss injury

surgical or traumatic loss of muscle tissue; loss of at least 20% of a given muscle's mass

causes of VML injuries

excessive exercise, contusions, lacerations, surgical resection or reconstruction, combat injuries

main characteristics of VML injury

- persistent inflammation

- ECM breakdown/stiffening

- fibrosis

- regenerative progenitors inhibited

functional outcomes of VML

- muscle weakness

- loss of range of motion

- gait impairments

- late amputations due to functional deficits of the limb

surgical intervention for VML

suture muscle tissue

autologous muscle transfer

graft healthy muscle and skin from a donor site

long term outcomes of autologous muscle transfer

- scar tissue formation

- loss of muscle strength and function

- graft failure (10% of surgeries)

ultrasound

tool that uses high-frequency sound waves to generate an image

sonogram

the image the ultrasound generates

T1W imaging for VML

fibrosis is hypointense

disruptions in muscle tissue are hyperintense

How is VML indicated on MRI and CT?

decrease in muscle volume

dynameter

measures isokinetic exercises; for any forces exerted, machine produces equivalent resistance

dynametric evaluation

measures isokinetic exercises; patient performs multiple repetitions of flexion and extension; assesses strength, work done, and endurance ratio

dorsiflexion

tilt ankle up

plantarflexion

tilt ankle down

effect of VML on isometric strength and range of motion?

reduced

why are endogenous repair mechanisms impaired after VML?

loss/dysfunction of satellite cells and loss/dysfunction of ECM

ECM function

provides structure and modulates behavior and communication of endogenous cells

ECM scaffold

transplantation of decellularized ECM provides a scaffold for repair and regeneration

functions of ECM scaffold

- provides structural support

- recruits endogenous cells

- provides trophic factor support

ECM scaffold preclinical findings

- improvements in muscle activation

- defect site filled with granulation in non-treated animals

- cellularized with host cells

ECM scaffold clinical findings

- promotes angiogenesis and recruitment of perivascular stem cells

- leads to formation of new skeletal muscle cells

- increases force production and muscle strength

3 ATP generator systems

glycolysis, krebs cycle, electron transport chain

molecule used to generate ATP in glycolysis

glucose

by-products of glycolysis

2 pyruvate, 2 NADH

anaerobic respiration systems

glycolysis

aerobic respiration systems

krebs cycle, electron transport chain

effect of mitochondrial damage due to VML injury

- reduced oxidative capacity

- less ATP produced in muscle cell that can be used for contraction

mitochondrial biogenesis

the process by which new mitochondria are formed in the cell

fissioned mitochondria -> fusion -> fused mitochondria -> fission

PGC1-a

protein that regulates mitochondrial biogenesis; inhibits protein degradation pathways in mitochondria

effect of VML on mitochondrial structure and function

impair function and disruipts mitochondrial networks

effect of treatment with PGC1-a?

improved mitochondrial function and muscle strength

What does PGC1-a upregulation promote?

fusion > fission

isometric exercise

muscle contracts without changing length or visible joint movement

isokinetic exercise

muscle contracts while joint moves at constant speed