Biomedical Engineering Reference
In-Depth Information
interaction with ECM may inhibit inflammatory cell apoptosis thereby
promoting the inflammatory response in the lungs. Further studies are
required to understand the mechanism of cigarette smoke-induced cell
death using both in vitro and in vivo models so as to define strategy for
safe resolution of inflammation or inhibit the alveolar wall destruction.
E. Muscle Dysfunction
Dysfunction of the respiratory and of peripheral skeletal muscles is known
to occur in patients with severe COPD. Weight loss, skeletal muscle dys-
function, and exercise limitation are increasingly recognized as important
features of systemic effects of COPD. Oxidative stress occurs in skeletal
muscle during skeletal muscle fatigue, weakness, and sepsis induced muscle
dysfunction, accompanied by an increased load imposed on the diaphragm
in patients with severe COPD (69). This may be due to hypoxia, impaired
mitochondrial metabolism, and increased cytochrome C oxidase activity in
skeletal muscle in patients with COPD (70). Ribera et al. (71) have
recently shown that mitochondrial electron transport chain function is
enhanced in inspiratory muscles of patients with COPD. This was asso-
ciated with an increase in functional demand on the muscles to endurance
training-like effect leading to increased oxidative stress. Engelen et al. (70)
have found reduced muscle glutamate (a precursor of glutathione) levels
associated with increased muscle glycolytic metabolism in patients with
severe COPD. Lowered levels of glutamate were associated with decreased
GSH levels, suggesting that oxidant
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antioxidant imbalance is involved in
skeletal muscle dysfunction in patients with COPD (72). A causal relation-
ship between abnormally low muscle redox potential at rest and the altera-
tions of protein metabolism observed in patients with emphysema has been
suggested. This is supported by Rabinovich et al. (69) who showed
decreased muscle redox capacity probably due to lower ability to synthe-
size GSH during endurance training in patients with COPD. Moreover,
this was clearly evident in patients who had low body mass index.
Recently Agusti et al. (73) have shown that apoptotic pathways may be
involved in skeletal muscle atrophy in patients with COPD. They hypothe-
size that this might be related to ''cachexia'' and accelerated ageing. Thus,
oxidative stress-mediated muscle atrophy may involve the loss of skeletal
myocytes
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myofibers through an apoptosis in patients with COPD. How-
ever, it remains to be determined whether oxidative stress and
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or poor
nutrition (alterations in calorie intake or lowered basal metabolic rate)
play a central role in mediating muscle mass wasting
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apoptosis, particu-
larly in susceptible subsets of patients with COPD. The other unanswered
question is whether the susceptibility of subgroups of COPD patients to
oxidative stress and injury in muscle wasting is due to their inability to
boost endogenous protective defense, and
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or defective repair.
