Biomedical Engineering Reference
In-Depth Information
transcription factors (MyoD, MEF-2), and those related to the process of
histone acetylation-deacetylation (CBP
=
p300; HDAC-5). The ACE gene
is known to influence the muscle response to training in athletes (91) or
the development of right ventricular hypertrophy in patients with COPD
(92). Further, a very recent report has shown that the use of ACE inhibitors
can reduce the normal decline of muscle mass that occurs in aging and can
improve exercise capacity (93), thus raising the possibility of using these
drugs therapeutically in patients with COPD and weight loss. The transcrip-
tion factors MyoD and MEF-2, as well as genes related to the histone acet-
ylation-deacetylation process (CBP
=
p300; HDAC-5), have very recently
been shown to play a fundamental role in the failure of muscle cells to regen-
erate after injury in patients with cancer cachexia (94,95). Whether they can
play any role in the pathogenesis of an SMD in some patients with COPD
has not been explored. The microarray technology may allow the investiga-
tion of differential gene expression in skeletal muscle of patients with COPD
with and without weight loss (96).
I. Other Mechanisms
There are other potential mechanisms that, alone or in combination, could
contribute to an SMD in patients with COPD. These include: (a) the abnor-
mal regulation of several hormone pathways, such as low testosterone and
growth hormone levels (97,98) and reduced plasma leptin concentration
(99-101). These pathways are important in the control of muscle mass
and body weight (48,49); (b) abnormal plasma electrolyte values, such as
low concentrations of potassium, phosphorus, calcium, and magnesium,
are not uncommon in patients with COPD and can also cause contractile
dysfunction and muscle weakness (102-105); and (c) many of the drugs used
in the treatment of COPD can interfere with skeletal muscle function. For
instance,
b
2
-adrenergic drugs increase oxygen consumption (52), a condition
that by itself can cause oxidative stress; treatment with oral corticoids can
clearly cause skeletal muscle weakness in patients with COPD (106-109)
and, more importantly, it also seems to jeopardize their prognosis (110).
V. OTHER POTENTIAL SYSTEMIC EFFECTS OF COPD
So far, systemic inflammation, weight loss, and skeletal muscle dysfunction
are the most commonly considered systemic effects of COPD. However, it is
possible that other organ systems might be also affected by the systemic
influences of COPD.
A. Cardiovascular Effects
Cardiovascular disease is common in COPD. This is, most likely, because
tobacco smoking is a common risk factor for both disease entities. Yet, in
