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1 Institut National de la
Santé et de la Recherche Médicale (INSERM) Unité 460 and 4 Services de Pneumologie des
Hôpitaux Bichat et Beaujon et INSERM Unité 408,
In striated muscle, chronic increases in
workload result in changes in myosin phenotype. The aim of this study
was to determine whether such changes occur in the diaphragm of
patients with severe chronic obstructive pulmonary disease, a situation
characterized by a chronic increase in respiratory load and lung
volume. Diaphragm biopsies were obtained from 22 patients who underwent
thoracic surgery. Myosin was characterized with electrophoresis in
nondenaturing conditions, SDS-glycerol PAGE, and Western blotting with
monoclonal antibodies specific for slow and fast myosin heavy chain
(MHC) isoforms. Flow volume curves, total lung capacity, and functional residual capacity were measured before surgery in 20 patients. We found
that the human diaphragm is composed of at least four myosin isoforms,
one slow and three fast, resulting from the combination of three MHC
species. Chronic overload was associated with an increase in the slow
-MHC species at the expense of the fast species (
-MHC, 78.2 ± 4.6 and 50.0 ± 6.5% in emphysematous and control patients,
respectively; P < 0.005). Linear
correlations were found between
-MHC percentage and forced
expiratory volume in 1 s (r =
0.52;
P < 0.02), total lung capacity
(r = 0.44;
P < 0.05), and functional residual
capacity (r = 0.65;
P < 0.003). The human adult
diaphragm is composed of a balanced proportion of slow and fast myosin
isoforms. In patients with chronic obstructive pulmonary disease, the
proportion of fast myosins decreases, whereas that of slow myosin
increases. This increase appears to be closely related to lung
hyperinflation and may reflect an adaptation of the diaphragm to the
new functional requirements.
human diaphragm; myosin electrophoresis; chronic obstructive pulmonary disease; lung distension
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