MYOSIN HEAVY-CHAIN GENE-EXPRESSION CHANGES IN THE DIAPHRAGM OF PATIENTS WITH CHRONIC LUNG HYPERINFLATION

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 obstru ctive pulmonary disease, a situation characterized by a chronic increa se in respiratory load and lung volume. Diaphragm biopsies were obtain ed from 22 patients who underwent thoracic surgery. Myosin was charact erized with electrophoresis in nondenaturing conditions, SDS-glycerol PAGE, and Western blotting with monoclonal antibodies specific for slo w and fast myosin heavy chain (MHC) isoforms. Flow volume curves, tota l 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 associ ated with an increase in the slow beta-MHC species at the expense of t he fast species (beta-MHC, 78.2 +/- 4.6 and 50.0 +/- 6.5% in emphysema tous and control patients, respectively; P < 0.005). Linear correlatio ns were found between beta-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 a dult diaphragm is composed of a balanced proportion of slow and fast m yosin isoforms. In patients with chronic obstructive pulmonary disease , the proportion of fast myosins decreases, whereas that of slow myosi n increases. This increase appears to be closely related to lung hyper inflation and may reflect an adaptation of the diaphragm to the new fu nctional requirements.