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Am J Physiol Lung Cell Mol Physiol 274: L527-L534, 1998;
1040-0605/98 $5.00
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Vol. 274, Issue 4, L527-L534, April 1998

Myosin heavy chain gene expression changes in the diaphragm of patients with chronic lung hyperinflation

Jean-Jacques Mercadier1, Ketty Schwartz2, Stefano Schiaffino3, Claudine Wisnewsky2, Simonetta Ausoni3, Michèle Heimburger1, Rolana Marrash4, René Pariente4, and Michel Aubier4

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, Hôpital Bichat, 75018 Paris; 2 INSERM Unité 153, Groupe Hospitalier Pitié-Salpétière, 75013 Paris, France; and 3 Dipartimento di Scienze Biomediche Sperementali, Centro Consiglio Nazionale delle Ricerche per la Biologia, Fisiopatologia Medicale, Università di Padova, 35121 Padua, Italy

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 beta -MHC species at the expense of the fast species (beta -MHC, 78.2 ± 4.6 and 50.0 ± 6.5% in emphysematous and control patients, respectively; P < 0.005). Linear correlations 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 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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