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J Appl Physiol 101: 1400-1405, 2006. First published July 13, 2006; doi:10.1152/japplphysiol.01614.2005
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Passive properties of the diaphragm in COPD

Alastair J. Moore,1 Alison Stubbings,1,5 Elisabeth B. Swallow,1 Michael Dusmet,2 Peter Goldstraw,2 Raphaël Porcher,3 John Moxham,4 Michael I. Polkey,1 and Michael A. Ferenczi5

1Respiratory Muscle Laboratory, Royal Brompton Hospital and National Heart Lung Institute, and 2Department of Thoracic Surgery, Royal Brompton Hospital, London, United Kingdom; 3Département de Biostatistique et Informatique, Médicale Hôpital Saint Louis, Paris, France; 4Respiratory Muscle Laboratory, King's College London School of Medicine, London; and 5Biomedical Sciences Division, Imperial College, London, United Kingdom

Submitted 22 December 2005 ; accepted in final form 6 July 2006

Structural adaptations that occur in the diaphragm muscle of patients with chronic obstructive pulmonary disease (COPD), namely an increase in type I fibers and a decrease in type II fibers, have been explored in terms of the active contractile properties of the diaphragm. The aim of this study was to test the passive properties of the diaphragm by measuring the force response of relaxed diaphragm muscle fibers to stretching to determine the effect of COPD on these properties. Costal diaphragm biopsies were taken from patients with COPD and from controls with normal pulmonary function. From these biopsies, titin expression was assessed in diaphragm homogenates by gel electrophoresis, and the restoring force was measured by incremental stretching of single fibers in the relaxed state and measuring the force response to stretching. A quadratic model was used to illustrate the relationship between restoring force and muscle fiber length, and it revealed that COPD fibers generate significantly lower restoring forces than control fibers as judged by the area under the force-length curve. Furthermore, this finding applies to both type I and type II fibers. Gel electrophoresis revealed different titin isoforms in COPD and controls, consistent with the conclusion that COPD results not only in a change in muscle fiber-type distribution but in a structural change in the titin molecule in all muscle fiber types within the diaphragm. This may assist the muscle with the energetic changes in the length of the diaphragm required during breathing in COPD.

titin; passive tension; chronic obstructive pulmonary disease



Address for reprint requests and other correspondence: A. J. Moore, Respiratory Muscle Lab, Royal Brompton Hospital, Fulham Rd., London SW3 6NP, UK (e-mail: a.moore{at}ic.ac.uk)




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