Diaphragm Dysfunction in Chronic Obstructive Pulmonary Disease

• DOI: 10.1164/rccm.200502-262oc
• Publication Date: 2005-04-23T00:33:37Z
• Authors: Coen A. C. Ottenh...; Leo M. A. Heunks; Gary C. Sieck; Wen-Zhi Zhan; Suzanne M. Jansen; Hans Degens; Theo de Boo; P. N. Richard Dek...
• Keywords: Diaphragm (acoustics)

Rationale: Hypercapnic respiratory failure because of inspiratory muscle weakness is the most important cause death in chronic obstructive pulmonary disease (COPD). However, pathophysiology diaphragm to generate force COPD part unclear. Objectives: The present study investigated contractile function and myosin heavy chain content single fibers from patients with COPD. Methods: Skinned were isolated biopsies eight mild moderate five without (mean FEV1 % predicted, 70 100%, respectively). Contractile was assessed, afterwards, determined these fibers. In homogenates, level ubiquitin-protein conjugation determined. Results: Diaphragm showed reduced generation per cross-sectional area, half sarcomere. addition, had decreased Ca2+ sensitivity generation, slower cross-bridge cycling kinetics. Our observations expressing slow 2A isoforms chain. Ubiquitin-protein increased homogenates Conclusions: Early development COPD, fiber impaired. data suggest that enhanced protein degradation through ubiquitin-proteasome pathway plays a role loss and, consequently, force.