title: Physiological properties of human diaphragm muscle fibres and the effect of chronic obstructive pulmonary disease.
abstract: The contractile and actomyosin ATPase properties of single fibres were examined in human diaphragm muscle obtained from patients with and without chronic obstructive pulmonary disease (COPD). Costal diaphragm biopsies were taken from five patients without evidence of COPD and from 11 age-matched individuals with varying degrees of the disease. Our aim was to establish whether changes in contractile properties of COPD diaphragm could be fully explained by the previously documented shift towards a greater proportion of type I myosin heavy chain isoform in COPD. The relative proportion of type I diaphragm fibres from non-COPD and COPD patients was measured by gel electrophoresis, and was negatively correlated with FEV(1) over the full range of values investigated. There was also significant atrophy of the type I fibre population in COPD diaphragms. Isometric tension was similar among the fibre types and between the COPD and non-COPD patients. The intrinsic energetic properties of diaphragm fibres were examined by monitoring the time-resolved actomyosin ATPase activity in COPD and non-COPD fibres that produced similar isometric forces. The isometric ATPase rate in COPD fibres was reduced to 50% of the rate in non-COPD fibres; hence, the cost of isometric contraction in type I and type IIA COPD fibres was reduced to between one-third and one-half of the tension cost calculated for non-COPD fibres. The rate of force development in type I COPD fibres was reduced to 50% of the rate seen in non-COPD type-I fibres. No difference in the rate of ATP consumption between COPD and non-COPD fibres was evident during isovelocity shortening. These data extend previous findings showing that aspects of breathing mechanics during progressive COPD are associated with remodelling of the diaphragm fibre-type distribution; on top of the increase in type I fibres there are fibre-specific reductions in force development rate (type I fibres) and ATPase rate that are consistent with the impairment of cross-bridge cycling kinetics.
authors: Molecular Medicine Section, National Heart & Lung Institute, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.
authors: Alison K
authors: AK
authors: Stubbings
authors: Alastair J
authors: AJ
authors: Moore
authors: Michael
authors: M
authors: Dusmet
authors: Peter
authors: P
authors: Goldstraw
authors: Timothy G
authors: TG
authors: West
authors: Michael I
authors: MI
authors: Polkey
authors: Michael A
authors: MA
authors: Ferenczi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003964:Diaphragm / Q000502:physiology*; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D007537:Isometric Contraction / Q000502:physiology; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000502:physiology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000503:physiopathology*