Fibre types in skeletal muscles of chronic obstructive pulmonary disease patients related to respiratory function and exercise tolerance

Abstract

F Fi ib br re e t ty yp pe es s iin n s sk ke el le et ta al l m mu us sc cl le es s o of f c ch hr ro on ni ic c o ob bs st tr ru uc ct ti iv ve e p pu ul lm mo on na ar ry y d di is se ea as se e p pa at ti ie en nt ts s r re el la at te ed d t to o r re es sp pi ir ra at to or ry y f fu un nc ct ti io on n a an nd d e ex xe er rc ci is se e t to ol le er ra an nc ce e A group of 22 COPD patients and 10 healthy control subjects were studied. In COPD patients, vital capacity (VC) and forced expiratory volume in one second (FEV1) were reduced to 79% and 51%, respectively. Diffusion indices (transfer factor of the lung for carbon monoxide (TL,CO) and carbon monoxide transfer coefficient (KCO)) were also reduced. Arterial oxygen tension (Pa,O 2 ) was normal or slightly altered. A maximal exercise test was performed and anaerobic threshold was calculated. Muscle samples from vastus lateralis were obtained by needle biopsy. Myosin heavy chain (MHC) and light chain (MLC) isoforms were separated by gel electrophoresis and quantified by densitometry. MHC isoforms were considered as molecular markers of fibre types.The proportion of the fast MHC-2B isoform was increased in COPD patients. TL,CO, KCO, VC and FEV1 were positively correlated with slow MHC isoform content. TL,CO and KCO were also negatively correlated with the content of the fast MHC-2B isoform. No correlation was found between exercise parameters and MHC isoform composition. The co-ordinated expression between MHC and MLC isoforms was altered in COPD patients.We conclude that reduced oxygen availability, probably in combination with muscle disuse, may determine muscle alterations in chronic obstructive pulmonary disease patients. The altered correlations between myosin heavy chain and light chain isoforms suggest that co-ordinated protein expression is lost in chronic obstructive pulmonary disease muscles. Eur Respir J 1997; 10: 2853-2860 Patients with chronic obstructive pulmonary disease (COPD) are characterized by poor quality of life and various degrees of limitation in their daily activity, mainly due to breathlessness. They are often self-limiting their level of activity into a downward spiral leading to further inactivity and muscle deconditioning. Exercise tolerance of COPD patients is determined by the level of ventilation that they can reach. Even at a rather low work rate the increase in ventilatory response and blood lactate concentration are higher than in normal subjects.Rehabilitation of COPD patients involves general exercise reconditioning. This is suggested as the best approach to the rehabilitation of COPD patients, and is usually performed by training large muscles of the lower and, less frequently, upper limbs [1]. The mechanisms underlying the improvement of the performance after general training in COPD subjects are still unclear.There is evidence that skeletal muscle function and structure are altered in COPD patients. Contractile strength is reduced [2] and energetic and oxidative metabolism are impaired [3][4][5]. Fibre-type compos...

A transcription factor involved in skeletal muscle gene expression is deleted in patients with Williams syndrome

“…There is evidence to suggest that a decrease in the proportion of fatigue-resistant slow fibres in skeletal muscle affects stamina. 42 In patients with chronic obstructive pulmonary disease the scarce oxygen availability and/or the inactivity and physical deconditioning are thought to cause fibre transformation, with an increase in the proportion of the fast fatiguable fibres that are responsible for lactate production and fatigue at low work rates. Investigations into the fibre composition in skeletal muscle biopsies from WS patients, as well as stamina tests, would be required to determine if this is also the case in Williams syndrome.…”

Muscle Blood Flow and Oxygen Utilization Measured by Near-Infrared Spectroscopy during Handgrip Exercise in Chronic Respiratory Patients

“…An inverse relationship between oxidative enzyme activities and lactic acidosis in COPD patients has also been shown. In addition, there was also evidence of muscle fiber type alterations in COPD patients who showed decrease in the proportion of fatigueresistant slow fibers 46) . As previously indicated, some patients with COPD have a higher than normal mixed venous partial pressure of oxygen during exercise.…”

Differential effects of emphysema on skeletal muscle fibre atrophy in hamsters

“…In contrast, other investigators [4,6,7] have reported that COPD patients have a lower proportion of type I fibres and an elevation in the per cent of type II fibres in the vastus lateralis muscle. In addition, two investigations [8,9] have demonstrated altered MyHC expression in vastus lateralis muscle biopsies from COPD patients. These investigations collectively indicate that alterations in muscle fibre composition induced by COPD may differ between humans and animals.…”

“…Such a shift would predispose skeletal muscle to greater fatigability and impair exercise tolerance. In addition, COPD patients with reduced work capacity present with alterations in peripheral skeletal muscle composition and structure, including altered fibre composition [4,6,7] and myosin heavy chain (MyHC) expression [8,9], atrophy of peripheral skeletal muscle type I and/or II fibres [7,10,11], and reductions in lean body mass [12]. Therefore, altered metabolic pathways, fibre transformation and fibre atrophy appear to underlie problems of enhanced skeletal muscle fatigability, reduced force production and exercise intolerance in patients with COPD.…”