Skeletal muscle fibre-type shifting and metabolic profile in patients with chronic obstructive pulmonary disease

Abstract

The aim of this study was to examine the nature of fibre-type redistribution in relation to fibre metabolic profile in the vastus lateralis in chronic obstructive pulmonary disease (COPD) and COPD subtypes.Fifteen COPD patients (eight with emphysema stratified by high-resolution computed tomography) and 15 healthy control subjects were studied. A combination of myofibrillar adenosine triphosphatase staining and immunohistochemistry was used to identify pure, as well as hybrid fibre types. For oxidative capacity, fibres were stained for cytochrome c oxidase and succinate dehydrogenase activities, and glycogen phosphorylase for glycolytic capacity.The proportion of type-I fibres in COPD patients was markedly lower (16% versus 42%), especially in emphysema, and the proportion of hybrid fibres was higher (29% versus 16%) compared to controls. The proportion of fibres staining positive for oxidative enzymes was lower in COPD patients, which correlated with the proportion of type-I fibres. In COPD oxidative capacity was lower within IIA fibres.The authors conclude that fibre-type transitions are involved in the fibre-type redistribution in chronic obstructive pulmonary disease. Low oxidative capacity is closely related to the proportion of type-I fibres, but an additional reduction of oxidative enzyme activity is present within IIA fibres. Fibre-type abnormalities may be aggravated in emphysema.

Myostatin up-regulation is associated with the skeletal muscle response to hypoxic stimuli

“…A c c e p t e d M a n u s c r i p t 5 among others, of peripheral muscle dysfunction in this disease (Couillard and Prefaut, 2005;Gosker et al, 2002). However, the exact mechanisms underlying skeletal muscle dysfunction in COPD remain unclear.…”

Cachexia in chronic obstructive pulmonary disease: new insights and therapeutic perspective

“…In addition, muscle wasting is apparent as a decrease in the size of individual muscle fibres, and this muscle fibre atrophy in COPD seems selective for type II fibres in peripheral muscle,15, 16 which is in line with other chronic diseases prone to cachexia such as chronic heart failure 17. Furthermore, a shift in muscle fibre composition from type I (oxidative) to type II (glycolytic), accompanied by a decrease in oxidative capacity, culminates in reduced muscle endurance 18. This not only contributes to reduced exercise capacity19 but may also affect muscle mass in COPD,20 because type I and II fibres display different responses to anabolic and catabolic signals 21, 22…”

“…These collective data may indicate that COPD patients use oxygen less efficiently and exhibit an altered energy metabolism during physical activity. This is not surprising in view of the shift in lower limb muscle fibre type composition in COPD towards less oxidative fibres, which appears to be more pronounced in the emphysematous phenotype 18. The opposite shift in muscle fibre type of the diaphragm relative to the limb muscle47, 48 indicates an adaptation to chronic increase in work of breathing.…”

Differential effects of emphysema on skeletal muscle fibre atrophy in hamsters

“…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.…”

“…Numerous peripheral mechanisms have been proposed to contribute to the dysfunction, including reductions in peripheral skeletal muscle blood flow, hypoxemia and alterations in metabolism. Previous investigations have demonstrated reductions in peripheral skeletal muscle oxidative capacity in COPD patients [1][2][3][4] and hamsters induced with EMP [5], which could alter metabolism by activating anaerobic pathways to generate the required energy production. Such a shift would predispose skeletal muscle to greater fatigability and impair exercise tolerance.…”