Muscle metabolic status in patients with severe COPD with and without long-term prednisolone

Abstract

Both abnormalities in high energy phosphate metabolism and a decreased oxidative enzyme capacity have been reported in skeletal muscle of stable chronic obstructive pulmonary disease (COPD) patients. The first aim of this study was to investigate whether these findings are present in anterior tibialis muscle and whether or not they are associated. Abnormalities in mitochondrial structure and function as well as signs of myopathy have been found during corticosteroid treatment. The second aim of this study, therefore, was to investigate whether in COPD patients prolonged use of low dose prednisolone has effects on muscle energy metabolism and qualitative morphology.In a cross-sectional study 15 COPD patients (forced expiratory volume in one second (FEV1) 33 9 (mean SD) % predicted) who were steroid-naive (CORT-) were compared with 10 healthy control subjects (HC) and with 14 COPD patients (FEV1 30 11 % pred), who had been using oral prednisolone for at least 1 yr (CORT+).It was found that adenosine triphosphate (ATP)/adenosine diphosphate was lower in CORT-compared to HC (5.7 versus 6.2, p=0.03). Inosine monophosphate was detected in 13 of 15 CORT-compared to 3 of 10 HC (p=0.004). However, although indications were found for an imbalance in production and utilization of ATP, comparing CORT-and HC, no differences in oxidative (citrate synthase and 3-hydroxy-acylcoenzyme A dehydrogenase) and glycolytic (hexokinase, lactate dehydrogenase and phosphofructokinase) enzyme capacities were found.When, comparing steroid-treated and steroid-naive patient subgroups, no differences in the above mentioned parameters of muscle energy metabolism and of muscle qualitative morphology were found. Eur Respir J 2000; 16: 247±252. Supported by a scholarship from ASTRA BV, the Netherlands.Exercise intolerance and dyspnoea are the most frequently occurring complaints in patients with severe chronic obstructive pulmonary disease (COPD). Weakness of both skeletal and respiratory muscles contributes significantly to these complaints [1]. Recently it has been shown that muscle weakness in COPD patients can predominantly be explained by muscle atrophy [2]. However, several studies suggested that exercise tolerance might also be impaired by alterations in muscle energy metabolism [3±5].Experimental evidence is accumulating that in COPD patients muscle energy metabolism is already disturbed at rest. JAKOBSSON et al. [6] found a decreased oxidative capacity and an increased glycolytic capacity in quadriceps femoris muscle. MALTAIS et al.[3] reported a decreased oxidative capacity in quadriceps femoris muscle. In another recent study [4], in tibialis anterior muscle, indications for an imbalance in adenosine triphosphate (ATP) utilization and resynthesis were found, as suggested by increased inosine monophosphate (IMP) levels, which were negatively related with ATP/adenosine diphosphate (ADP) ratios. However, in that study oxidative and glycolytic enzyme capacities were not investigated.In view of the above mentioned findings in skel...

Chronic corticosteroid administration causes mitochondrial dysfunction in skeletal muscle

“…Previous studies indicated abnormal protein catabolism/anabolism [1][2][3]. Decreased oxidative capacity is observed in mitochondria [6,7] but this mechanism is yet controversial [17,18]. The present study demonstrated that serum lactate levels during exercise were significantly elevated in corticosteroid-treated patients.…”

Skeletal muscle microbiopsy: a validation study of a minimally invasive technique

“…This might be sufficient to perform the biochemical and cellular analyses required for several purposes in COPD patients [25] and patients with neuromuscular disorders [12]. In addition, nutritional status did not appear to be a limitation to the microbiopsy technique.…”

Reduced mitochondrial density in the vastus lateralis muscle of patients with COPD

“…As opposed to the vastus lateralis, the diaphragm of these patients is characterised by an increased oxidative capacity [7][8][9] and, strikingly, an augmented mitochondrial density was found when compared with healthy age-matched controls [6]. Similarly, since normal oxidative enzyme activities have been reported for COPD in another peripheral muscle, the tibialis anterior [10], a normal mitochondrial fractional area is anticipated in this muscle.…”