Low Oxidative Capacity in Skeletal Muscle of Both ...

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MDLinx. Peripheral Insulin Sensitivity and · Mitochondrial Capacity Reduced in · AfricanAmerican NonObese Women. PracticeUpdate, 2014. Nutrition as a ...
5/9/2017

Low Oxidative Capacity in Skeletal Muscle of Both the Upper and Lower Limbs in COPD Patients

The FASEB Journal www.fasebj.org

April 2017

The FASEB Journal vol. 31 no. 1 Supplement 1020.9

Low Oxidative Capacity in Skeletal Muscle of Both the Upper and Lower Limbs in COPD Patients Alessandra Adami, Rogerio B. Corvino, Richard Casaburi, Robert Cao, Robert Calmelat, Janos Porszasz and Harry B. Rossiter +

Author Affiliations

Abstract Chronic obstructive pulmonary disease (COPD) is associated with a progressive loss of muscle mass and endurance, together with a loss of mitochondrial oxidative capacity, mitochondrial dysfunction and capillary rarefaction in the peripheral muscles. Leg muscle dysfunction exacerbates dyspnea, contributes to exercise intolerance and morbidity. The mechanisms leading to leg muscle dysfunction are debated, with both deconditioning and intrinsic (circulating) factors proposed to contribute. Comparison of upper and lower limb performance in COPD, proposed to reveal relative influence of behavioral and disease-related factors, show conflicting results: Franssen et al. (MSSE 37:2–9, 2005) reported preserved biceps brachii endurance compared with the quadriceps, while Miranda et al. (Respiratory Care 59:62–9, 2014) found decreased endurance and greater fatigability in the upper limbs. We therefore aimed to determine whether loss of muscle oxidative capacity was different between the upper and lower limbs in COPD patients and also in smokers with normal spirometry. Twenty COPD patients (GOLD 2/3/4, n=7/7/6; FEV1%pred 46.5±3.39; M/F=15/5; age 64±9yrs; body weight 73±17kg; height 1.72±0.1m) and 20 current or former smokers with normal spirometry (CON; M/F=15/5; age 63±7yrs; body weight 77±15kg; height 1.69±0.1m) volunteered. Oxidative capacity of the nondominant medial forearm and medial gastrocnemius was measured using nearinfrared spectroscopy. After a 10–15s of brief forearm/thigh muscle contractions, the muscle O2 consumption recovery rate constant (k, min−1) was determined using repeated intermittent arterial occlusions. k was estimated from the mean of two repetitions in each limb on a single study visit. 2-way ANOVA (group × limb) was used to assess potential differences. One COPD patient and 1 control could not tolerate the arterial occlusions required for the assessment, and were excluded from the study. There was a significant main effect of group on muscle oxidative capacity (F=11.2, ηp2=0.13, p=0.001): COPD patients had significantly lower k in both upper and lower limb muscles (upper 1.01±0.17, lower 1.05±0.24 min−1) compared with CON (1.25±0.49, 1.49±0.65 min−1). However, there was no effect of limb (F=1.8, ηp2=0.02, p=0.18) and no group × limb interaction (p=0.35). COPD patients showed a lower muscle oxidative capacity than controls in the skeletal muscles of both upper and lower limbs. Compared with age- and sexmatched smokers with normal spirometry, k tended to be reduced by a greater extent in the gastrocnemius (−30%) than the forearm (−20%) of COPD patients; however, this difference was not significant (p=0.06). These data suggest that muscle oxidative capacity is systemically impaired in COPD patients, and not simply a consequence of inactivity-induced muscular deconditioning; this latter would be expected to be manifest as greater impairments in the lower limb muscles compared to the upper limb. The systemic variables contributing to deficiency in muscle oxidative capacity in COPD warrant further study.

Support or Funding Information Supported by SNSF P300PB_167767; PERF; ATS Foundation/Breathe California of Los Angeles

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5/9/2017

Low Oxidative Capacity in Skeletal Muscle of Both the Upper and Lower Limbs in COPD Patients

Skeletal Muscle Mitochondrial Respiratory Capacity and Function Are Diminished in Patients with Advanced Peripheral Artery Disease and Critical Limb Ischemia Victoria G Rontoyanni et al., FASEB J, 2017 TNF­α­induced loss of IKK­α in skeletal muscle: implications for skeletal muscle oxidative phenotype Alexander Remels et al., FASEB J, 2012 Diaphragm and limb muscles adapt differently to chronic normobaric hypoxia in mice Jorge Luis Gamboa et al., FASEB J, 2011 Energy production in patients with chronic obstructive pulmonary disease: Evidence of mitochondrial and not O2 supply limitation

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Gwenael Layec1 et al., FASEB J, 2016 The response of genes implicated in muscle oxidative metabolism and oxidative stress to acute exercise in COPD Ilse Slot et al., FASEB J, 2012

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