Original articlePlasma branched-chain amino acid levels and muscle energy metabolism in patients with chronic obstructive pulmonary disease
Introduction
Recent studies have demonstrated that reduced oxidative capacity in skeletal muscles correlates with an accelerated lactate response to exercise in patients with chronic obstructive pulmonary disease (COPD).1, 2 We previously found, using 31-phosphorus nuclear magnetic resonance spectroscopy (31P-MRS), that the skeletal muscle metabolism of patients with chronic respiratory impairment undergoes specific changes.3, 4 Skeletal muscle intracellular pH (pHi) and high-energy phosphate compounds can be dynamically measured using noninvasive 31P-MRS.5 A decrease in pHi during exercise suggests lactic acid accumulation in exercising muscle.5, 6 Patients with chronic respiratory impairment have significant decreases in phosphocreatine (PCr) and in pHi during even mild exercise, suggesting that adenosine triphosphate (ATP) production is reduced and that lactate rapidly accumulates in their muscles. Several factors such as inactivity, malnutrition or hypoxemia might contribute to altered muscle metabolism.3, 7, 8, 9
Muscle wasting contributes to muscle weakness and exercise limitations in patients with COPD10 in whom weight loss and muscle wasting are common features.11 Skeletal muscle is the major protein store that supplies amino acids to other tissues under specific conditions. Plasma-free amino acid concentrations express the balance between exogenous uptake and intercurrent metabolites in protein synthesis and breakdown.12 Several investigators have reported that the amino acid profile is altered in the plasma and skeletal muscles of patients with COPD.13, 14, 15, 16 Most of these studies have shown that the plasma concentrations of the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine are reduced.13, 15, 16 Yoneda et al.15 demonstrated that decreased concentrations of BCAAs in COPD are specifically related to weight loss and decreased muscle mass.
Muscle energy metabolism might be affected by BCAAs during exercise as energy sources and as substrates that expand the pool of tricarboxylic acid (TCA) cycle intermediates.12 However, few studies have investigated whether changes in amino acid profiles in plasma affect exercise metabolism in COPD patients.17 Muscle energy metabolism is similarly altered in patients with liver cirrhosis who also usually have decreased plasma BCAAs, that is, a significant decrease in PCr and in pHi during forearm exercise.18 The present study uses 31P-MRS to clarify whether or not plasma amino acid profiles, especially those of BCAAs, are related to the altered energy metabolism of exercising muscle in patients with COPD.
Section snippets
Patients and controls
We studied 23 ambulatory male outpatients with stable COPD (aged 69.2 ± 5.1 years) diagnosed according to spirometric findings from moderate to very severe airflow limitation (FEV1/FVC <70% and FEV1/FEV1pred <80%; FEV1, forced expiratory volume in 1 s; FVC, forced vital capacity).19 None of the patients had ever received systemic corticosteroid therapy and 3 of them had been treated with oxygen inhalation only while walking. The exclusion criteria were malignancy, cardiac failure, renal failure,
Physical characteristics
Table 1 shows the physical characteristics of the participants. None of BMI, forearm circumference, %fat or grip power significantly differed between the patients and healthy individuals, although 4 of the patients were malnourished (BMI <20). Table 2 shows the spirometric data from the healthy individuals and the patients with COPD. The FEV1 value was 1.14 ± 0.35 L in the patients. Based on the GOLD criteria,19 COPD in 9 of the 23 patients corresponded to stage II, 10 to stage III and 4 to stage
Discussion
We investigated the relationship between the plasma branched-chain amino acid profile and muscle energy metabolism in COPD patients and found that plasma concentrations of leucine, isoleucine and valine correlated with pHi and PCr index at the completion of exercise. These findings suggested that the plasma concentrations of BCAAs contribute to alterations in muscle energy metabolism during exercise in COPD patients.
Conflicts of interest
The authors have no conflict of interest regarding the subject of the manuscript.
Acknowledgements
This study was supported in part by a grant from the Department of Home Care Service, Tokai University School of Medicine.
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