Oral N-acetylcysteine and exercise tolerance in mild chronic obstructive pulmonary disease

Oral N-acetylcysteine and exercise tolerance in mild chronic obstructive pulmonary disease

Author Hirai, Daniel M. Autor UNIFESP Google Scholar
Jones, Joshua H. Google Scholar
Zelt, Joel T. Google Scholar
da Silva, Marianne L. Google Scholar
Bentley, Robert F. Google Scholar
Edgett, Brittany A. Google Scholar
Gurd, Brendon J. Google Scholar
Tschakovsky, Michael E. Google Scholar
O'Donnell, Denis E. Google Scholar
Neder, J. Alberto Google Scholar
Abstract Heightened oxidative stress is implicated in the progressive impairment of skeletal muscle vascular and mitochondrial function in chronic obstructive pulmonary disease (COPD). Whether accumulation of reactive oxygen species contributes to exercise intolerance in the early stages of COPD is unknown. The purpose of the present study was to determine the effects of oral antioxidant treatment with N-acetylcysteine (NAC) on respiratory, cardiovascular, and locomotor muscle function and exercise tolerance in patients with mild COPD. Thirteen patients [ forced expiratory volume in 1 s (FEV1)-to-forced vital capacity ratio < lower limit of normal (LLN) and FEV1 >= LLN) were enrolled in a double-blind, randomized crossover study to receive NAC (1,800 mg/day) or placebo for 4 days. Severe-intensity constant-load exercise tests were performed with noninvasive measurements of central hemodynamics (stroke volume, heart rate, and cardiac output via impedance cardiography), arterial blood pressure, pulmonary ventilation and gas exchange, quadriceps muscle oxygenation (near-infrared spectroscopy), and estimated capillary blood flow. Nine patients completed the study with no major adverse clinical effects. Although NAC elevated plasma glutathione by similar to 27% compared with placebo (P < 0.05), there were no differences in exercise tolerance (placebo: 325 +/- 47 s, NAC: 336 +/- 51 s), central hemodynamics, arterial blood pressure, pulmonary ventilation or gas exchange, locomotor muscle oxygenation, or capillary blood flow from rest to exercise between conditions (P > 0.05 for all). In conclusion, modulation of plasma redox status with oral NAC treatment was not translated into beneficial effects on central or peripheral components of the oxygen transport pathway, thereby failing to improve exercise tolerance in non-hypoxemic patients with mild COPD. NEW & NOTEWORTHY Acute antioxidant treatment with N-acetylcysteine (NAC) elevated plasma glutathione but did not modulate central or peripheral components of the O-2 transport pathway, thereby failing to improve exercise tolerance in patients with mild chronic obstructive pulmonary disease (COPD).
Keywords capillary hemodynamics
fatigue
oxygen uptake
skeletal muscle
xmlui.dri2xhtml.METS-1.0.item-coverage Bethesda
Language English
Sponsor Academic Health Science Center (AHSC) Alternate Funding Plan (AFP) Innovation Fund
Senate Advisory Research Committee (SARC) Postdoctoral Fellow Support Program
John A. Stewart Fellowship from the Department of Medicine, Queen's University
Date 2017
Published in Journal Of Applied Physiology. Bethesda, v. 122, n. 5, p. 1351-1361, 2017.
ISSN 8750-7587 (Sherpa/Romeo, impact factor)
Publisher Amer Physiological Soc
Extent 1351-1361
Origin http://dx.doi.org/10.1152/japplphysiol.00990.2016
Access rights Closed access
Type Article
Web of Science ID WOS:000402405400032
URI https://repositorio.unifesp.br/handle/11600/54569

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