title: OralN-acetylcysteine and exercise tolerance in mild chronic obstructive pulmonary disease.
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 withN-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 ~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 nonhypoxemic patients with mild COPD.NEW & NOTEWORTHYAcute antioxidant treatment withN-acetylcysteine (NAC) elevated plasma glutathione but did not modulate central or peripheral components of the O2transport pathway, thereby failing to improve exercise tolerance in patients with mild chronic obstructive pulmonary disease (COPD).
authors.affiliation: Laboratory of Clinical Exercise Physiology, Division of Respirology, Department of Medicine, Queen's University, Kingston, Ontario, Canada; d.hirai@yahoo.com.|Pulmonary Function and Clinical Exercise Physiology Unit, Respiratory Division, Department of Medicine, Federal University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Hirai
authors.affiliation: Laboratory of Clinical Exercise Physiology, Division of Respirology, Department of Medicine, Queen's University, Kingston, Ontario, Canada.
authors.forename: Joshua H
authors.initials: JH
authors.lastname: Jones
authors.affiliation: Laboratory of Clinical Exercise Physiology, Division of Respirology, Department of Medicine, Queen's University, Kingston, Ontario, Canada.
authors.forename: Joel T
authors.initials: JT
authors.lastname: Zelt
authors.affiliation: Laboratory of Clinical Exercise Physiology, Division of Respirology, Department of Medicine, Queen's University, Kingston, Ontario, Canada.|Division of Physical Therapy, University of Brasilia, Brasilia, Brazil.
authors.forename: Marianne L
authors.initials: ML
authors.lastname: da Silva
authors.affiliation: Human Vascular Control Laboratory, School of Kinesiology and Health Studies, Queen's University, Kingston, Ontario, Canada.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Bentley
authors.affiliation: Queen's Muscle Physiology Laboratory, School of Kinesiology and Health Studies, Queen's University, Kingston, Ontario, Canada; and.
authors.forename: Brittany A
authors.initials: BA
authors.lastname: Edgett
authors.affiliation: Queen's Muscle Physiology Laboratory, School of Kinesiology and Health Studies, Queen's University, Kingston, Ontario, Canada; and.
authors.forename: Brendon J
authors.initials: BJ
authors.lastname: Gurd
authors.affiliation: Human Vascular Control Laboratory, School of Kinesiology and Health Studies, Queen's University, Kingston, Ontario, Canada.
authors.forename: Michael E
authors.identifier: http://orcid.org/0000-0002-6461-8534
authors.initials: ME
authors.lastname: Tschakovsky
authors.affiliation: Respiratory Investigation Unit, Division of Respirology, Department of Medicine, Queen's University, Kingston, Ontario, Canada.
authors.forename: Denis E
authors.initials: DE
authors.lastname: O'Donnell
authors.affiliation: Laboratory of Clinical Exercise Physiology, Division of Respirology, Department of Medicine, Queen's University, Kingston, Ontario, Canada.
authors.forename: J Alberto
authors.initials: JA
authors.lastname: Neder
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000368:Aged; D000975:Antioxidants / Q000494:pharmacology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D015444:Exercise / Q000502:physiology*; D017079:Exercise Tolerance / Q000187:drug effects*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008124:Locomotion / Q000187:drug effects; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism / Q000503:physiopathology*; D012129:Respiratory Function Tests / Q000379:methods
chemical_list: D000975:Antioxidants; D010100:Oxygen; D000111:Acetylcysteine
keywords: capillary hemodynamics; fatigue; oxygen uptake; skeletal muscle