{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T17:28:38Z","timestamp":1789925318836,"version":"4.0.1"},"reference-count":87,"publisher":"American Physiological Society","issue":"5","funder":[{"name":"AHSC-AFP Innovation Fund"},{"name":"SARC Postdoctoral Fellow Support Program, Dept. of Medicine, Queen's University"},{"name":"John A. Stewart Fellowship, Dept. of Medicine, Queen's University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Applied Physiology"],"published-print":{"date-parts":[[2017,5,1]]},"abstract":"<jats:p> 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 (FEV<jats:sub>1<\/jats:sub>)-to-forced vital capacity ratio &lt; lower limit of normal (LLN) and FEV<jats:sub>1<\/jats:sub> \u2265 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 &lt; 0.05), there were no differences in exercise tolerance (placebo: 325 \u00b1 47 s, NAC: 336 \u00b1 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 &gt; 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. <\/jats:p><jats:p> NEW &amp; NOTEWORTHY Acute antioxidant treatment with N-acetylcysteine (NAC) elevated plasma glutathione but did not modulate central or peripheral components of the O<jats:sub>2<\/jats:sub> transport pathway, thereby failing to improve exercise tolerance in patients with mild chronic obstructive pulmonary disease (COPD). <\/jats:p>","DOI":"10.1152\/japplphysiol.00990.2016","type":"journal-article","created":{"date-parts":[[2017,3,2]],"date-time":"2017-03-02T21:20:31Z","timestamp":1488489631000},"page":"1351-1361","source":"Crossref","is-referenced-by-count":13,"title":["Oral <i>N<\/i>-acetylcysteine and exercise tolerance in mild chronic obstructive pulmonary disease"],"prefix":"10.1152","volume":"122","author":[{"given":"Daniel M.","family":"Hirai","sequence":"first","affiliation":[{"name":"Laboratory of Clinical Exercise Physiology, Division of Respirology, Department of Medicine, Queen\u2019s University, Kingston, Ontario, Canada;"},{"name":"Pulmonary Function and Clinical Exercise Physiology Unit, Respiratory Division, Department of Medicine, Federal University of Sao Paulo, Sao Paulo, Brazil;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua H.","family":"Jones","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Exercise Physiology, Division of Respirology, Department of Medicine, Queen\u2019s University, Kingston, Ontario, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel T.","family":"Zelt","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Exercise Physiology, Division of Respirology, Department of Medicine, Queen\u2019s University, Kingston, Ontario, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne L.","family":"da Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Exercise Physiology, Division of Respirology, Department of Medicine, Queen\u2019s University, Kingston, Ontario, Canada;"},{"name":"Division of Physical Therapy, University of Brasilia, Brasilia, Brazil;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert F.","family":"Bentley","sequence":"additional","affiliation":[{"name":"Human Vascular Control Laboratory, School of Kinesiology and Health Studies, Queen\u2019s University, Kingston, Ontario, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brittany A.","family":"Edgett","sequence":"additional","affiliation":[{"name":"Queen\u2019s Muscle Physiology Laboratory, School of Kinesiology and Health Studies, Queen\u2019s University, Kingston, Ontario, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendon J.","family":"Gurd","sequence":"additional","affiliation":[{"name":"Queen\u2019s Muscle Physiology Laboratory, School of Kinesiology and Health Studies, Queen\u2019s University, Kingston, Ontario, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6461-8534","authenticated-orcid":false,"given":"Michael E.","family":"Tschakovsky","sequence":"additional","affiliation":[{"name":"Human Vascular Control Laboratory, School of Kinesiology and Health Studies, Queen\u2019s University, Kingston, Ontario, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis E.","family":"O\u2019Donnell","sequence":"additional","affiliation":[{"name":"Respiratory Investigation Unit, Division of Respirology, Department of Medicine, Queen\u2019s University, Kingston, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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