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 contribute to exercise intolerance in the early stages of COPD is unknown. We examined 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 with forced expiratory volume in one second and forced vital capacity ratio (FEV1/FVC) < lower limit of normal (LLN) and FEV1 ≥ LLN were enrolled in a double-blind, randomized crossover study to receive NAC (1800 mg/day) or placebo for 4 days. Severe intensity constant-load exercise tests were performed with non-invasive 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 to placebo (P<0.05), there were no differences in exercise tolerance (placebo:325±47; 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.
- capillary hemodynamics
- oxygen uptake
- skeletal muscle
- Copyright © 2016, Journal of Applied Physiology