thesisThe overall objective of this thesis was to examine skeletal muscle function and the development of peripheral quadriceps fatigue in health and in patients with chronic obstructive pulmonary disease (COPD). The aim of the first study was to further elucidate the role of afferent feedback in the regulation of locomotor muscle fatigue during dynamic exercise by varying the amount of active muscle mass. Utilizing cycling (BIKE) and single-leg knee extensor (KE) exercise, far greater quadriceps fatigue at exhaustion was observed following KE exercise. These data imply that when the source of skeletal muscle afferent feedback is confined to a small muscle mass, the central nervous system tolerates a greater magnitude of peripheral fatigue, and likely a greater intramuscular metabolic disturbance; a finding that has important implications for the adoption of small muscle mass exercise in rehabilitative medicine. The second study sought to determine the impact of an acute oral antioxidant cocktail (AOC), with previously documented efficacy, on free radical concentration and KE exercise performance in patients with COPD. In this population, recognized to have elevated oxidative stress, administration of the AOC significantly attenuated resting free radical levels, which were negatively correlated with the degree of airflow limitation and baseline MVC force. Upon secondary analysis, however, a dichotomous response to the AOC was recognized, whereby the AOC appeared to be most efficacious in those patients with high initial free radical levels, with minimal effects when the initial free radical load was low. Despite these antioxidant effects, no differences in KE exercise performance or the magnitude of peripheral quadriceps fatigue were evident following consumption of the AOC. These findings revealed that acutely reducing free radicals with an oral AOC does not translate to improved exercise capacity and fatigue resistance in patients with COPD. Collectively, this research has provided novel insight into the role of active muscle mass and the regulation of peripheral fatigue, and has better elucidated the link between free radicals, antioxidants, and fatigue in patients with COPD