The impact of oxidative stress on oxygen transport and utilization in health and disease
Creators: name: Rossman, Matthew J
Publisher: name: University of Utah
Year: 2016
Subjects: COPD
exercise

description: The overall objective of this dissertation was to examine the impact of oxidative stress on oxygen transport and utilization, and ultimately physiological function, in older individuals and patients with chronic obstructive pulmonary disease (COPD). The goal of the first study was to better understand the age-associated attenuation in leg blood flow (LBF), with a focus on the role of redox balance, at rest and during exercise. Under control conditions, by experimental design, aging was associated with ~15% reduction in LBF. During knee extensor exercise (KE), the old also exhibited greater leg free radical outflow, assessed by electron paramagnetic resonance (EPR) spectroscopy, than the young. At rest, administration of an acute, oral antioxidant cocktail (AOC) increased antioxidant capacity, decreased the EPR signal, and consequently, restored LBF in the old such that it was not different from the young. During exercise, however, the AOC did not alter free radical outflow from the muscle or LBF. Thus, these data document exaggerated free radical production during exercise in older individuals exhibiting attenuated LBF, and identify a favorable effect of decreasing oxidative stress on resting hemodynamics in these individuals. However, the inability of the oral AOC to alter free radical outflow or LBF during exercise suggests that the formidable, pro-oxidant state elicited by exercise in the old likely necessitates a more potent antioxidant strategy to alter free radical outflow and potentially improve LBF in this population. The second study sought to determine the impact of acute, oral AOC administration on oxygen transport and utilization in a population recognized to have elevated oxidative stress, patients with chronic obstructive pulmonary disease (COPD). AOC administration led to an improvement in LBF during submaximal KE exercise, which was accompanied by an increase in muscle oxygen consumption, in the patients with COPD, but minimal effects in healthy subjects. Additionally, arterial oxygen saturation was improved in the patients with COPD, but unaltered in the healthy subjects. These results reveal detrimental consequences of elevated oxidative stress in patients with COPD in terms of vascular control, and oxygen transport and utilization during exercise. The third study examined the functional consequences of reducing oxidative stress in patients with COPD in terms of skeletal muscle fatigue development. Following intravenous ascorbate administration, an overall attenuation in the ventilatory and metabolic responses to high-intensity KE performed for the same duration and at the same intensity as the placebo condition was observed. Additionally, following the exercise matched for time, the patients exhibited less peripheral quadriceps fatigue. These results suggest a beneficial role for antioxidant administration in COPD, and further implicate oxidative stress in the systemic, pathophysiological consequences of the condition. Collectively, this research has identified novel, biological mechanisms by which oxidative stress may adversely impact oxygen transport and utilization in health and disease.