Chronic Obstructive Pulmonary Disease (COPD) is a disease primarily affecting the pulmonary system, most commonly resulting from prolonged exposure to cigarette smoke. While systemic respiratory disturbances in COPD are apparent, the chemical regulation within the brainstem and at the carotid bodies is unclear. Furthermore, the role that cerebral blood flow contributes to respiratory disturbances is poorly understood. Recent studies have demonstrated peripheral vascular impairments in COPD, which may have further implications for exercise –hyperemia. Oxidative stress serves as a plausible mechanism leading to vascular impairments, and the overall increased risk of stroke and cardiovascular disease.
This collection of studies set out to define the ventilatory and cerebrovascular responses to acute alterations in PCO2 and PO2 in COPD patients, and the relationship to oxidative stress. A secondary focus was to characterize both cerebral and peripheral blood flow during exercise. The thesis begins by investigating the cerebrovascular and ventilatory responses to acute euoxic-hypercapnia in mild-moderate COPD patients, and the relationship between these physiological parameters, and markers systemic of oxidative stress. Second, the cerebrovascular responses during moderate cycling exercise are defined. The final three studies collectively investigate the effect of the antioxidant, vitamin C, on the cerebrovascular and ventilatory responses to acute hyperoxic-hypercapnia, isocapnic-hypoxia, and on forearm blood flow during handgrip exercise, in COPD patients and healthy controls.
This thesis demonstrates that the cerebrovascular and ventilatory responses to hypercapnia, but not hypoxia, are impaired in COPD. Vitamin C was found to augment the ventilatory response to hyperoxic-hypercapnia suggesting oxidative stress contributes to the overall ventilatory limitations in COPD. Dynamic cycling exercise (at a matched relative intensity), evoked a similar cerebrovascular response between COPD and controls, however, a modest increase in workload increased cerebral blood flow in COPD to levels greater than controls, reducing the cerebrovascular reserve capacity. Lastly, forearm blood flow in COPD patients during exercise was similar to controls, and was not affected by vitamin C. Overall, this series of experiments provides a better understanding of the complex systemic consequences of COPD in an integrated nature, thereby advancing knowledge in this important area of study.