Human cerebral blood flow control during hypoxia: focus on chronic pulmonary obstructive disease and obstructive sleep apnea

The brain is a vital organ that relies on a constant and adequate blood flow to match oxygen and glucose delivery with the local metabolic demands of active neurons. Thus exquisite regulation of cerebral blood flow (CBF) is particularly important under hypoxic conditions to prevent a detrimental decrease in the partial pressure of oxygen within the brain tissues. Cerebrovascular sensitivity to hypoxia, assessed as the change in CBF during a hypoxic challenge, represents the capacity of cerebral vessels to respond to, and compensate for, a reduced oxygen supply, and has been shown to be impaired or blunted in a number of conditions. For instance, this is observed with aging, and in clinical conditions such as untreated obstructive sleep apnea (OSA) and in healthy humans exposed to intermittent hypoxia. This review will 1) provide a brief overview of cerebral blood flow regulation and results of pharmacological intervention studies which we have performed to better elucidate the basic mechanisms of cerebrovascular regulation in humans; and 2) present data from studies in clinical and healthy populations, using a translational physiology approach, to investigate human CBF control during hypoxia. Results from studies in patients with chronic obstructive pulmonary disease and OSA will be presented to identify the effects of the disease processes on cerebrovascular sensitivity to hypoxia. Data emerging from experimental human models of intermittent hypoxia during wakefulness will also be reviewed to highlight the effects of intermittent hypoxia on the brain.