Grant: Project Grant

In healthy humans, brain blood flow is influenced by changes in the levels of oxygen and carbon dioxide in the circulating blood. However, the brain's important ability to regulate its blood flow is impaired in disease processes such as obstructive sleep apnea (OSA). People who have OSA stop breathing intermittently throughout the night, resulting in repeated episodes of low oxygen and high carbon dioxide in the blood. Because of these repeated episodes, the ability of the brain vessels to regulate blood flow becomes impaired. This impairment can lead to hypertension and stroke. The mechanisms that regulate brain blood flow in health, and how these mechanisms become impaired with disease, is poorly understood. It is thought that endothelial-mediated mechanisms play a major role in regulating blood flow in several vascular beds, including the brain. In a first series of studies, we will determine, in an experimental human model of intermittent hypoxia (IH) during sleep, the effects of intermittent hypoxia on the regulation of brain blood flow and the role of changes in brain blood flow on the stability of breathing. In a second series of studies, we will determine the extent to which the brain blood flow response to low oxygen is altered in a broad range of patients with moderate to severe OSA. Our research will determine if the brain blood flow impairments observed in untreated OSA patients are related to a novel physiologically based measure called "hypoxia burden" (HB) that appears to better capture OSA severity. This work may help us better understand conditions such as hypertension, OSA, stroke and aging, in which endothelium-dependent relaxation (i.e., relaxation of cells that line brain blood vessels) is impaired. Our research will provide useful information about HB and vascular function, which may help elucidate the mechanism linking IH to stroke in OSA. Ultimately, this will translate into improved health and disease prevention for Canadians.