Cerebrovascular responses to hypoxia and altitude

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The proposed work aims to investigate the longer-term alterations that occur in the cerebral circulation in response to hypoxia and altitude over a period ranging from several hours to 14 days. The research program will be conducted in the laboratory at the University of Calgary, and in the Yukon at the Kluane Lake Research Station (KLRS) and on a high plateau (Mount Queen Mary) in the St. Elias Mountain Range. The studies in Calgary will investigate the alterations that occur in the cerebrovascular control system of men and women volunteers, during wakefulness and during sleep, when the arterial blood gas tensions are altered in a pre-defined and fully controlled manner for a period ranging from minutes to several (i.e., 8-12) hours. Studies in the Yukon will investigate the adaptive nature of the cerebrovascular responses to prolonged exposure to hypoxia at rest and during exercise by studying healthy men and women near sea level (at KLRS) and during acclimatization (i.e., over 10-14 days) to altitude (on Mount Queen Mary; 3,245 m above sea level). We have established an important and necessary collaboration with the Arctic Institute of North America (AINA) for the proposed studies in the Yukon. The AINA is based at the University of Calgary but operates the KLRS, where the infrastructure and human resources are in place to support a high altitude research program. The proposed program will have a major impact in helping advance our knowledge of human cerebrovascular physiology and the adaptations that ensue with exposure to hypoxia and altitude. The proposed studies are innovative and important because they will help elucidate the effects of hypoxia and altitude on cerebrovascular regulation in humans and they will address the mechanisms involved. Upon completion, we expect to 1) characterize the alterations in CBF that unfold during the initial acclimatization (< 12 hours) and acclimatization (1-14 days) phases of exposure to the hypoxia of altitude, and 2) determine the role of oxygen sensing genes and some of its induced genes on the observed alterations in CBF with exposure to hypoxia and altitude.