Cerebrovascular responses to hypoxia and altitude

这项工作的目的是研究在几个小时到14天的时间内，大脑循环对缺氧和海拔高度的反应发生的长期变化。研究计划将在卡尔加里大学的实验室、育空地区的克卢恩湖研究站（KLRS）和圣埃利亚斯山脉的高原（玛丽皇后山）进行。 卡尔加里的研究将调查男性和女性志愿者在清醒和睡眠期间脑血管控制系统中发生的变化，当动脉血气张力以预定义和完全控制的方式改变几分钟到几分钟（即，8-12）小时。在育空地区进行的研究将通过研究海平面附近（KLRS）和适应期间（即，超过10-14天）到海拔（玛丽皇后山;海拔3，245米）。我们与北美北极研究所建立了重要和必要的合作关系，以便在育空地区开展拟议的研究。AINA总部设在卡尔加里大学，但经营KLRS，那里的基础设施和人力资源到位，以支持高海拔研究计划。拟议的计划将产生重大影响，有助于推进我们对人类脑血管生理学的认识，以及随之而来的缺氧和高原适应。拟议的研究是创新和重要的，因为它们将有助于阐明缺氧和海拔对人类脑血管调节的影响，并将解决所涉及的机制。完成后，我们期望1）表征在暴露于低氧的初始习服（< 12小时）和习服（1-14天）阶段期间呈现的CBF的改变，以及2）确定氧敏感基因及其诱导的一些基因在暴露于低氧和海拔的CBF中观察到的改变中的作用。

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.