Cerebrovascular responses to hypoxia and altitude

这项拟议的工作旨在调查在几个小时到14天的时间内，脑循环因缺氧和海拔而发生的较长期变化。研究计划将在卡尔加里大学的实验室、育空地区的克鲁恩湖研究站(KLRS)和圣埃利亚斯山脉的高高原(玛丽女王山)进行。卡尔加里的这项研究将调查男性和女性志愿者在清醒和睡眠期间发生的脑血管控制系统的变化，当动脉血气紧张以预先定义的和完全可控的方式改变时，时间从几分钟到几个小时(即8-12小时)不等。育空地区的研究将通过研究健康的男性和女性在海平面附近(在KLRS)和在适应(即超过10-14天)海拔(在玛丽女王山；海拔3245米)期间对长期暴露在低氧环境中的脑血管反应的适应性。我们与北美北极研究所(AINA)就育空地区拟议的研究建立了重要和必要的合作。AINA的总部设在卡尔加里大学，但运营着KLRS，那里的基础设施和人力资源已经到位，可以支持高海拔研究项目。拟议的计划将对帮助我们提高对人类脑血管生理学以及随后暴露在低氧和高原下的适应能力的知识产生重大影响。这项拟议的研究具有创新性和重要性，因为它们将有助于阐明低氧和海拔对人类脑血管调节的影响，并将解决涉及的机制。完成后，我们期望1)表征在暴露于高原低氧的初始习服(12小时)和习服(1-14天)阶段中CBF的变化，以及2)确定氧敏感基因及其一些诱导基因在暴露于低氧和海拔条件下观察到的CBF变化中的作用。

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.