Metabolic Adaptation to Chronic Hypobaric Hypoxia: PET Study

对慢性低压缺氧的代谢适应：PET 研究

• 批准号: 9215245
• 负责人: James Holden
• 金额: $ 2.88万
• 依托单位: University of Wisconsin-Madison
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-06-15 至 1993-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9215245&HistoricalAwards=false
• 关键词: Metabolic; Adaptation; Chronic; Hypobaric; Hypoxia

The use of organisms that are naturally tolerant to limiting supplies of oxygen to probe nature's molecular and metabolic defense strategies against hypoxia is a tried and tested experimental paradigm in biology. We have found in recent studies that the present day descendent of the lowlanders. In pilot position emission tomography (PET) studies of glucose metabolism in heart and brain in these subjects, we found that biomedical adaptations were utilized in order to maintain each organ in energy balance despite the imposed and chronic hypoxia of their home environments. The heart data demonstrated a significant dependence on glucose for basal energy needs, even following an overnight fast. This provisionally has been interpreted as an adaptation, serving to maximize the amount of useful energy obtainable per unit amount of oxygen. Interestingly, the subjects resolved partially, and in one case entirely, to the normal pattern of substrate preference after only 20 days living at sea level. Brain uptake levels of glucose were at the extreme upper end of the normal range and may indicate at least some non-oxygen dependent metabolism to maintain energy balance. Because control and manipulation of the adaptive response could be of immense practical importance, it is imperative to ascertain if these defense mechanisms are general to the human species. For that reason, we propose to extend our study to include subjects that would be expected both genetically and individually also to be hypoxia-adapted, the Sherpas of Nepal.

使用自然耐受限制的生物体 提供氧气来探测自然界的分子和代谢 对缺氧的防御策略是一个久经考验的 生物学的实验范例我们在最近的研究中发现 今天的低地人的后裔。在试点 葡萄糖代谢的正电子发射断层扫描（PET）研究 在这些受试者的心脏和大脑中，我们发现， 为了维持每个器官的能量， 平衡，尽管强加和慢性缺氧的家园 环境.心脏数据显示出 对葡萄糖的基础能量需求，即使在一夜之间， 快了这暂时被解释为一种适应， 用于使每单位可获得的有用能量最大化的 氧气量。有趣的是，受试者部分消退， 并且在一种情况下完全地与基底的正常图案相关联 在海平面上生活了20天后，脑摄取 葡萄糖水平处于正常范围的最高值 并且可以指示至少一些非氧依赖性代谢， 保持能量平衡。因为控制和操纵 适应性反应可能具有巨大的实际意义， 必须确定这些防御机制是否普遍适用于 人类物种。因此，我们建议延长研究 包括那些在基因上和 也能适应缺氧环境，尼泊尔的夏尔巴人。