Human respiratory and neurocirculatory plasticity induced by intermittent hypoxia

间歇性缺氧引起的人体呼吸和神经循环可塑性

• 批准号: RGPIN-2020-04010
• 负责人: Foster, Glen
• 金额: $ 2.91万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=716072
• 关键词: Human; respiratory; neurocirculatory; plasticity; induced

Periodic exposure to low blood oxygen, termed intermittent hypoxia (IH), is common in the natural environment. For example, IH is a characteristic of diving mammals, geese flying over high-altitude peaks, and in squirrels during winter hibernation. Similarly, humans are exposed to IH during mountain climbing sojourns, shift work in high altitude mines, and during sleep where sleep apnea can develop in otherwise normal people. In my previous NSERC Discovery program, I showed that IH leads to functional changes in how we control our breathing and circulation. My recent progress shows that IH reduces blood flow and the force of blood against the lining of blood vessels. Additionally, we found that IH leads to long-lasting increases in breathing and blood pressure. These findings suggest that IH has a long-lasting effect in how our body controls breathing and our circulation. Specifically, IH increases activity of the body's peripheral chemical receptor, increases oxidative stress, and reduces the production of blood vessel relaxing factors. Consequently, sympathetic neurotransmission may be increased by IH resulting in greater blood vessel constriction. My research program objectives will determine if changes in blood flow patterns, oxidative stress, and blood flow to the body's peripheral chemical receptor can influence breathing and circulation control following IH. I will use novel experimental paradigms and methodological approaches to manipulate blood flow dynamics, oxidative stress, and measure blood flow within the human peripheral chemical receptor. Blood flow dynamics will be manipulated using multiple approaches including localized heating, exercise, and blood flow restriction. Oxidative stress will be reduced using antioxidants. Finally, peripheral chemical receptor blood flow will be measured non-invasively using an innovative contrast ultrasound approach. With each manipulation, I will determine how IH changes the body's control of breathing and circulation. The proposed research program impact contributes to a greater understanding of the human response to a common physiological stress. It will generate new scientific knowledge regarding how blood flow dynamics and oxidative stress change the control of breathing and circulation following IH. Additionally, the proposed research develops an innovative methodology to measure human peripheral chemical receptor blood flow for the first time. This methodology will determine how changes in receptor blood flow influence breathing and circulation control and is likely to generate a novel field of study. I recognize that equity, diversity, and inclusion strengthen the quality, relevance and impact of research. As a result, my HQP training program objectives are designed to include all levels of HQP from a diverse pool of international applicants. My research program trains highly successful HQP to produce leading edge natural sciences and engineering research in Canada.

周期性暴露于低血氧，称为间歇性缺氧（IH），在自然环境中很常见。例如，IH是潜水哺乳动物、飞越高海拔山峰的鹅和冬眠期间的松鼠的特征。同样，人类在登山逗留期间暴露于IH，在高海拔矿井中轮班工作，以及在睡眠期间，睡眠呼吸暂停可能在其他正常人中发展。在我之前的NSERC探索计划中，我展示了IH导致我们如何控制呼吸和循环的功能变化。 我最近的进展表明，IH减少血液流动和血液对血管内壁的力量。此外，我们发现IH会导致呼吸和血压的长期增加。这些发现表明，胰岛素抵抗对我们的身体控制呼吸和循环有长期影响。具体来说，IH增加了身体外周化学受体的活性，增加了氧化应激，并减少了血管舒张因子的产生。因此，IH可增加交感神经传递，导致更大的血管收缩。我的研究项目目标将确定血流模式、氧化应激和流向身体外周化学受体的血流的变化是否会影响IH后的呼吸和循环控制。 我将使用新的实验范例和方法来操纵血流动力学，氧化应激，并测量人体外周化学受体内的血流。血流动力学将使用多种方法进行操纵，包括局部加热、运动和血流限制。使用抗氧化剂将减少氧化应激。最后，外周化学受体血流将使用创新的造影超声方法进行非侵入性测量。通过每次操作，我将确定IH如何改变身体对呼吸和循环的控制。 拟议的研究计划的影响有助于更好地了解人类对常见生理压力的反应。它将产生关于血流动力学和氧化应激如何改变IH后呼吸和循环控制的新科学知识。此外，这项研究还开发了一种创新的方法，首次测量人类外周化学受体血流。这种方法将确定受体血流的变化如何影响呼吸和循环控制，并可能产生一个新的研究领域。我认识到，公平，多样性和包容性加强了研究的质量，相关性和影响力。因此，我的HQP培训计划目标旨在包括来自不同国际申请人的所有HQP级别。我的研究项目培养了非常成功的HQP，在加拿大进行前沿的自然科学和工程研究。