The Role of Respiratory Chemoreflexes at Work, Rest and Play

呼吸化学反射在工作、休息和娱乐中的作用

• 批准号: RGPIN-2016-04915
• 负责人: Day, Trevor
• 金额: $ 2.26万
• 依托单位: Mount Royal University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=753447
• 关键词: Role; Respiratory; Chemoreflexes; Work; Rest

For decades, modern biological research has progressed down an increasingly microscopic scale, where understanding cellular, molecular and genetic mechanisms has been the dominant theme. Although important new discoveries toward understanding basic cellular mechanisms have resulted, this genomic perspective has been less predictive than anticipated on understanding body function, and surprisingly few medical advances have resulted. Integrative physiologists, who focus on understanding the functions of and relationships between organ systems, are now re-taking center stage in the pursuit of understanding biological function. One important biological function that still requires the research efforts of integrative physiologists is the control of breathing. Breathing is a fundamental homeostatic behavior we perform over 700 times/hour, largely without conscious control, keeping blood gases (e.g., CO2 and O2) within narrow ranges. The control of breathing is mediated through complex coordination between the lungs, heart, and brain. This integrated control includes interactions between (a) ventilation for the exchange of blood gases, (b) cardiovascular regulation of blood flow to the brain, and (c) stimulation of respiratory chemoreceptors, which detect changes in blood gases (e.g., high CO2 and low O2) and mediate the feedback control of breathing. In this proposal, I explore the integrated coordination between the respiratory, cardiovascular, and cerebrovascular systems in contexts of work, rest and play. Specifically, the proposed program of research focuses on developing novel methods and perspectives to understand how healthy humans respond to blood gas challenges, particularly across diverse contexts including (a) trekking and sleeping at altitude, where individuals are susceptible to acute mountain sickness and sleep apnea, and (b) workplace exposures to low oxygen (hypoxia). Following these investigations into the interactions and interrelationships between the respiratory, cardiovascular, and cerebrovascular systems, a comprehensive and integrative picture of the control of breathing will emerge. In addition, the development of new, portable, and simple methodologies and models will increase our capacity to make meaningful measurements in the lab, clinic, and austere field environments in large groups of healthy people. Through arriving at a comprehensive understanding of the normal human responses to blood gas challenges, we can better apply integrative perspectives to understanding body function in health and disease. A number of clear outcomes will emerge, including developing a better understanding of (a) who will get sick at altitude and how to prevent it, which will have profound implications for trekking, climbing, and military forays to altitude and (b) the long term effects of repeated exposures to hypoxia in the workplace.

几十年来，现代生物学研究已经在越来越微观的尺度上取得了进展，其中理解细胞、分子和遗传机制一直是主导主题。尽管在理解基本细胞机制方面有了重要的新发现，但在理解身体功能方面，这种基因组观点的预测性比预期的要低，令人惊讶的是，几乎没有医学上的进展。专注于理解器官系统的功能和相互关系的综合生理学家，现在重新占据了追求理解生物功能的中心舞台。一个重要的生物学功能仍然需要综合生理学家的研究努力是呼吸的控制。呼吸是一种基本的体内平衡行为，我们每小时进行700次以上，基本上没有有意识的控制，将血液气体（如二氧化碳和氧气）保持在狭窄的范围内。呼吸的控制是通过肺、心和脑之间复杂的协调来调节的。这种综合控制包括(a)血液气体交换的通气，(b)血液流向大脑的心血管调节，以及(c)呼吸化学感受器的刺激，呼吸化学感受器检测血液气体的变化（例如，高CO2和低O2）并介导呼吸的反馈控制。在这个提案中，我探讨了呼吸、心脑血管系统在工作、休息和娱乐环境中的综合协调。具体而言，拟议的研究计划侧重于开发新的方法和观点，以了解健康人类如何应对血气挑战，特别是在不同的环境下，包括(a)在高海拔地区徒步旅行和睡眠，个人容易患急性高原病和睡眠呼吸暂停，以及(b)工作场所暴露于低氧（缺氧）。随着这些对呼吸、心血管和脑血管系统之间的相互作用和相互关系的研究，呼吸控制的全面和综合的图景将出现。此外，新的、便携的、简单的方法和模型的发展将提高我们在实验室、诊所和严峻的野外环境中对大量健康人群进行有意义测量的能力。通过全面了解人类对血气挑战的正常反应，我们可以更好地应用综合视角来理解健康和疾病中的身体功能。一些明确的结果将会出现，包括更好地理解(A)谁会在高海拔地区生病以及如何预防，这将对徒步旅行、登山和军事行动产生深远影响；(b)在工作场所反复暴露于缺氧的长期影响。