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: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=615377
• 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发展到越来越微观的规模，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，但这种基因组视角在理解身体功能方面的预测性低于预期，而且令人惊讶的是，几乎没有医学进展。综合生理学家，谁专注于了解器官系统的功能和之间的关系，现在重新采取中心舞台在追求理解生物功能。一个重要的生物学功能，仍然需要综合生理学家的研究工作是呼吸的控制。 呼吸是一种基本的自我平衡行为，我们每小时进行700多次，很大程度上没有意识控制，保持血液气体（例如，CO2和O2）在窄范围内。呼吸的控制是通过肺、心脏和大脑之间的复杂协调来调节的。这种综合控制包括（a）用于血液气体交换的通气，（B）对流向大脑的血流的心血管调节，以及（c）呼吸化学感受器的刺激之间的相互作用，所述呼吸化学感受器检测血液气体的变化（例如，高CO2和低O2）并调节呼吸的反馈控制。 在这个建议中，我探讨了呼吸，心血管和脑血管系统在工作，休息和玩耍的背景下的综合协调。具体来说，拟议的研究计划侧重于开发新的方法和观点，以了解健康的人如何应对血气挑战，特别是在不同的情况下，包括（a）在海拔地区徒步旅行和睡眠，其中个人容易患急性高山病和睡眠呼吸暂停，以及（B）工作场所暴露于低氧（缺氧）。 在对呼吸系统、心血管系统和脑血管系统之间的相互作用和相互关系进行这些研究之后，将出现呼吸控制的全面和综合的画面。此外，新的，便携式的，简单的方法和模型的开发将提高我们的能力，使有意义的测量在实验室，诊所，并在大群体的健康人严峻的现场环境。 通过全面了解人体对血气挑战的正常反应，我们可以更好地应用综合观点来理解健康和疾病中的身体功能。将出现一些明确的结果，包括更好地了解（a）谁会在高海拔地区生病以及如何预防它，这将对徒步旅行，攀登和军事冒险产生深远的影响，以及（B）在工作场所反复暴露于缺氧的长期影响。