The Role of Respiratory Chemoreflexes at Work, Rest and Play

几十年来，现代生物学研究在越来越微观的尺度上取得了进展，其中，了解细胞、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已经有了重要的新发现，但这种基因组学观点在理解身体功能方面的预测性不如预期，而且令人惊讶的是，医学上的进展很少。专注于了解器官系统的功能和相互关系的综合生理学家，现在正在重新占据理解生物功能的中心舞台。一项重要的生物学功能仍然需要综合生理学家的研究努力，那就是呼吸的控制。 呼吸是一种基本的动态平衡行为，我们每小时执行超过700次，主要是在没有意识控制的情况下，将血气(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、心和脑之间的复杂协调来调节的。这种综合控制包括(A)用于交换血气的通风，(B)心血管对流向大脑的血液的调节，以及(C)呼吸化学感受器的刺激之间的相互作用，呼吸化学感受器检测血气的变化(例如，高二氧化碳和低氧气)并调节呼吸的反馈控制。 在这项建议中，我探讨了在工作、休息和玩耍的情况下，呼吸、心血管和脑血管系统之间的综合协调。具体地说，拟议的研究计划侧重于开发新的方法和视角，以了解健康的人类如何应对血气挑战，特别是在不同的环境中，包括(A)徒步旅行和在海拔睡觉，那里的个人容易发生急性高原反应和睡眠呼吸暂停，以及(B)工作场所暴露在低氧(缺氧)中。 在对呼吸、心血管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，呼吸控制的全面和综合的图景将会出现。此外，新的、便携的和简单的方法和模型的开发将增加我们在实验室、诊所和严酷的野外环境中对大量健康人进行有意义的测量的能力。 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身体功能在健康和疾病中的作用。将出现一些明确的结果，包括更好地了解(A)谁会在高原上生病以及如何预防，这将对徒步旅行、攀登和军事登高产生深远影响，以及(B)工作场所反复暴露在低氧环境下的长期影响。

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.