Utilizing the oxygen cascade to understand the biology of exercise

运动是一种强大的生理压力源，可以用来解决基本的生物学问题。同样，缺氧也提供了一种强有力的生理刺激，可以与运动相结合，显著地刺激生物系统。“氧气级联”描述了允许环境氧气被输送并被工作肌肉使用的生理过程，是基础生物学的基础。确定每个方面和/或氧气级联中的“限制步骤”的具体作用以及它如何影响运动一直是动物和人类生理学家长期存在的问题。我的研究计划的长期目标是了解在运动和缺氧的生理相关条件下氧的运输和利用机制。我的项目的首要方法是研究氧的传导（通气、肺、心脏和肌肉）及其相互作用。在接下来的5年里，我的短期研究目标是通过三个不同但相互关联的目标来研究氧级联和运动之间的相互作用。每个目标将利用人体解剖学和生理学的自然（目标1和3）或药理学诱导（目标2）变化，并研究对氧传导和综合运动反应的最终影响。目的1：利用已知的气道解剖和气体交换的性别差异，以更好地了解肺系统如何在运动中限制氧气的运输和利用。目的2将使用药理学方法来控制血气稳态，并确定在常氧和缺氧情况下，这对骨骼肌力量产生和运动耐量的影响。目的3：将利用天然改变血红蛋白亲和力的人来确定运动和急性缺氧时血红蛋白亲和力与氧级联之间的相互作用。这些目标是通过操纵氧级联联系在一起的，但通过不同的机制。通过使用不同的操作方法，我的研究项目可以单独或联合探测氧级联的各个方面，以研究综合人体生理学。总的来说，我的研究计划将通过使用新颖的方法和综合实验方法来确定运动过程中每个“步骤”在氧气级联中的作用。每个目标都旨在确保本科生和研究生HQP的重要培训机会。

Exercise is a powerful physiological stressor that can be utilized to address questions of basic biology. Similarly, hypoxia also provides a potent physiological stimulus and can be combined with exercise to significantly stress biological systems. The `oxygen cascade' describes the physiological processes permitting environmental oxygen to be delivered and used by working muscle and is fundamental to basic biology. Determining the specific role of each aspect and/or the `limiting step' in the oxygen cascade and how it influences exercise has been a long-standing question for animal and human physiologists. The LONG-TERM OBJECTIVE of my research program is to understand the mechanisms of oxygen transport and utilization under physiologically relevant conditions of exercise and hypoxia. The overarching approach of my program is to study conductance of oxygen (ventilation, pulmonary, cardiac and muscle) and their interaction. Over the next 5 years, my SHORT-TERM RESEARCH OBJECTIVE is to investigate the interaction between the oxygen cascade and exercise by using three distinct but inter-related aims. Each aim will utilize either natural (Aim 1 & 3) or pharmacologically-induced (Aim 2) variations in human anatomy and physiology and investigate the resultant effects on oxygen conductance and the integrative exercise response. Aim 1: To exploit the known sex-differences in airway anatomy and gas exchange to better understand how the pulmonary system limits oxygen transport and utilization during exercise. Aim 2 will use a pharmacological approach to manipulate blood gas homeostasis and determine how this contributes skeletal muscle force production and exercise tolerance in normoxia and hypoxia. Aim 3: Will utilize humans with naturally altered hemoglobin affinity to determine the interaction between oxyhemoglobin affinity and the oxygen cascade during exercise and acute hypoxia. The aims are linked by manipulation of the oxygen cascade, but through different mechanisms. By utilizing different manipulations my research program can probe each aspect of the oxygen cascade in isolation or combined to study integrative human physiology. Overall my research program will seek to identify the role of each `step' in the oxygen cascade during exercise by using novel methods and integrative experimental approaches. Each aim is designed to ensure significant training opportunity for undergraduate and graduate HQP.