Respiratory and neurovascular adaptation to physiological stress

呼吸和神经血管对生理应激的适应

• 批准号: RGPIN-2017-03749
• 负责人: Sheel, Andrew
• 金额: $ 5.03万
• 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=710409
• 关键词: Respiratory; neurovascular; adaptation; physiological; stress

The heart, circulation, lungs, and chest wall act together in a highly coordinated fashion. While studying each system in isolation can provide valuable information, examining how these systems work together provides a more comprehensive understanding of basic physiology. My program seeks to further our understanding of the anatomic and physiological relationships between these systems using a human model. Biological sex has been rarely considered when exploring cardiorespiratory interactions however, important differences have now been identified. For example, skeletal muscle fatigability differs between the sexes. Women are usually less fatigable than men during single-limb contractions but little is known about sex differences in the fatigability of the respiratory musculature. The LONG-TERM OBJECTIVE of my program is to understand how the cardiovascular and respiratory systems interact and adapt to physiological challenges. My SHORT-TERM OBJECTIVES build upon recent progress along four specific aims. Aim 1 seeks to understand how the respiratory muscles compete for oxygen delivery. Participants will perform exercise while the respiratory musculature is manipulated experimentally with a unique ventilator and blood flow to the exercising limbs will be measured directly. Aim 2 will determine the effect of respiratory muscle work on sympathetic vasoconstrictor outflow and blood pressure during exercise. Continuous measures of nerve activity will be acquired to provide an understanding of the neural consequences of breathing. Aim 3 will use novel imaging methodologies to quantify male and female airways. Coupling in vivo airway measures with lung mechanics during exercise permits a comprehensive assessment of the relationship between airway structure and physiological function. Aim 4 will determine if respiratory muscle fatigue differs between the sexes. To assess the independent effect of respiratory muscle contraction participants will perform high intensity contractions of the diaphragm against high airway resistance. Diaphragm fatigue will be assessed using magnetic stimulation of the phrenic nerves. Each aim is designed such that they provide a significant training opportunity for HQP ranging from undergraduates to postdoctoral fellows. Novel methods and integrative experimental approaches will provide mechanistic knowledge of how the human respiratory system influences cardiovascular control a relationship that is not well understood.

心脏、循环、肺和胸壁以高度协调的方式共同作用。虽然单独研究每个系统可以提供有价值的信息，但研究这些系统如何协同工作可以更全面地理解基本生理学。我的计划试图利用人体模型来加深我们对这些系统之间的解剖和生理关系的理解。在探索心肺相互作用时，生物性别很少被考虑，然而，现在已经确定了重要的差异。例如，骨骼肌的疲劳性在性别之间是不同的。女性在单肢收缩时通常比男性更不容易疲劳，但对呼吸肌肉系统疲劳性的性别差异知之甚少。我的项目的长期目标是了解心血管和呼吸系统如何相互作用并适应生理挑战。我的短期目标建立在最近在四个具体目标上取得的进展的基础上。目标1试图了解呼吸肌是如何竞争氧气输送的。参与者将进行锻炼，同时呼吸肌肉系统通过独特的呼吸器进行实验操作，运动肢体的血流量将被直接测量。目的2研究呼吸肌作功对运动中交感血管收缩物质流出和血压的影响。将获得神经活动的连续测量，以提供对呼吸的神经后果的理解。AIM 3将使用新的成像方法来量化男性和女性的呼吸道。将运动中的活体气道测量与肺力学相结合，可以全面评估呼吸道结构和生理功能之间的关系。目标4将确定呼吸肌疲劳是否在性别之间存在差异。为了评估呼吸肌收缩的独立效应，参与者将对高呼吸道阻力进行高强度的横隔膜收缩。通过对膈神经的磁刺激来评估横隔膜疲劳。每个目标都是这样设计的，它们为从本科生到博士后研究员的HQP提供了重要的培训机会。新的方法和综合的实验方法将提供关于人类呼吸系统如何影响心血管控制的机械知识，这种关系还没有被很好地理解。