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-2022-02977
• 负责人: Sheel, Andrew
• 金额: $ 5.68万
• 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: 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=757943
• 关键词: Respiratory; neurovascular; adaptation; physiological; stress

The heart, circulation, lungs, and chest wall act together in a highly coordinated fashion. A change to one system results in a change to the other. How it is the different systems interact under biologically relevant conditions is complex and not fully understood. My program seeks to further our understanding of the anatomic and physiological relationships between these organ systems using a human model. Traditionally, biological sex has rarely been considered when exploring cardiorespiratory interactions leading to a significant knowledge gap; however, important sex-differences have recently been identified. The LONG-TERM OBJECTIVES of my program are: to understand how the human respiratory and cardiovascular systems interact, respond and adapt to physiological stressors, and identify potential sex-based differences and explain the mechanistic basis for them. My approach explores the integration of the respiratory and cardiovascular systems to provide a framework to better understand biological complexities. Three SHORT-TERM OBJECTIVES that build upon recent progress will inform my long-term goals. The first objective is to determine how the respiratory system influences the distribution of blood flow during exercise. To accomplish this a novel ventilator has been created that can manipulate the respiratory system during exercise. We will measure how the nervous system controls how much blood needs to be directed towards working muscle. The second objective seeks to understand how sex-differences in airway anatomy can influence how the muscles of breathing contract. To accomplish this, we will use innovative imaging methodologies to quantify male and female airways. Coupling complex airway measures with lung mechanics during exercise permits a comprehensive assessment of the relationship between airway structure and physiological function. This approach is unique and will provide measures that have, to date, not been possible to acquire. The third objective seeks to understand the effects of healthy aging and biological sex on how it is the heart and lung interact. Aging is associated with a progressive decline in pulmonary structure and function. While much is known about exercise, aging and the lung, the interactions between the biology of aging and sex-based differences in pulmonary structure and function are not fully understood. Studying isolated organ systems provides valuable information but examining how these systems work together provides a more detailed understanding of basic physiology. The proposed work will create a stimulating training environment where each objective is designed such that they provide a significant training opportunity for HQP ranging from undergraduates to postdoctoral fellows. Original methods and integrative experimental approaches will provide foundational knowledge of how the human respiratory system influences cardiovascular control and why this may differ on the basis of biological sex.

心脏、循环、肺和胸壁以高度协调的方式共同作用。一个系统的改变会导致另一个系统的改变。不同的系统在生物学相关条件下如何相互作用是复杂的，尚未完全理解。我的计划旨在进一步了解这些器官系统之间的解剖和生理关系，使用人体模型。传统上，在探索心肺相互作用时很少考虑生物性别，这导致了显著的知识差距;然而，最近发现了重要的性别差异。我的计划的长期目标是：了解人类呼吸和心血管系统如何相互作用，响应和适应生理压力，并确定潜在的性别差异，并解释它们的机械基础。我的方法探索了呼吸和心血管系统的整合，以提供一个框架，更好地理解生物学的复杂性。基于近期进展的三个短期计划将为我的长期目标提供信息。第一个目标是确定呼吸系统如何影响运动过程中的血流分布。为了实现这一点，已经创造了一种新型的呼吸机，可以在运动期间操纵呼吸系统。我们将测量神经系统如何控制需要多少血液流向工作肌肉。第二个目的是了解气道解剖结构的性别差异如何影响呼吸肌肉的收缩。为了实现这一目标，我们将使用创新的成像方法来量化男性和女性气道。在运动过程中，将复杂的气道测量与肺力学相结合，可以全面评估气道结构与生理功能之间的关系。这一方法是独特的，将提供迄今为止尚无法获得的措施。第三个目标是了解健康老龄化和生物性别对心脏和肺如何相互作用的影响。衰老与肺结构和功能的进行性下降有关。虽然人们对运动、衰老和肺了解很多，但衰老生物学与肺结构和功能的性别差异之间的相互作用尚未完全了解。研究孤立的器官系统提供了有价值的信息，但研究这些系统如何协同工作提供了对基本生理学更详细的了解。拟议的工作将创造一个刺激的培训环境，每个目标的设计，使他们提供了一个重要的培训机会，从本科生到博士后研究员的HQP。原始方法和综合实验方法将为人类呼吸系统如何影响心血管控制以及为什么这可能因生物性别而异提供基础知识。