Sex-differences in respiratory sensation and muscle function during conditions of physiological stress

生理应激条件下呼吸感觉和肌肉功能的性别差异

• 批准号: RGPIN-2019-04053
• 负责人: Guenette, Jordan
• 金额: $ 3.42万
• 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: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=737369
• 关键词: Sex; differences; respiratory; sensation; muscle

My previous NSERC funded work has shown that during exercise, women: 1) are more likely to develop ventilatory constraints; 2) have a higher work of breathing; 3) have increased operating lung volumes; and 4) experience more intense ratings of dyspnea (i.e., breathlessness) compared to men. Funding from my most recent NSERC Discovery Grant (DG) resulted in two novel discoveries that have increased our understanding of sex differences in respiratory physiology in healthy humans. First, we showed that in addition to reporting higher dyspnea intensity ratings during exercise, women experienced different qualities of dyspnea relative to men. Specifically, women were significantly more likely to select dyspnea phrases alluding to inspiratory difficulty and shallow breathing relative to men. However, the precise physiological mechanisms for this sex difference in respiratory sensation remain unknown. Our second major discovery was that healthy women recruit their inspiratory muscles differently than men during exercise. Specifically, women rely more heavily on their `extradiaphragmatic' inspiratory muscles during exercise. Why women recruit these muscles more than men and the corresponding physiological and sensory consequences also remain unknown. Accordingly, this NSERC DG renewal will seek to expand on these two recent discoveries. Ultimately, the long-term objective of this research program is to enhance our understanding of sex differences in respiratory physiology during conditions of increased physiological stress. Short-term objective 1 will systematically examine the physiological mechanism underlying sex differences in both the intensity and qualitative dimensions of dyspnea in healthy humans. The overarching hypothesis is that women report more intense dyspnea ratings due to an increase in neural respiratory drive (NRD), whereas sex differences in the qualitative descriptors of dyspnea are primarily due to differences in the relationship between NRD and the mechanical output of the respiratory system [i.e. neuromechanical uncoupling (NMU)]. Short-term objective 2 will examine the mechanisms and consequences of sex differences in respiratory muscle recruitment during both whole-body exercise and inspiratory muscle loading. The overarching hypothesis is that women recruit their extradiaphragmatic inspiratory muscles more than men as a strategy to minimize diaphragmatic work/fatigue at the expense of increased dyspnea. The proposed 5-year research program will enhance our fundamental understanding of how men and women breathe during conditions of increased physiological stress and will provide novel insight into sex differences in respiratory sensation and muscle recruitment. Ultimately, this applied human physiology research program will have a direct impact on our ability to design more effective interventions to enhance respiratory muscle strength and exercise tolerance in humans.

我之前由NSERC资助的研究表明，与男性相比，女性在锻炼过程中：1)更有可能出现呼吸受限；2)呼吸功更大；3)操作肺容量增加；4)经历更严重的呼吸困难(即呼吸困难)。我最近从NSERC发现赠款(DG)获得的资金导致了两项新的发现，这两项发现增加了我们对健康人类呼吸生理学中的性别差异的理解。首先，我们发现，除了在运动期间报告更高的呼吸困难强度等级外，女性与男性相比经历了不同的呼吸困难质量。具体地说，与男性相比，女性更有可能选择暗示吸气困难和呼吸浅的呼吸困难短语。然而，这种呼吸感觉性别差异的确切生理机制仍不清楚。我们的第二个重大发现是，健康的女性在运动时招募吸气肌的方式与男性不同。具体地说，女性在锻炼时更多地依赖于她们的“隔外”吸气肌。为什么女性比男性更多地招募这些肌肉，以及相应的生理和感官后果也尚不清楚。因此，此次NSERC DG更新将寻求在这两个最新发现的基础上扩展。最终，这项研究计划的长期目标是加强我们对生理应激增加条件下呼吸生理学的性别差异的理解。短期目标1将系统地研究健康人呼吸困难强度和质量两个维度的性别差异背后的生理机制。最主要的假设是，由于神经呼吸驱动(NRD)的增加，女性报告的呼吸困难程度更高，而呼吸困难的定性描述的性别差异主要是由于NRD与呼吸系统的机械输出之间的关系[即神经机械解偶联(NMU)]的差异。短期目标2将研究在全身运动和吸气肌负荷过程中呼吸肌招募的性别差异的机制和后果。最重要的假设是，女性比男性更多地招募他们的横隔膜外吸气肌，作为一种策略，以增加呼吸困难为代价，最大限度地减少横隔膜的工作/疲劳。拟议的5年研究计划将加强我们对男性和女性在生理压力增加的情况下如何呼吸的基本理解，并将为呼吸感觉和肌肉招募方面的性别差异提供新的见解。最终，这一应用的人体生理学研究计划将直接影响我们设计更有效的干预措施以增强人类呼吸肌力量和运动耐力的能力。