Understanding the limits of human heat tolerance from the cell to the whole-body response

了解人体从细胞到全身反应的耐热极限

• 批准号: RTI-2022-00041
• 负责人: Kenny, Glen
• 金额: $ 9.28万
• 依托单位: University of Ottawa
• 依托单位国家: 加拿大
• 项目类别: Research Tools and Instruments
• 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=743016
• 关键词: Understanding; limits; human; heat; tolerance

Temperature regulation is a vital aspect of human survival. However, exercise and/or exposure to hot environments can lead to dangerous increases in body temperature. To offset this increase, highly developed autonomic thermoeffector responses (cutaneous vasodilation and sweating) are activated to facilitate whole-body heat loss during heat stress. Using the world's only air calorimetry (a device that provides a very precise measurement of the heat dissipated by the human body), we showed that physiological control of thermoeffector responses and therefore whole-body heat loss can vary as a function of several inter-individual factors (e.g., age, sex, other) and intra--individual factors (e.g., fitness, hydration, exposure duration). This includes the influence of non-thermal factors associated with the activation of sensory receptors (e.g., baroreceptors, metaboreceptors). While our calorimetry-based research has advanced our understanding of the factors limiting human heat tolerance, our emerging work evaluating the cellular heat stress response is uncovering the complex cellular mechanisms that contribute to heat-related vulnerabilities. To continue advancing this important work, I am seeking to replace older, inadequate instruments and obtain new tools to increase our capacity to conduct this innovative research and maximize our research output. Specifically, the aim of this proposal is to expand the scope and impact of our research activities by replacing our calorimeter's antiquated data acquisition interface platform for the monitoring of physiological responses (i.e., scalable system enabling the addition of a data acquisition system capable of accommodating a range of hardware interfaces needed to record multiple physiological variables under one system). This would eliminate our dependence on multiple monitoring stations employing different data acquisition systems and software platforms and provide capacity for future expansion for the monitoring of other physiological variables in our calorimetry-based studies. Further, we are seeking to replace older tools and acquire newer instruments (e.g., centrifuge, platform rocker, waving rotator, Western blot imaging system, Western blot electrophoresis system) to meet our needs and enhance our capacity to evaluate protein and gene responses to study the cellular mechanisms underlying heat vulnerabilities. This would allow us to bridge the gap in our understanding of the factors mediating human heat tolerance from the cell to the whole-body response, helping us achieve the next echelon of discovery and innovation. Importantly, it will attract a new cadre of trainees and drive a new generation and culture of scientific growth to address real-world challenges faced by industry and other sectors of our population affected by extreme heat spurred by a warming planet.

温度调节是人类生存的重要方面。但是，运动和/或接触热环境可能会导致体温危险升高。为了抵消这种增加，高度发达的自主神热反应（皮肤血管舒张和出汗）被激活，以促进热应激期间的全身热量损失。我们使用世界唯一的空气量热法（一种提供了人体散发热量的非常精确测量的设备），我们表明，热效应响应的生理控制，因此全身热量损失可能随着几个个体间个体的函数而变化因素（例如，年龄，性别，其他）和 - 个体内部因素（例如健身，水合，暴露时间）。这包括与感官受体激活（例如压力感受器，分类受体）相关的非热因子的影响。虽然我们基于量热法的研究提高了我们对限制人类热耐受性的因素的理解，但我们评估细胞热应激反应的新兴工作正在发现有助于热有关的脆弱性的复杂细胞机制。为了继续推进这项重要的工作，我正在寻求取代较旧的，不足的工具，并获得新的工具，以提高我们进行这项创新研究并最大化我们的研究成果的能力。具体而言，该提案的目的是通过替换量热计的过时数据采集接口平台来扩大我们的研究活动的范围和影响，以监视生理反应（即，可扩展的系统，促进了能够适应能够适应一种数据采用系统在一个系统下记录多个生理变量所需的硬件接口范围）。这将消除我们对使用不同数据采集系统和软件平台的多个监测站的依赖，并为我们的基于量热法的研究提供了未来扩展其他生理变量的能力。此外，我们正在寻求更换较旧的工具并获取新的仪器（例如离心机，平台摇动，挥舞旋转器，蛋白质印迹成像系统，蛋白质印迹电泳系统），以满足我们的需求，并增强我们评估蛋白质和基因响应的能力，以进行研究热脆弱性的细胞机制。这将使我们能够在理解从细胞到整体反应的人类耐热性的因素中弥合差距，从而帮助我们实现下一个发现和创新的梯队。重要的是，它将吸引新的学员干部，并推动新一代的科学增长和文化，以应对行业和我们人口其他部门所面临的现实挑战，受到温暖星球刺激的极端热量影响。