Chemoreflex control of breathing and the circulation

Chemoreflex 控制呼吸和循环

• 批准号: RGPIN-2021-03980
• 负责人: Keir, Daniel
• 金额: $ 2.4万
• 依托单位: University of Western Ontario
• 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=741919
• 关键词: Chemoreflex; control; breathing; circulation

Anyone who has ever held their breath will have felt an overwhelming urge to resume breathing and a coincident rise in heart contractions. This response is governed by chemoreflexes arising from specialized carbon dioxide/acid sensors in the brainstem and arteries that activate breathing and the circulation (via the sympathetic nervous system) in ways that counteract the acidifying and blood pressure lowering effects of carbon dioxide. Often, in environments (e.g. poorly ventilated areas), activities (e.g. exercise) and conditions (e.g. sleep) that challenge carbon dioxide removal, central and peripheral chemoreflexes are engaged simultaneously but their relative contributions to breathing and circulatory responses have yet to be established. A source of controversy is whether they compete with each other and with other reflexes that are stimulated by breathing and blood pressure changes. The objective of my research program is to determine whether central and peripheral chemoreflexes interact with each other in the control of breathing and with other sympathetic nervous system sensors that regulate the resistance to flow within the small vessels of skeletal muscle when pH falls. My research program will explore the hypothesis that central and peripheral chemoreflexes do not interact in the control of breathing (their drives are additive) but their ability to reflexively raise sympathetic outflow is modulated by other respiratory and cardiovascular reflexes. My approach employs techniques to study the impact of alterations in tissue oxygen and carbon dioxide (stimulus) pressures on the respiratory, sympathetic and cardiovascular systems (response) in humans. I apply breath-by-breath measures of flow, volume and gas exchange to quantify ventilation and to measure end-tidal gas pressures. With this method, I can precisely alter blood gas pressures, and thus known input to central and peripheral chemoreceptors, by manipulating inspired gas concentrations in unique ways. To capture the respiratory and sympathetic output in response to chemoreceptor stimulation, I assess ventilation in concert with the technique of microneurography to directly record the firing discharge of vasoconstrictive sympathetic nerves innervating muscle vasculature. My research will develop new models of respiratory and sympathetic control via the chemoreflexes and provide a high-quality training environment for trainees to develop desirable research skills in human cardiorespiratory investigation. Chemoreflexes are increasingly recognized in the pathophysiology of conditions that impact the respiratory (sleep apnea; lung disease) and cardiovascular systems (heart failure, hypertension); as a mechanism of disordered breathing and source of excess sympathetic nervous system activation. Chemoreflex control models will impact therapies and trials designed to intervene at the central and peripheral chemoreceptors to stabilize breathing or inhibit their sympathetic output.

任何曾经屏住呼吸的人都会感到一种强烈的冲动，想要恢复呼吸，同时心脏收缩也会加剧。这种反应是由脑干和动脉中专门的二氧化碳/酸传感器产生的化学反射控制的，这些化学反射激活呼吸和循环（通过交感神经系统），以抵消二氧化碳的酸化和降血压作用。通常，在环境（例如通风不良的区域）、活动（例如运动）和条件（例如睡眠）中，中枢和外周化学反射同时进行，但它们对呼吸和循环反应的相对贡献尚未确定。争议的一个来源是它们是否相互竞争，以及是否与呼吸和血压变化所刺激的其他反射相竞争。我的研究项目的目的是确定当pH值下降时，中枢和外周化学反射是否在控制呼吸和其他交感神经系统传感器中相互作用，这些传感器调节骨骼肌小血管内的血流阻力。我的研究计划将探索这样一种假设，即中枢和外周化学反射在控制呼吸方面没有相互作用（它们的驱动是附加的），但它们反射性地提高交感神经外流的能力是由其他呼吸和心血管反射调节的。我的方法采用技术来研究组织氧和二氧化碳（刺激）压力对人类呼吸、交感和心血管系统（反应）的改变的影响。我用每一次呼吸的流量，体积和气体交换来量化通风和测量潮汐末的气体压力。有了这种方法，我可以精确地改变血气压力，从而通过以独特的方式操纵激发气体浓度来改变中枢和外周化学感受器的已知输入。为了捕捉化学感受器刺激下的呼吸和交感神经输出，我结合微神经摄影技术评估通气，直接记录支配肌肉脉管系统的血管收缩交感神经的放电。我的研究将通过化学反射发展呼吸和交感神经控制的新模型，并为学员提供高质量的培训环境，以培养他们在人类心肺研究方面所需的研究技能。化学反射在影响呼吸系统（睡眠呼吸暂停、肺病）和心血管系统（心力衰竭、高血压）的病理生理学中得到越来越多的认识；作为呼吸紊乱的机制和过度交感神经系统激活的来源。化学反射控制模型将影响旨在干预中枢和外周化学感受器以稳定呼吸或抑制其交感神经输出的治疗和试验。