Regulation of gas exchange and metabolism in exercise, system limits and age-related modulation

运动中气体交换和新陈代谢的调节、系统限制和年龄相关调节

• 批准号: RGPGP-2015-00084
• 负责人: Kowalchuk, John
• 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 - Group
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=655950
• 关键词: Regulation; gas; exchange; metabolism; exercise

Our research is in integrative physiology at the systems level in humans. Our research programme examines the control and interrelationship amongst gas exchange, cardiovascular responses, muscle blood flow, muscle microvascular oxygenation, and muscle metabolism during exercise. Our `ageing' model is used to illustrate the plasticity of these systems, and older adults provide a model to discern cardiovascular control factors, regulation of gas exchange and muscle metabolism, and limiting factors in the exercise response. A theme in our research is our studies of the time course of adjustment of pulmonary O2 uptake (VO2P kinetics) which provides information on control mechanisms and the dynamic `coupling' between cardiovascular and muscle O2 utilization (mitochondrial respiration) adjustments to the energy demands of exercise. An objective of our research is to identify mechanisms controlling VO2 kinetics and the constraints imposed by O2 delivery and/or O2 utilization. The scientific approach uses breath-by-breath alveolar gas exchange coupled with measures of beat-by-beat conduit artery blood flow by Doppler ultrasound, near-infrared spectroscopy (NIRS) measures of local muscle microvascular oxy/deoxygenation, and biopsy sampling of muscle tissue during exercise transients to measure changes in muscle substrate provision, metabolite content and enzyme activities. We are unique in combining both non-invasive and invasive measures into our research programme, and we are recognized nationally and internationally for our studies on VO2p `kinetics'. We consistently report slower VO2P (and muscle blood flow and O2 delivery) kinetics i) in healthy old vs young adults, ii) in less fit, untrained individuals, iii) in exercise transitions from a high vs low baseline metabolic rate, iv) consequent to induction of a hyperventilation-induced hypocapnic alkalosis, and v) after consuming high fat vs high carbohydrate diets, which implicates both O2 dependent and independent mechanisms contributing to the regulation of mitochondrial energy production. With this grant cycle we plan to examine relationships amongst VO2P kinetics and muscle O2 utilization, blood flow and O2 delivery, and muscle metabolism and mitochondrial respiration kinetics in young and older adults. We also plan to examine the relationships amongst VO2P and exercise training, muscle substrate availability (through dietary intervention), baseline metabolic rate, and time course of change in endothelial function and blood flow adjustment consequent to exercise training. These studies contribute to our understanding of control of energy provision for physical activity, and provide direction for preventing and reversing age-related changes to the cardiovascular and/or metabolic systems which may contribute to exercise intolerance.**

我们的研究是人类系统层面的综合生理学。我们的研究项目探讨了运动过程中气体交换、心血管反应、肌肉血流、肌肉微血管氧合和肌肉代谢之间的控制和相互关系。我们的“衰老”模型用于说明这些系统的可塑性，老年人提供了一个模型来辨别心血管控制因素，调节气体交换和肌肉代谢，以及运动反应中的限制因素。我们研究的一个主题是我们对肺氧气摄取（VO2P动力学）调节的时间过程的研究，它提供了控制机制和心血管和肌肉氧气利用（线粒体呼吸）调节运动能量需求之间的动态“耦合”信息。我们研究的一个目标是确定控制VO2动力学的机制以及由O2输送和/或O2利用施加的约束。科学的方法是使用呼吸肺泡气体交换，通过多普勒超声测量每一次搏动的导管动脉血流，近红外光谱（NIRS）测量局部肌肉微血管氧/脱氧，并在运动瞬间对肌肉组织进行活检取样，以测量肌肉底物供应、代谢物含量和酶活性的变化。我们在将非侵入性和侵入性措施结合到我们的研究计划中是独一无二的，我们在VO2p“动力学”方面的研究在国内和国际上得到了认可。我们一致报告了VO2P（以及肌肉血流量和氧气输送）动力学减慢的情况：(1)健康老年人与年轻人，(2)不太健康、未经训练的个体，(3)从高基线代谢率与低基线代谢率的运动过渡，(4)由于诱导过度通气引起的低碳水化合物碱中毒，(5)在摄入高脂肪与高碳水化合物饮食后。这意味着O2依赖性和独立机制都有助于线粒体能量产生的调节。在这个资助周期中，我们计划研究年轻人和老年人VO2P动力学与肌肉O2利用、血流和O2输送、肌肉代谢和线粒体呼吸动力学之间的关系。我们还计划研究VO2P与运动训练、肌肉底物可用性（通过饮食干预）、基线代谢率以及运动训练后内皮功能和血流调节变化的时间过程之间的关系。这些研究有助于我们理解身体活动能量供应的控制，并为预防和逆转心血管和/或代谢系统的年龄相关变化提供方向，这些变化可能导致运动不耐受