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

我们的研究是在人类系统层面上进行的综合生理学。我们的研究项目考察了运动中气体交换、心血管反应、肌肉血流量、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”模型被用来说明这些系统的可塑性，而老年人提供了一个模型来辨别心血管控制因素、气体交换和肌肉代谢的调节以及运动反应中的限制因素。我们研究的一个主题是对肺氧摄取调节的时间进程(VO2P动力学)的研究，它提供了关于控制机制以及心血管和肌肉氧气利用(线粒体呼吸)对运动能量需求的动态“耦合”调节的信息。我们研究的一个目标是确定控制VO2动力学的机制以及O2输送和/或O2利用施加的限制。这种科学方法使用逐次呼吸的肺泡气体交换，结合多普勒超声测量逐跳导管动脉血流，局部肌肉微血管氧化/去氧的近红外光谱(NIRS)测量，以及运动瞬变期间肌肉组织的活组织采样，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方面是独一无二的，我们对VO2p的动力学研究在国内和国际上都得到了认可。我们一贯报告，在健康的老年人和年轻人中，VO2P(以及肌肉血流和氧气输送)动力学I)较慢，ii)在不太健康、未受过训练的个人中，III)在运动中从高基线代谢率到低基线代谢率，iv)由于过度换气导致的低碳酸碱中毒，以及v)在食用高脂肪和高碳水化合物饮食后，这意味着对线粒体能量产生的调节既依赖氧气又独立的机制。通过这个赠款周期，我们计划研究VO2P动力学和肌肉氧气利用、血流和氧气输送以及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、肌肉底物可获得性(通过饮食干预)、基线代谢率以及运动训练导致的内皮功能和血流调节变化的时间进程之间的关系。这些研究有助于我们理解对体力活动能量供应的控制，并为预防和逆转可能导致运动不耐受的心血管和/或代谢系统与年龄有关的变化提供方向。

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.**