Cardiovascular and muscle oxidative adaptations to exercise

肌肉在运动过程中的耗氧量取决于对流输氧量、氧从毛细血管向线粒体的扩散以及肌肉线粒体的激活状态、氧亲和力和呼吸能力。长期目标是了解循环系统和肌肉氧化系统在定义急性运动期间人体肌肉摄氧量方面的相对贡献，以及这些系统是如何调节和适应体育训练的。我的短期目标建立在最新进展的基础上，整合了以两个主题为中心的氧气瀑布的组成部分。*主题I侧重于中央循环的作用，以及通过自主神经系统和局部肌肉血管扩张机制的相互作用来调节流向肌肉的血流的区域分布的机制。这项研究建立在最近的工作基础上，该研究采用新的方法来量化人类运动期间心脏、区域肢体和肌肉微循环血流量，并通过运动肢体的动脉和静脉采样。*主题II检查了从毛细血管到肌肉线粒体的氧气扩散的组成部分，以及肌肉线粒体如何在结构和功能上进行调节。这项工作结合了测量四肢血流量的方法，采血测量氧含量的方法，以及肌肉活检中线粒体的呼吸功能。*目的1.循环在增加训练中肌肉最大摄氧量方面的作用。运动训练增加肌肉线粒体体积和肌肉氧化能力。然而，更高的肌肉摄氧量可以通过将血流量更大地分配到收缩肌肉、更大的血管密度、减缓血细胞通过肌肉的速度来实现，从而允许更大的氧气扩散和更高的线粒体相对活性。这项研究计划将量化中央、区域和微循环以及肌肉氧化能力的相对作用，以促进我们对人类氧级联成分的适应性反应的理解。*目标2.运动中线粒体在肌肉氧提取中的作用。*很早就知道训练增加了肌肉氧提取。这项研究计划将研究线粒体对氧的亲和力的变化如何增加肌肉的摄氧量。这个研究项目将通过改变线粒体的激活速度来研究氧亲和力是如何被敏锐地调节的。还需要检查的是，线粒体中表达的与氧结合的酶(细胞色素c氧化酶)的形式是否会随着运动训练的时间而改变。利用电子显微镜的先进成像技术，将确定产生最大细胞能量的线粒体内膜体积的变化，以研究一种新的氧摄取调节机制。

Oxygen consumption by muscle during exercise depends on convective oxygen delivery, diffusion of oxygen from the capillaries to mitochondria and the activation state, oxygen affinity and respiratory capacity of muscle mitochondria. The long-term objective is to understand the relative contributions of the circulatory and muscle oxidative systems in defining muscle oxygen uptake in humans during acute exercise and how these systems are regulated and adapt to physical training. My short-term objectives build upon recent advances integrating components of the oxygen cascade that center on two main themes.****Theme I focuses on the role the central circulation, and the mechanisms regulating regional distribution of blood flow to muscle through the interaction of autonomic nervous system and local muscle vasodilatory mechanisms. This research builds on recent work employing novel methods to quantify blood pumped by the heart, regional limb and muscle microcirculatory blood flow during exercise in humans combined with arterial and venous sampling across an exercising limb.****Theme II examines the components of oxygen diffusion from the capillaries to muscle mitochondria, and how muscle mitochondria are regulated structurally and functionally. This work integrates methods to measure blood flow in the limbs, blood sampling to measure oxygen content, and mitochondrial respiratory function in muscle biopsies.****Aim 1. The role of the circulation for increasing peak muscle oxygen uptake with training. Exercise training increases muscle mitochondrial volume and muscle oxidative capacity. However, a higher muscle oxygen uptake can be achieved through a greater distribution of blood flow to contracting muscle, a greater density of blood vessels, slowing of the rate of passage of blood cells through the muscle allow greater diffusion of oxygen and a higher relative activation of mitochondria. This research program will quantify the relative roles of the central, regional and microcirculations and muscle oxidative capacity to advance our understanding of adaptive response of the components of the oxygen cascade in humans.****Aim 2. The role of mitochondria in muscle oxygen extraction during exercise.****It has long been known that training increases muscle oxygen extraction. This research plan will examine how changes in the affinity of mitochondria for oxygen increases muscle oxygen uptake. This program of research will examine how oxygen affinity is regulated acutely by altering the rate at which mitochondria are activated. Also to be examined is whether the form of enzyme expressed in mitochondria that binds oxygen (cytochrome c oxidase) is altered over time with exercise training. Using advanced imaging with electron microscopy, changes in the volume of the inner mitochondrial membrane where most cellular energy is produced will be determined to examine a novel mechanism regulating oxygen uptake.**