MR DIAGNOSIS OF MUSCLE METABOLISM AND FUNCTION

描述：该项目的目标是开发诊断程序 使用31-P/1-H NMR光谱和1-H NMR测定人体肌肉功能 成像与第一次开发的能量平衡原理一起 补助期。 申请人的工作假设是， 能量平衡提供了定义正常能量的基本机械信息 并解释正常人肢体的异常肌肉功能。 的 前三个具体目标发展了综合大众的概念， 能量平衡 PCR内容衡量供需平衡之间 肌肉ATP酶和氧化磷酸化。 肌红蛋白去饱和 测量氧化磷酸化和 肌肉灌注 细胞内pH值和乳酸盐测量了 净糖酵解通量和灌注洗脱。 收缩经济 人肢体肌肉将通过表征ATP酶来定量， 肌原纤维力的产生和兴奋-收缩偶联。 运动期间PCr水平是否是局部灌注和O2之间的联系 需求将受到测试， 将量化运动期间的糖原分解通量。 第四特定 目的将探讨两个临床问题的不平衡，在一个或多个 肌肉能量学的组成部分。 充血性心力衰竭患者 将探测ATP、H+和氧平衡的异常， 1型糖尿病患者将被探索在异常之间进行权衡 导致肌肉的功能降低，但接近正常的整合 能量学

DESCRIPTION: The goal of this project is to develop diagnostic procedures for human muscle function using 31-P/1-H NMR spectroscopy and 1-H NMR imaging together with principles of energy balance developed in the first grant period. The applicants working hypothesis is that integration of energy balance provides mechanistic information essential to define normal and to interpret abnormal muscle function in the intact human limb. The first three specific aims develop the notions of an integrative mass and energy balance. PCr content measures the supply-demand balance between muscle ATPases and oxidative phosphorylation. Myoglobin desaturation measures the supply-demand balance between oxidative phosphorylation and muscle perfusion. Intracellular pH and lactate measures the balance between net glycolytic flux and washout by perfusion. The contractile economy in human limb muscles will be quantified by characterizing the ATPase due to myofibrillar force generation and to excitation-contraction coupling. Whether PCr level during exercise is the link between local perfusion and O2 demand will be tested and the magnitude and time course of the glycogenolytic flux during exercise will be quantified. The fourth specific aim will probe two clinical problems for imbalances in one or more components of muscle energetics. Patients with congestive heart failure will be probed for abnormalities in ATP, H+ and oxygen balances and patients with type 1 diabetes will be probed for a trade-off in abnormalities resulting in lower functional, but near-normal integration of muscle energetics.