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.
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