Validity and accuracy of calculating oxidative ATP synthesis in vivo during high-intensity skeletal muscle contractions.

Several methods have been developed for using P-MRS to calculate rates of oxidative ATP synthesis (ATP ) during muscular contractions based on assumptions that (1) the ATP cost of force generation (ATP ) remains constant or (2) Michaelis-Menten coupling between cytosolic ADP and ATP does not change. However, growing evidence suggests that one, or both, of these assumptions are invalid during high-intensity fatigue protocols. Consequently, there is a need to examine the validity and accuracy of traditional ATP calculation methods under these conditions. To address this gap, we measured phosphate concentrations and pH in the vastus lateralis muscle of nine young adults during four rest-contraction-recovery trials lasting 24, 60, 120, and 240 s. The initial velocity of phosphocreatine resynthesis (V ) following each trial served as the criterion measure of ATP because this method makes no assumptions of constant ATP or Michaelis-Menten coupling between changes in cytosolic ADP and ATP . Subsequently, we calculated ATP throughout the 240 s trial using several traditional calculation methods and compared estimations of ATP from each method with time-matched measurements of V . Method 1, which assumes that ATP does not change, was able to model changes in V over time, but showed poor accuracy for predicting V across a wide range of ATP values. In contrast, Michaelis-Menten methods, which assume that the relationship between changes in cytosolic ADP and ATP remains constant, were invalid because they could not model the decline in V . However, adjusting these Michaelis-Menten methods for observed changes in maximal ATP capacity (i.e., V ) permitted modeling of the decline in V and markedly improved accuracy. The results of these comprehensive analyses demonstrate that valid, accurate measurements of ATP can be obtained during high-intensity contractions by adjusting Michaelis-Menten ATP calculations for changes in V observed from baseline to post-fatigue.