Dissociation of [H+] from fatigue in human muscle detected by high time resolution 31P‐NMR

Previous in vivo studies of skeletal muscle fatigue have demonstrated significant relationships between the decline of muscular force and changes in muscle metabolism. However, these studies performed measurements over relatively long time intervals or during steady state exercise, thereby obscuring rapid metabolic changes occurring at the onset of exercise and recovery. To overcome these limitations, fatigue of human calf musculature during sustained isometric foot plantar flexion was quantified continuously as the decline in maximal voluntary contraction force (MVC), while concentrations of phosphocreatine (PCr), inorganic phosphate (Pi), intracellular free hydrogen ion (H+), and monovalent phosphate (H2PO4-) were simultaneously measured at 2-second intervals by 31P nuclear magnetic resonance. The first major finding was that [H+], which has been thought to be a mediator of muscle fatigue, actually declined during the first 10 seconds of exercise when force was declining and rose immediately postexercise, when force partially recovered. Second, the correlations of [H+], [H2PO4-] and Pi with MVC during the first minute of exercise were determined to be curvilinear and not linear as previously suggested. Furthermore, using either a linear or curvilinear regression model, [H2PO4-] and Pi demonstrated a closer correlation to MVC than [H+] during the first minute of exercise. Thus, these results reveal nuances in the relationships of MVC to metabolites previously undetected by low time-resolution measurements. These findings suggest that during sustained isometric exercise, rising [H+] is not likely to be the sole mechanism of muscle fatigue and are consistent with the view that a rise of Pi or [H2PO4-] is a major causation factor in force reduction.