On the role of skeletal muscle acidosis and inorganic phosphates as determinants of central and peripheral fatigue: A P-MRS study.

Intramuscular hydrogen ion (H ) and inorganic phosphate (Pi) concentrations were dissociated during exercise to challenge their relationships with peripheral and central fatigue in vivo. Ten recreationally active, healthy men (27 ± 5 years; 180 ± 4 cm; 76 ± 10 kg) performed two consecutive intermittent isometric single-leg knee-extensor trials (60 maximal voluntary contractions; 3 s contraction, 2 s relaxation) interspersed with 5 min of rest. Phosphorus magnetic resonance spectroscopy ( P-MRS) was used to continuously quantify intramuscular [H ] and [Pi] during both trials. Using electrical femoral nerve stimulation, quadriceps twitch force (Q ) and voluntary activation (VA) were quantified at rest and throughout both trials. Decreases in Q and VA from baseline were used to determine peripheral and central fatigue, respectively. Q was strongly related to both [H ] (β coefficient: -0.9, P < 0.0001) and [Pi] (-1.1, P < 0.0001) across trials. There was an effect of trial on the relationship between Q and [H ] (-0.5, P < 0.0001), but not Q and [Pi] (0.0, P = 0.976). This suggests that, unlike the unaltered association with [Pi], a given level of peripheral fatigue was associated with a different [H ] in Trial 1 vs. Trial 2. VA was related to [H ] (-0.3, P < 0.0001), but not [Pi] (-0.2, P = 0.243), across trials and there was no effect of trial (-0.1, P = 0.483). Taken together, these results support intramuscular Pi as a primary cause of peripheral fatigue, and muscle acidosis, probably acting on group III/IV muscle afferents in the interstitial space, as a contributor to central fatigue during exercise. KEY POINTS: We investigated the relationship between intramuscular metabolites and neuromuscular function in humans performing two maximal, intermittent, knee-extension trials interspersed with 5 min of rest. Concomitant measurements of intramuscular hydrogen (H ) and inorganic phosphate (Pi) concentrations, as well as quadriceps twitch-force (Q ) and voluntary activation (VA), were made throughout each trial using phosphorus magnetic resonance spectroscopy ( P-MRS) and electrical femoral nerve stimulations. Although [Pi] fully recovered prior to the onset of the second trial, [H ] did not. Q was strongly related to both [H ] and [Pi] across both trials. However, the relationship between Q and [H ] shifted leftward from the first to the second trial, whereas the relationship between Q and [Pi] remained unaltered. VA was related to [H ], but not [Pi], across both trials. These in vivo findings support the hypotheses of intramuscular Pi as a primary cause of peripheral fatigue, and muscle acidosis, probably acting on group III/IV muscle afferents, as a contributor to central fatigue.