Central and peripheral determinants of fatigue in acute hypoxia

Abstract

Fatigue is defined as an exercise-induced decrease in maximal voluntary force produced by a muscle. Fatigue may arise from central and/or peripheral mechanisms. Supraspinal fatigue (a component of central fatigue) is defined as a suboptimal output from the motor cortex and measured using transcranial magnetic stimulation (TMS). Reductions in O2 supply (hypoxia) exacerbate fatigue and as the severity of hypoxia increases, central mechanisms of fatigue are thought to contribute more to exercise intolerance. In study 1, the feasibility of TMS to measure cortical voluntary activation and supraspinal fatigue of human knee-extensors was determined. TMS produced reliable measurements of cortical voluntary activation within- and between-days, and enabled the assessment of supraspinal fatigue. In study 2, the mechanisms of fatigue during single-limb exercise in normoxia (arterial O2 saturation [SaO2] ~98%), and mild to severe hypoxia (SaO2 93-80%) were determined. Hypoxia did not alter neuromuscular function or cortical voluntary activation of the knee-extensors at rest, despite large reductions in cerebral oxygenation. Maximal force declined by ~30% after single-limb exercise in all conditions, despite reduced exercise time in severe-hypoxia compared to normoxia (15.9 ± 5.4 vs. 24.7 ± 5.5 min; p < 0.05). Peripheral mechanisms of fatigue contributed more to the reduction in force generating capacity of the knee-extensors following single-limb exercise in normoxia and mild- to moderate-hypoxia, whereas supraspinal fatigue played a greater role in severe-hypoxia. In study 3, the effect of constant-load cycling exercise to the limit of tolerance in hypoxia (SaO2 ~80%) and normoxia was investigated. Time to the limit of tolerance was significantly shorter in hypoxia compared to normoxia (3.6 ± 1.3 vs. 8.1 ± 2.9 min; p < 0.001). The reductions in maximal voluntary force and knee-extensor twitch force at task-failure were not different in hypoxia compared to normoxia. However, the level of supraspinal fatigue was exacerbated in hypoxia, and occurred in parallel with reductions in cerebral oxygenation and O2 delivery. Supraspinal fatigue contributes to the decrease in whole-body exercise tolerance in hypoxia, presumably as a consequence of inadequate O2 delivery to the brain.