Severity of arterial hypoxaemia affects the relative contributions of peripheral muscle fatigue to exercise performance in healthy humans

Abstract

We examined the effects of hypoxia severity on peripheral versus central determinants of exercise performance. Eight cyclists performed constant-load exercise to exhaustion at various fractions of inspired O2 fraction (FIO2 0.21/0.15/0.10). At task failure (pedal frequency < 70% target) arterial hypoxaemia was surreptitiously reversed via acute O2 supplementation (FIO2 = 0.30) and subjects were encouraged to continue exercising. Peripheral fatigue was assessed via changes in potentiated quadriceps twitch force (DeltaQ(tw,pot)) as measured pre- versus post-exercise in response to supramaximal femoral nerve stimulation. At task failure in normoxia (haemoglobin saturation (SpO2) approximately 94%, 656 +/- 82 s) and moderate hypoxia (SpO2) approximately 82%, 278 +/- 16 s), hyperoxygenation had no significant effect on prolonging endurance time. However, following task failure in severe hypoxia (SpO2) approximately 67%; 125 +/- 6 s), hyperoxygenation elicited a significant prolongation of time to exhaustion (171 +/- 61%). The magnitude of DeltaQ(tw,pot) at exhaustion was not different among the three trials (-35% to -36%, P = 0.8). Furthermore, quadriceps integrated EMG, blood lactate, heart rate, and effort perceptions all rose significantly throughout exercise, and to a similar extent at exhaustion following hyperoxygenation at all levels of arterial oxygenation. Since hyperoxygenation prolonged exercise time only in severe hypoxia, we repeated this trial and assessed peripheral fatigue following task failure prior to hyperoxygenation (125 +/- 6 s). Although Q(tw,pot) was reduced from pre-exercise baseline (-23%; P < 0.01), peripheral fatigue was substantially less (P < 0.01) than that observed at task failure in normoxia and moderate hypoxia. We conclude that across the range of normoxia to severe hypoxia, the major determinants of central motor output and exercise performance switches from a predominantly peripheral origin of fatigue to a hypoxia-sensitive central component of fatigue, probably involving brain hypoxic effects on effort perception.

Figures

Figure 1

Quadriceps twitch force (Qtw; A) and M-wave amplitudes (rectus femoris, vastus medialis, vastus lateralis; B) as a direct response to magnetic stimulation of the femoral nerve applying single twitches at increasing stimulator power settings. Means ± s.e.m., n = 8.

Figure 2. Representative example showing the effects of increases in arterial O2 content on pedal frequency and endurance time to exhaustion

The arrow indicates the point at which the inspirate was switched from either normoxia (A; FIO2 0.21), moderate hypoxia (B; FIO2 0.15), or severe hypoxia (C; FIO2 0.10) to hyperoxia (FIO2 0.30). The criterion for increasing the FIO2 was a drop in pedal frequency below 70% of the respective individual target rev min−1 for ≥5 s (67 rev min−1 in this case). The exercise was terminated following a further reduction in pedal frequency below 60% of the respective individual target rev min−1 for ≥5 s (57 rev min−1).

Figure 3. Capillary blood lactate (A) and heart rate (B) during various exercise trials

Filled symbols represent values obtained in the respective FIO2 condition (0.21/0.15/0.10), open symbols indicate values at exhaustion in hyperoxia (FIO2 0.30). §P < 0.05 versus exhaustion in normoxia and moderate hypoxia. †P < 0.05 versus exhaustion in hyperoxia.

Figure 4. Peripheral quadriceps fatigue (Qtw,pot, potentiated twitch force) assessed 2 min following various trials with different values for FIO2

Time performed in the respective FIO2 (0.21/0.15/0.10) and the additional exercise time following reoxygenation via a hyperoxic inspirate (FIO2 0.30) are indicated below the x-axis. No fatigue data are available for the point of exhaustion in normoxia (immediately prior to switch to hyperoxia). The trial in severe hypoxia (125 ± 6 s; FIO2 0.10) was also repeated in normoxia (isotime-severe hypoxia) to reveal the effects of severe hypoxia on locomotor muscle fatigue. *P < 0.05 versus FIO2 0.15 and 0.30; †P < 0.05 versus FIO2 0.10, 0.15 and 0.30.

Figure 5. Myoelectrical activity (integrated EMG (iEMG)) of vastus lateralis during exercise at 333 ± 9 W in normoxia and two levels of hypoxia

Values are normalized to the mean of first minute of each trial. The mean value for iEMG during each muscle contraction (cycle revolution) was calculated and averaged over each 60 s period. Filled symbols represent values obtained in the respective FIO2 condition (0.21/0.15/0.10), open symbols indicate iEMG values obtained at the termination of exercise (final exhaustion) after the switch to the hyperoxic inspirate (FIO2 0.30). *P < 0.05 from previous value. †P < 0.05 from normoxia at isotime.

Figure 6. Micromolar changes in oxyhaemoglobin (O2Hb) from normoxic rest period (0 μm) to exhaustion for a single subject

A, normoxia; B, moderate hypoxia; C, severe hypoxia. Dark lines represent cerebral [O2Hb] and light lines represent vastus lateralis [O2Hb]. The arrows indicate the points at which the inspirate was switched from either normoxia (A; FIO2 0.21), moderate hypoxia (B; FIO2 0.15), or severe hypoxia (C; FIO2 0.10) to hyperoxia (FIO2 0.30), and the end termination of exercise (exhaustion).