CO2 Clamping, Peripheral and Central Fatigue during Hypoxic Knee Extensions in Men

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The central nervous system can play a critical role in limiting exercise performance during hypoxic conditions. Hypocapnia, which is associated with hypoxia-induced hyperventilation, may affect cerebral perfusion. We hypothesized that CO2 clamping during hypoxic isometric knee extensions would improve cerebral oxygenation and reduce central fatigue.


Fifteen healthy men (mean ± SD: age, 25 ± 8 yr; body mass, 72 ± 11 kg; height, 179 ± 7 cm) performed intermittent isometric knee extensions at ∼50% of maximal voluntary contraction to task failure in normoxia, hypoxia with CO2 clamping (arterial O2 saturation, 80% ± 2%; end-tidal CO2 partial pressure, 40 ± 2 mm Hg), and hypoxia without CO2 clamping (arterial O2 saturation, 80% ± 3%). Transcranial magnetic stimulation and femoral nerve electrical stimulation were used to assess central and peripheral determinants of fatigue. Prefrontal cortex and quadriceps femoris oxygenation were monitored by multichannel near-infrared spectroscopy.


Exercise duration was reduced to a similar extent in hypoxia with CO2 clamping (997 ± 460 s) or hypoxia without CO2 clamping (929 ± 412 s) compared to normoxia (1473 ± 876 s; P < 0.001). Prefrontal cortex and quadriceps oxygenation were increased (+5.3 ± 8.6 and +2.6 ± 3.0 μmol·cm at task failure, respectively; P < 0.01) during hypoxia with CO2 clamping compared to hypoxia without CO2 clamping. Transcranial magnetic stimulation maximal voluntary activation decreased to a greater extent at task failure in hypoxia without CO2 clamping (−18% ± 8%) compared to hypoxia with CO2 clamping (−9% ± 9%; P < 0.01) and normoxia (−10% ± 7%; P < 0.05). Conversely, exercise-induced peripheral fatigue was larger in hypoxia with CO2 clamping than in hypoxia without CO2 clamping (e.g., Db10-to-Db100 ratio of 0.54 ± 0.12 and 0.63 ± 0.11 at task failure, respectively; P < 0.05).


The results demonstrate that CO2 clamping can alter central and peripheral mechanisms that contribute to neuromuscular fatigue during hypoxic isometric knee extensions in men. Hypocapnia impairs cerebral oxygenation and central drive but exerts a protective effect against fatigability in muscles.

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