Neuromuscular fatigue during hypoxia is mediated by the hypoxic ventilatory response
© Hartley et al. 2015
Published: 14 September 2015
Neurons of the corticospinal tract are inherently sensitive to oxygen availability and, in response to hypoxia, reduce their metabolic requirements and activity . Consequently, hypoxia is associated with neuromuscular fatigue, attributed in part to central (i.e., CNS) mechanisms . Although changes in cerebral blood flow (CBF), mediated by the ratio of hypoxia induced vasodilation to hypoxic ventilatory response (HVR) induced hypocapnia (i.e., PETCO2) , may be implicated in the development of central fatigue, the contribution from the chemoreflex control of HVR and CBF vs. reductions in CBF per se has yet to be isolated.
Neuromuscular function, indicated by voluntary torque production, motor evoked potentials (MEP), M-waves and cortical voluntary activation (cVA) of the flexor carpal radialis muscle during isometric wrist flexion was assessed (n = 8; 27 ± 8 y) during 3 separate conditions: 1) poikilocapnic hypoxia (Poikilo); 2) isocapnic hypoxia (Iso); and 3) isocapnic hypoxia and cyclooxygenase inhibition using Indomethacin (Indo) to selectively reduce CBF (estimated using transcranial Doppler ultrasound). End-tidal forcing was used to control PETO2 (51.5 ± 5.1 mmHg) during all conditions and PETCO2 at eucapnia during Iso (43.4 ± 4.0 mmHg) and Indo (41.6 ± 3.8 mmHg). Measurements were taken during baseline and upon steady-state response (i.e., stable SaO2) to hypoxia (approximately 5 minutes).
The experimental conditions successfully isolated CBF and PETCO2. Iso and Indo were associated with a pronounced HVR (0.93 ± 0.60 L·min-1.SaO2-1 and 1.15 ± 0.72 L·min-1.SaO2-1) vs. Poikilo (0.26 ± 0.15 L·min-1·SaO2-1, p < 0.05). Torque was reduced from baseline in all conditions (-10.9 ± 13.7 Nm, p = 0.03). MEP amplitude (% M-wave) decreased in Poikilo (-4.5 ± 3.5%, p = 0.02) and Indo (-4.5 ± 4.8%, p = 0.02) vs. Iso (0.8 ± 2.8%; p = 0.9). No changes were observed in M-wave (p = 0.81). cVA decreased in all conditions (p < 0.01); however, reductions were greater during Iso (-11.5 ± 9.3%, p = 0.01) and Indo (-12.5 ± 9.1%, p = 0.04) vs. Poikilo (-3.8 ± 11.5%, p = 0.77).
Consistent with previous research , hypoxia resulted in impaired neuromuscular function (i.e., reduced torque) in all conditions. These reductions were mediated by the CNS, as cVA decreased in the absence of changes in M-wave. Reductions in cVA were greater during Iso and Indo, suggesting an association with the magnitude of the HVR. Reduced CBF during Poikilo and Indo was associated with decreased motor cortex excitability; however, was not associated with decrements in torque or cVA.
This study demonstrates that the severity of CNS-mediated neuromuscular fatigue during hypoxia is dependent on the magnitude of the HVR, independent of changes in CBF.
- Neubauer JA, Sunderram J: Oxygen-sensing neurons in the central nervous system. J Appl Physiol. 2004, 96 (1): 367-374.View ArticlePubMedGoogle Scholar
- Amann M, Romer LM, Subudhi AW, Pegelow DF, Dempsey JA: Severity of arterial hypoxaemia affects the relative contributions of peripheral muscle fatigue to exercise performance in healthy humans. J Physiol. 2007, 581 (Pt 1): 389-403. 10.1113/jphysiol.2007.129700.PubMed CentralView ArticlePubMedGoogle Scholar
- Ainslie PN, Lucas SJE, Burgess KR: Breathing and sleep at high altitude. Respir Physiol Neurobiol. 2013, 188 (3): 233-256. 10.1016/j.resp.2013.05.020.View ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.