Neurophysiological responses to rest and fatiguing exercise in severe hypoxia in healthy humans

• Main Author: Twomey, Rosemary
• Published: University of Brighton 2016
• Subjects: 616.8; C600 Sport and Exercise Science
• Online Access: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.725500

The central nervous system is highly sensitive to reductions in oxygen availability but the neurophysiological responses in healthy human lowlanders are not well understood. In severe hypoxia, whole-body exercise tolerance is impaired and neuromuscular fatigue, defined as any exercise-induced reduction in the ability of a muscle to generate force or power, reversible by rest, may be largely due to cerebral perturbations. The primary aim of this thesis was to determine the mechanisms of exercise-induced neuromuscular fatigue and the related neurophysiological responses to acute, chronic and intermittent severe hypoxia in healthy humans. In acute severe hypoxia (AH), exercise tolerance was, in part, mediated by a hypoxia-sensitive source of central fatigue, measured as a decrease in voluntary activation (VA) of the knee extensors (Study 1 – 4). This coincided with a significant challenge to systemic (arterial oxygen saturation [SpO2] ≈ 70%, Study 1 - 4) and cerebral oxygen availability at end-exercise (Study 3 - 4). The rate of development of peripheral locomotor muscle fatigue was blunted at task failure in AH in comparison to normoxia (Study 1 – 2). Corticospinal excitability and the neuromuscular mechanisms of fatigue were measured after a prolonged (two-week) exposure to high altitude in Study 3 (5260 m above sea level, Mount Chacaltaya, Bolivia). This was the first study to show that acclimatisation to chronic severe hypoxia (CH) alleviates the development of supraspinal fatigue induced by whole-body exercise in AH. This occurred in parallel to an improved cerebral oxygen delivery and cerebral oxygenation. Interestingly, the neurophysiological responses at rest in CH were characterised by an increased corticospinal and muscle membrane excitability. The peripheral contribution to neuromuscular fatigue was not attenuated following acclimatisation to high altitude. In study 4, a two-week protocol of intermittent hypoxia (IH) attenuated exercise-induced supraspinal fatigue measured in AH and substantially improved constant-power cycling in severe hypoxia. Total haemoglobin mass was unaltered by IH, but arterial oxygen content was improved due to an increase in SpO2, secondary to an enhanced ventilatory response to exercise. Peripheral locomotor muscle fatigue was lower following IH, which may be related to exercise training in hypoxia. Although corticospinal excitability was unchanged following a single 2-h exposure to severe hypoxia, repeated exposures of IH resulted in a transient increase in motor cortex excitability without changes in intracortical inhibition. (Study 5). In conclusion, in acute severe hypoxia, whole-body exercise tolerance is impaired through oxygensensitive mechanisms which exacerbate central fatigue. The acute response can be alleviated following both chronic and intermittent severe hypoxia.