The overall aim of this thesis was to increase understanding of physiological responses to altitude and identify modifiable factors that could enhance health and exercise performance at altitude.
With this in mind, the specific aims of the first study (Chapter 2) were to determine the relationship between sea-level fitness and submaximal exercise responses and AMS during chronic altitude exposure, and to determine the utility of sea-level fitness and hypoxic exercise testing before an expedition. Greater sea-level fitness (VO_2max) was associated with, and predicted, lower sense of effort (RPE_ascent r = -0.43; p < 0.001; RPE_fixed; r = -0.69; p < 0.001) and higher step rate (STEP_RPE35; r = 0.62; p < 0.01), but not worse AMS (r = 0.13; p = 0.4) or arterial oxygen desaturation (r = 0.07; p = 0.7). Lower RPE_ascent was also associated with better mood, including less fatigue (r = 0.57; p < 0.001) on a high-altitude expedition. Hypoxic sensitivity was not associated with, and did not add to the prediction of, submaximal exercise responses or AMS. This study concluded that greater sea-level fitness is related to lower sense of effort during submaximal exercise and better mood (less fatigue, tension, and confusion) at altitude.
The second study (Chapter 3) aimed to determine the efficacy of chronic dietary nitrate supplementation as an AMS prophylactic and ergogenic aid at altitude. Five days nitrate supplementation (6.4 mmol nitrate daily) increased plasma NO metabolites compared to placebo but did not reduce AMS or improve exercise performance. After 4 h hypoxia, nitrate increased AMS (Acute Cerebral Mountain Sickness score; AMS-C) and headache severity (visual analogue scale (VAS); whole sample Δ10[1,20] mm; p = 0.03) compared to placebo. In addition, after 5 h hypoxia, nitrate increased sense of effort during submaximal exercise (Δ7 [-1,14]; p = 0.07). This study concluded that dietary nitrate increases AMS and sense of effort during exercise, particularly in AMS-susceptible individuals. Dietary nitrate is therefore not recommended as an AMS prophylactic or ergogenic aid non-acclimatized individuals at altitude.
Finally, the third study (Chapter 4) aimed to increase understanding of cerebral physiology in hypoxia, specifically to characterise the anatomical distribution of regional changes in resting cerebral blood flow (CBF) and neurovascular activity during cognitive tasks in hypoxia. Acute hypoxia induced reductions in regional CBF (rCBF) to default mode network (DMN) regions including the posterior cingulate cortex (PCC) and right angular gyrus (AG). These reductions persisted during a DMN-dependent memory task where we observed an inversion of the haemodynamic response to neural activity, despite no impairment in memory task performance. In contrast, hypoxia induced increases in visual search-related activations in visual attention network (VAN) regions including the middle temporal areas (MT), frontal eye fields (FEF), and left intraparietal sulcus (IPS). This increase in activation, coupled with no change in task performance, indicates the maintenance of oxygen delivery in hypoxia despite reduced blood oxygenation. This study concluded that acute hypoxia induces region-dependent alterations in neurovascular responses.