Systemic molecular adaptations to intermittent hypoxia: impact on microvascular oxygenation and hypoxic exercise performance

Intermittent hypoxia (IH) presents a less arduous training tool than chronic exposure for athletes seeking to improve cardiorespiratory fitness. While the sea-level (normoxic) performance benefits of IH remain equivocal (1, 2), less is known regarding its impact on hypoxic performance. Therefore, we examined if IH had the capacity to improve cardiorespiratory fitness in hypoxia and if so, identify the haemodynamic and molecular responses driving this adaptation. Eighteen healthy human male participants (22 ± 4 years) were randomly assigned single-blind to an intermittent normoxia (IN; 21% O2, n = 9) or IH (10% O2, n = 9) group. They completed ten sessions in a normobaric environmental chamber, each of which incorporated nine exposure periods (in normoxia or hypoxia depending on group). Each period was 5-minutes in length and separated by 5-minutes of exposure to normal ambient air (21% O2). Peak oxygen uptake (VO2peak) was assessed in hypoxia (10% O2) via online respiratory gas analysis during an incremental cycling test to exhaustion prior to and following the IH/IN programme. Continuous wave near-infrared spectroscopy was employed before and during exercise to monitor concentration changes in cerebral and muscular (vastus lateralis) oxy- and deoxyhaemoglobin (O2Hb and HHb), which also served as an index of regional changes in blood volume (O2Hb + HHb). Antecubital blood samples obtained at rest and VO2peak were analysed to assess oxidative (ascorbate radical (A●- ) by electron paramagnetic resonance spectroscopy), nitrosative (nitric oxide metabolites by ozonebased chemiluminescence) and inflammatory (sVCAM-1 and sICAM-1 by enzyme-linked immunosorbent assay) stress. Data were analysed using a three-way repeated measures ANOVA. VO2peak increased by 2.3% following IH, whereas no changes were observed following IN. Furthermore, submaximal VO2 at a workload of 60 watts decreased by 4.5% following IH, compared to a decrease of 1.6% following IN. Notably, improvements in exercise performance subsequent to IH were accompanied by significant increases in nitric oxide at rest and VO2peak (P < 0.05), and augmented levels of sVCAM-1 and sICAM-1 at VO2peak (P < 0.05). Moreover, A●- accumulation was attenuated at VO2peak succeeding IH, however this difference was non-significant (P = 0.10). Additionally, significant increases in cerebral oxygenation at rest and VO2peak (P < 0.05), and elevated blood flow at the muscle site during exercise (P < 0.05) were observed following IH. This is paramount given that hypoxic exercise performance is limited by cerebral and muscular deoxygenation (3). Collectively, these findings indicate that enhanced hypoxic exercise performance subsequent to IH may be due to attenuated oxidative-nitrosative-inflammatory stress and consequential improvements in microvascular oxygenation. Tadibi V, Dehnert C, Menold E, Bärtsch P. Unchanged anaerobic and aerobic performance after short-term intermittent hypoxia. Medicine and science in sports and exercise. 2007;39(5):858-64. Hamlin MJ, Hellemans J. Effect of intermittent normobaric hypoxic exposure at rest on haematological, physiological, and performance parameters in multi-sport athletes. Journal of sports sciences. 2007;25(4):431-41. Woodside JD, Gutowski M, Fall L, James PE, McEneny J, Young IS, Ogoh S, Bailey DM. Systemic oxidative–nitrosative–inflammatory stress during acute exercise in hypoxia; implications for microvascular oxygenation and aerobic capacity. Experimental physiology. 2014;99(12):1648-62. D.M Bailey is a Royal Society Wolfson Research Fellow. Where applicable, the authors confirm that the experiments described here conform with the ethical requirements.