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Title: Human adaptation to hypobaric hypoxia at high altitude
Author: Martin, D. S.
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2013
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As humans ascend to high altitude, the resulting hypobaric hypoxia necessitates adaptation in order continue functioning. Whilst much is known about changes that facilitate a restoration of systemic oxygen delivery during ascent, less is know about alterations in the peripheral microcirculation and how these affect acclimatisation and performance at altitude. The limit of human adaptation to hypoxia is also undefined. Using data derived from a number of studies conducted on healthy volunteers at high altitude, this thesis explores changes in skeletal muscle oxygenation and sublingual microcirculatory blood flow, and how these may relate to the process of acclimatisation. In addition, exercise was used to perturbate the relationship between oxygen delivery and utilisation at altitude, and experiments at extreme altitude sought to define the limits of human tolerance to hypoxia. Data relating to four subjects resting just below the summit of Mount Everest (at 8400m), demonstrated a degree of systemic hypoxia never before reported in humans. Given sufficient time, arterial oxygen content remained steady during ascent to 7100m. Sublingual microcirculatory blood flow declined at altitude, whilst the density of blood vessels increased. At altitude, absolute skeletal muscle oxygenation declined; the response to a brief ischaemic episode was a reduction in rate of subsequent muscle reoxygenation; and the rate of muscle desaturation during exercise increased. Systemic oxygen extraction during exercise at altitude remained unchanged from that observed at sea level. These results support the hypothesis that a significant barrier to oxygen flux exists within tissues that is heightened at altitude. Restoration of convective oxygen delivery does little to improve tissue oxygenation, and adaptations within the microcirculation may differentiate phenotypic responses observed on prolonged exposure to hypoxia. Graded ascent to altitude by healthy volunteers provides valid data that may herald further research in the clinical arena, bringing about improved outcome in critically ill patients.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available