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Howe, Connor A.

University of British Columbia

Hypoxic environments elicit multiple physiological responses in order to maintain sufficient oxygen delivery, and ultimately, maintain function. The brain is particularly susceptible to hypoxic environments as it has essentially no metabolic storage capacity; therefore, it relies on a constant, well titrated supply of oxygen to match metabolic demand. The aim of this thesis was to investigate cerebral blood flow (CBF) regulation under acute and chronic severe environmental hypoxic conditions. Study 1 investigated regional and global patterns of CBF and oxygen delivery (CDO₂) in Andean and Sherpa high-altitude populations and in lowlanders, all residing at an altitude of ~5000m. The findings showed that Sherpa possess a unique CBF phenotype whereby CDO₂ is markedly lower compared to Andeans and lowlanders. Andeans, however, presented with a CBF pattern more similar to lowlanders, but with larger extracranial vessels. In Study 2, it was explored how children and adolescents residing in the highest city in the world (La Rinconada, Peru; 5100m) regulate CBF and whether it differed when compared to Sherpa living at 3800m, and lowlanders living in Wales, UK. The findings revealed that despite Andean children being more hypoxemic, their global CBF was not different compared to the other populations; however, their posterior CBF was ~24% lower. Finally, Study 3 investigated the effect of mild-hypothermia on CBF, CDO₂, cerebral metabolic rate of oxygen (CMRO₂), and blood brain biomarkers in healthy humans during progressive maximal hypercapnic hypoxia, simulating avalanche burial. The main findings were that 1) mild hypothermia reduced CBF during room-air breathing, primarily due to reductions in the partial pressure of arterial CO₂; and 2) CMRO₂ was not different with hypothermia under room-air conditions and during progressive hypercapnic-hypoxia; however, blood brain biomarkers of neuronal and axonal damage, and blood brain barrier permeability were reduced, indicating some selected neuroprotection. This dissertation furthers our understanding of how populations indigenous to high-altitude have divergent adaptations within the cerebrovasculature despite living under a similar environmental stressor. Additionally, it was shown for the first time that mild hypothermia does not alter cerebral metabolism during room-air breathing or during progressive hypercapnic-hypoxia, but may potentialy contribute to some unique aspects of neuroprotection.

Text

2024-09-12

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/89229

Kinesiology

University of British Columbia

UBCO

http://creativecommons.org/licenses/by-nc-nd/4.0/