| Summary: | Due to the high metabolic rate of brain tissue and nominal substrate storage, brain perfusion must be precisely regulated to ensure continuous delivery of oxygen and substrates. Cerebral blood flow (CBF) is principally regulated by tissue metabolism, perfusion pressure, autonomic nervous activity, and the partial pressures of arterial oxygen (PaO₂)and carbon dioxide (PaCO₂) – an integrative process thus involving the marked influence of pulmonary gas exchange and cardiovascular function, in addition to intracranial mediators of cerebrovascular resistance. This thesis explicates the roles of PaO₂ and PaCO₂ in human regulation of regional CBF. In study 1, to elucidate their discrete roles, PaO₂ and PaCO₂ were independently manipulated at sea level through the widest range tolerated in humans. Flow reactivity to hypocapnia (low PaCO₂) and hypoxia (low PaO₂) was greater in the vertebral (VA) than internal carotid (ICA) artery, whereas similar reactivity was observed during hypercapnia (high PaCO₂) and hyperoxia (high PaO2₂. Cerebral oxygen delivery was well protected except in cases of extreme hypocapnia. The ventilatory response to hypoxia mitigates falling PaO₂ and reduces PaCO₂, particularly during initial exposure to high altitude. Study 2 assessed regional CBF during ascent to 5050m and every 12 hours during the first 3 days of acclimatization. Although total CBF increased by ~50% and was modestly related to reductions in oxygen saturation of hemoglobin, no regional CBF differences were observed. To extend these findings, Study 3 aimed to determine if cerebrovascular responses to changes in PaO₂ and PaCO₂ differed at 5050m compared to sea level. Despite respiratory alkalosis and partial metabolic compensation at 5050m restoration of PaO₂ to sea level values decreased CBF, and CBF sensitivity to acutely altered PaCO₂ remained similar to sea level. To elucidate the interactive effect on CBF of profound hypoxemia and hypercapnia, study 4 examined the temporal changes in elite breath-hold divers during maximum apneas. Despite 40-50% reductions in arterial oxygen content, CBF elevations were regionally similar (up to +100%) thereby facilitating maintenance of brain oxygen delivery throughout apnea. Although the regulation of CBF is multifaceted, the cerebrovasculature prioritizes oxygen delivery and adjusts to chronic changes in arterial blood gases.
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