UBC-Nepal expedition: phenotypical evidence for evolutionary adaptation in the control of cerebral blood flow and oxygen delivery at high altitude.

Debilitating side effects of hypoxia manifest within the central nervous system; however, high-altitude natives of the Tibetan plateau, the Sherpa, experience negligible cerebral effects compared to lowland natives at extreme altitude. Phenotypical optimization of the oxygen cascade has been demonstrated in the systemic circulation of Tibetans and Sherpa, likely underscoring their adapted capacity to thrive at altitude. Yet, little is known as to how the cerebral circulation of Sherpa may be adapted. To examine potential differences in cerebral oxygen delivery in Sherpa compared to lowlanders we measured arterial blood gases and global cerebral blood flow (duplex ultrasound) during a 9 day ascent to 5050 m. Although cerebral oxygen delivery was maintained during ascent in lowlanders, it was significantly reduced in the Sherpa at 3400 m (-30.3 ± 21.6%; P < 0.01) and 4371 m (-14.2 ± 10.7%; P = 0.03). Furthermore, linear mixed effects modelling indicated that independent of differences in mean arterial pressure, pH and blood viscosity, race accounts for an approximately 100 mL min-1 (∼17-34%) lower cerebral blood flow in Sherpa compared to lowlanders across ascent to altitude (P = 0.046). To ascertain the role of chronic hypoxia independent of the ascent, Sherpa who had not recently descended were also examined at 5050 m. In these Sherpa, cerebral oxygen delivery was also lower compared to lowlanders (∼22% lower; P < 0.01). We highlight new information about the influence of race and genetic adaptation in the regulation of cerebral oxygen delivery. The lower cerebral oxygen delivery in the Sherpa potentially represents a positive adaptation considering Sherpa endure less deleterious cerebral consequences than lowlanders at altitude.