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

Abstract

Key points Sherpa have lived in the Nepal Himalaya for 25–40 thousand years and display positive physiological adaptations to hypoxia. Sherpa have previously been demonstrated to suffer less negative cerebral side effects of ascent to extreme altitude, yet little is known as to whether or not they display differential regulation of oxygen delivery to the brain compared to lowland natives. We demonstrate that Sherpa have lower brain blood flow during ascent to and acclimatization at high altitude compared to lowlanders and that this difference in flow is not attributable to factors such as mean arterial pressure, blood viscosity and pH. The observed lower cerebral oxygen delivery in Sherpa likely represents a positive adaptation that may indicate a cerebral hypometabolic conservation of energy at altitude and/or decreased risk of other cerebral consequences such as vasogenic oedema. Abstract 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.

Relationship between cardiorespiratory phase coherence during hypoxia and genetic polymorphism in humans

“…2018; Hoiland et al . 2019; Simpson et al . 2019) or Andes (Julian & Moore, 2019), with those of lowlanders, including faster recovery of peripheral muscle fatigue in Sherpas (Ruggiero et al .…”

“…2018), bringing phenotypical evidence for evolutionary adaptation in the control of cerebral blood flow and oxygen delivery at high altitude (Hoiland et al . 2019). A recent review suggested a need for further exploration of the interaction among genetic, epigenetic and environmental factors in shaping patterns of adaptation to high altitude.…”

“…High altitude physiology has been investigated for decades and has recently gained much attention (Davies et al 2018;Ruggiero et al 2018;Hoiland et al 2019;Julian & Moore, 2019;Simpson et al 2019). Clear physiological differences have been demonstrated comparing the physiological parameters of highlanders, from Himalaya (Ruggiero et al 2018;Hoiland et al 2019;Simpson et al 2019) or Andes (Julian & Moore, 2019), with those of lowlanders, including faster recovery of peripheral muscle fatigue in Sherpas (Ruggiero et al 2018), bringing phenotypical evidence for evolutionary adaptation in the control of cerebral blood flow and oxygen delivery at high altitude (Hoiland et al 2019). A recent review suggested a need for further exploration of the interaction among genetic, epigenetic and environmental factors in shaping patterns of adaptation to high altitude.…”

The 2018 Global Research Expedition on Altitude Related Chronic Health (Global REACH) to Cerro de Pasco, Peru: an Experimental Overview

“…Moreover, based on the previous experience of our research team with high altitude expeditions, adjustments were made to account for expected participant dropout (e.g. Foster et al., 2014; Hoiland et al., 2019; Lewis et al., 2014; Simpson et al., 2019; Smith et al., 2014; Stembridge et al., 2019; Tremblay, Thom, Yang, & Ainslie, 2017; Tymko et al., 2017; Willie et al., 2014). Sample sizes were determined using statistical power tests that assumed a minimum statistical power of 80% (or 0.8).…”

“…Plasma 3-nitrotyrosine, a biomarker reflecting the oxidative inactivation of NO, was measured by hs-ELISA. Foster et al, 2014;Hoiland et al, 2019;Lewis et al, 2014;Simpson et al, 2019;Smith et al, 2014;Stembridge et al, 2019;Tremblay, Thom, Yang, & Ainslie, 2017;Tymko et al, 2017;Willie et al, 2014). Sample sizes were determined using statistical power tests that assumed a minimum statistical power of 80% (or 0.8).…”