Sustained vasomotor control of skin microcirculation in Sherpas versus altitude‐naive lowlanders: Experimental evidence from Xtreme Everest 2

Abstract

Enhanced oxygen delivery, consequent to an increased microvascular perfusion, has been postulated to play a key role in the physiological adaptation of Tibetan highlanders to the hypobaric hypoxia encountered at high altitude. We tested the hypothesis that Sherpas, when exposed to graded hypobaric hypoxia, demonstrate enhanced vasomotor and neurovascular control to maintain microcirculatory flux, and thus tissue oxygenation, when compared with altitude-naive lowlanders. Eighty-three lowlanders [39 men and 44 women, 38.8 (13.1) years old; mean (SD)] and 61 Sherpas [28 men and 33 women, 27.9 (6.9) years old] were studied on ascent to Everest Base Camp over 11 days. Skin blood flux and tissue oxygen saturation were measured simultaneously using combined laser Doppler fluximetry and white light spectroscopy at baseline, 3500 and 5300 m. In both cohorts, ascent resulted in a decline in the sympathetically mediated microvascular constrictor response (P < 0.001), which was more marked in lowlanders than in Sherpas (P < 0.001). The microvascular dilator response evaluated by postocclusive reactive hyperaemia was significantly greater in Sherpas than in lowlanders at all sites (P < 0.002). Spectral analysis of the blood flux signals revealed enhanced myogenic (vasomotion) activity in Sherpas, which was unaffected by ascent to 5300 m. Although skin tissue oxygenation was lower in Sherpas than in lowlanders, the oxygen unloading rate was faster, and deoxyhaemoglobin levels higher, at all altitudes. Together, these data suggest that Sherpas, when exposed to hypobaric hypoxia, demonstrated superior preservation of peripheral microcirculatory perfusion compared with altitude-naive lowlanders. The physiological differences in local microvasculature vasomotor and neurovascular control may play a key role in Sherpa adaptation to high-altitude hypobaric hypoxia by sustaining local perfusion and tissue oxygenation.

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

“…As NOTCH4 is related to the functioning of the vascular endothelium (Wu et al 2005), our study supports the recent observation by Simpson et al (2019) that mechanisms other than peripheral chemoreflex activation contribute to vascular sympathetic resetting at high altitude. Furthermore, our study corroborates the findings by Davies et al (2018) that differences in local microvasculature vasomotor and neurovascular control account for the ability of Sherpas to adapt to high-altitude hypobaric hypoxia by sustaining local perfusion and tissue oxygenation. The results of our study extend these recent findings by postulating that even smaller differences in altitude may lead to different genotypes and hence to different responses to hypoxia.…”

“…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).…”

The overlooked significance of plasma volume for successful adaptation to high altitude in Sherpa and Andean natives

“…The positive relationship between hemoglobin mass and exercise capacity in Sherpa at high altitude conflicts with the current understanding of oxygen transport in hypoxia, given that the convective elements are thought to have diminished importance with increasing altitude (11). We propose that this may only be the case when examined in isolation from other unique elements of adaptive physiology in Sherpa that include minimal hypoxic pulmonary vasoconstriction (12), higher lung diffusing capacity (13), capillary density, microcirculatory flow (14), and faster oxygen unloading rate (15). Collectively, these adaptations could shift the balance back toward the convectional components, as seen at sea level.…”

Hypoxia-tolerant vascular endothelial growth factor-A (VEGF-A) and the genetic variations ofVEGFAin Sherpa highlanders

“…Compared to non-Sherpa lowlanders, Sherpa highlanders show significantly greater capillary density in muscle cross-section [9], and higher sublingual microcirculatory blood flow and greater capillary density at high altitude [10]. These findings indicate efficient and effective oxygen transport to tissues in Sherpa highlanders, supporting the notion that microcirculation plays a critical role in the mechanism underlying adaptation to hypoxia [11].…”