UBC-Nepal expedition: upper and lower limb conduit artery shear stress and flow-mediated dilation on ascent to 5,050 m in lowlanders and Sherpa

Abstract

The study of conduit artery endothelial adaptation to hypoxia has been restricted to the brachial artery, and comparisons to highlanders have been confounded by differences in altitude exposure, exercise, and unknown levels of blood viscosity. To address these gaps, we tested the hypothesis that lowlanders, but not Sherpa, would demonstrate decreased mean shear stress and increased retrograde shear stress, and subsequently reduced flow-mediated dilation (FMD), in the upper and lower limb conduit arteries on ascent to 5050m. Healthy lowlanders (n=22, 28±6 years [mean±SD]) and Sherpa (n=12, 34±11 years) ascended over 10 days, with measurements taken on non-trekking days at 1400m (baseline), 3440m (day 4), 4371m (day 7), and 5050m (day 10). Arterial blood gases, blood viscosity, shear stress and FMD (duplex ultrasound of the brachial [BA] and superficial femoral [SFA] arteries) were acquired at each time-point. Ascent decreased mean and increased retrograde shear stress in the upper and lower limb of lowlanders and Sherpa. Although BA FMD decreased in the lowlanders from 7.1±3.9% to 3.8±2.8% at 5050m versus 1400m (P<0.001), SFA FMD was preserved. In the Sherpa, neither BA nor SFA FMD were changed upon ascent to 5050m. In lowlanders, the ascent-related exercise may favorably influence endothelial function in the active limb (SFA); selective impairment in FMD in the BA in lowlanders is likely mediated via the low mean or high oscillatory baseline shear stress. In contrast, Sherpa presented protected endothelial function, suggesting a potential vascular aspect of high-altitude acclimatization/adaptation.

The impact of hypoxaemia on vascular function in lowlanders and high altitude indigenous populations

“…Although similar shear stress changes occur in the superficial femoral artery on ascent to 5050 m, endothelial function is preserved (Tremblay et al . ; see Fig. ).…”

“…In Kathmandu (1400 m), partially de‐acclimatized Sherpa who live and work at high altitude present similar endothelial function compared to lowlanders (Tremblay et al . ). On ascent to 5050 m, although both Sherpa and lowlanders demonstrate changes in shear stress, only lowlanders experience reductions in endothelial function (Tremblay et al .…”

“…On ascent to 5050 m, although both Sherpa and lowlanders demonstrate changes in shear stress, only lowlanders experience reductions in endothelial function (Tremblay et al . ). Thus, Sherpa may be resistant to hypoxia‐ and/or shear stress‐associated reductions in endothelial function.…”

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

“…Endothelial function, as indexed in the brachial artery, is greater in Sherpa at 5050 m following ascent in the same cohort of individuals tested in this present study (Tremblay et al . ). When compared between acclimatized (∼2 weeks) lowlanders and Sherpa, endothelial function appears similar (Lewis et al .…”

“…; Tremblay et al . ). Therefore, it is reasonable to expect that the Sherpa brain may possess its own unique phenotype for the regulation of oxygen delivery.…”