Thomas Davies1, Edward Gilbert-Kawai1, Stephen Wythe1, Paula Meale1, Monty Mythen1, Denny Levett1,2,3,4, Kay Mitchell1, Michael Grocott1,2,3,4, Geraldine Clough5, Daniel Martin1,6. 1. University College London Centre for Altitude Space and Extreme Environment Medicine, UCLH NIHR Biomedical Research Centre, Institute of Sport and Exercise Health, London, UK. 2. Faculty of Medicine (CES) and Institute for Life Science, University of Southampton, Southampton, UK. 3. NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK. 4. Centre for Human Integrative Physiology, Faculty of Medicine, University of Southampton, Southampton, UK. 5. Institute of Developmental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK. 6. Critical Care Unit, Royal Free Hospital, London, UK.
Abstract
NEW FINDINGS: What is the central question of this study? Do Sherpa highlanders, when exposed to graded hypobaric hypoxia, exhibit enhanced vasomotor and neurovascular control to maintain microcirculatory flux, and thus tissue oxygenation, when compared with altitude-naive lowlanders? What is the main finding and its importance? Sherpas, when exposed to hypobaric hypoxia at high altitude, demonstrated superior preservation of their peripheral microcirculatory perfusion, a greater oxygen unloading rate and sustained microvascular reactivity with enhanced vasomotion, when compared with altitude-naive lowlanders. These differences have not been reported previously and may improve our understanding of the multifactorial responses to sustained environmental hypoxia. 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.
NEW FINDINGS: What is the central question of this study? Do Sherpa highlanders, when exposed to graded hypobaric hypoxia, exhibit enhanced vasomotor and neurovascular control to maintain microcirculatory flux, and thus tissue oxygenation, when compared with altitude-naive lowlanders? What is the main finding and its importance? Sherpas, when exposed to hypobaric hypoxia at high altitude, demonstrated superior preservation of their peripheral microcirculatory perfusion, a greater oxygen unloading rate and sustained microvascular reactivity with enhanced vasomotion, when compared with altitude-naive lowlanders. These differences have not been reported previously and may improve our understanding of the multifactorial responses to sustained environmental hypoxia. 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.
Authors: Mike Stembridge; Alexandra M Williams; Christopher Gasho; Tony G Dawkins; Aimee Drane; Francisco C Villafuerte; Benjamin D Levine; Rob Shave; Philip N Ainslie Journal: Proc Natl Acad Sci U S A Date: 2019-07-29 Impact factor: 11.205
Authors: Deborah Carey; Marjola Thanaj; Thomas Davies; Edward Gilbert-Kawai; Kay Mitchell; Denny Z H Levett; Michael G Mythen; Daniel S Martin; Michael P Grocott; Andrew J Chipperfield; Geraldine F Clough Journal: Sci Rep Date: 2019-10-07 Impact factor: 4.379