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

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          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.

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          Most cited references44

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          Wavelet analysis of oscillations in the peripheral blood circulation measured by laser Doppler technique.

          The wavelet transform technique, a time-frequency method with logarithmic frequency resolution, was used to analyze oscillations in human peripheral blood flow measured by laser Doppler flowmetry. The oscillations extended over a wide frequency scale and their periods varied in time. Within the frequency range studied, 0.0095-1.6 Hz, five characteristic oscillations were revealed, arising from both local and central regulatory mechanisms. After the insertion of endothelium-dependent and endothelium-independent vasodilators the spectra of blood flow markedly differed in the frequency interval 0.0095-0.02 Hz. In this way it was demonstrated that endothelial activity is a rhythmic process that contributes to oscillations in blood flow with a characteristic frequency of around 0.01 Hz. The study illustrates the potential of laser Doppler flowmetry combined with dynamical systems analysis for studies of both the micro- and macroscopic mechanisms of blood flow regulation in vivo.
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            The human cutaneous circulation as a model of generalized microvascular function.

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              Methodological issues in the assessment of skin microvascular endothelial function in humans.

              The study of microvascular function can be performed in humans using laser Doppler flowmetry of the skin. This technology lends itself to a wide range of applications for studying the endothelial function of skin blood vessels. We review the advantages and limitations of postocclusive hyperemia, local thermal hyperemia, acetylcholine iontophoresis, flowmotion and association with microdialysis as tools with which to investigate skin microvascular endothelial function in humans. Postocclusive hyperemia, thermal hyperemia and acetylcholine iontophoresis provide integrated indexes of microvascular function rather than specific endothelial markers. However, they are valuable tools and can be used as surrogate endpoints in clinical trials in which the assessment of microvascular function in humans is required.
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                Author and article information

                Journal
                Experimental Physiology
                Exp Physiol
                Wiley
                09580670
                November 2018
                November 2018
                September 12 2018
                : 103
                : 11
                : 1494-1504
                Affiliations
                [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
                Article
                10.1113/EP087236
                d92713cd-050e-46b7-8e42-900538e3f9cf
                © 2018

                http://doi.wiley.com/10.1002/tdm_license_1.1

                http://onlinelibrary.wiley.com/termsAndConditions#vor

                History

                Social policy & Welfare,Medicine,Biochemistry,Ecology,Environmental studies,Life sciences

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