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      Changes in labial capillary density on ascent to and descent from high altitude

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          Abstract

          Present knowledge of how the microcirculation is altered by prolonged exposure to hypoxia at high altitude is incomplete and modification of existing analytical techniques may improve our knowledge considerably. We set out to use a novel simplified method of measuring in vivo capillary density during an expedition to high altitude using a CytoCam incident dark field imaging video-microscope.

          The simplified method of data capture involved recording one-second images of the mucosal surface of the inner lip to reveal data about microvasculature density in ten individuals. This was done on ascent to, and descent from, high altitude. Analysis was conducted offline by two independent investigators blinded to the participant identity, testing conditions and the imaging site.  Additionally we monitored haemoglobin concentration and haematocrit data to see if we could support or refute mechanisms of altered density relating to vessel recruitment. Repeated sets of paired values were compared using Kruskall Wallis Analysis of Variance tests, whilst comparisons of values between sites was by related samples Wilcoxon Signed Rank Test. Correlation between different variables was performed using Spearman’s rank correlation coefficient, and concordance between analysing investigators using intra-class correlation coefficient.

          There was a significant increase in capillary density from London on ascent to high altitude; median capillaries per field of view area increased from 22.8 to 25.3 (p=0.021). There was a further increase in vessel density during the six weeks spent at altitude (25.3 to 32.5, p=0.017). Moreover, vessel density remained high on descent to Kathmandu (31.0 capillaries per field of view area), despite a significant decrease in haemoglobin concentration and haematocrit.

          Using a simplified technique, we have demonstrated an increase in capillary density on early and sustained exposure to hypobaric hypoxia at thigh altitude, and that this remains elevated on descent to normoxia. The technique is simple, reliable and reproducible.

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          Most cited references25

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          Biophysical aspects of blood flow in the microvasculature.

          The main function of the microvasculature is transport of materials. Water and solutes are carried by blood through the microvessels and exchanged, through vessel walls, with the surrounding tissues. This transport function is highly dependent on the architecture of the microvasculature and on the biophysical behavior of blood flowing through it. For example, the hydrodynamic resistance of a microvascular network, which determines the overall blood flow for a given perfusion pressure, depends on the number, size and arrangement of microvessels, the passive and active mechanisms governing their diameters, and on the apparent viscosity of blood flowing in them. Suspended elements in blood, especially red blood cells, strongly influence the apparent viscosity, which varies with several factors, including vessel diameter, hematocrit and blood flow velocity. The distribution of blood flows and red cell fluxes within a network, which influences the spatial pattern of mass transport, is determined by the mechanics of red cell motion in individual diverging bifurcations. Here, our current understanding of the biophysical processes governing blood flow in the microvasculature is reviewed, and some directions for future research are indicated.
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            Morphological adaptations of human skeletal muscle to chronic hypoxia.

            Muscle structural changes during typical mountaineering expeditions to the Himalayas were assessed by taking muscle biopsies from 14 mountaineers before and after their sojourn at high altitude (greater than 5000 m for over 8 weeks). M. vastus lateralis samples were analyzed morphometrically from electron micrographs. A significant reduction (-10%) of muscle cross-sectional area was found on CT scans of the thigh. Morphologically this loss in muscle mass appeared as a decrease in muscle fiber size mainly due to a loss of myofibrillar proteins. A loss of muscle oxidative capacity was also evident, as indicated by a decrease in the volume of muscle mitochondria (-25%). In contrast, the capillary network was mostly spared from catabolism. It is therefore concluded that oxygen availability to muscle mitochondria after prolonged high-altitude exposure in humans is improved due to an unchanged capillary network, supplying a reduced muscle oxidative capacity.
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              Microvascular response to red blood cell transfusion in patients with severe sepsis.

              Microvascular alterations may play a role in the development of multiple organ failure in severe sepsis. The effects of red blood cell transfusions on microvascular perfusion are not well defined. We investigated the effects of red blood cell transfusion on sublingual microvascular perfusion in patients with sepsis. Prospective, observational study. A 31-bed, medical-surgical intensive care unit of a university hospital. Thirty-five patients with severe sepsis requiring red blood cell transfusions. Transfusion of one to two units of leukocyte-reduced red blood cells. The sublingual microcirculation was assessed with an Orthogonal Polarization Spectral device before and 1 hr after red blood cell transfusion. Red blood cell transfusions increased hemoglobin concentration from 7.1 (25th-75th percentile, 6.7-7.6) to 8.1 (7.5-8.6) g/dL (p 8% compared with those who did not (57 [52-64] vs. 75 [70-79]; p < .01), while hemodynamic and global oxygen transport variables were similar in the two groups. Red blood cell storage time had no influence on the microvascular response to red blood cell transfusion. The sublingual microcirculation is globally unaltered by red blood cell transfusion in septic patients; however, it can improve in patients with altered capillary perfusion at baseline.
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                Author and article information

                Journal
                F1000Res
                F1000Res
                F1000Research
                F1000Research
                F1000Research (London, UK )
                2046-1402
                30 August 2016
                2016
                : 5
                : 2107
                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 ]Integrative Physiology and Critical Illness Group, Clinical and Experimental Sciences, Mailpoint 810, Sir Henry Wellcome Laboratories, Faculty of Medicine, University of Southampton, University Hospital Southampton NHS Foundation Trust, Southhampton, UK
                [3 ]Anaesthesia and Critical Care Research Unit, University Hospital Southampton NHS Foundation Trust, Southhampton, UK
                [4 ]Department of Intensive Care, Erasmus MC University Hospital Rotterdam, Rotterdam, Netherlands
                [5 ]University College London, Division of Surgery and Interventional Science, Royal Free Hospital, London, UK
                [6 ]Erasmus MC-Sophia Children's Hospital, Rotterdam, Netherlands
                [1 ]Medical Intensive Care Unit, University Hospital of Zurich, Zurich, Switzerland
                [1 ]Department of Critical Care, Kings College London University, London, UK
                Author notes

                E G-K: design of study, collection of data, analysis of data, writing manuscript

                JC: collection of data, analysis of data, writing manuscript

                PH: analysis of data, writing manuscript

                MG: design of study, writing manuscript

                CI: design of study, writing manuscript

                DM: design of study, analysis of data, writing manuscript

                All authors have seen and agreed to the final content of the manuscript

                Competing interests: Braedius Medical, a company owned by a relative of Can Ince, has developed and designed a hand held microscope called CytoCam-IDF imaging. Can Ince has no financial relation with Braedius Medical of any sort; he never owned shares, or received consultancy or speaker fees from Braedius Medical.

                Competing interests: No competing interests were disclosed.

                Competing interests: No competing interests were disclosed.

                Article
                10.12688/f1000research.7649.1
                5043444
                c99830ca-ecd7-4bde-87b3-f16d12e38f36
                Copyright: © 2016 Gilbert-Kawai E et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 26 August 2016
                Funding
                Funded by: Royal Free Hospital NHS Trust Charity
                Funded by: Special Trustees of University College London Hospital NHS Foundation Trust
                Funded by: Southampton University Hospital Charity
                Funded by: UCL Institute of Sports Exercise and Health
                Funded by: The London Clinic
                Funded by: University College London
                Funded by: University of Southampton
                Funded by: Duke University Medical School
                Funded by: United Kingdom Intensive Care Society
                Funded by: National Institute of Academic Anaesthesia
                Funded by: Rhinology and Laryngology Research Fund
                Funded by: The Physiological Society
                Funded by: Smiths Medical
                Funded by: Deltex Medical
                Funded by: Atlantic Customer Solutions
                Funded by: National Institute for Health Research Biomedical Research Center
                Xtreme Everest 2 was supported by the Royal Free Hospital NHS Trust Charity, the Special Trustees of University College London Hospital NHS Foundation Trust, the Southampton University Hospital Charity, the UCL Institute of Sports Exercise and Health, The London Clinic, University College London, University of Southampton, Duke University Medical School, the United Kingdom Intensive Care Society, the National Institute of Academic Anaesthesia, the Rhinology and Laryngology Research Fund, The Physiological Society, Smiths Medical, Deltex Medical, Atlantic Customer Solutions and the Xtreme Everest 2 volunteer participants who trekked to Everest Base Camp.
                Some of this work was undertaken at University College London Hospital-University College London Biomedical Research Centre, which received a proportion of funding from the United Kingdom Department of Health’s National Institute for Health Research Biomedical Research Centers funding scheme. Some of this work was undertaken at University Hospital Southampton-University of Southampton Respiratory Biomedical Research Unit, which received a proportion of funding from the United Kingdom Department of Health’s National Institute for Health Research Biomedical Research Units funding scheme.
                The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Articles
                Airway/Respiratory Physiology
                Extrapulmonary Disorders & Therapeutic Interventions

                capillaries,microcirculation,altitude,microscopy,oxygen
                capillaries, microcirculation, altitude, microscopy, oxygen

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