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Design and conduct of Xtreme Everest 2: an observational cohort study of Sherpa and lowlander responses to graduated hypobaric hypoxia

Design and conduct of Xtreme Everest 2: an observational cohort study of Sherpa and lowlander responses to graduated hypobaric hypoxia
Design and conduct of Xtreme Everest 2: an observational cohort study of Sherpa and lowlander responses to graduated hypobaric hypoxia
Objective: oxygen availability falls with ascent to altitude and also as a consequence of critical illness. Because cellular sequelae and adaptive processes may be shared in both circumstances, high altitude exposure (‘physiological hypoxia’) assists in the exploration of the response to pathological hypoxia. We therefore studied the response of healthy participants to progressive hypobaric hypoxia at altitude. The primary objective of the study was to identify differences between high altitude inhabitants (Sherpas) and lowland comparators.

Methods: we performed an observational cohort study of human responses to progressive hypobaric hypoxia (during ascent) and subsequent normoxia (following descent) comparing Sherpas with lowlanders. Studies were conducted in London (35m), Kathmandu (1300m), Namche Bazaar (3500m) and Everest Base Camp (5300m). Of 180 healthy volunteers departing from Kathmandu, 64 were Sherpas and 116 were lowlanders. Physiological, biochemical, genetic and epigenetic data were collected. Core studies focused on nitric oxide metabolism, microcirculatory blood flow and exercise performance. Additional studies performed in nested subgroups examined mitochondrial and metabolic function, and ventilatory and cardiac variables. Of the 180 healthy participants who left Kathmandu, 178 (99%) completed the planned trek. Overall, more than 90% of planned testing was completed. Forty-four study protocols were successfully completed at altitudes up to and including 5300m. A subgroup of identical twins (all lowlanders) was also studied in detail.

Conclusion: this programme of study (Xtreme Everest 2) will provide a rich dataset relating to human adaptation to hypoxia, and the responses seen on re-exposure to normoxia. It is the largest comprehensive high altitude study of Sherpas yet performed. Translational data generated from this study will be of relevance to diseases in which oxygenation is a major factor
hypoxia, critical care, sherpa, high altitude, microcirculation, nitric oxide, mitochondria
90
Gilbert-Kawai, Edward
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Sheperdigian, Adam
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Adams, Thomas
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Mitchell, Kay
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Feelisch, Martin
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Murray, Andrew
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Peters, Mark
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Gilbert-Kawai, Grace
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Montgomery, Hugh
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Levett, Denny
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Kumar, Rajendra
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Mythen, Michael
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Grocott, Michael
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Martin, Daniel
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Gilbert-Kawai, Edward
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Sheperdigian, Adam
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Adams, Thomas
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Mitchell, Kay
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Feelisch, Martin
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Murray, Andrew
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Peters, Mark
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Gilbert-Kawai, Grace
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Montgomery, Hugh
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Levett, Denny
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Kumar, Rajendra
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Mythen, Michael
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Grocott, Michael
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Martin, Daniel
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Gilbert-Kawai, Edward, Sheperdigian, Adam, Adams, Thomas, Mitchell, Kay, Feelisch, Martin, Murray, Andrew, Peters, Mark, Gilbert-Kawai, Grace, Montgomery, Hugh, Levett, Denny, Kumar, Rajendra, Mythen, Michael, Grocott, Michael and Martin, Daniel (2015) Design and conduct of Xtreme Everest 2: an observational cohort study of Sherpa and lowlander responses to graduated hypobaric hypoxia F1000 Research, 4, p. 90. (doi:10.12688/f1000research.6297.1). (PMID:26064476).

Record type: Article

Abstract

Objective: oxygen availability falls with ascent to altitude and also as a consequence of critical illness. Because cellular sequelae and adaptive processes may be shared in both circumstances, high altitude exposure (‘physiological hypoxia’) assists in the exploration of the response to pathological hypoxia. We therefore studied the response of healthy participants to progressive hypobaric hypoxia at altitude. The primary objective of the study was to identify differences between high altitude inhabitants (Sherpas) and lowland comparators.

Methods: we performed an observational cohort study of human responses to progressive hypobaric hypoxia (during ascent) and subsequent normoxia (following descent) comparing Sherpas with lowlanders. Studies were conducted in London (35m), Kathmandu (1300m), Namche Bazaar (3500m) and Everest Base Camp (5300m). Of 180 healthy volunteers departing from Kathmandu, 64 were Sherpas and 116 were lowlanders. Physiological, biochemical, genetic and epigenetic data were collected. Core studies focused on nitric oxide metabolism, microcirculatory blood flow and exercise performance. Additional studies performed in nested subgroups examined mitochondrial and metabolic function, and ventilatory and cardiac variables. Of the 180 healthy participants who left Kathmandu, 178 (99%) completed the planned trek. Overall, more than 90% of planned testing was completed. Forty-four study protocols were successfully completed at altitudes up to and including 5300m. A subgroup of identical twins (all lowlanders) was also studied in detail.

Conclusion: this programme of study (Xtreme Everest 2) will provide a rich dataset relating to human adaptation to hypoxia, and the responses seen on re-exposure to normoxia. It is the largest comprehensive high altitude study of Sherpas yet performed. Translational data generated from this study will be of relevance to diseases in which oxygenation is a major factor

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Published date: 10 April 2015
Keywords: hypoxia, critical care, sherpa, high altitude, microcirculation, nitric oxide, mitochondria
Organisations: Clinical & Experimental Sciences

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Local EPrints ID: 378730
URI: http://eprints.soton.ac.uk/id/eprint/378730
PURE UUID: ebf059dd-3fa0-482c-a2ad-eb65d31890ae
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

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Date deposited: 09 Jul 2015 11:12
Last modified: 17 Jul 2017 20:49

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Contributors

Author: Edward Gilbert-Kawai
Author: Adam Sheperdigian
Author: Thomas Adams
Author: Kay Mitchell
Author: Martin Feelisch ORCID iD
Author: Andrew Murray
Author: Mark Peters
Author: Grace Gilbert-Kawai
Author: Hugh Montgomery
Author: Denny Levett
Author: Rajendra Kumar
Author: Michael Mythen
Author: Michael Grocott
Author: Daniel Martin

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