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https://theses.gla.ac.uk/ Theses Digitisation: https://www.gla.ac.uk/myglasgow/research/enlighten/theses/digitisation/ This is a digitised version of the original print thesis. Copyright and moral rights for this work are retained by the author A copy can be downloaded for personal non-commercial research or study, without prior permission or charge This work cannot be reproduced or quoted extensively from without first obtaining permission in writing from the author The content must not be changed in any way or sold commercially in any format or medium without the formal permission of the author When referring to this work, full bibliographic details including the author, title, awarding institution and date of the thesis must be given Enlighten: Theses https://theses.gla.ac.uk/ [email protected] Human ^spouses to CoùCandHypojçia: ImpCications fo r Mountaineers Thesis (Presentedfor the (Degree o f Doctor o f PhiCosophy (By Çeorgios-Ioannis Tsianos UNIVERSITY o f GLASGOW PacuCty of(BiomedtcaC and Life Sciences (Division o f SLeurosciences and(BiomedicaCSystems DecemSer 2004 ProQuest Number: 10390954 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a com plete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest ProQuest 10390954 Published by ProQuest LLO (2017). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States C ode Microform Edition © ProQuest LLO. ProQuest LLO. 789 East Eisenhower Parkway P.Q. Box 1346 Ann Arbor, Ml 48106- 1346 f^ÂSGOW UNIVERSITY LIBRA î ''WouZdryouyk4TOw Ct andi^hT2{A/eâll/you4^ hopBya^ha4% ci'? Ho4agûporuthe^crci04ât'a^0r(Puite4Ttth4PLt'maJce^'ycyur n e^ step a^dehcUBs hetwee40/the' thdng^yoiA/cvre^j and^the^thCng^you/may become!^ Scottish Mountaineering Journal To TYVKj QrancâtHers, Q eorgios Katsigras & Vassilios T sia n o s Declaration I hereby deelare that this thesis has been conducted by me. All soiu'ces of infonnation have been specifically acknowledged by means of referenees. Acknowledgements I am grateful to my supervisor-Stan Grant, assessor-Nanette Mutrie, the volunteers in my studies, as well as all University of Glasgow members of staff and outside collaborators who assisted and guided me throughout my Ph.D. research training. I have personally shown my appreciation to all. Finally, thank you to David Miller, an educator, a listener, and of course, director of the IBLS Graduate School. WCtfvTiAXro'Hngfe'dcHibtj m y a n d m<>ther deserve'm y htghed complunenty. I may not have gone where I intended to go, but I think I have ended up where I intended to be. Thank you Scotland! Contents Page Declaration 2 Acknowledgements 3 Contents 4 List o f Abbreviations 7 List of Figures 9 List o f Tables 11 Summary 12 Thesis Results 16 Chapter 1: General Introduction 17 1.1 O f Men and Mountains 18 1.2 Hypothermia 20 1.2.1 Hypothermia Definitions 20 1.2.2 Physiological Responses to Cold 21 1.2.3 Heat Balance 22 1.2.4 Exposure Hazards 23 1.2.5 Mountain Rescue 24 1.2.6 Rewarming 25 1.2.7 Equipment for the Management of Hypothermia 25 1.3 Altitude Hypoxia 28 1.3.1 Physiological Changes at Altitude 30 1.3.2 Acute Mountain Sickness (AMS) 33 1.3.3 Arterial Oxygen Saturation (SaOf) and Acute Mountain Sickness 35 1.3.4 Hypoxic Ventilatory Response (HVR) and Acute Mountain Sickness 35 1.3.5 Acute Mountain Sickness Susceptibility and Prediction 36 L3.6 Acute Mountain Sickness Treatment 37 1.3.7 Central Nervous System (CNS) Model Of AMS Pathophysiology 37 1.3.8 High Altitude Pulmonary And Cerebral Edemas (HAPE and HACE) 38 1.3.9 Recommendations for Safe Ascent to Altitude 40 1.4 Genetics 41 1.4.1 Angiotensin Converting Enzyme (ACE) 41 1.4.2 ACE I/D Polymorphism and Human Physical Performance 42 1.4.3 ACE I/D Polymorphism and Hypoxia 43 1.4.4 ACE and AMS 45 1.5 Aims O f Thesis 46 Chapter 2: A Comparison of a Bubble-Wrap Bag and a Mountain Rescue Casualty Bag in a Cold Windy Environment 47 2.1 Introduction 48 2.2 Methods 49 2.3 Results 55 2.4 Discussion 64 Chapter 3A: Factors Affecting a Climber’s Ability During a Rapid Ascent o f Mont Blanc, 4807m 69 3A. I Introduction 70 3A. 2 Methods 71 3A. 3 Results 72 3A. 4 Discussion 84 Chapter 3B: Performance at Altitude and Angiotensin Converting Enzyme Genotype 88 3B. 1 Introduction 89 3B. 2 Methods 90 3B. 3 Results 92 3B. 4 Discussion 95 Chapter 4: The Effect of ACE Genotype and Hypoxic Ventilatory Response on Arterial Oxygen Saturation and Other Physiological Measurements During a Staged Ascent to 5000m 9 7 4.1 Introduction 98 4.2 Methods 100 4.3 Results 104 4.4 Discussion 108 Chapter 5: ACE Genotype and Mount Everest Climbers, 8850m 112 5.1 Introduction 113 5.2 Methods 114 5.3 Results 115 5.4 Discussion 116 Chapter 6: General Discussion 119 References 126 Appendix 140 List of Abbreviations ACE Angiotensin Converting Enzyme AMS Acute Mountain Sickness ANGI Angiotensin I ANGII Angiotensin II ANOVA Analysis o f Variance BBB Blood Brain Barrier BC Base Camp BW Bubble Wrap °C Degrees Celsius CBV Cerebral Blood Volume CNS Central Nervous System CO Cardiac Output % Carbon Dioxide Cl Confidence Interval CB Casualty Bag HA High Altitude HACE High Altitude Cerebral Edema HAPE High Altitude Pulmonary Edema Hb Haemoglobin HR Heart Rate HVR Hypoxic Ventilatory Response m Meters MPS Metallised Plastic Sheeting mmHg Millimetres of Mercury MOD Ministry o f Defence O2 Oxygen Partial Pressure o f Arterial Oxygen Partial Pressure of Alveolar Carbon Dioxide Partial Pressure of Alveolar Oxygen PETCO2 Partial Pressure o f End-Tidal Carbon Dioxide PO2 Partial Pressure o f Oxygen RR Respiratory Rate Sa02 Arterial Blood Oxygen Saturation SD Standard Deviation SV Stoke Volume Tcore Core Temperature Tskin Skin Temperature VC02 Volume of Carbon Dioxide Produced Ve Minute Ventilation VO2 max Maximal Oxygen Uptake FO2 Oxygen Uptake List of Figures Figure Title Page 1.1 Mount Everest, 8850m. 18 1.2 Relationship between altitude and inspired oxygen pressure. 28 1.3 PO2 values from inspired air to mixed venous blood a sea level and in residents at an altitude of4600m (West, 2000). 29 1.4 Resting PETCO2 in 2 groups measured at sea level and during 12 and 19~day sojourns at 4300m. Values decrease due to hyperventilation. 30 1.5 Changes is variables relating to ventilation in subjects at 1600m, and first 5 days at an altitude of4300m (Huang et al, 1984). 32 1.6 Radiograph of patient with HAPE and 4 days later (Ward et al, 2000). 39 1.7. Sa02 at various altitudes by ACE genotype. Sa02 with ascent was better sustained in the Il-allele subjects (Woods et al, 2002) 44 2.1 Casualty Bag. 50 2.2 Bubble-Wrap Bag. 51 2.3A Core temperature changes from baseline - BW. 55 2.3B Core temperature changes from baseline - CB. 55 2.4A Mean skin temperature changes from baseline -BW . 56 2.4B Mean skin temperature changes from baseline - CB. 56 2.5A Mean triceps temperature changes from baseline - BW. 57 2.5B Mean triceps temperature changes from baseline - CB. 57 2.6A Mean pectoral temperature changes from baseline -B W . 58 2.6B Mean pectoral temperature changes from baseline - CB. 58 2.7A Mean thigh temperature changes fiôm baseline — BW. 58 2.7B Mean thigh temperature changes from baseline - CB. 58 2.8A Mean calf temperature changes from baseline — BW. 59 2.8B Mean calf temperature changes from baseline - CB. 59 2.9A Heart Rate changes from baseline — BW. 59 2.9B Heart Rate changes from baseline - CB. 59 2.10A VO 2 changes from baseline - BW. 60 2.1 OB VO2 changes from baseline - CB. 60 2.1 lA Cold comfort changes from baseline -BW. 61 2.1 IB Cold comfort changes from baseline — CB. 61 2.12 Shivering status of subjects by group. 62 3A1. Coûter Hut, 3817m. 71 3A. 2 Collection of physiological measurements in Coûter Hut. 73 3A. 3 Classification Tree for the Ascent Outcome o f Mont Blanc from the Coûter Hut for the 210 subjects. 77 3A.4 Non-Parametric Regressions on Age for the Ascent Time of Mont Blanc from the Coûter Hut by level o f Climbing Profile in the previous 14 days. 78 3A.5 Regiêssion Tree for the Ascent Time o f Mont Blanc from the Coûter Hut for the 197 subject. 79 3A. 6 Plots of raw AMS scores before and after attempted ascent of Mont Blanc from the Coûter Hut labelled by Ascent Outcome. 82 3A. 7 Pair-wise plots of all physiological variables and raw AMS score taken at arrival at Coûter Hut. 83 3B. 1 Craph showing percentage of subjects successful in reaching the Mont Blanc summit for each ACE I/D genotype. Success for those returning by the same route was dependent upon ACE genotype. 93 4.1 Research/Chamlang Base Camp, 5000m. 100 4.2 HVR assessment. 102 4.3 Relationship between SaO2 vs HVR. 104 4.4 Craph showing mean SaO2 by altitude and ACE genotype. 105 4.5 p values for difference in percentage change in SaO2 by ACE genotype between changes in altitude.

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