Doctoral theses at NTNU, 2018:322 F atima Zohra Kiboub atima Zohra Fatima Zohra Kiboub Commercial Saturation Divers: oral thesis oral Blood biochemistry and perceptions of Doct acclimatization to oxygen and oxidative stress; in saturation and back to surface ISBN 978-82-326-3434-7 (printed ver.) ISBN 978-82-326-3435-4 (electronic ver.) ISSN 1503-8181 Doctoral theses at NTNU, 201 NTNU Philosophiae Doctor Philosophiae Thesis for the Degree of the Degree Thesis for 8 :322 Faculty of Medicine and Health Sciences of Medicine and Health Sciences Faculty egian University of Science and Technology of Science egian University Department of Circulation and Medical Imaging and Medical Department of Circulation Norw Fatima Zohra Kiboub Commercial Saturation Divers: Blood biochemistry and perceptions of acclimatization to oxygen and oxidative stress; in saturation and back to surface Thesis for the Degree of Philosophiae Doctor Trondheim, Januar 2019 Norwegian University of Science and Technology Faculty of Medicine and Health Sciences Department of Circulation and Medical Imaging NTNU Norwegian University of Science and Technology Thesis for the Degree of Philosophiae Doctor Faculty of Medicine and Health Sciences Department of Circulation and Medical Imaging © Fatima Zohra Kiboub ISBN 978-82-326-3434-7 (printed ver.) ISBN 978-82-326-3435-4 (electronic ver.) ISSN 1503-8181 Doctoral theses at NTNU, 2018:322 Printed by NTNU Grafisk senter Kommersiell Metning Dykkere: Blodbiokjemi og oppfatninger av akklimatisering til oksygen og oksidativt stress; i metning og tilbake til overflaten. Metningsdykking for olje- og gassvirksomhet i Nordsjøen har gjennomgått stor utvikling siden starten på 60-tallet. Dykkernes sikkerhet er forbedret, og det blitt registrert svært få dekompresjonssykdommer i løpet av de siste 20 årene, takket være mer konservative dykkeprosedyrer. Vår kunnskap om helsevirkningen av metningsdykking, dvs. å leve og arbeide under trykk og forhøyet oksygenpartialtrykk (ppO2) i lengre perioder, kan fortsatt forbedres. I dette prosjektet har vi undersøkt metningsdykkere under arbeid på norsk og britisk kontinentalsokkel gjennom delstudier av genuttrykk i blodceller, biomarkører for vaskulær funksjon, virkninger av vitamin C og E-inntak, blodnivåer av hemoglobin (Hb) og erytropoietin (EPO) samt dykkernes oppfatning av egen fysisk tilstand. Vi fant flere indikasjoner på at dykkere fysiologisk akklimatiseres til det hyperbar miljøet. I metning fikk de en reduksjon av kapasiteten for oksygentransport i blod, som økte i løpet av det første døgnet direkte etter metning. Globalt genuttrykk og blodnivåer av biomarkører indikerte at deres vaskulære funksjon returnerte til en tilstand som ligner pre- metning i det dykkerne kom ut av metning; og det var en økning av dykkernes eget antioksidantforsvar som potensielt gjorde inntaket av ekstra antioksidant-kosttilskudd unødvendig. Navn kandidat: Fatima Zohra Kiboub Institutt: Institutt for sirkulasjon og bildediagnostikk Veiledere: Ingrid Eftedal, Øyvind Loennechen Finansieringskilde: Technip Norge AS og Forskiningsrådet Ovennevnte avhandling er funnet verdig til å forsvares offentlig for graden PhD i Molekular Medisin. Disputas finner sted i Auditoriet ØHA11, Øya Helsehus 17. januar 2019, kl. 10:30 3 4 Contents Acknowledgments ................................................................................................................. 7 Norsk sammendrag – Summary in Norwegian ...................................................................... 9 Executive summary ............................................................................................................. 11 Abbreviations ...................................................................................................................... 13 Definitions ........................................................................................................................... 15 Preface ................................................................................................................................. 17 1 Introduction ............................................................................................................. 19 1.1 Brief history and applications of saturation diving in Norway ............................ 19 1.2 Commercial saturation diving accidents in the NCS ........................................... 22 1.3 Physiological challenges during saturation diving .............................................. 22 1.3.1 Oxidative stress and redox biology.............................................................. 23 1.3.2 Antioxidant supplements ............................................................................. 23 1.3.3 Functional and biochemical markers of vascular function .......................... 24 1.3.4 Gene-wide gene expression profiling: ......................................................... 24 2 Aims and hypotheses ............................................................................................... 26 3 Methodology ............................................................................................................ 28 3.1 Ethical approval ................................................................................................... 28 3.2 Study population .................................................................................................. 28 3.3 Compression and saturation period ..................................................................... 29 3.4 Vessel diving system ........................................................................................... 30 3.5 Diving standards, procedures and risk assessments ............................................ 32 3.6 Activities during the diving excursions ............................................................... 33 3.7 Decompression .................................................................................................... 33 4 Experimental protocol ............................................................................................. 34 4.1 Pre- and post-saturation medical examinations ................................................... 34 4.2 Maximum oxygen uptake .................................................................................... 34 4.3 Flow mediated dilation ........................................................................................ 35 4.4 Antioxidant vitamins C and E ............................................................................. 35 4.5 Blood sampling .................................................................................................... 36 4.5.1 Paper I .......................................................................................................... 36 4.5.2 Paper II ........................................................................................................ 37 4.5.3 Paper III ....................................................................................................... 37 5 5 Results and discussion ............................................................................................. 39 5.1 Paper I .................................................................................................................. 39 5.1.1 Blood biomarkers changes ........................................................................... 39 5.2 Paper II ................................................................................................................ 39 5.2.1 Haemoglobin and erythropoietin changes ................................................... 39 5.2.2 Mechanism of EPO regulation .................................................................... 39 5.3 Paper III ............................................................................................................... 40 6 Study limitations ...................................................................................................... 41 7 Conclusions ............................................................................................................. 43 8 Future research and way forward ............................................................................ 44 9 References ............................................................................................................... 45 10 Appendices .............................................................................................................. 48 10.1 Appendix 1 .......................................................................................................... 48 Appendix 2 ...................................................................................................................... 51 10.2 Appendix 3 .......................................................................................................... 53 10.3 Appendix 4 .......................................................................................................... 55 11 Papers ...................................................................................................................... 57 6 Acknowledgments This Industrial PhD project was conducted from 2014 to 2018 at the department of Circulation and Medical Imaging, the Norwegian University of Science and Technology (NTNU), Norway; with the collaboration of TechnipFMC in Norway (former Technip Norge AS) and the partial funding of the Norwegian Research Council (NRC). My warmest thanks go to my academic supervisor Ingrid Eftedal. Ingrid’s continuous and tireless support helped