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Intravenous Administration of Perfluorocarbon Emulsions As a Non-Recompression Therapy for Decompression Sickness

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Intravenous Administration of Perfluorocarbon Emulsions As a Non-Recompression Therapy for Decompression Sickness Virginia Commonwealth University VCU Scholars Compass Theses and Dissertations Graduate School 2008 Intravenous Administration of Perfluorocarbon Emulsions as a Non-Recompression Therapy for Decompression Sickness Cameron Smith Virginia Commonwealth University Follow this and additional works at: https://scholarscompass.vcu.edu/etd Part of the Physiology Commons © The Author Downloaded from https://scholarscompass.vcu.edu/etd/1555 This Dissertation is brought to you for free and open access by the Graduate School at VCU Scholars Compass. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of VCU Scholars Compass. For more information, please contact [email protected]. School of Medicine Virginia Commonwealth University This is to certify that the dissertation prepared by Cameron Reid Smith entitled INTRAVENOUS ADMINISTRATION OF PERFLUOROCARBON EMULSIONS AS A NON-RECOMPRESSION THERAPY FOR DECOMPRESSION SICKNESS has been approved by his or her committee as satisfactory completion of the thesis or dissertation requirement for the degree of Doctor of Philosophy Bruce D. Spiess, M.D., Director of Dissertation, School of Medicine George D. Ford, Ph.D., School of Medicine Roland N. Pittman, Ph.D., School of Medicine R. Wayne Barbee, Ph.D., School of Medicine Malcolm Ross Bullock, M.D., Ph.D., School of Medicine, University of Miami Diomedes E. Logothetis, Ph.D., Department Chair Jerome F. Strauss, III, M.D., Ph.D., Dean, School of Medicine Dr. F. Douglas Boudinot, Dean of the School of Graduate Studies Signed this 16th day of June, 2008 © Cameron Reid Smith, 2008 All Rights Reserved INTRAVENOUS ADMINISTRATION OF PERFLUOROCARBON EMULSIONS AS A NON-RECOMPRESSION THERAPY FOR DECOMPRESSION SICKNESS A Dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University. by CAMERON REID SMITH B.Sc., University of Guelph, Canada, 2000 M.Sc., University of Toronto, Canada, 2004 Director: BRUCE D. SPIESS, M.D. PROFESSOR DEPARTMENTS OF ANESTHESIOLOGY AND EMERGENCY MEDICINE Virginia Commonwealth University Richmond, Virginia June 2008 ii Acknowledgements There are numerous individuals and corporations without whose assistance and guidance this dissertation would not have been possible. First I would like to thank my advisor, Dr. Bruce D. Spiess. His willingness to invest his time, energy, and research resources in my training was invaluable. Without his instruction, direction, patience, and willingness to listen to my crazy ideas none of this work would have been possible. I am eternally grateful for his mentorship and hope only that I will one day be able to properly honour his example when training students of my own. I would also like to thank the members of my committee, Dr. George Ford, Dr. Roland Pittman, Dr. Wayne Barbee, and Dr. M. Ross Bullock. Their suggestions and criticisms were extremely helpful in shaping my thinking during the design, execution, analysis, and publication of this work. I must also acknowledge the assistance and instruction I received from the other staff in the laboratory, Dr. Jiepei Zhu, Dr. Ricardo Weis, and Dr. J. Travis Parsons. Their insight and ideas helped shape this project into what it has become. None of this work would have been possible were it not for the funding received from the Office of Naval Research and the generous provision of perfluorocarbon emulsion, Oxycyte®, by Synthetic Blood International. Last, but certainly not least, I would like to thank my family. The support I have received, and continue to receive from my wife, Sara, is immeasurable. Her willingness iii to pick up and leave our home in Canada and move to a strange city in a new country because I wanted to study there was as vital to this project as the support of my professors or grant money from funding agencies. Thank you for your willingness to follow me on this crazy adventure. The love and support of my parents and extended family has also been instrumental in carrying me through the ups and downs that research is made of. I cannot overstate my appreciation for your love, support, patience, and financing. iv Table of Contents Page Acknowledgements............................................................................................................. ii List of Tables .................................................................................................................... vii List of Figures.................................................................................................................... ix List of Abbreviations ......................................................................................................... xi List of Units of Measurements......................................................................................... xiv Abstract..............................................................................................................................xv Chapter 1 General Introduction..........................................................................................1 Short History of Diving.................................................................................1 Breath-Hold Diving.................................................................................1 Diving Equipment ...................................................................................2 Decompression Sickness.........................................................................6 Decompression Planning.......................................................................10 Haldanian Theory .............................................................................10 Neo-Haldanian Developments..........................................................15 Other Hypotheses..............................................................................17 Physiology and Pathophysiology of Decompression Sickness ...................23 What is Decompression Sickness? ........................................................23 v How and Why Bubbles Form................................................................27 Where Bubbles Form and Where They Are Found...............................30 Non-Mechanical Effects of Bubbles .....................................................33 Perfluorocarbons .........................................................................................35 Perfluorocarbons and Oxygen ...............................................................35 Perfluorocarbon Emulsions ...................................................................38 Perfluorocarbons and Decompression Sickness....................................40 2 Intravenous Perfluorocarbon Emulsions Increase Whole-Body Oxygenation After Severe Decompression Sickness........................................................44 Introduction .................................................................................................44 Materials and Methods ................................................................................46 Results .........................................................................................................51 Discussion and Conclusions........................................................................53 3 Intravenous Perfluorocarbon Emulsions Increase the Extent, but not the Rate While Helium-Oxygen Breathing Increases the Rate, but not the Extent of Nitrogen Washout After Severe Decompression Sickness .........................64 Introduction .................................................................................................64 Materials and Methods ................................................................................67 Results .........................................................................................................72 Discussion and Conclusions........................................................................77 vi 4 General Discussion and Conclusions...............................................................94 Literature Cited ................................................................................................................102 Appendices.......................................................................................................................119 A Appendix A....................................................................................................119 Vita...................................................................................................................................152 vii List of Tables Page Table 1: Table I of appendix IV from J. S. Haldane’s ‘The prevention of compressed air illness’................................................................................................................................13 Table 2: Table II of appendix IV from J. S. Haldane’s ‘The prevention of compressed air illness’................................................................................................................................14 Table 3: Workman M-values. ............................................................................................16 Table 4: Partial pressures of respiratory gases at 1 ATA...................................................18 Table 5: Frequency of signs and symptoms in 935 cases of decompression sickness. .....25 Table 6: Oxygen solubility of various perfluorochemicals................................................37 Table 7: Best-fit values resulting from the fit of a single exponential
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