Blood Substitutes

Professor Winslow received his M.D. degree and postgraduate training in internal medicine and hematology at the Johns Hopkins University and Hospital. He studied hemoglobin biochemistry at the Massachusetts Institute of Technology and Molecular Biology at the National Institutes of Health. His research, for more than 30 years, has been aimed at the intersection of the synthesis, structure and function of hemoglobin, in such areas as sickle cell anemia, high altitude physiology and hemoglobin-based oxygen carriers. Professor Winslow previously headed the Blood Research Division at the Letterman Army Institute of Research, responsible for the US Army's blood substitute program. Between 1991 and 1998, he was a Professor of Medicine, leading a blood substitute program at the University of California at San Diego (UCSD), supported by the National Institutes of Health. Professor Winslow has also served as a consultant to many private companies and has been an advisor for, among others, the Federal Aviation Administration (FAA), Food and Drug Administration (FDA), the Institute of Medicine of the National Academy of Science, the Pan American Health Organization, the National Institutes of Health, the Department of Defense and a number of foreign governments. He has written more than 200 scientific articles on clinical, physiological and biochemical aspects of hemoglobin and oxygen transport.

"Robert Winslow's new book Blood Substitutes, is useful in many ways. It brings together well-written summaries of the work of many of the most important investigators of the last 2 decades in the broad group of interrelated fields. Moreover, it also has some excellent chapters of scientific and medical background that provide context for the work. It also gives a historical snapshot of the thinking and attitudes of workers in the field. As an introduction to the field, this book is outstanding." --John R. Hess MD, MPH, FACPa, University of Maryland Medical Center for TRANSFUSION MEDICINE REVIEWS (2006)"There aren't too many all in one books on this subject, let alone one written this clearly, concisely, and with perspective. If you are interested in this field, get this book." --Doody's 3 Star Review by Valerie L. Ng, PhD, MD, Alameda County Medical Center/Highland Hospital (2006)"This is a serious, comprehensive, authoritative and highly readable textbook on a most relevant and challenging topic – the search for blood substitutes. ...The Editor and publishers have clearly given considerable thought to the readability as well as the academic rigour of the 46 chapters and 548 pages. In this reviewer’s opinion, they have been most successful. The font and the page layouts are easy on the eye, the illustrations of good quality, and the references for each chapter are comprehensive and up to date. The potential readership for this book will undoubtedly be broadly based. This is a quality text book, and, although it is always difficult to define quality, we do recognise it when we come across it." --Professor Ken Taylor, British Heart Foundation Professor of Cardiac Surgery, University of London and Director of Cardiac Services, Hammersmith Hospital, London, UK

• Section 1: BackgroundIntroductionChapter 1: Historical BackgroundChapter 2: Transfusion MedicineChapter 3: Regulatory Perspectives on Clinical Trials for Oxygen Therapeutics in Trauma and Transfusion PracticeSection 2: Physiological BasisIntroductionChapter 4: Clinical Physiology: Oxygen Transport and the Transfusion TriggerChapter 5: The Role of Oxygen and Hemoglobin Diffusion in Oxygen Transport by Cell-free HemoglobinsChapter 6: Oxygen Transport Properties of Hemoglobin-Based Oxygen Carriers: Studies using Artificial Capillaries and Mathematical SimulationChapter 7: Mechanisms of Oxygen Transport in the Microcirculation: Effects of Cell-Free Oxygen CarriersChapter 8: Shear Stress Mechanotransduction and the Flow Properties of BloodChapter 9: Local Regulation of Blood FlowSection 3: Clinical ApplicationsIntroductionChapter 10: Clinical Indications for Blood Substitutes and Optimal PropertiesChapter 11: Crystalloid SolutionsChapter 12: Hemoglobin-Based Oxygen Carriers as Resuscitative Solutions for Trauma and Combat Casualty CareChapter 13: Surgical HemorrhageChapter 14: Clinical Trials in Cardiac SurgeryChapter 15: HemodilutionChapter 16: Clinical HemodilutionChapter 17: Potential for Blood Substitutes in Tissue IschemiaSection 4: Toxicity and Side EffectsIntroductionChapter 18: Redox and Radical Reactions of Hemoglobin Solutions: Toxicities and Protective StrategiesChapter 19: Pro-Oxidant Activity of Hemoglobin and Endothelial CytotoxicityChapter 20: Renal ToxicityChapter 21: Hemoglobin and NeurotoxicityChapter 22: The Role of Inflammation in the Toxicity of Hemoglobin-Based Oxygen CarriersChapter 23: Hemoglobin-Induced Myocardial LesionsSection 5: Perfluorocarbon-Based Oxygen CarriersIntroductionChapter 24: Fluorocarbon Emulsions as in vivo Oxygen Delivery Systems: Background and ChemistryChapter 25: Fluosol®: The First Commercial Injectable Perfluorocarbon Oxygen CarrierChapter 26: Perftoran®Chapter 27: Rational Development of Oxyfluor™Chapter 28: Oxygent™, a Perfluorochemical-Based Oxygen Therapeutic for Surgical PatientsSection 6: Hemoglobin-Based Oxygen CarriersIntroductionChapter 29: The Structural and Functional Properties of Hemoglobin and their Relevance for a Hemoglobin-Based Blood SubstituteChapter 30: Hemoglobin ModificationChapter 31: Designing Recombinant Hemoglobin for Use as a Blood SubstituteChapter 32: Design, Conformational, Functional and Physiological Characterization of Recombinant Polymeric Heme-ProteinsChapter 33: αα-Crosslinked HemoglobinChapter 34: DCLHb and rHb1.1Chapter 35: Clinical Studies with DCLHbChapter 36: Hemopure® (HBOC-201, Hemoglobin Glutamer-250 (Bovine)): Preclinical StudiesChapter 37: HBOC-201 (Hemoglobin Glutamer-250 (Bovine), Hemopure®): Clinical StudiesChapter 38: Polyhemoglobin–Enzymes as New-Generation Blood Substitutes and Oxygen TherapeuticsChapter 39: Surface Decoration of Hemoglobin with Polyethylene GlycolChapter 40: Hemospan® (MP4), A Human Hemoglobin Modified with Maleimide-Polyethylene GlycolChapter 41: Dextran–HemoglobinChapter 42: Development of Non-Extravasating Hemoglobin-Based Oxygen CarriersSection 7: Liposomes and Related ProductsIntroductionChapter 43: Liposome-Encapsulated Hemoglobin: History, Preparation and EvaluationChapter 44: Hemoglobin Vesicles as a Molecular Assembly: Characteristics of Preparation Process and Performances as Artificial Oxygen CarriersChapter 45: Nanodimension Biodegradable Polymeric Membrane Artificial Red Blood CellsChapter 46: Albumin-Heme: A Synthetic Heme-Based Oxygen Carrier