Blood Substitutes - 1st Edition - ISBN: 9780127597607, 9780080454146

Blood Substitutes

1st Edition

Authors: Robert Winslow
Hardcover ISBN: 9780127597607
eBook ISBN: 9780080454146
Imprint: Academic Press
Published Date: 5th October 2005
Page Count: 576
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Description

  • List of Contributors
  • Preface
  • Acknowledgements
  • Abbreviations
  • Introduction
  • Section 1: Background
    • Introduction
    • Chapter 1: Historical Background
      • INTRODUCTION
      • BLOOD CIRCULATION AND TRANSFUSION
      • WORLD WAR II
      • FIRST ‘BLOOD SUBSTITUTES’
      • BLOOD PLASMA, SERUM AND ALBUMIN
      • CELL-FREE HEMOGLOBIN
      • CURRENT STATUS
      • SUMMARY
    • Chapter 2: Transfusion Medicine
      • HISTORY OF BLOOD TRANSFUSION
      • ORGANIZATION OF BLOOD SERVICES
      • AVAILABILITY OF BLOOD
      • RED BLOOD CELL COMPONENTS
      • RED CELL COMPATIBILITY
      • UNIVERSAL RED CELLS
      • RED CELL MODIFICATION
      • ADVERSE EVENTS ASSOCIATED WITH RED CELL TRANSFUSION
      • IMMUNOMODULATORY EFFECTS
      • THE COST OF RED CELLS
      • THE ROLE OF RED CELL SUBSTITUTES
    • Chapter 3: Regulatory Perspectives on Clinical Trials for Oxygen Therapeutics in Trauma and Transfusion Practice
      • GENERAL REGULATORY BACKGROUND IN THE UNITED STATES
      • CONSIDERATIONS FOR CLINICAL TRIALS IN TRAUMA
      • CONSIDERATIONS IN TRANSFUSION AVOIDANCE
      • SUMMARY
  • Section 2: Physiological Basis
    • Introduction
    • Chapter 4: Clinical Physiology: Oxygen Transport and the Transfusion Trigger
      • INTRODUCTION
      • OXYGEN REQUIREMENTS
      • LOCAL REGULATION OF OXYGEN SUPPLY: THE MICROCIRCULATION
      • OXYGEN UPTAKE IN THE LUNG
      • THE ‘OPTIMAL’ HEMATOCRIT
      • OXYGEN DELIVERY, OXYGEN UPTAKE AND THE ‘CRITICAL OXYGEN’
      • BLOOD TRANSFUSION AND OXYGEN SUPPLY
      • THE ‘TRANSFUSION TRIGGER’
    • Chapter5: The Role of Oxygen and Hemoglobin Diffusion in Oxygen Transport by Cell-free Hemoglobins
      • INTRODUCTION
      • OXYGEN DIFFUSION AND ITS BARRIERS IN THE CIRCULATION
      • FACILITATED DIFFUSION OF OXYGEN BY OXYHEMOGLOBIN
      • RATE LIMITING STEPS OF IN VIVO GAS EXCHANGE
      • FACILITATED OXYGEN TRANSPORT AND VASOCONSTRICTION
      • FACILITATED DIFFUSION AND HYPEROXYGENATION OF ARTERIOLES
      • SUMMARY
    • Chapter 6: Oxygen Transport Properties of Hemoglobin-Based Oxygen Carriers: Studies using Artificial Capillaries and Mathematical Simulation
      • INTRODUCTION
      • IN VITRO SIMULATION OF OXYGEN TRANSPORT
      • CURRENT STATE OF OXYGEN CARRIER STUDIES IN ARTIFICIAL CAPILLARIES
      • CURRENT STATE OF MATHEMATICAL SIMULATION STUDIES
      • EXAMPLES OF EXPERIMENTS AND SIMULATIONS
      • IMPLICATIONS FOR IN VIVO OXYGEN TRANSPORT
      • SUMMARY
    • Chapter 7: Mechanisms of Oxygen Transport in the Microcirculation: Effects of Cell-Free Oxygen Carriers
      • INTRODUCTION
      • THE DISTRIBUTION OF OXYGEN ON THE CIRCULATION
      • OXYGEN DELIVERY AND CONSUMPTION
      • ANEMIA AND HYPEROXIA
      • THE HEMOGLOBIN – OXYGEN EQUILIBRIUM CURVE
      • TISSUE RESPIRATION
      • SUMMARY
      • ACKNOWLEDGMENTS
    • Chapter 8: Shear Stress Mechanotransduction and the Flow Properties of Blood
      • INTRODUCTION
      • SHEAR STRESS AND THE RELEASE OF VASOACTIVE MEDIATORS
      • MECHANOTRANSDUCTION AND MECHANOSENSORS
      • THE ROLE OF THE GLYCOCALYX
      • CHANGES OF SHEAR STRESS IN THE MICROCIRCULATION
      • EFFECTS IN THE PLASMA LAYER
      • BLOOD SUBSTITUTES AND MECHANOTRANSDUCTION
      • ACKNOWLEDGMENTS
    • Chapter 9: Local Regulation of Blood Flow
      • INTRODUCTION
      • TISSUE OXYGEN SUPPLY AND DEMAND
      • CELLULAR METABOLIC FEEDBACK
      • OXYGEN-SENSITIVE MECHANISMS
      • MECHANISMS OF FUNCTIONAL HYPEREMIA
      • MECHANICAL STIMULI FOR FLOW REGULATION
      • INTEGRATIVE ASPECTS OF FLOW REGULATION
      • ACKNOWLEDGMENTS
  • Section 3: Clinical Applications
    • Introduction
    • Chapter 10: Clinical Indications for Blood Substitutes and Optimal Properties
      • INTRODUCTION
      • TRAUMA/RESUSCITATION
      • ELECTIVE SURGERY
      • RED CELL INCOMPATIBILITY
      • ISCHEMIC DISEASE AND ANGIOPLASTY
      • EXTRACORPOREAL ORGAN PERFUSION
      • CELL CULTURE MEDIA
      • HEMATOPOIETIC STIMULATION
      • CARDIOPLEGIA
      • SICKLE-CELL ANEMIA
      • TUMOR THERAPY
      • CHRONIC ANEMIA
      • RESEARCH
      • REQUIREMENTS FOR A BLOOD SUBSTITUTE
    • Chapter 11: Crystalloid Solutions
      • INTRODUCTION
      • PHYSIOLOGICAL PRINCIPLES
      • DISTRIBUTION VOLUMES OF WATER, SODIUM AND PROTEIN
      • KINETIC DISTRIBUTION VOLUMES OF FLUIDS
      • CRYSTALLOID SOLUTIONS
      • USE OF CRYSTALLOID FLUIDS IN SURGICAL PROCEDURES
      • USE OF CRYSTALLOID FLUIDS FOR REPLACEMENT OF BLOOD LOSS
      • OTHER EFFECTS OF CRYSTALLOID INFUSION
      • SUMMARY
    • Chapter 12: Hemoglobin-Based Oxygen Carriers as Resuscitative Solutions for Trauma and Combat Casualty Care
      • INTRODUCTION
      • REQUIREMENTS FOR COMBAT CASUALTY CARE
      • RELEVANT PROPERTIES OF HBOCs FOR TRAUMA AND COMBAT CASUALTY CARE
      • INTRAOPERATIVE TRIALS
      • PRE-HOSPITAL RESUSCITATION
      • PLASMA VOLUME EXPANSION
      • CARDIAC OUTPUT
      • OXYGEN UPTAKE VERSUS OXYGEN DELIVERY
      • HYPOTENSIVE RESUSCITATION
      • NEW FORMULATIONS
      • SUMMARY
    • Chapter 13: Surgical Hemorrhage
      • INTRODUCTION
      • POTENTIAL CLINICAL BENEFITS OF HBOCs IN SURGICAL CARE
      • POTENTIAL ROLE OF HBOCs IN SURGICAL CARE
      • EXCEPTION FROM INFORMED CONSENT FOR TRAUMA TRIALS
      • CLINICAL EVALUATION OF TETRAMERIC HEMOGLOBIN IN TRAUMA
      • CLINICAL SAFETY OF POLYHEME™ IN TRAUMA
      • CLINICAL EFFICACY OF POLYHEME TRAUMA CARE
      • THE NEXT GENERATION OF HBOCs FOR SURGICAL CARE
      • ACKNOWLEDGMENTS
    • Chapter 14: Clinical Trials in Cardiac Surgery
      • INTRODUCTION
      • HEMOGLOBIN SOLUTIONS
      • PERFLUOROCARBON EMULSIONS
      • SUMMARY
    • Chapter 15: Hemodilution
      • INTRODUCTION
      • MECHANISMS OF ADAPTATION TO REDUCED HEMOGLOBIN
      • MICROCIRCULATORY CHANGES AND TISSUE OXYGENATION
      • TISSUE OXYGENATION
      • BRAIN FUNCTION IN DILUTIONAL ANEMIA
      • PLASMA VISCOSITY
      • EXTREME HEMODILUTION
      • HYPEROXIC HEMODILUTION
      • SUMMARY
    • Chapter 16: Clinical Hemodilution
      • INTRODUCTION
      • INDICATIONS FOR ACUTE NORMOVOLEMIC HEMODILUTION
      • PHYSIOLOGICAL COMPENSATORY MECHANISMS
      • HEMODILUTION PROCEDURES
      • EFFICACY OF HEMODILUTION
      • ADJUNCTS TO ANH
      • SUMMARY
    • Chapter 17: Potential for Blood Substitutes in Tissue Ischemia
      • INTRODUCTION
      • PERIPHERAL ARTERIAL OCCLUSIVE DISEASE
      • TREATMENT AVAILABLE FOR CHRONIC CRITICAL LEG ISCHEMIA
      • POTENTIAL FOR BLOOD SUBSTITUTES IN THE TREATMENT OF CCLI
      • SUMMARY
  • Section 4: Toxicity and Side Effects
    • Introduction
    • Chapter 18: Redox and Radical Reactions of Hemoglobin Solutions: Toxicities and Protective Strategies
      • INTRODUCTION
      • OXIDATIVE MECHANISMS
      • HEMOGLOBIN AND CELL-SIGNALING PATHWAYS
      • ANTIOXIDATIVE PROTECTIVE STRATEGIES
      • SUMMARY
    • Chapter 19: Pro-Oxidant Activity of Hemoglobin and Endothelial Cytotoxicity
      • INTRODUCTION
      • PRO-OXIDANT ACTIVITY OF HEMOGLOBIN
      • HEMOGLOBIN-MEDIATED ENDOTHELIAL CYTOTOXICITY IN VITRO
      • PRO-OXIDANT ACTIVITY OF HEMOGLOBIN AND VASCULAR TOXICITY IN VIVO
      • SUMMARY
    • Chapter 20: Renal Toxicity
      • INTRODUCTION
      • HISTORY AND BACKGROUND
      • CURRENT STATE OF KNOWLEDGE
      • HEMOGLOBIN TOXICITY TO RENAL VASCULATURE
      • FUNCTIONAL CONSEQUENCES OF HEMOGLOBIN TOXICITY
      • ACUTE RENAL FAILURE
      • SUMMARY
      • FUTURE DIRECTIONS
    • Chapter 21: Hemoglobin and Neurotoxicity
      • INTRODUCTION
      • IN VITRO EXPERIMENTS
      • IN VIVO EXPERIMENTS
      • TISSUE RESPONSE TO HEMOGLOBIN METABOLITES AND POSSIBLE NEUROPROTECTION
      • CLINICAL EXPERIENCE WITH HBOCs
    • Chapter 22: The Role of Inflammation in the Toxicity of Hemoglobin-Based Oxygen Carriers
      • INTRODUCTION
      • THE INFLAMMATORY RESPONSE
      • BLOOD VESSELS
      • BLOOD SUBSTITUTES AND INFLAMMATION
      • MICROVESSELS AND INTESTINAL MUCOSA
      • CLINICAL IMPLICATIONS OF INFLAMMATION DURING USE OF BLOOD SUBSTITUTES
      • ANTICIPATED FUTURE DIRECTIONS
      • SUMMARY
    • Chapter 23: Hemoglobin-Induced Myocardial Lesions
      • INTRODUCTION
      • BACKGROUND
      • ANIMAL MODELS
      • LESION CHARACTERISTICS
      • MECHANISM OF HEMOGLOBIN-INDUCED MYOCARDIAL LESIONS
      • CO-MEDICAMENTS
      • SUMMARY
      • ACKNOWLEDGEMENTS
  • Section 5: Perfluorocarbon-Based Oxygen Carriers
    • Introduction
    • Chapter 24: Fluorocarbon Emulsions as in vivo Oxygen Delivery Systems: Background and Chemistry
      • FLUOROCARBON CHEMISTRY
      • OXYGEN DISSOLVING AND DELIVERING CAPACITY: GAS-LIKE LIQUIDS
      • PERFLUOROCARBON EMULSIONS FOR IN VIVO OXYGEN TRANSPORT
      • DEVELOPMENT OF INJECTABLE FLUOROCARBON EMULSIONS
      • THE SEARCH FOR IMPROVED EMULSIONS
    • Chapter 25: Fluosol®: The First Commercial Injectable Perfluorocarbon Oxygen Carrier
      • INTRODUCTION
      • ORIGINS OF FLUOSOL
      • CHEMISTRY, COMPOSITION AND PRODUCTION
      • PRECLINICAL STUDIES
      • CLINICAL TRIALS
      • Studies in North America
      • FAILURE OF REGULATORY APPROVAL OF FLUOSOL FOR THE TREATMENT OF ANEMIA
      • PERCUTANEOUS TRANSLUMINAL CORONARY ANGIOPLASTY
      • OTHER APPLICATIONS FOR FLUOSOL
      • LESSONS LEARNED FROM FLUOSOL
      • OTHER ‘FIRST-GENERATION’ EMULSIONS
    • Chapter 26: Perftoran®
      • INTRODUCTION
      • HISTORY AND COMPOSITION OF PERFTORAN
      • PRECLINICAL STUDIES
      • CLINICAL TRIALS WITH PERFTORAN
      • CURRENT USAGE OF PERFTORAN
      • CLINICAL IMPLICATIONS
      • THE FUTURE OF PERFTORAN
      • SUMMARY
      • ACKNOWLEDGMENTS
    • Chapter 27: Rational Development of Oxyfluor™
      • INTRODUCTION
      • EVOLUTION OF PERFLUOROCARBONS FOR OXYGEN TRANSPORT
      • DEVELOPMENT OF OXYFLUOR™
      • OXYFLUOR REGULATORY STATUS
      • THE FUTURE OF OXYFLUOR AND HEMAGEN
    • Chapter 28: Oxygent™, a Perfluorochemical-Based Oxygen Therapeutic for Surgical Patients
      • INTRODUCTION
      • EMULSION CHARACTERISTICS
      • NON-CLINICAL SAFETY
      • CLINICAL SAFETY
      • PRECLINICAL EFFICACY
      • POTENTIAL CLINICAL APPLICATIONS
      • PHASE II CLINICAL STUDIES
      • PHASE III CLINICAL STUDIES
      • FUTURE CLINICAL DEVELOPMENT
      • ACKNOWLEDGMENTS
  • Section 6: Hemoglobin-Based Oxygen Carriers
    • Introduction
    • Chapter 29: The Structural and Functional Properties of Hemoglobin and their Relevance for a Hemoglobin-Based Blood Substitute
      • INTRODUCTION
      • THE STRUCTURE OF HEMOGLOBIN
      • DERIVATIVES WITH HEME LIGANDS
      • SUBUNIT INTERFACES AND TETRAMER–DIMER DISSOCIATION
      • COOPERATIVE OXYGEN BINDING
      • STEREOCHEMICAL CONSEQUENCES OF LIGAND BINDING
      • CONTROL OF OXYGEN AFFINITY
      • NON-HEME LIGANDS: H+, Cl−, CO2 AND 2,3-DPG
      • NITRIC OXIDE
      • AUTOXIDATION
      • ACKNOWLEDGMENTS
    • Chapter 30: Hemoglobin Modification
      • INTRODUCTION
      • REACTIVITY OF HEMOGLOBIN
      • AMINO-TERMINAL MODIFICATION
      • MODIFICATION AT THE 2,3-DPG BINDING SITE
      • αα-CROSSLINK (LYSINE G6(99) α1–LYSINE G6(99)α2)
      • SURFACE, MULTISITE POLYMERIZING REAGENTS
      • CONJUGATED HEMOGLOBIN
      • RECOMBINANT HEMOGLOBIN
      • HEMOGLOBIN SOURCES
    • Chapter 31: Designing Recombinant Hemoglobin for Use as a Blood Substitute
      • INTRODUCTION
      • GENETICALLY CROSSLINKED HEMOGLOBIN
      • OXYGEN DELIVERY
      • THE HYPERTENSIVE SIDE EFFECT
      • NO DIOXYGENATION BY OXYHEMOGLOBIN
      • EXPRESSION OF rHB IN E. COLI
      • SUMMARY
      • ACKNOWLEDGMENTS
    • Chapter 32: Design, Conformational, Functional and Physiological Characterization of Recombinant Polymeric Heme-Proteins
      • INTRODUCTION
      • DESIGN OF RECOMBINANT HEME PROTEIN POLYMERS
      • BIOCHEMICAL PROPERTIES
      • PHYSIOLOGICAL PROPERTIES
      • ENDOTHELIAL PERMEABILITY (EXTRAVASATION)
      • SUMMARY
      • ACKNOWLEDGMENTS
    • Chapter 33: αα-Crosslinked Hemoglobin
      • THE NEED FOR A BLOOD SUBSTITUTE
      • PRODUCTION
      • CHARACTERIZATION
      • PHARMACOKINETICS
      • VASOCONSTRICTION
      • HEMODYNAMICS
      • MICROCIRCULATION
      • ENDOTHELIUM
      • OXYGEN TRANSPORT
      • OXIDATION
      • CENTRAL NERVOUS SYSTEM
    • Chapter 34: DCLHb and rHb1.1
      • ‘TETRAMERIC’ MODIFIED HEMOGLOBINS
      • DCLHb
      • RECOMBINANT HEMOGLOBINS
      • RETROSPECTIVE
    • Chapter 35: Clinical Studies with DCLHb
      • INTRODUCTION
      • PRECLINICAL CARDIAC LESIONS
      • PHASE I STUDY
      • PHASE II STUDIES
      • PHASE III STUDIES
      • EUROPEAN PRODUCT APPLICATION FOR CARDIAC SURGERY
      • TRAUMA STUDIES: THE BEGINNING OF THE END
      • THE END OF DCLHb
      • LESSONS LEARNED
    • Chapter 36: Hemopure® (HBOC-201, Hemoglobin Glutamer-250 (Bovine)): Preclinical Studies
      • INTRODUCTION
      • PRODUCT CHARACTERISTICS
      • PHARMACOLOGICAL ACTION
      • PRECLINICAL STUDIES OF TISSUE OXYGENATION AND TRAUMA
      • CARDIOVASCULAR STUDIES
      • HEMODILUTION AND COMPLETE BLOOD REPLACEMENT
      • CARDIAC FUNCTION, OUTPUT AND METABOLISM
      • POTENTIAL INDICATIONS FOR HBOC-201
      • SUMMARY
    • Chapter 37: HBOC-201 (Hemoglobin Glutamer-250 (Bovine), Hemopure®): Clinical Studies
      • INTRODUCTION
      • PHASE I STUDIES IN HUMAN VOLUNTEERS
      • PHASE I/II STUDIES
      • PHASE II STUDIES
      • PHASE III STUDY
      • OTHER POPULATIONS AND CASE STUDIES
      • SUMMARY
    • Chapter 38: Polyhemoglobin–Enzymes as New-Generation Blood Substitutes and Oxygen Therapeutics
      • INTRODUCTION
      • POLYHEMOGLOBIN–CATALASE–SUPEROXIDE DISMUTASE
      • POLYHEMOGLOBIN–TYROSINASE
      • SUMMARY
    • Chapter 39: Surface Decoration of Hemoglobin with Polyethylene Glycol
      • PROTEIN MODIFICATION WITH PEG
      • HEMOGLOBIN MODIFICATION WITH PEG
      • VASOACTIVITY OF PEG-MODIFIED HEMOGLOBIN
      • NEW PARADIGMS FOR THE DESIGN OF HEMOGLOBIN-BASED BLOOD SUBSTITUTES
      • NEW PEG CHEMISTRY STRATEGIES
      • Structural and functional properties of Hb-PEG5K6
      • MODIFICATION NEEDED TO NEUTRALIZE VASOACTIVITY
      • MOLECULAR SHIELDING BY PEG MODIFICATION
      • SUMMARY
      • ACKNOWLEDGMENTS
    • Chapter 40: Hemospan® (MP4), A Human Hemoglobin Modified with Maleimide-Polyethylene Glycol
      • INTRODUCTION
      • THE AUTOREGULATORY HYPOTHESIS
      • CHEMISTRY AND PHYSICAL PROPERTIES
      • NON-CLINICAL STUDIES
      • TOXICOLOGY/SAFETY
      • CLINICAL LABORATORY INTERFERENCE
      • CLINICAL INDICATIONS
      • CLINICAL TRIALS
      • SUMMARY
    • Chapter 41: Dextran–Hemoglobin
      • INTRODUCTION
      • HIGH YIELD OF DxHB
      • PROTECTION OF KIDNEYS
      • NON-ENTRY INTO LYMPH
      • OXYGEN AFFINITY
      • PHYSICAL STABILITY
      • IN VIVO STUDIES
      • POTENTIAL FOR DxHb
    • Chapter 42: Development of Non-Extravasating Hemoglobin-Based Oxygen Carriers
      • INTRODUCTION
      • FUMARYL-CROSSLINKED BOVINE HEMOGLOBIN
      • SEBACYL-CROSSLINKED TETRAMERIC HEMOGLOBIN (DECA)
      • ADIPYL-CROSSLINKED BOVINE HEMOGLOBIN
      • ZERO-LINK POLYMERIC HEMOGLOBIN
      • OXYGEN DELIVERY BY HIGH AND LOW AFFINITY CARRIERS
      • SUMMARY
      • ACKNOWLEDGMENTS
  • Section 7: Liposomes and Related Products
    • Introduction
    • Chapter 43: Liposome-Encapsulated Hemoglobin: History, Preparation and Evaluation
      • HISTORICAL PERSPECTIVE
      • PREPARATION OF LIPOSOME-ENCAPSULATED HEMOGLOBIN
      • PROPERTIES
      • ENDOTOXIN INTERACTION
      • CIRCULATION TIME
      • TOXICITY
      • OXYGEN DELIVERY
      • STORAGE STABILITY
      • SUMMARY
      • ACKNOWLEDGMENTS
    • Chapter 44: Hemoglobin Vesicles as a Molecular Assembly: Characteristics of Preparation Process and Performances as Artificial Oxygen Carriers
      • IMPORTANCE OF CELLULAR STRUCTURE
      • PREPARATION OF HEMOGLOBIN VESICLES
      • REGULATION OF OXYGEN AFFINITY
      • STORAGE STABILITY
      • ENDOTOXIN
      • HEMOGLOBIN VESICLES AS OXYGEN CARRIERS IN VIVO
      • SUMMARY
      • ACKNOWLEDGMENTS
    • Chapter 45: Nanodimension Biodegradable Polymeric Membrane Artificial Red Blood Cells
      • INTRODUCTION
      • PROPERTIES OF HEMOGLOBIN POLYLACTIDE NANOCAPSULES
      • PEG-PLA COPOLYMER Hb NANOCAPSULES
      • Effect of crosslinking the newly formed Hb nanocapsules
      • ENZYMES AND MULTIENZYMES
      • PREVENTION OF METHEMOGLOBIN FORMATION
      • IMPLICATIONS FOR BLOOD SUBSTITUTE DEVELOPMENT
      • ACKNOWLEDGMENTS
    • Chapter 46: Albumin-Heme: A Synthetic Heme-Based Oxygen Carrier
      • INTRODUCTION
      • RATIONALE FOR ALBUMIN-HEME
      • OXYGEN BINDING AND PHYSICOCHEMICAL CHARACTERISTICS
      • BLOOD COMPATIBILITY IN VITRO
      • IN VIVO EFFECTS
      • PRECLINICAL SAFETY
      • FUTURE RESEARCH
      • ACKNOWLEDGMENTS
  • Index
  • Plate

Key Features

  • Includes chapters necessary to the understanding of blood substitutes, including history, toxicity, physiology, and clinical applications
  • Presents detailed descriptions of the various products that have been developed and have advanced to clinical trials, and some that are in earlier states of development

Readership

Hematologists, blood bankers, biochemists, and biotechnologists working in the hemoglobin area, as well as surgeons working with blood

Table of Contents

  • List of Contributors
  • Preface
  • Acknowledgements
  • Abbreviations
  • Introduction
  • Section 1: Background
    • Introduction
    • Chapter 1: Historical Background
      • INTRODUCTION
      • BLOOD CIRCULATION AND TRANSFUSION
      • WORLD WAR II
      • FIRST ‘BLOOD SUBSTITUTES’
      • BLOOD PLASMA, SERUM AND ALBUMIN
      • CELL-FREE HEMOGLOBIN
      • CURRENT STATUS
      • SUMMARY
    • Chapter 2: Transfusion Medicine
      • HISTORY OF BLOOD TRANSFUSION
      • ORGANIZATION OF BLOOD SERVICES
      • AVAILABILITY OF BLOOD
      • RED BLOOD CELL COMPONENTS
      • RED CELL COMPATIBILITY
      • UNIVERSAL RED CELLS
      • RED CELL MODIFICATION
      • ADVERSE EVENTS ASSOCIATED WITH RED CELL TRANSFUSION
      • IMMUNOMODULATORY EFFECTS
      • THE COST OF RED CELLS
      • THE ROLE OF RED CELL SUBSTITUTES
    • Chapter 3: Regulatory Perspectives on Clinical Trials for Oxygen Therapeutics in Trauma and Transfusion Practice
      • GENERAL REGULATORY BACKGROUND IN THE UNITED STATES
      • CONSIDERATIONS FOR CLINICAL TRIALS IN TRAUMA
      • CONSIDERATIONS IN TRANSFUSION AVOIDANCE
      • SUMMARY
  • Section 2: Physiological Basis
    • Introduction
    • Chapter 4: Clinical Physiology: Oxygen Transport and the Transfusion Trigger
      • INTRODUCTION
      • OXYGEN REQUIREMENTS
      • LOCAL REGULATION OF OXYGEN SUPPLY: THE MICROCIRCULATION
      • OXYGEN UPTAKE IN THE LUNG
      • THE ‘OPTIMAL’ HEMATOCRIT
      • OXYGEN DELIVERY, OXYGEN UPTAKE AND THE ‘CRITICAL OXYGEN’
      • BLOOD TRANSFUSION AND OXYGEN SUPPLY
      • THE ‘TRANSFUSION TRIGGER’
    • Chapter5: The Role of Oxygen and Hemoglobin Diffusion in Oxygen Transport by Cell-free Hemoglobins
      • INTRODUCTION
      • OXYGEN DIFFUSION AND ITS BARRIERS IN THE CIRCULATION
      • FACILITATED DIFFUSION OF OXYGEN BY OXYHEMOGLOBIN
      • RATE LIMITING STEPS OF IN VIVO GAS EXCHANGE
      • FACILITATED OXYGEN TRANSPORT AND VASOCONSTRICTION
      • FACILITATED DIFFUSION AND HYPEROXYGENATION OF ARTERIOLES
      • SUMMARY
    • Chapter 6: Oxygen Transport Properties of Hemoglobin-Based Oxygen Carriers: Studies using Artificial Capillaries and Mathematical Simulation
      • INTRODUCTION
      • IN VITRO SIMULATION OF OXYGEN TRANSPORT
      • CURRENT STATE OF OXYGEN CARRIER STUDIES IN ARTIFICIAL CAPILLARIES
      • CURRENT STATE OF MATHEMATICAL SIMULATION STUDIES
      • EXAMPLES OF EXPERIMENTS AND SIMULATIONS
      • IMPLICATIONS FOR IN VIVO OXYGEN TRANSPORT
      • SUMMARY
    • Chapter 7: Mechanisms of Oxygen Transport in the Microcirculation: Effects of Cell-Free Oxygen Carriers
      • INTRODUCTION
      • THE DISTRIBUTION OF OXYGEN ON THE CIRCULATION
      • OXYGEN DELIVERY AND CONSUMPTION
      • ANEMIA AND HYPEROXIA
      • THE HEMOGLOBIN – OXYGEN EQUILIBRIUM CURVE
      • TISSUE RESPIRATION
      • SUMMARY
      • ACKNOWLEDGMENTS
    • Chapter 8: Shear Stress Mechanotransduction and the Flow Properties of Blood
      • INTRODUCTION
      • SHEAR STRESS AND THE RELEASE OF VASOACTIVE MEDIATORS
      • MECHANOTRANSDUCTION AND MECHANOSENSORS
      • THE ROLE OF THE GLYCOCALYX
      • CHANGES OF SHEAR STRESS IN THE MICROCIRCULATION
      • EFFECTS IN THE PLASMA LAYER
      • BLOOD SUBSTITUTES AND MECHANOTRANSDUCTION
      • ACKNOWLEDGMENTS
    • Chapter 9: Local Regulation of Blood Flow
      • INTRODUCTION
      • TISSUE OXYGEN SUPPLY AND DEMAND
      • CELLULAR METABOLIC FEEDBACK
      • OXYGEN-SENSITIVE MECHANISMS
      • MECHANISMS OF FUNCTIONAL HYPEREMIA
      • MECHANICAL STIMULI FOR FLOW REGULATION
      • INTEGRATIVE ASPECTS OF FLOW REGULATION
      • ACKNOWLEDGMENTS
  • Section 3: Clinical Applications
    • Introduction
    • Chapter 10: Clinical Indications for Blood Substitutes and Optimal Properties
      • INTRODUCTION
      • TRAUMA/RESUSCITATION
      • ELECTIVE SURGERY
      • RED CELL INCOMPATIBILITY
      • ISCHEMIC DISEASE AND ANGIOPLASTY
      • EXTRACORPOREAL ORGAN PERFUSION
      • CELL CULTURE MEDIA
      • HEMATOPOIETIC STIMULATION
      • CARDIOPLEGIA
      • SICKLE-CELL ANEMIA
      • TUMOR THERAPY
      • CHRONIC ANEMIA
      • RESEARCH
      • REQUIREMENTS FOR A BLOOD SUBSTITUTE
    • Chapter 11: Crystalloid Solutions
      • INTRODUCTION
      • PHYSIOLOGICAL PRINCIPLES
      • DISTRIBUTION VOLUMES OF WATER, SODIUM AND PROTEIN
      • KINETIC DISTRIBUTION VOLUMES OF FLUIDS
      • CRYSTALLOID SOLUTIONS
      • USE OF CRYSTALLOID FLUIDS IN SURGICAL PROCEDURES
      • USE OF CRYSTALLOID FLUIDS FOR REPLACEMENT OF BLOOD LOSS
      • OTHER EFFECTS OF CRYSTALLOID INFUSION
      • SUMMARY
    • Chapter 12: Hemoglobin-Based Oxygen Carriers as Resuscitative Solutions for Trauma and Combat Casualty Care
      • INTRODUCTION
      • REQUIREMENTS FOR COMBAT CASUALTY CARE
      • RELEVANT PROPERTIES OF HBOCs FOR TRAUMA AND COMBAT CASUALTY CARE
      • INTRAOPERATIVE TRIALS
      • PRE-HOSPITAL RESUSCITATION
      • PLASMA VOLUME EXPANSION
      • CARDIAC OUTPUT
      • OXYGEN UPTAKE VERSUS OXYGEN DELIVERY
      • HYPOTENSIVE RESUSCITATION
      • NEW FORMULATIONS
      • SUMMARY
    • Chapter 13: Surgical Hemorrhage
      • INTRODUCTION
      • POTENTIAL CLINICAL BENEFITS OF HBOCs IN SURGICAL CARE
      • POTENTIAL ROLE OF HBOCs IN SURGICAL CARE
      • EXCEPTION FROM INFORMED CONSENT FOR TRAUMA TRIALS
      • CLINICAL EVALUATION OF TETRAMERIC HEMOGLOBIN IN TRAUMA
      • CLINICAL SAFETY OF POLYHEME™ IN TRAUMA
      • CLINICAL EFFICACY OF POLYHEME TRAUMA CARE
      • THE NEXT GENERATION OF HBOCs FOR SURGICAL CARE
      • ACKNOWLEDGMENTS
    • Chapter 14: Clinical Trials in Cardiac Surgery
      • INTRODUCTION
      • HEMOGLOBIN SOLUTIONS
      • PERFLUOROCARBON EMULSIONS
      • SUMMARY
    • Chapter 15: Hemodilution
      • INTRODUCTION
      • MECHANISMS OF ADAPTATION TO REDUCED HEMOGLOBIN
      • MICROCIRCULATORY CHANGES AND TISSUE OXYGENATION
      • TISSUE OXYGENATION
      • BRAIN FUNCTION IN DILUTIONAL ANEMIA
      • PLASMA VISCOSITY
      • EXTREME HEMODILUTION
      • HYPEROXIC HEMODILUTION
      • SUMMARY
    • Chapter 16: Clinical Hemodilution
      • INTRODUCTION
      • INDICATIONS FOR ACUTE NORMOVOLEMIC HEMODILUTION
      • PHYSIOLOGICAL COMPENSATORY MECHANISMS
      • HEMODILUTION PROCEDURES
      • EFFICACY OF HEMODILUTION
      • ADJUNCTS TO ANH
      • SUMMARY
    • Chapter 17: Potential for Blood Substitutes in Tissue Ischemia
      • INTRODUCTION
      • PERIPHERAL ARTERIAL OCCLUSIVE DISEASE
      • TREATMENT AVAILABLE FOR CHRONIC CRITICAL LEG ISCHEMIA
      • POTENTIAL FOR BLOOD SUBSTITUTES IN THE TREATMENT OF CCLI
      • SUMMARY
  • Section 4: Toxicity and Side Effects
    • Introduction
    • Chapter 18: Redox and Radical Reactions of Hemoglobin Solutions: Toxicities and Protective Strategies
      • INTRODUCTION
      • OXIDATIVE MECHANISMS
      • HEMOGLOBIN AND CELL-SIGNALING PATHWAYS
      • ANTIOXIDATIVE PROTECTIVE STRATEGIES
      • SUMMARY
    • Chapter 19: Pro-Oxidant Activity of Hemoglobin and Endothelial Cytotoxicity
      • INTRODUCTION
      • PRO-OXIDANT ACTIVITY OF HEMOGLOBIN
      • HEMOGLOBIN-MEDIATED ENDOTHELIAL CYTOTOXICITY IN VITRO
      • PRO-OXIDANT ACTIVITY OF HEMOGLOBIN AND VASCULAR TOXICITY IN VIVO
      • SUMMARY
    • Chapter 20: Renal Toxicity
      • INTRODUCTION
      • HISTORY AND BACKGROUND
      • CURRENT STATE OF KNOWLEDGE
      • HEMOGLOBIN TOXICITY TO RENAL VASCULATURE
      • FUNCTIONAL CONSEQUENCES OF HEMOGLOBIN TOXICITY
      • ACUTE RENAL FAILURE
      • SUMMARY
      • FUTURE DIRECTIONS
    • Chapter 21: Hemoglobin and Neurotoxicity
      • INTRODUCTION
      • IN VITRO EXPERIMENTS
      • IN VIVO EXPERIMENTS
      • TISSUE RESPONSE TO HEMOGLOBIN METABOLITES AND POSSIBLE NEUROPROTECTION
      • CLINICAL EXPERIENCE WITH HBOCs
    • Chapter 22: The Role of Inflammation in the Toxicity of Hemoglobin-Based Oxygen Carriers
      • INTRODUCTION
      • THE INFLAMMATORY RESPONSE
      • BLOOD VESSELS
      • BLOOD SUBSTITUTES AND INFLAMMATION
      • MICROVESSELS AND INTESTINAL MUCOSA
      • CLINICAL IMPLICATIONS OF INFLAMMATION DURING USE OF BLOOD SUBSTITUTES
      • ANTICIPATED FUTURE DIRECTIONS
      • SUMMARY
    • Chapter 23: Hemoglobin-Induced Myocardial Lesions
      • INTRODUCTION
      • BACKGROUND
      • ANIMAL MODELS
      • LESION CHARACTERISTICS
      • MECHANISM OF HEMOGLOBIN-INDUCED MYOCARDIAL LESIONS
      • CO-MEDICAMENTS
      • SUMMARY
      • ACKNOWLEDGEMENTS
  • Section 5: Perfluorocarbon-Based Oxygen Carriers
    • Introduction
    • Chapter 24: Fluorocarbon Emulsions as in vivo Oxygen Delivery Systems: Background and Chemistry
      • FLUOROCARBON CHEMISTRY
      • OXYGEN DISSOLVING AND DELIVERING CAPACITY: GAS-LIKE LIQUIDS
      • PERFLUOROCARBON EMULSIONS FOR IN VIVO OXYGEN TRANSPORT
      • DEVELOPMENT OF INJECTABLE FLUOROCARBON EMULSIONS
      • THE SEARCH FOR IMPROVED EMULSIONS
    • Chapter 25: Fluosol®: The First Commercial Injectable Perfluorocarbon Oxygen Carrier
      • INTRODUCTION
      • ORIGINS OF FLUOSOL
      • CHEMISTRY, COMPOSITION AND PRODUCTION
      • PRECLINICAL STUDIES
      • CLINICAL TRIALS
      • Studies in North America
      • FAILURE OF REGULATORY APPROVAL OF FLUOSOL FOR THE TREATMENT OF ANEMIA
      • PERCUTANEOUS TRANSLUMINAL CORONARY ANGIOPLASTY
      • OTHER APPLICATIONS FOR FLUOSOL
      • LESSONS LEARNED FROM FLUOSOL
      • OTHER ‘FIRST-GENERATION’ EMULSIONS
    • Chapter 26: Perftoran®
      • INTRODUCTION
      • HISTORY AND COMPOSITION OF PERFTORAN
      • PRECLINICAL STUDIES
      • CLINICAL TRIALS WITH PERFTORAN
      • CURRENT USAGE OF PERFTORAN
      • CLINICAL IMPLICATIONS
      • THE FUTURE OF PERFTORAN
      • SUMMARY
      • ACKNOWLEDGMENTS
    • Chapter 27: Rational Development of Oxyfluor™
      • INTRODUCTION
      • EVOLUTION OF PERFLUOROCARBONS FOR OXYGEN TRANSPORT
      • DEVELOPMENT OF OXYFLUOR™
      • OXYFLUOR REGULATORY STATUS
      • THE FUTURE OF OXYFLUOR AND HEMAGEN
    • Chapter 28: Oxygent™, a Perfluorochemical-Based Oxygen Therapeutic for Surgical Patients
      • INTRODUCTION
      • EMULSION CHARACTERISTICS
      • NON-CLINICAL SAFETY
      • CLINICAL SAFETY
      • PRECLINICAL EFFICACY
      • POTENTIAL CLINICAL APPLICATIONS
      • PHASE II CLINICAL STUDIES
      • PHASE III CLINICAL STUDIES
      • FUTURE CLINICAL DEVELOPMENT
      • ACKNOWLEDGMENTS
  • Section 6: Hemoglobin-Based Oxygen Carriers
    • Introduction
    • Chapter 29: The Structural and Functional Properties of Hemoglobin and their Relevance for a Hemoglobin-Based Blood Substitute
      • INTRODUCTION
      • THE STRUCTURE OF HEMOGLOBIN
      • DERIVATIVES WITH HEME LIGANDS
      • SUBUNIT INTERFACES AND TETRAMER–DIMER DISSOCIATION
      • COOPERATIVE OXYGEN BINDING
      • STEREOCHEMICAL CONSEQUENCES OF LIGAND BINDING
      • CONTROL OF OXYGEN AFFINITY
      • NON-HEME LIGANDS: H+, Cl−, CO2 AND 2,3-DPG
      • NITRIC OXIDE
      • AUTOXIDATION
      • ACKNOWLEDGMENTS
    • Chapter 30: Hemoglobin Modification
      • INTRODUCTION
      • REACTIVITY OF HEMOGLOBIN
      • AMINO-TERMINAL MODIFICATION
      • MODIFICATION AT THE 2,3-DPG BINDING SITE
      • αα-CROSSLINK (LYSINE G6(99) α1–LYSINE G6(99)α2)
      • SURFACE, MULTISITE POLYMERIZING REAGENTS
      • CONJUGATED HEMOGLOBIN
      • RECOMBINANT HEMOGLOBIN
      • HEMOGLOBIN SOURCES
    • Chapter 31: Designing Recombinant Hemoglobin for Use as a Blood Substitute
      • INTRODUCTION
      • GENETICALLY CROSSLINKED HEMOGLOBIN
      • OXYGEN DELIVERY
      • THE HYPERTENSIVE SIDE EFFECT
      • NO DIOXYGENATION BY OXYHEMOGLOBIN
      • EXPRESSION OF rHB IN E. COLI
      • SUMMARY
      • ACKNOWLEDGMENTS
    • Chapter 32: Design, Conformational, Functional and Physiological Characterization of Recombinant Polymeric Heme-Proteins
      • INTRODUCTION
      • DESIGN OF RECOMBINANT HEME PROTEIN POLYMERS
      • BIOCHEMICAL PROPERTIES
      • PHYSIOLOGICAL PROPERTIES
      • ENDOTHELIAL PERMEABILITY (EXTRAVASATION)
      • SUMMARY
      • ACKNOWLEDGMENTS
    • Chapter 33: αα-Crosslinked Hemoglobin
      • THE NEED FOR A BLOOD SUBSTITUTE
      • PRODUCTION
      • CHARACTERIZATION
      • PHARMACOKINETICS
      • VASOCONSTRICTION
      • HEMODYNAMICS
      • MICROCIRCULATION
      • ENDOTHELIUM
      • OXYGEN TRANSPORT
      • OXIDATION
      • CENTRAL NERVOUS SYSTEM
    • Chapter 34: DCLHb and rHb1.1
      • ‘TETRAMERIC’ MODIFIED HEMOGLOBINS
      • DCLHb
      • RECOMBINANT HEMOGLOBINS
      • RETROSPECTIVE
    • Chapter 35: Clinical Studies with DCLHb
      • INTRODUCTION
      • PRECLINICAL CARDIAC LESIONS
      • PHASE I STUDY
      • PHASE II STUDIES
      • PHASE III STUDIES
      • EUROPEAN PRODUCT APPLICATION FOR CARDIAC SURGERY
      • TRAUMA STUDIES: THE BEGINNING OF THE END
      • THE END OF DCLHb
      • LESSONS LEARNED
    • Chapter 36: Hemopure® (HBOC-201, Hemoglobin Glutamer-250 (Bovine)): Preclinical Studies
      • INTRODUCTION
      • PRODUCT CHARACTERISTICS
      • PHARMACOLOGICAL ACTION
      • PRECLINICAL STUDIES OF TISSUE OXYGENATION AND TRAUMA
      • CARDIOVASCULAR STUDIES
      • HEMODILUTION AND COMPLETE BLOOD REPLACEMENT
      • CARDIAC FUNCTION, OUTPUT AND METABOLISM
      • POTENTIAL INDICATIONS FOR HBOC-201
      • SUMMARY
    • Chapter 37: HBOC-201 (Hemoglobin Glutamer-250 (Bovine), Hemopure®): Clinical Studies
      • INTRODUCTION
      • PHASE I STUDIES IN HUMAN VOLUNTEERS
      • PHASE I/II STUDIES
      • PHASE II STUDIES
      • PHASE III STUDY
      • OTHER POPULATIONS AND CASE STUDIES
      • SUMMARY
    • Chapter 38: Polyhemoglobin–Enzymes as New-Generation Blood Substitutes and Oxygen Therapeutics
      • INTRODUCTION
      • POLYHEMOGLOBIN–CATALASE–SUPEROXIDE DISMUTASE
      • POLYHEMOGLOBIN–TYROSINASE
      • SUMMARY
    • Chapter 39: Surface Decoration of Hemoglobin with Polyethylene Glycol
      • PROTEIN MODIFICATION WITH PEG
      • HEMOGLOBIN MODIFICATION WITH PEG
      • VASOACTIVITY OF PEG-MODIFIED HEMOGLOBIN
      • NEW PARADIGMS FOR THE DESIGN OF HEMOGLOBIN-BASED BLOOD SUBSTITUTES
      • NEW PEG CHEMISTRY STRATEGIES
      • Structural and functional properties of Hb-PEG5K6
      • MODIFICATION NEEDED TO NEUTRALIZE VASOACTIVITY
      • MOLECULAR SHIELDING BY PEG MODIFICATION
      • SUMMARY
      • ACKNOWLEDGMENTS
    • Chapter 40: Hemospan® (MP4), A Human Hemoglobin Modified with Maleimide-Polyethylene Glycol
      • INTRODUCTION
      • THE AUTOREGULATORY HYPOTHESIS
      • CHEMISTRY AND PHYSICAL PROPERTIES
      • NON-CLINICAL STUDIES
      • TOXICOLOGY/SAFETY
      • CLINICAL LABORATORY INTERFERENCE
      • CLINICAL INDICATIONS
      • CLINICAL TRIALS
      • SUMMARY
    • Chapter 41: Dextran–Hemoglobin
      • INTRODUCTION
      • HIGH YIELD OF DxHB
      • PROTECTION OF KIDNEYS
      • NON-ENTRY INTO LYMPH
      • OXYGEN AFFINITY
      • PHYSICAL STABILITY
      • IN VIVO STUDIES
      • POTENTIAL FOR DxHb
    • Chapter 42: Development of Non-Extravasating Hemoglobin-Based Oxygen Carriers
      • INTRODUCTION
      • FUMARYL-CROSSLINKED BOVINE HEMOGLOBIN
      • SEBACYL-CROSSLINKED TETRAMERIC HEMOGLOBIN (DECA)
      • ADIPYL-CROSSLINKED BOVINE HEMOGLOBIN
      • ZERO-LINK POLYMERIC HEMOGLOBIN
      • OXYGEN DELIVERY BY HIGH AND LOW AFFINITY CARRIERS
      • SUMMARY
      • ACKNOWLEDGMENTS
  • Section 7: Liposomes and Related Products
    • Introduction
    • Chapter 43: Liposome-Encapsulated Hemoglobin: History, Preparation and Evaluation
      • HISTORICAL PERSPECTIVE
      • PREPARATION OF LIPOSOME-ENCAPSULATED HEMOGLOBIN
      • PROPERTIES
      • ENDOTOXIN INTERACTION
      • CIRCULATION TIME
      • TOXICITY
      • OXYGEN DELIVERY
      • STORAGE STABILITY
      • SUMMARY
      • ACKNOWLEDGMENTS
    • Chapter 44: Hemoglobin Vesicles as a Molecular Assembly: Characteristics of Preparation Process and Performances as Artificial Oxygen Carriers
      • IMPORTANCE OF CELLULAR STRUCTURE
      • PREPARATION OF HEMOGLOBIN VESICLES
      • REGULATION OF OXYGEN AFFINITY
      • STORAGE STABILITY
      • ENDOTOXIN
      • HEMOGLOBIN VESICLES AS OXYGEN CARRIERS IN VIVO
      • SUMMARY
      • ACKNOWLEDGMENTS
    • Chapter 45: Nanodimension Biodegradable Polymeric Membrane Artificial Red Blood Cells
      • INTRODUCTION
      • PROPERTIES OF HEMOGLOBIN POLYLACTIDE NANOCAPSULES
      • PEG-PLA COPOLYMER Hb NANOCAPSULES
      • Effect of crosslinking the newly formed Hb nanocapsules
      • ENZYMES AND MULTIENZYMES
      • PREVENTION OF METHEMOGLOBIN FORMATION
      • IMPLICATIONS FOR BLOOD SUBSTITUTE DEVELOPMENT
      • ACKNOWLEDGMENTS
    • Chapter 46: Albumin-Heme: A Synthetic Heme-Based Oxygen Carrier
      • INTRODUCTION
      • RATIONALE FOR ALBUMIN-HEME
      • OXYGEN BINDING AND PHYSICOCHEMICAL CHARACTERISTICS
      • BLOOD COMPATIBILITY IN VITRO
      • IN VIVO EFFECTS
      • PRECLINICAL SAFETY
      • FUTURE RESEARCH
      • ACKNOWLEDGMENTS
  • Index
  • Plate

Details

No. of pages:
576
Language:
English
Copyright:
© Academic Press 2005
Published:
Imprint:
Academic Press
eBook ISBN:
9780080454146
Hardcover ISBN:
9780127597607

About the Author

Robert Winslow

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.

Affiliations and Expertise

University of California, Department of Medicine and Veterans Affairs Medical Center, San Diego, U.S.A.

Reviews

"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