Blood substitutes are solutions designed for use in patients who need blood transfusions, but for whom whole blood is not available, or is not safe. This interest has intensified in the wake of the AIDS and hepatitis C epidemics. Blood Substitutes describes the rationale, current approaches, clinical efficacy, and design issues for all blood substitutes now in clinical trials. The many summary diagrams and tables help make the book accessible to readers such as surgeons and blood bankers, who have less technical expertise than the biochemists and hematologists who are designing and testing blood substitutes.
Section 1: Background
Introduction
Chapter 1: Historical Background
Chapter 2: Transfusion Medicine
Chapter 3: Regulatory Perspectives on Clinical Trials for Oxygen Therapeutics in Trauma and Transfusion Practice
Section 2: Physiological Basis
Introduction
Chapter 4: Clinical Physiology: Oxygen Transport and the Transfusion Trigger
Chapter 5: The Role of Oxygen and Hemoglobin Diffusion in Oxygen Transport by Cell-free Hemoglobins
Chapter 6: Oxygen Transport Properties of Hemoglobin-Based Oxygen Carriers: Studies using Artificial Capillaries and Mathematical Simulation
Chapter 7: Mechanisms of Oxygen Transport in the Microcirculation: Effects of Cell-Free Oxygen Carriers
Chapter 8: Shear Stress Mechanotransduction and the Flow Properties of Blood
Chapter 9: Local Regulation of Blood Flow
Section 3: Clinical Applications
Introduction
Chapter 10: Clinical Indications for Blood Substitutes and Optimal Properties
Chapter 11: Crystalloid Solutions
Chapter 12: Hemoglobin-Based Oxygen Carriers as Resuscitative Solutions for Trauma and Combat Casualty Care
Chapter 13: Surgical Hemorrhage
Chapter 14: Clinical Trials in Cardiac Surgery
Chapter 15: Hemodilution
Chapter 16: Clinical Hemodilution
Chapter 17: Potential for Blood Substitutes in Tissue Ischemia
Section 4: Toxicity and Side Effects
Introduction
Chapter 18: Redox and Radical Reactions of Hemoglobin Solutions: Toxicities and Protective Strategies
Chapter 19: Pro-Oxidant Activity of Hemoglobin and Endothelial Cytotoxicity
Chapter 20: Renal Toxicity
Chapter 21: Hemoglobin and Neurotoxicity
Chapter 22: The Role of Inflammation in the Toxicity of Hemoglobin-Based Oxygen Carriers
Chapter 23: Hemoglobin-Induced Myocardial Lesions
Section 5: Perfluorocarbon-Based Oxygen Carriers
Introduction
Chapter 24: Fluorocarbon Emulsions as in vivo Oxygen Delivery Systems: Background and Chemistry
Chapter 25: Fluosol®: The First Commercial Injectable Perfluorocarbon Oxygen Carrier
Chapter 26: Perftoran®
Chapter 27: Rational Development of Oxyfluor(TM)
Chapter 28: Oxygent(TM), a Perfluorochemical-Based Oxygen Therapeutic for Surgical Patients
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
Chapter 30: Hemoglobin Modification
Chapter 31: Designing Recombinant Hemoglobin for Use as a Blood Substitute
Chapter 32: Design, Conformational, Functional and Physiological Characterization of Recombinant Polymeric Heme-Proteins
Chapter 33: aa-Crosslinked Hemoglobin
Chapter 34: DCLHb and rHb1.1
Chapter 35: Clinical Studies with DCLHb
Chapter 36: Hemopure® (HBOC-201, Hemoglobin Glutamer-250 (Bovine)): Preclinical Studies
Chapter 37: HBOC-201 (Hemoglobin Glutamer-250 (Bovine), Hemopure®): Clinical Studies
Chapter 38: Polyhemoglobin-Enzymes as New-Generation Blood Substitutes and Oxygen Therapeutics
Chapter 39: Surface Decoration of Hemoglobin with Polyethylene Glycol
Chapter 40: Hemospan® (MP4), A Human Hemoglobin Modified with Maleimide-Polyethylene Glycol
Chapter 41: Dextran-Hemoglobin
Chapter 42: Development of Non-Extravasating Hemoglobin-Based Oxygen Carriers
Section 7: Liposomes and Related Products
Introduction
Chapter 43: Liposome-Encapsulated Hemoglobin: History, Preparation and Evaluation
Chapter 44: Hemoglobin Vesicles as a Molecular Assembly: Characteristics of Preparation Process and Performances as Artificial Oxygen Carriers
Chapter 45: Nanodimension Biodegradable Polymeric Membrane Artificial Red Blood Cells
Chapter 46: Albumin-Heme: A Synthetic Heme-Based Oxygen Carrier
Show moreBlood substitutes are solutions designed for use in patients who need blood transfusions, but for whom whole blood is not available, or is not safe. This interest has intensified in the wake of the AIDS and hepatitis C epidemics. Blood Substitutes describes the rationale, current approaches, clinical efficacy, and design issues for all blood substitutes now in clinical trials. The many summary diagrams and tables help make the book accessible to readers such as surgeons and blood bankers, who have less technical expertise than the biochemists and hematologists who are designing and testing blood substitutes.
Section 1: Background
Introduction
Chapter 1: Historical Background
Chapter 2: Transfusion Medicine
Chapter 3: Regulatory Perspectives on Clinical Trials for Oxygen Therapeutics in Trauma and Transfusion Practice
Section 2: Physiological Basis
Introduction
Chapter 4: Clinical Physiology: Oxygen Transport and the Transfusion Trigger
Chapter 5: The Role of Oxygen and Hemoglobin Diffusion in Oxygen Transport by Cell-free Hemoglobins
Chapter 6: Oxygen Transport Properties of Hemoglobin-Based Oxygen Carriers: Studies using Artificial Capillaries and Mathematical Simulation
Chapter 7: Mechanisms of Oxygen Transport in the Microcirculation: Effects of Cell-Free Oxygen Carriers
Chapter 8: Shear Stress Mechanotransduction and the Flow Properties of Blood
Chapter 9: Local Regulation of Blood Flow
Section 3: Clinical Applications
Introduction
Chapter 10: Clinical Indications for Blood Substitutes and Optimal Properties
Chapter 11: Crystalloid Solutions
Chapter 12: Hemoglobin-Based Oxygen Carriers as Resuscitative Solutions for Trauma and Combat Casualty Care
Chapter 13: Surgical Hemorrhage
Chapter 14: Clinical Trials in Cardiac Surgery
Chapter 15: Hemodilution
Chapter 16: Clinical Hemodilution
Chapter 17: Potential for Blood Substitutes in Tissue Ischemia
Section 4: Toxicity and Side Effects
Introduction
Chapter 18: Redox and Radical Reactions of Hemoglobin Solutions: Toxicities and Protective Strategies
Chapter 19: Pro-Oxidant Activity of Hemoglobin and Endothelial Cytotoxicity
Chapter 20: Renal Toxicity
Chapter 21: Hemoglobin and Neurotoxicity
Chapter 22: The Role of Inflammation in the Toxicity of Hemoglobin-Based Oxygen Carriers
Chapter 23: Hemoglobin-Induced Myocardial Lesions
Section 5: Perfluorocarbon-Based Oxygen Carriers
Introduction
Chapter 24: Fluorocarbon Emulsions as in vivo Oxygen Delivery Systems: Background and Chemistry
Chapter 25: Fluosol®: The First Commercial Injectable Perfluorocarbon Oxygen Carrier
Chapter 26: Perftoran®
Chapter 27: Rational Development of Oxyfluor(TM)
Chapter 28: Oxygent(TM), a Perfluorochemical-Based Oxygen Therapeutic for Surgical Patients
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
Chapter 30: Hemoglobin Modification
Chapter 31: Designing Recombinant Hemoglobin for Use as a Blood Substitute
Chapter 32: Design, Conformational, Functional and Physiological Characterization of Recombinant Polymeric Heme-Proteins
Chapter 33: aa-Crosslinked Hemoglobin
Chapter 34: DCLHb and rHb1.1
Chapter 35: Clinical Studies with DCLHb
Chapter 36: Hemopure® (HBOC-201, Hemoglobin Glutamer-250 (Bovine)): Preclinical Studies
Chapter 37: HBOC-201 (Hemoglobin Glutamer-250 (Bovine), Hemopure®): Clinical Studies
Chapter 38: Polyhemoglobin-Enzymes as New-Generation Blood Substitutes and Oxygen Therapeutics
Chapter 39: Surface Decoration of Hemoglobin with Polyethylene Glycol
Chapter 40: Hemospan® (MP4), A Human Hemoglobin Modified with Maleimide-Polyethylene Glycol
Chapter 41: Dextran-Hemoglobin
Chapter 42: Development of Non-Extravasating Hemoglobin-Based Oxygen Carriers
Section 7: Liposomes and Related Products
Introduction
Chapter 43: Liposome-Encapsulated Hemoglobin: History, Preparation and Evaluation
Chapter 44: Hemoglobin Vesicles as a Molecular Assembly: Characteristics of Preparation Process and Performances as Artificial Oxygen Carriers
Chapter 45: Nanodimension Biodegradable Polymeric Membrane Artificial Red Blood Cells
Chapter 46: Albumin-Heme: A Synthetic Heme-Based Oxygen Carrier
Show moreSection 1: Background
Introduction
Chapter 1: Historical Background
Chapter 2: Transfusion Medicine
Chapter 3: Regulatory Perspectives on Clinical Trials for Oxygen
Therapeutics in Trauma and Transfusion Practice
Section 2: Physiological Basis
Introduction
Chapter 4: Clinical Physiology: Oxygen Transport and the
Transfusion Trigger
Chapter 5: The Role of Oxygen and Hemoglobin Diffusion in Oxygen
Transport by Cell-free Hemoglobins
Chapter 6: Oxygen Transport Properties of Hemoglobin-Based Oxygen
Carriers: Studies using Artificial Capillaries and Mathematical
Simulation
Chapter 7: Mechanisms of Oxygen Transport in the Microcirculation:
Effects of Cell-Free Oxygen Carriers
Chapter 8: Shear Stress Mechanotransduction and the Flow Properties
of Blood
Chapter 9: Local Regulation of Blood Flow
Section 3: Clinical Applications
Introduction
Chapter 10: Clinical Indications for Blood Substitutes and Optimal
Properties
Chapter 11: Crystalloid Solutions
Chapter 12: Hemoglobin-Based Oxygen Carriers as Resuscitative
Solutions for Trauma and Combat Casualty Care
Chapter 13: Surgical Hemorrhage
Chapter 14: Clinical Trials in Cardiac Surgery
Chapter 15: Hemodilution
Chapter 16: Clinical Hemodilution
Chapter 17: Potential for Blood Substitutes in Tissue Ischemia
Section 4: Toxicity and Side Effects
Introduction
Chapter 18: Redox and Radical Reactions of Hemoglobin Solutions:
Toxicities and Protective Strategies
Chapter 19: Pro-Oxidant Activity of Hemoglobin and Endothelial
Cytotoxicity
Chapter 20: Renal Toxicity
Chapter 21: Hemoglobin and Neurotoxicity
Chapter 22: The Role of Inflammation in the Toxicity of
Hemoglobin-Based Oxygen Carriers
Chapter 23: Hemoglobin-Induced Myocardial Lesions
Section 5: Perfluorocarbon-Based Oxygen Carriers
Introduction
Chapter 24: Fluorocarbon Emulsions as in vivo Oxygen Delivery
Systems: Background and Chemistry
Chapter 25: Fluosol®: The First Commercial Injectable
Perfluorocarbon Oxygen Carrier
Chapter 26: Perftoran®
Chapter 27: Rational Development of Oxyfluor™
Chapter 28: Oxygent™, a Perfluorochemical-Based Oxygen Therapeutic
for Surgical Patients
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
Chapter 30: Hemoglobin Modification
Chapter 31: Designing Recombinant Hemoglobin for Use as a Blood
Substitute
Chapter 32: Design, Conformational, Functional and Physiological
Characterization of Recombinant Polymeric Heme-Proteins
Chapter 33: αα-Crosslinked Hemoglobin
Chapter 34: DCLHb and rHb1.1
Chapter 35: Clinical Studies with DCLHb
Chapter 36: Hemopure® (HBOC-201, Hemoglobin Glutamer-250 (Bovine)):
Preclinical Studies
Chapter 37: HBOC-201 (Hemoglobin Glutamer-250 (Bovine), Hemopure®):
Clinical Studies
Chapter 38: Polyhemoglobin–Enzymes as New-Generation Blood
Substitutes and Oxygen Therapeutics
Chapter 39: Surface Decoration of Hemoglobin with Polyethylene
Glycol
Chapter 40: Hemospan® (MP4), A Human Hemoglobin Modified with
Maleimide-Polyethylene Glycol
Chapter 41: Dextran–Hemoglobin
Chapter 42: Development of Non-Extravasating Hemoglobin-Based
Oxygen Carriers
Section 7: Liposomes and Related Products
Introduction
Chapter 43: Liposome-Encapsulated Hemoglobin: History, Preparation
and Evaluation
Chapter 44: Hemoglobin Vesicles as a Molecular Assembly:
Characteristics of Preparation Process and Performances as
Artificial Oxygen Carriers
Chapter 45: Nanodimension Biodegradable Polymeric Membrane
Artificial Red Blood Cells
Chapter 46: Albumin-Heme: A Synthetic Heme-Based Oxygen Carrier
Brings together current information about O2-carriers, or Blood Substitutes and how they are designed to be used in place of red blood cell transfusions
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
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