Advances in Blood Substitutes, Volume 3: Industrial Opportunities and Medical Challenges (Advances in Blood Substitutes, Vol 3)

Each chapter of this volume is a contribution from an expert in the field, chosen by the editors to contribute to the 1997 "Current Issues in Blood Substitute Research and Development" course given in San Diego, March 17-19. The contributors were selected because of their expertise in areas which the editors believe to be critical to the advancement of the field, and which reflect activity in "hot" areas of relevant research. While there is a continuity in style for the annual course, each year brings changes in emphasis and content. In previous years, we were often not able to provide time for participants to present their views and opinions. Consequently, this year we encouraged discussion after each presentation. These sessions were recorded, transcribed, and are printed with the chapters herein. We believe that the product is very close to the capturing this year's course in print, and trust readers will enjoy reading the always candid and often provocative remarks from the audience. The price paid for inclusion of the discussion transcriptions was a delay in publication. Each author was allowed to edit his/her discussion section as well as the final version of the chapters prior to publication. The changes are mainly for grammar, and we tried, when possible, not to alter the conversational style of these interchanges.

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.

• 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

David J. Dries

This is a first edition of a hardbound collection of essays on topics related to the development of blood substitutes. Compiled are a series of chapters providing the foundation for didactic lectures on clinical and basic science issues related to blood substitute development. The format begins with fundamental concepts and epidemiology and proceeds to specific discussion of contemporary problems in this field. Clinicians and basic scientists with an interest in the clinical problem of resuscitation from various shock states are an appropriate audience for this work. The authors represent an international group of authorities; many are from University of California at San Diego. Twelve chapters make up this compact, attractive hardbound text. The presentations begin with an overview of recent literature (1995) describing developments in the field of blood substitutes followed by a description of the blood usage problem, the physiology of shock, and derangement of oxygen transport in this state. Next, the authors develop various issues surrounding biological effects of blood substitutes including interaction of hemoglobin with endotoxin and oxygen transport in the microcirculation. Recent understanding of the relation between hemoglobin solutions, nitric oxide, and carbon monoxide is also summarized. Chapters are brief and headings divided by numbered outline points. An ample list of carefully selected references is provided. In addition, the authors strive to keep the list of references as current as possible. The table of contents provides only chapter headings and authors. A small but adequate index is provided. Illustrations are infrequent but of adequate quality(black-and-white) when provided. This book is a compact and effective educational tool. It is nicely organized to bring even the inexperienced reader up to speed with contemporary problems facing workers interested in the development and application of blood substitute technology.

This volume contains a collection of essays by selected authors who are active in the field of blood substitutes research or closely allied disciplines. These essays were delivered as lectures by the authors at the second annual'Current Issues in Blood Substitute Research and Development - 1995'course sponsored jointly by the Departments of Medicine and Bioengineer­ ing, University of California, San Diego, the National Institutes of Health (NHLBI), and the U.S. Army on March 30, 31, and April 1, 1995 in San Diego. This course had three goals: to present fundaniental discussions of scientific issues critical to further development of artificial oxygen carriers, to provide academicians a forum to discuss their current research, and to provide the companies involved in developing products the opportunity to update the audience on their progress. The organization owes much to the solicited comments of the attendees of the 1994 course. We would like especially to thank the U.S. Army, particularly through the efforts of COL John Hess, who provided significant funding to make publication of this volume possible. In addition, a number of the participating companies provided additional financial support to offset the costs of the course. These include Alliance Pharmaceutical Corp., Hemosol, Nippon Oil and Fat, Northfield Laboratories, and Ortho Biotech. Front Matter....Pages i-xiv Blood Substitutes: 1996 in the Literature....Pages 1-18 Blood Substitutes and the Intestinal Microcirculation: Extravasation and Ultrastructural Alterations....Pages 19-37 A Discussion of Pharmacoeconomics Applied to Blood Substitutes....Pages 38-45 Tumor Microcirculation: Role in Drug and Nutrient Delivery....Pages 46-70 The Pressor Effect of Hemoglobin-Good or Bad?....Pages 71-90 Perflubron-based Emulsion: Efficacy as Temporary Oxygen Carrier....Pages 91-132 The Other Blood Substitute:Antigenically Inert Erythrocytes....Pages 133-150 Hemoglobin Encapsulation With Polyethylene Glycol-modified and Unmodified Vesicles: Systemic and Microvascular Hemodynamics at 80% Blood Substitution....Pages 151-166 Hemoglobin Oxygen Affinity and the Design of Red Cell Substitutes....Pages 167-188 The Mechanism of Tissue Oxygenation and the Design of Oxygen Carrying Plasma Expanders....Pages 189-206 Colloid Osmotic Effects of Hemoglobin-based Oxygen Carriers....Pages 207-232 Dextran-Hemoglobin....Pages 233-250 Modification of Molecules and Particles With Polyethylene Glycol (PEG): Long-circulating Pharmaceuticals....Pages 251-297 The Reaction of Nitric Oxide with Cell-free Hemoglobin Based Oxygen Carriers: Physiological Implications....Pages 298-327 Back Matter....Pages 328-338 "The development of a substitute for transfused red blood cells is a highly sought-after goal. Such products potentially would be safer than human (allogeneic) blood because they would eliminate the possibility of transmitting infectious agents such as HIV, which causes the deadly syndrome AIDS. In addition, red cell substitutes will revolutionize the practice of transfusion medicine: they will eliminate the need for cross-matching, and could lead to an overhaul of current blood bank operations because they may be more stable and thus easier to store than blood. Before reaching this ambitious goal, the fundamental obstacles appears to be lack of understanding of the way in which cell-free oxygen carriers transport oxygen, with consequent implications for clinical trials and eventual approval of new products." "This volume is a collection of essays by outstanding authorities in a wide range of fields. Each chapter focuses on the problem of red cell substitutes from a different perspective. The discussion in the first chapter of the world-wide impact that blood substitute products would have is of particular interest and importance. All in all, this collection elucidates the current status of red cell substitutes research and development in a unique and timely manner."--BOOK JACKET This book is not a'proceedings'volume. Rather the chapters are essays by experts in the field of blood substitutes, invited by the editors to con­ tribute to the 1996'Current Issues in Blood Substitutes Research and Development'course given in San Diego, March 18-21. The contributors were selected because of their expertise in areas deemed by the editors to be critical to the advancement of the field. The course, as in past years, is heavily influenced by feedback from par­ ticipants, and by research in this and related fields. In addition to the didactic lectures (for which these chapters are the foundation), the course also offers the opportunity for presentation of research reports, progress reports from the various companies currently commercializing products, and round table discussions of selected subjects. Thus, we are grateful to past participants for their helpful comments. Production of a book, especially on a short timeline, is not an easy feat. The development of a substitute for transfused red blood cells is a highly sought-after goal, especially as these products would be potentially safer then human blood. This volume is a collection of essays by authorities in a wide range of fields, each bringing a new focus on the problem. Rather the chapters are essays by experts in the field of blood substitutes, invited by the editors to con­ tribute to the 1996 "Current Issues in Blood Substitutes Research and Development" course given in San Diego, March 18-21. The year 1996 in the "blood substitute" literature continued to follow the trends set in 1994 and 1995.