Blood Substitutes Hemoglobin Based Oxygen Carriers

Currently, hemoglobin (Hb)-based oxygen carriers (HBOCs) are leading candidates as red blood cell substitutes. In addition, HBOCs are also potential oxygen therapeutics for treatment of patients with critical ischemic conditions due to atherosclerosis, diabetes and other conditions. This book will provide readers a comprehensive review of topics involved in the HBOC development. It focusses on current products and clinical applications as well as on emerging technologies and future prospects.

This book functions as a comprehensive and authoritative reference book in blood transfusion and blood substitutes. It is a collection of the latest developments and the newest investigations, and individual chapters are written by world experts in the arena. The book begins with a historical review on the practice of transfusions as well as the components and physiology of blood. The following chapters cover various topics, including platelet substitutes, hemoglobin-based oxygen carriers, perfluorocarbon based oxygen carriers, and safety issues related to artificial hemoglobin. All chapters provide a bulleted highlights list to facilitate readers in mastering the main points of each individual chapter. Blood Substitutes and Oxygen Biotherapeutics is an invaluable reference book for perioperative care providers, hematologists, anesthesiologists, surgeons, obstetricians and gynecologists.

This volume of the Keio University International Symposia for Life Sciences and Medicine contains the proceedings of the 13th symposium held under the sponsorship of the Keio University Medical Science Fund. The fund was est- lished by the generous donation of the late Dr. Mitsunada Sakaguchi. The Keio University International Symposia for Life Sciences and Medicine constitute one of the core activities sponsored by the fund,of which the objective is to contribute to the international community by developing human resources, promoting scienti?c knowledge, and encouraging mutual exchange. Each year, the Committee of the International Symposia for Life Sciences and Medicine selects the most signi?cant symposium topics from applications received from the Keio medical community. The publication of the proce- ings is intended to publicize and distribute the information arising from the lively discussions of the most exciting and current issues presented during the symposium. On behalf of the Committee, I am most grateful to the late Dr. Sakaguchi, who made the series of symposia possible. We are also grateful to the prominent speakers for their contribution to this volume. In addition, we would like to acknowledge the ef?cient organizational work performed by the members of the program committee and the staff of the fund. Naoki Aikawa, M. D. , D. M. Sc. , F. A. C. S.

Human blood performs many important functions including defence against disease and transport of biomolecules, but perhaps the most important is to carry oxygen – the fundamental biochemical fuel - and other blood gases around the cardiovascular system. Traditional therapies for the impairment of this function, or the rapid replacement of lost blood, have centred around blood transfusions. However scientists are developing chemicals (oxygen therapeutics, or “blood substitutes”) which have the same oxygen-carrying capability as blood and can be used as replacements for blood transfusion or to treat diseases where oxygen transport is impaired. Chemistry and Biochemistry of Oxygen Therapeutics: From Transfusion to Artificial Blood links the underlying biochemical principles of the field with chemical and biotechnological innovations and pre-clinical development. The first part of the book deals with the chemistry, biochemistry, physiology and toxicity of oxygen, including chapters on hemoglobin reactivity and regulation; the major cellular and physiological control mechanisms of blood flow and oxygen delivery; hemoglobin and myoglobin; nitric oxide and oxygen; and the role of reactive oxygen and nitrogen species in ischemia/reperfusion Injury. The book then discusses medical needs for oxygen supply, including acute traumatic hemorrhage and anemia; diagnosis and treatment of haemorrhages in "non-surgical" patients; management of perioperative bleeding; oxygenation in the preterm neonate; ischemia normobaric and hyperbaric oxygen therapy for ischemic stroke and other neurological conditions; and transfusion therapy in β thalassemia and sickle cell disease Finally “old”and new strategies for oxygen supply are described. These include the political, administrative and logistic issues surrounding transfusion; conscientious objection in patient blood management; causes and consequences of red cell incompatibility; biochemistry of red blood cell storage; proteomic investigations on stored red blood cells; red blood cells from stem cells; the universal red blood cell; allosteric effectors of hemoglobin; hemoglobin-based oxygen carriers; oxygen delivery by natural and artificial oxygen carriers; cross-linked and polymerized hemoglobins as potential blood substitutes; design of novel pegylated hemoglobins as oxygen carrying plasma expanders; hb octamers by introduction of surface cysteines; hemoglobin-vesicles as a cellular type hemoglobin-based oxygen carrier; animal models and oxidative biomarkers to evaluate pre-clinical safety of extracellular hemoglobins; and academia – industry collaboration in blood substitute development. Chemistry and Biochemistry of Oxygen Therapeutics: From Transfusion to Artificial Blood is an essential reference for clinicians, haematologists, medicinal chemists, biochemists, molecular biologists, biotechnologists and blood substitute researchers.

This definitive volume will provide the reader with up to date information and the most recent science of the fast-evolving area of nanobiotherapeutic-based blood substitutes. Long studied, there are recent updates that make their use in patients more promising, and with one product approved for human use, many more in the pipeline. These include 2nd generations and even third generation ones, the later with enhancement of red blood cell functions. In addition, there are carefully written and referenced updates on the recent history and products in the field, complete with pathophysiologic and pharmacologic studies to validate and verify the efficacy and safety of many of these new products.

This presentation describes various aspects of the regulation of tissue oxygenation, including the roles of the circulatory system, respiratory system, and blood, the carrier of oxygen within these components of the cardiorespiratory system. The respiratory system takes oxygen from the atmosphere and transports it by diffusion from the air in the alveoli to the blood flowing through the pulmonary capillaries. The cardiovascular system then moves the oxygenated blood from the heart to the microcirculation of the various organs by convection, where oxygen is released from hemoglobin in the red blood cells and moves to the parenchymal cells of each tissue by diffusion. Oxygen that has diffused into cells is then utilized in the mitochondria to produce adenosine triphosphate (ATP), the energy currency of all cells. The mitochondria are able to produce ATP until the oxygen tension or PO2 on the cell surface falls to a critical level of about 4–5 mm Hg. Thus, in order to meet the energetic needs of cells, it is important to maintain a continuous supply of oxygen to the mitochondria at or above the critical PO2 . In order to accomplish this desired outcome, the cardiorespiratory system, including the blood, must be capable of regulation to ensure survival of all tissues under a wide range of circumstances. The purpose of this presentation is to provide basic information about the operation and regulation of the cardiovascular and respiratory systems, as well as the properties of the blood and parenchymal cells, so that a fundamental understanding of the regulation of tissue oxygenation is achieved.

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.