Hemoglobin-Based Oxygen Carriers as Red Cell Substitutes and Oxygen Therapeutics

Front Matter....Pages i-xxiii
Front Matter....Pages 1-1
From Hemoglobin Based Oxygen Carrier to Oxygen Therapeutics, Blood Substitutes, Nanomedicine and Artificial Cells....Pages 3-26
From the Atmosphere to the Mitochondrion: The Oxygen Cascade....Pages 27-53
Biochemistry of Hemoglobin....Pages 55-73
The Role of Blood and Plasma Viscosity in Restoring Oxygen Delivery Capacity....Pages 75-93
Front Matter....Pages 95-95
Pathophysiology of Hemorrhagic Shock and Resuscitation....Pages 97-116
Allogeneic Blood Transfusion for Surgical and Traumatic Hemorrhage....Pages 117-126
Pre-Hospital Fluid Resuscitation in Civilian and Military Populations....Pages 127-138
Front Matter....Pages 139-139
NIH/FDA/DOD Interagency Working Group on Oxygen Therapeutics....Pages 141-147
Regulatory Framework for Hemoglobin-Based Oxygen Carrier Trials....Pages 149-156
Front Matter....Pages 157-157
HBOCs from Chemical Modification of Hb....Pages 159-183
Design of Nonhypertensive Conjugated Hemoglobins as Novel Resuscitation Fluids....Pages 185-234
Cellular-Type Hemoglobin-Based Oxygen Carriers to Mimic the Red Blood Cell Structure....Pages 235-247
Recombinant Octameric Hemoglobins as Resuscitation Fluids in a Murine Model of Traumatic Brain Injury Plus Hemorrhagic Shock....Pages 249-272
Liposome-Encapsulated Hemoglobin as an Artificial Oxygen Carrier: Technological Features, Manufacturing and Issues for Practical Application....Pages 273-282
Zero-Link Hemoglobin (OxyVita ® ): Impact of Molecular Design Characteristics on Pre-clinical Studies....Pages 283-297
Polynitroxylated Pegylated Hemoglobin (PNPH): A Nanomedicine for Critical Care and Transfusion....Pages 299-313
ATP-Adenosine-GSH Crosslinked Hb, An Oxygen Carrier with Pharmacological Properties for Multiple Therapeutic Indications....Pages 315-337
Albumin-Heme Oxygen Carriers....Pages 339-348
Recombinant Human Hb‐SOD Fusion Proteins....Pages 349-358
In‐Vitro Production of Functional RBCs from Hematopoietic Stem Cells....Pages 359-366
Front Matter....Pages 367-367
Liposome-Encapsulated Hemoglobin: Potential Clinical Applications....Pages 369-383
Biocompatibility of Hemoglobin Vesicles, a Cellular-Type Artificial Oxygen Carrier, on Blood Cells and Plasma Proteins In Vitro and In Vivo....Pages 385-397
Polymerized Human Placenta Hemoglobin: Organ Protective Effects and Alternative Clinical Uses....Pages 399-410
Low Volume Resuscitation with HBOCs in Hemorrhagic Shock....Pages 411-433
Ischemic Rescue with Hemoglobin-Based Oxygen Carriers....Pages 435-453
Front Matter....Pages 455-455
Pre-clinical Evaluation of Hemoglobin Based Oxygen Carriers: Animal Models and Biomarkers....Pages 457-474
The Hemoglobin-Based Oxygen Carrier, HBOC-201, as a Resuscitation Fluid for Traumatic Hemorrhagic Shock: The Naval Medical Research Center Experience....Pages 475-499
Cellular-Type Hemoglobin-Based Oxygen Carrier as a Resuscitative Fluid for Hemorrhagic Shock: Acute and Long-Term Safety Evaluation Using Beagle Dogs....Pages 501-524
Front Matter....Pages 525-525
Key Adverse Events in Recent HBOC Phase III Clinical Trials and Their Causal Relationship to Test HBOC’s....Pages 527-542
Some Critical Comments on the Major HBOC Clinical Trials....Pages 543-562
Compassionate Use Cases Treated with Hemoglobin-Based Oxygen Carriers....Pages 563-584
Front Matter....Pages 585-585
Acellular Hemoglobin-Based Oxygen Carrier Mediated Blood Pressure Elevation and Vasoconstriction: A Review of Proposed Mechanisms and Contributing Factors....Pages 587-620
HBOCs and Cardiac Integrity....Pages 621-646
Effects of Hemoglobin-Based Oxygen Carriers on Blood Coagulation....Pages 647-664
Redox Activity of Cell-Free Hemoglobin: Implications for Vascular Oxidative Stress and Endothelial Dysfunction....Pages 665-682
HBOC Interferences with Routine Clinical Laboratory Tests....Pages 683-692
Vasoconstriction, Hypertension and Oxidative Toxicity are Regulated by Polymerized Hemoglobin Size....Pages 693-711
Acellular Hemoglobin-Based Oxygen Carrier Induced Vasoactivity: A Brief Review of Potential Pharmacologic Remedies....Pages 713-733
Front Matter....Pages 735-735
International Consortium for Development of Hemoglobin-Based Oxygen Carriers, Oxygen Therapeutics and Multifunctional Resuscitation Fluids–A White Paper....Pages 737-746