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

Part I. Introduction and Scientific Principles

1. From Hemoglobin Based Oxygen Carrier to Oxygen Therapeutics, Blood Substitutes, Nanomedicine and Artificial Cells
Thomas Ming Swi Chang

2. From the Atmosphere to the Mitochondrion: The Oxygen Cascade
George P. Biro

3. Biochemistry of Hemoglobin
Andrea Mozzarelli, Stefano Bruno, Luca Ronda

4. The Role of Blood and Plasma Viscosity in Restoring Oxygen Delivery Capacity
Amy G. Tsai, Judith Martini, Beatriz Y. Salazar Vázquez, Pedro Cabrales, Seetharama A. Acharya, Marcos Intaglietta

Part II. Hemorrhagic Shock and Current Treatments

5. Pathophysiology of Hemorrhagic Shock and Resuscitation
Fredric M. Pieracci, Walter L. Biffl

6. Allogeneic Blood Transfusion for Surgical and Traumatic Hemorrhage
Mercy Kuriyan, Jeffrey L. Carson

7. Pre-Hospital Fluid Resuscitation in Civilian and Military Populations
Robert M. Haren, Chad M. Thorson, Col Lorne H. Blackbourne, Kenneth G. Proctor

Part III. Current Issues of HBOCs and Regulatory Framework

8. NIH/FDA/DOD Interagency Working Group on Oxygen Therapeutics
Phyllis Mitchell, Richard Weiskopf, Warren M. Zapol

9. Regulatory Framework for Hemoglobin-Based Oxygen Carrier Trials
Basil Golding

Part IV. Approaches to HBOCs

10. HBOCs from Chemical Modification of Hb
Ronald Kluger, Francine E. Lui

11. Design of Nonhypertensive Conjugated Hemoglobins as Novel Resuscitation Fluids
Seetharama A. Acharya, Marcos Intaglietta, Amy G. Tsai, Fantao Meng

12. Cellular-Type Hemoglobin-Based Oxygen Carriers to Mimic the Red Blood Cell Structure
Hiromi Sakai

13. Recombinant Octameric Hemoglobins as Resuscitation Fluids in a Murine Model of Traumatic Brain Injury Plus Hemorrhagic Shock
Xianren Wu, Nancy T. Ho, Tong-Jian Shen, Vincent Vagni, David K. Shellington, Keri Janesko-Feldman, Tsuey Chyi S. Tam, Ming F. Tam, Patrick M. Kochanek, Chien Ho, Virgil Simplaceanu

14. Liposome-Encapsulated Hemoglobin as an Artificial Oxygen Carrier: Technological Features, Manufacturing and Issues for Practical Application
Shinichi Kaneda, Takanobu Ishizuka, Hiroshi Goto, Hiroaki Kasukawa

15. Zero-Link Hemoglobin (OxyVita®): Impact of Molecular Design Characteristics on Pre-clinical Studies
John P. Harrington, Hanna Wollocko

16. Polynitroxylated Pegylated Hemoglobin (PNPH): A Nanomedicine for Critical Care and Transfusion
Li Ma, Frances M. Thompson, Dong Wang, Carleton J. C. Hsia

17. ATP-Adenosine-GSH Crosslinked Hb, An Oxygen Carrier with Pharmacological Properties for Multiple Therapeutic Indications
Jan Simoni, Grace Simoni, John F. Moeller

18. Albumin-Heme Oxygen Carriers
Teruyuki Komatsu

19. Recombinant Human Hb‐SOD Fusion Proteins
Marie Grey, Khuanpiroon Ratanasopa, Leif Bülow

20. In‐Vitro Production of Functional RBCs from Hematopoietic Stem Cells
Eun Jung Baek, Hyun Ok Kim

Part V. Potential Applications of HBOCs

21. Liposome-Encapsulated Hemoglobin: Potential Clinical Applications
Akira T. Kawaguchi, Chieko Murayama, Fumiaki Yoshiba, Hiroyuki Furuya, Mariko Yamano, Munetaka Haida

22. Biocompatibility of Hemoglobin Vesicles, a Cellular-Type Artificial Oxygen Carrier, on Blood Cells and Plasma Proteins In Vitro and In Vivo
Hiroshi Azuma, Mitsuhiro Fujihara, Hiromi Sakai

23. Polymerized Human Placenta Hemoglobin: Organ Protective Effects and Alternative Clinical Uses
Tao Li, Chengmin Yang, Jin Liu, Jiaxin Liu, Wang Hong

24. Low Volume Resuscitation with HBOCs in Hemorrhagic Shock
P. S. Reynolds, R. W. Barbee, K. R. Ward

25. Ischemic Rescue with Hemoglobin-Based Oxygen Carriers
Raymond C. Koehler

Part VI. Preclinical Evaluations of HBOCs

26. Pre-clinical Evaluation of Hemoglobin Based Oxygen Carriers: Animal Models and Biomarkers
Paul W. Buehler, Felice D’Agnillo

27. The Hemoglobin-Based Oxygen Carrier, HBOC-201, as a Resuscitation Fluid for Traumatic Hemorrhagic Shock: The Naval Medical Research Center Experience
Charles Auker, Paula Moon-Massat, Anke Scultetus, Richard McCarron, Daniel Freilich

28. Cellular-Type Hemoglobin-Based Oxygen Carrier as a Resuscitative Fluid for Hemorrhagic Shock: Acute and Long-Term Safety Evaluation Using Beagle Dogs
Tatsuhiko Ikeda, Hirohisa Horinouchi, Yoraro Izumi, Hiromi Sakai, Koichi Kobayashi

Part VII. HBOC Clinical Trials

29. Key Adverse Events in Recent HBOC Phase III Clinical Trials and Their Causal Relationship to Test HBOC’s
Colin F. Mackenzie

30. Some Critical Comments on the Major HBOC Clinical Trials
George P. Biro

31. Compassionate Use Cases Treated with Hemoglobin-Based Oxygen Carriers
Paula Moon-Massat, Daniel Freilich

Part VIII. HBOC-Mediated Adverse Effects

32. Acellular Hemoglobin-Based Oxygen Carrier Mediated Blood Pressure Elevation and Vasoconstriction: A Review of Proposed Mechanisms and Contributing Factors
Hae Won Kim

33. HBOCs and Cardiac Integrity
T. N. Estep

34. Effects of Hemoglobin-Based Oxygen Carriers on Blood Coagulation
Jonathan S. Jahr, Molly Chung, Afsaneh Anvarhosseini, Hae Won Kim

35. Redox Activity of Cell-Free Hemoglobin: Implications for Vascular Oxidative Stress and Endothelial Dysfunction
Felice D’Agnillo

36. HBOC Interferences with Routine Clinical Laboratory Tests
Younes Smani

37. Vasoconstriction, Hypertension and Oxidative Toxicity are Regulated by Polymerized Hemoglobin Size
Brian M. Belcik, Andre F. Palmer

38. Acellular Hemoglobin-Based Oxygen Carrier Induced Vasoactivity: A Brief Review of Potential Pharmacologic Remedies
Hae Won Kim, Chi-Ming Hai, A. Gerson Greenburg

Part IX. A Call for Collaborative Research and Development

39. International Consortium for Development of Hemoglobin-Based Oxygen Carriers, Oxygen Therapeutics and Multifunctional Resuscitation Fluids–A White Paper
Hae Won Kim, Jonathan S. Jahr, Andrea Mozzarelli, Hiromi Sakai

Keywords: Materials Science, Biomaterials, Molecular Medicine, Medicinal Chemistry, Hematology