Current Status of Artificial o2 Carriers

Donor blood is a limited resource, and its transfusion is associated with significant adverse effects. Therefore, alternatives such as artificial oxygen (o2) carriers have been researched. Two general classes of artificial o2 carriers are currently under development: hemoglobin (Hb)-based solutions and perfluorocarbon (PFC) emulsions. The native human hemoglobin molecule in hemoglobinbased artificial o2 carriers must be stabilized to prevent dissociation of the a2b2-hemoglobin tetramer into ab-dimers to prolong intravascular retention and to eliminate nephrotoxicity. Other modifications serve to decrease o2 affinity to improve o2 off-loading to tissues. In addition, polymerization is used to increase the hemoglobin concentration at physiologic colloid oncotic pressure. Perfluorocarbons are carbon-fluorine compounds characterized by a high gas-dissolving capacity for o2 and co2 and chemical and biologic inertness. Perfluorocarbons are not miscible with water and therefore must be brought into emulsion for intravenous application. This article describes product specifications, physiologic effects, efficacy to decrease the need for donor blood in surgery, and side effects of diaspirin cross-linked hemoglobin, human recombinant hemoglobin version 1.1 (rHb1.1) and rHb2.0 (Baxter Healthcare Corp., Deerfield, Illinois), polymerized bovine hemoglobin-based o2 carrier (HBOC)-201 (Biopure Corp., Cambridge, Massachusetts), human polymerized hemoglobin (PolyHeme, Northfield Laboratories, Inc., Evanston Illinois), hemoglobin raffimer (Hemolink, Hemosol, Inc., Toronto, Ontario, Canada), maleimide-activated polyethylene glycol-modified hemoglobin (MP4, Sangart Inc., San Diego, California), and perflubron emulsion (Oxygent, Alliance Pharmaceutical Corp., San Diego, California). In addition, hemoglobin-containing vesicles (nano-dimension artifi