ABSTRACT

The search for an oxygen-carrying resuscitation fluid composed of encapsulated hemoglobin is inspired by an appreciation of the highly specialized vehicle that nature uses to capture and deliver oxygen, the red blood cell (RBC). This biconcave discoid cell contains, in a simplistic view, three discrete parts that are essential for its critical function. First, the erythrocyte contains an oxygencarrying molecule, the hemoglobin tetramer, that can readily load and unload oxygen. Second, there is an intracellular compartment containing enzymes (e.g., metreductase system) and other agents (e.g., glutathione, catalase) that minimize hemoglobin oxidation and optimize the environment for its perfor­ mance. Third, the RBC has an elastic membrane that facilitates its transport through capillaries and expresses a glycosylated surface to permit long circula-

tion persistence (144 days). It is these fundamental concepts of RBC delivery of oxygen with which investigators have approached the research and develop­ ment of artificial oxygen delivery systems composed of hemoglobin entrapped within a cell-like structure. This chapter reviews the history, current research issues, and commercial development of such encapsulated hemoglobin systems, with particular focus on the most researched and developed product, liposomeencapsulated hemoglobin (LEH).