ABSTRACT
Safety and adequate availability of blood is still a major concern in transfusion medicine. The requirement of pretransfusion processing, storage, and crossmatching of blood are other factors that have given impetus to the search for safe, shelf-stable, and efficacious oxygen-carrying fluids. Several fluids containing modified hemoglobin as an oxygen carrier are in advanced stages of preclinical or clinical trials (Table 1). Such preparations would save many lives in situations of acute blood loss or when persons refuse homologous blood transfusion on religious grounds. The earliest attempts to use purified hemoglobin were met with several problems. Hemoglobin has a tendency to break down into constituent a-and b-chains and has significant toxic effects upon administration (10-13). A simple approach of cross-linking hemoglobin chains, diaspirin-cross-linked or a-a-cross-linked hemoglobin, was the first attractive option to prevent its dissociation (6,14-16). Subsequently, hemoglobin was conjugated to poly(ethylene glycol) or PEG to impart prolonged circulation (17). These small-sized modified hemoglobins extravasate through the endothelium and sequester nitric oxide (NO), causing a significant vasoconstriction (14,18-20). An alternative design of recombinantly mutating hemoglobin to prevent NO-binding
and reduce oxygen affinity of hemoglobin is also currently under investigation (21). All these modified hemoglobin preparations are essentially in solution phase and are not spatially isolated in the same manner as is the hemoglobin inside the red blood cells (RBCs). A more complete oxygen carrier would be hemoglobin that is encapsulated and supplemented with the oxidoreductive system of RBC.
