Review of Modified Hemoglobin Solutions for Use as Temporary Blood Substitutes

摘要

The present review will focus on blood substitutes using hemoglobin solutions as oxygen carriers. It will review the more recent developments and discuss the limitations and problems associated with the present hemoglobin preparations. This will be covered under the headings of purification of hemoglobin, modification and polymerization of the hemoglobin molecule and the biological activities of the hemoglobin solutions. Polymerization of hemoglobin is currently the only means of obtaining a physiological concentration of hemoglobin which is iso-oncotic with plasma. Polymerized pyridoxylated hemoglobin is currently the most widely used example of such an iso-oncotic hemoglobin solution having normal oxygen carrying capacity. Such solutions, however, are heterogeneous polydispersed mixtures of widely different molecular weight. In addition, these solutions still contain about 20% of the unpolymerized tetramer which is rapidly eliminated in the urine. These solutions also have oxygen affinities which are considerably higher than those found in the red blood cells. In addition to their effectiveness, the hemoglobin solutions must be shown to be safe. Safety studies on the polymerized and modified homoglobin solutions must address issues such as hematological responses, vasoactive effects, effect on the reticuloendothelial system, effect on immunocompetence, antigenicity, nephrotoxicity, and iron toxicity.