Abstract
Stroma-free hemoglobin solutions, as potential oxygen-delivering resuscitative fluid, have two main limitations: the high oxygen affinity of the protein and its low intravascular persistence compared to those of hemoglobin in the red cells. To overcome these two drawbacks, a great many investigators have proposed a variety of reactions for the chemical modification of the hemoglobin molecule. This article presents a review of our work in this field, including two kinds of approaches, both based on the utilization of biocompatible and non-immunogenic polymers. The first consisted in initially decreasing the oxygen affinity of hemoglobin by reaction with pyridoxal phosphate and then increasing its molecular weight by linking the resulting derivative to polyoxyethylene. In the second approach, both operations were carried out in a single step, by linking to hemoglobin, dextran or polyoxyethylene functionalized in such a way that they lowered its oxygen affinity. The results of this work are analyzed in terms of oxygen-carrying properties of modified hemoglobin, of rheological characteristics of the solution and of scale-up feasibility.
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