AUTOOXIDATION AND STABILITY OF CROSSLINKED HEMOGLOBINS

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Spontaneous autoxidation of hemoglobin is an important concern in the use of chemically modified hemoglobin as an oxygen carrier. The formation of methemoglobin not only compromises the oxygen transport but also gives rise to reactive oxygen species. The mechanism of auto oxidation of crosslinked hemoglobins though is different from chemical oxidation, both follow common pathway in which methemoglobin is formed first followed by precipitation via hemichrome formation. We have established that there is an inverse relationship between the rate of autoxidation and the oxygen affinity and stability of these hemoglobins in solution. Chemically induced oxidation in presence of excess hydrogen peroxide (1 heme:10 H2O2) had a striking effect on the spectral change of unmodified hemoglobin indicative of an early precipitation (10 minutes). Precipitation of crosslinked hemoglobins occurs much later (>120 minutes). However, greater stabilization of the oxidized tetramer in solution was achieved with the Beta-Beta crosslinked hemoglobins as opposed to those crosslinked within the alpha-alpha subunits. We have recently expanded on this work by examining the anion-induced oxidation of crosslinked hemoglobins using a fast scanning spectrophotometer in Dr. V. Macdonald's laboratory (at Letterman Army Institute of Research). Data collected so far has been presented, in part, at the IVth Int. Congress on Blood Substitutes, August, 1991 and is being compiled for publication.