Site-specific modifications and toxicity of blood substitutes - The case of diaspirin cross-linked hemoglobin

Safe and effective hemoglobin-based blood substitutes may be advantageous o ver conventional therapies for certain clinical settings requiring short te rm blood replacement such as emergency resuscitation and hemodilution in su rgery. Many advances have been made in developing these oxygen therapeutics , however safety concerns continue to slow their clinical progress. An impo rtant and often overlooked consideration in evaluating the safety of modifi ed hemoglobins is the impact of chemical and/or genetic modifications on th e redox chemistry of these proteins. Diaspirin cross-linked hemoglobin (DBB F-Hb) has been extensively evaluated in vitro and in animal models, and thu s represents a useful model to explore possible correlations between struct ural-functional alterations and toxicity of hemoglobin-based blood substitu tes. (C) 2000 Published by Elsevier Science BN. All rights reserved.