title: Red cell substitutes.
abstract: Oxygen-carrying plasma expanders (blood substitutes) have been sought for over a century. Development of current products is a result of evolution in the understanding of proteins in general, of hemoglobin in particular, and of how cell-free hemoglobin interacts with the control of local blood flow to ensure adequate tissue oxygenation. Hemoglobin-based products are considered in four "generations" corresponding to major improvements. First-generation products consisted of hemoglobin, freed of red cell membranes (stroma-free hemoglobin [SFH]), which was renal toxic and vasoactive. Second-generation products were polymerized with aldehyde reagents to reduce or eliminate the renal toxicity, but the products were heterogeneous and still vasoactive. Third-generation products employed more specific intramolecular crosslinking to eliminate polymerization and promote homogeneity, but they also remained vasoactive. Fourth-generation products are based on a new understanding of the way in which microvascular blood flow is controlled and the influence of O(2) delivery to vascular walls. After more than a century of research, one of these new solutions should find use as an alternative to red cells for transfusion in certain clinical settings.
authors.affiliation: Sangart, Inc, and Department of Bioengineering, University of California, San Diego, CA 92121, USA. rwinslow@sangart.com
authors.forename: Robert M
authors.initials: RM
authors.lastname: Winslow
mesh_terms: D000818:Animals; D001802:Blood Substitutes / Q000737:chemistry / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D006454:Hemoglobins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D023421:Models, Animal; D010100:Oxygen / Q000097:blood*
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins; D010100:Oxygen