Evaluating new red cell substitutes: a critical analysis of toxicity models.
Because red cell substitutes (RCS) will improve oxygen delivery to tissues rendered hypoxic or anoxic they are presumed to be effective. Prior to clinical application the safety--toxicity of any proposed solution must be established. Models used to demonstrate efficacy do not necessarily evaluate toxicity. Infusion of human hemoglobin (Hb) solutions into animals raises one issue of immune response but obviates looking at the human response to similar materials. Differentiating the cause of an immunologic effect may be difficult. Effects seen in acute models may not have chronic implications; they may be transients of no consequence. Differentiating the effects of volume load intravascularly from the effects of the solution is also a problem. Identification of proper controls is essential for evaluation. However, the control solution may have problems of its own that must be defined. For any proposed RBS a menu of models exploring cellular, tissue, organ and organism responses to the solution, its residual modifiers and the products of metabolism are needed to define primary and secondary effects.
Greenburg
A G
AG
Brown University, Miriam Hospital, Providence, Rhode Island 02906.
Kim
H W
HW
D000818:Animals; D001802:Blood Substitutes / Q000633:toxicity*; D001810:Blood Volume; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006454:Hemoglobins / Q000276:immunology / Q000633:toxicity; D006801:Humans; D007668:Kidney / Q000187:drug effects; D008954:Models, Biological; D012449:Safety
D001802:Blood Substitutes; D006454:Hemoglobins