The long range goals of this research proposal are to synthesize polymeric compounds with hemoglobin (Hgb) that will be capable of a total blood replacement. Stroma-free hemoglobin (SFH) solutions are promising blood substitutes because of their oxygen transport properties, adequate oncotic pressure and low viscosity. However, SFH lacks sufficient dwell times to render them totally satisfactory. On the other hand there are polymers which have low toxicity and can be used for plasma expanders but lack the necessary oxygen binding capacity. However, new synthetic methods have been developed recently to functinalize these polymers for reactions with Hgb. Thus it now appears possible to synthesize an oxygen-carrying polymer that will meet the biophysical, biochemical and physiological criteria for a blood substitute and also be inexpensive to manufacture from readily available starting materials. For the period requested for the support of this proposal, the following goals will be realized: a) starch-Hgb polymer will be synthesized and isolated in research quantities. b) these polymers will be characterized with respect to their molecular weight, viscosity and oxygen-carrying capacity. c) these compounds will be tested in vitro in an isolated working rat heart preparation. d) the most promising polymers will be used for total blood replacement in transfusion-exchange experiments in rats.
