Hemoglobin–albumin cluster: physiological responses after exchange transfusion into rats and blood circulation persistence in dogs

Abstract

A core–shell protein cluster comprising hemoglobin and human serum albumins, hemoglobin–albumin cluster (Hb–HSA3), was designed and synthesized for use as an artificial O2 carrier and red blood cell (RBC) substitute. For initial preclinical safety evaluation of the Hb–HSA3 solution, we observed blood compatibility in vitro, physiological responses after exchange transfusion into rats and blood circulation lifetime in dogs. Dilution of human whole blood with Hb–HSA3 showed an appropriate decrease in blood cell number, proportional to the mixing volume ratio. Time courses in the circulation parameters and blood gas parameters after 20% exchange transfusion with Hb–HSA3 in anesthetized rats were almost identical to those observed in a sham group (without infusion) and an HSA group (with HSA administration) for 6 h. Serum biochemical tests of the withdrawn blood indicated safety of the protein cluster. Furthermore, fluorescent Hb–HSA3 was infused into beagle dogs to assess blood retention. Fluorescence measurements of the blood samples enabled us to ascertain the cluster half-life within the intravascular space. Histopathologic inspections of the vital organs imply no abnormality in tissues. All these results indicate sufficient initial preclinical safety of Hb–HSA3 as an alternative material for use in RBC transfusion.