Hemoglobin–albumin clusters as an artificial O2 carrier: Physicochemical properties and resuscitation from hemorrhagic shock in rats

A bovine hemoglobin (HbBv) or human adult hemoglobin (HbA) wrapped covalently by human serum albumins (HSAs), hemoglobin–albumin clusters (HbBv–HSA3 and HbA–HSA3), are artificial O2 carriers used as a red blood cell substitute. This article describes the physicochemical properties of the HbBv–HSA3 and HbA–HSA3 solutions, and their abilities to restore the systemic condition after resuscitation from hemorrhagic shock in anesthetized rats. The HbBv–HSA3 and HbA–HSA3, which have high colloid osmotic activity, showed equivalent solution characteristics and O2 binding parameters. Shock was induced by 50% blood withdrawal. Rats exhibited hypotension and significant metabolic acidosis. After 15 min, the rats were administered shed autologous blood (SAB), HbBv–HSA3, HbA–HSA3, or Ringer's lactate (RL) solution. Survival rates, circulation parameters, hematological parameters, and blood gas parameters were monitored during the hemorrhagic shock and for 6 h after administration. All rats in the SAB, HbBv–HSA3, and HbA–HSA3 groups survived for 6 h. The HbBv–HSA3 and HbA–HSA3 groups restored mean arterial pressure after the resuscitation. No remarkable difference was observed in the time courses of blood gas parameters in any resuscitated group except for the RL group. Serum biochemical tests showed increases in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the HbBv–HSA3 and HbA–HSA3 groups compared to the SAB group. Therefore, we observed other rats awakened after resuscitation with HbA–HSA3 for 7 days. The blood cell count, AST, and ALT recovered to the baseline values by 7 days. All the results implied that HbBv–HSA3 and HbA–HSA3 clusters provide restoration from hemorrhagic shock as an alternative material for SAB transfusion.