Pyridoxylated Polyhemoglobin as a Red Cell Substitute for Resuscitation of Lethal Hemorrhagic Shock in Conscious Rats

Abstract

In our previous work, pyridoxylated polyhemoglobin (PP-PolyHb) was shown to have a P₅₀=16–18 torr, and a half-life (T 1/2) of 20 hrs in the circulation of rats given a 75% isovolemic exchange transfusion. For the present study, a rapid and lethal hemorrhagic shock model has been specifically designed to assess the ability of PP-PolyHb to function as an emergency resuscitation fluid. Using 48 fully conscious rats with special chronic arterial and venous cannulations, shock was induced by bleeding 67% of total blood volume in less than 40 min; producing 100% mortality in nonresuscitated controls. Resuscitation was carried out using one of the following infusion fluids equivalent in volume to the bled volume: Ringer's solution, albumin solution, stroma-free Hb (SFHb), pyridoxylated SFHb (PP-SFHb), PP-PolyHb, and whole blood. Long-term (>8 day) survival rate of rats (n=12) resuscitated with PP-PolyHb was 75% compared to 83% for autologous whole blood. Survival following resuscitation with the other fluids was substantially lower. These results indicate that PP-PolyHb could effectively resuscitate lethal hemorrhagic shock in conscious rats, and provide long-term survival afterwards, even in the absence of any additional fluid maintenance.