Intravenous infusion of Hb-vesicles (artificial oxygen carriers) after repetitive blood exchange with a series of plasma expanders (water-soluble biopolymers) in a rat model

Hemoglobin-vesicles (HbV) are artificial oxygen carriers developed for use as a transfusion alternative. The extremely high concentration of the HbV suspension (solutes, ca. 16g/dl; volume fraction, ca. 40vol%) provides a sufficient oxygen carrying capacity to maintain oxygen metabolism. A suspension of HbV has no colloid osmotic pressure (COP). Consequently, a combination of a plasma expander is necessary for a massive dose of HbV. Clinically available plasma expanders include hydroxyethyl starch (HES), modified gelatin (MFG), or recombinant human serum albumin (rHSA). Our previous studies confirmed that these water-soluble biopolymers interact with HbV to induce flocculation of HbV reversibly by depletion interaction, especially with MFG and high molecular weight HES. It remains unknown whether such flocculate formation in blood might affect animal's hemodynamics. Using a rat model, we tested infusion of a series of plasma expander to maintain the blood volume (level of blood exchange led to 60%) at repeated hemorrhages and the subsequent infusion of HbV (20ml/kg, 36% of blood volume). All rats survived for 4hr after the infusion of HbV; hemodynamic and respiratory functions were preserved, indicating that the flocculation does not induce capillary embolism. Blood exchange with rHSA and subsequent infusion of HbV showed more stable systemic parameters because of the longer retention of rHSA in blood than other plasma substitutes, indicating that rHSA is suitable for combination with HbV in this experimental model.