Hydroxyethyl Starch–Bovine Hemoglobin Conjugate as an Effective Oxygen Carrier with the Ability to Expand Plasma

[Image: see text] Hemorrhagic shock leads to intravasal volume deficiency, tissue hypoxia, and cellular anaerobic metabolism. Hemoglobin (Hb) could deliver oxygen for hypoxic tissues but is unable to expand plasma. Hydroxyethyl starch (HES) could compensate for the intravasal volume deficiency but cannot deliver oxygen. Thus, bovine Hb (bHb) was conjugated with HES (130 kDa and 200 kDa) to develop an oxygen carrier with the ability to expand plasma. Conjugation with HES increased the hydrodynamic volume, colloidal osmotic pressure, and viscosity of bHb. It slightly perturbed the quaternary structure and heme environment of bHb. The partial oxygen pressures at 50% saturation (P(50)) of the two conjugates (bHb-HES130 and bHb-HES200) were 15.1 and 13.9 mmHg, respectively. The two conjugates showed no apparent side effects on the morphology and rigidity, hemolysis, and platelet aggregation of red blood cells of Wistar rats. Thus, bHb-HES130 and bHb-HES200 were expected to function as an effective oxygen carrier with the ability to expand plasma.