Some potential blood substitutes

Abstract

The oxygen-carrying resuscitative fluids called blood substitutes, have been synthesized from a hydroxyethyl starch (HES) modified to a polymeric trialdehyde and hemoglobins (Hgb) which are stabilized with either glyoxalic acid or 1,2-cyclohexanedione. The molecular weights of the starting HES polymers were 450,000, 264,000 and 59,000. The modified HES compounds averaged about 35% aldehyde. After synthesis, the new polymers shifted the P₅₀ from 14.9 mmHg for a 6% Hgb solution to about 35 mmHg. From the preliminary studies in this laboratory, it appears feasible to produce a suitable substance in a freeze-dried form. In vivo experiments included exchange-transfusion in rats following the hemoglobin retention kinetics in the plasma and the excretion in the urine. The results indicate that these blood substitutes are hemodiluents, can provide adequate oncotic pressure as well as the necessary oxygen transport for animal survival. Using these new polymers, final hematocrits below 15% were much easier to obtain with a vastly improved survival rate. Electrophoretic mobility patterns of the plasma during the transfusion-exchange indicate a step-wise breakdown of the polymer. In some cases, the substitute remained in the plasma up to 72 hours.