[The use of stroma-free hemoglobin solutions as blood substitute]

Solutions of stroma free human hemoglobin and of polymerized hemoglobin were used for perfusion of isolated organs of the experimental animal (Wistar rats). Both preparations proved to be suited for maintainance of sufficient oxygen transport. Following intravenous infusion of greater amounts of hemoglobin or polymerized hemoglobin in the experimental animals (3.0 g/kg body weight), the renal losses amounted 30% and less than 10% respectively. Half live was only two hours in the case of hemoglobin and 13 hours with the polymerized hemoglobin, despite molecular weight was only doubled in the latter preparation. Since the minor amount of the different hemoglobin preparation was excreted by the kidneys, the greater amount was stored in the organism or metabolized respectively. The intravenous infusion did not cause chemically demonstrable signs of liver toxicity. Neither bilirubin concentration nor enzyme activity showed significant alterations. Additionally, all animals survived the high dosed intravenous infusions. However, histological evaluations showed distinct alterations caused by the hemoglobin preparations. Hemoglobin was found inside the liver parenchymal cells. The liver cells and kidney cells showed signs of toxic effects. The polymerized hemoglobin was not found in liver parenchymal cells. In contrast to hemoglobin this preparation was stored inside the Kupffer's cells. In contrast to hemoglobin the polymerized form behaves like erythrocytes. The rapid elimination of hemoglobin (half live only two hours) renders this substance unsuited for blood substitution. However, half life of polymerized hemoglobin is 13 hours, and from this point of view the polymerized form is suited for blood substitution. Considering the histologically demonstrable alterations additional experiments are required before hemoglobin solutions are used in human subjects.