Förster H, Hoos I, Schneider M, Hauk H
Infusionsther Klin Ernahr. 1977 Apr;4(2):122-6.
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.
无基质人血红蛋白溶液和聚合血红蛋白溶液用于灌注实验动物（Wistar大鼠）的离体器官。两种制剂都被证明适合维持充足的氧运输。在实验动物中静脉输注大量血红蛋白或聚合血红蛋白（3.0克/千克体重）后，肾脏损失分别为30%和不到10%。血红蛋白的半衰期仅为两小时，而聚合血红蛋白的半衰期为13小时，尽管后者制剂的分子量仅增加了一倍。由于不同血红蛋白制剂的少量经肾脏排泄，大量则分别储存在生物体内或被代谢。静脉输注未引起化学上可证实的肝毒性迹象。胆红素浓度和酶活性均未显示出明显变化。此外，所有动物都在高剂量静脉输注后存活下来。然而，组织学评估显示血红蛋白制剂引起了明显变化。在肝实质细胞内发现了血红蛋白。肝细胞和肾细胞显示出毒性作用的迹象。在肝实质细胞中未发现聚合血红蛋白。与血红蛋白相反，这种制剂储存在库普弗细胞内。与血红蛋白相反，聚合形式的行为类似于红细胞。血红蛋白的快速清除（半衰期仅两小时）使其不适合用于血液替代。然而，聚合血红蛋白的半衰期为13小时，从这一角度来看，聚合形式适合用于血液替代。考虑到组织学上可证实的变化，在将血红蛋白溶液用于人体之前还需要进行额外的实验。
