Abstract
A liposome-encapsulated human hemoglobin (Neo Red Cell, (NRC) has been developed and evaluated as an artificial oxygen carrier. The NRC is a liposome-encapsulated highly concentrated (>45%) stroma-free human hemoglobin with inositol hexaphosphate (IHP as an allosteric effector), a coenzyme and substrates for reducing methemoglobin (metHb). The NRC's surface was coated with polyethylene glycol to prevent aggregation in plasma and to prolong their retention time in the blood stream. The oxygen binding behavior of the NRC in vitro was investigated and it was found that it effectively transports oxygen in vivo as an oxygen carrier. The oxygen binding behavior and kinetics were studied by the stopped-flow method and the oxygen binding curve of the NRC was determined. The oxygen binding speed and binding coefficient (Kon) of NRC, washed human red blood cells (WRBC) and stroma-free human hemoglobin (SFHb) were measured by stopped-flow method. The oxygen binding speed of SFHb was the highest, while that of RBC was the lowest and that of NRC was intermediate. The oxygen binding of NRC ended within 60 msec when deoxy-NRC was mixed with oxygen. The Kon of NRC was 2.9 × 105, 10 times faster than that of RBC. The oxygen binding curve and P50O2 of NRC that contained various IHP concentrations were measured. The oxygen-binding curve of the NRC sequentially shifted to the right as the IHP content was increased. Exchange transfusion of 70% was carried out for rats with NRC containing various concentrations of IHP and of Hb, and investigated the optimum concentration of NRC in vivo. The lactate value after exchange transfusion was three times higher than before exchange transfusion, when rats were subjected to exchange transfused with NRC that did not contain IHP. But the increase of lactate was suppressed when rats were transfused with NRC that contained IHP. When the Hb concentration of NRC was 5 and 6%, exchange transfused rats recovered to normality just like rats transfused with RBC. Copyright © 2000 John Wiley & Sons, Ltd.
Published Version
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