Intravascular reduction of methemoglobin in plasma of the rat in vivo

The formation and reduction of extracellular methemoglobin (metHb) in plasma was studied in vivo in conscious rats after isovolemic exchange transfusions with polymerized hemoglobin solutions. After exchange transfusions of 40 and 70% of the blood volume with hemoglobin solutions, containing less than 6% methemoglobin, the methemoglobin level remained below 15%, whereas exchange transfusions of greater than 90% resulted in an increase in the metHb level to about 30% after 24 hours. The reduction of metHb was studied after exchange transfusions with fully oxidized hemoglobin. A gradual decrease in the metHb level to 20% was observed after exchanges of 5 or 40%. A higher exchange transfusion (70%) resulted also in a decrease in the metHb level but only to approximately 40% in 24 hours. In another series of experiments the reduction of metHb was studied in vitro with isolated human erythrocytes. Incubation of the erythrocytes in the presence of oxidized polymerized hemoglobin (3 g%) resulted in a decrease in the percentage of metHb from 91% to 64%. In the presence of 0.2 mM ascorbic acid the metHb level declined to 22%, suggesting a synergistic effect. These results indicate (1) that there is a potent reducing mechanism present in blood that can reduce extracellular oxidized polymerized hemoglobin and (2) that isolated erythrocytes have a large capacity to reduce extracellular metHb, and may also play an important role in the reduction of extracellular metHb in vivo.