Oxygen-dependent circulation of sickle erythrocytes

The effects of in vivo hyperoxia and hypoxia on the intravascular survival of 51Cr-labeled human sickle erythrocytes (SS RBS's) were studied after transfusion into rats and guinea pigs. The function of these animals' reticuloendothelial and complement systems had been previously inhibited by ethyl palmitate and cobra venom factor, thus allowing extension of the survival of the heterologous human RBC's. In the blood of rats breathing ambient air the 51Cr half-life survival of RBC's from 11 patients with sickle-cell anemia (mean, 7.1 hours; range, 2.0 to 16.5 hours) was significantly shorter (p less than 0.001) than that of five control subjects (mean, 17.5 hours; range, 12.0 to 26.5 hours). When rats transfused with sickle RBC's were exposed to 100 per cent O2, a mean increment of 16.5 per cent blood 51Cr activity was observed within the first 15 to 60 minutes of hyperoxia. Subsequent oxygen deprivation (7 to 8 per cent O2) resulted in an equally rapid decrease (mean, 35.6 per cent) in blood 51Cr activity. Continuation of hypoxia for up to 17 hours did not cause further acceleration of 51Cr activity. Continuation of hypoxia for up to 17 hours did not cause further acceleration of 51 Cr RBC clearance. Under these conditions the slope of the sickle RBC survival curve was similar to that in animals kept in ambient air. After hypoxic rats were allowed to breate room air again, mean 51Cr blood activity increased by 41.7 per cent. Sickle RBC's transfused to guinea pigs exhibited similar oxygen-dependent survival characteristics. The survival of 51Cr RBC's from four adult control subjects and of unlabeled fetal RBC's from three human cord blood samples was unaffected by oxygen changes. When rats that had been transfused with sickle reticulocytes labeled in vitro with 59Fe were made hypoxic, a decrease in blood 59Fe activity was observed. The extent of this decrease was comparable to that in rats transfused with 51Cr labeled RBC's from the same patients. There was increased liver and spleen 51Cr activity in animals transfused with 51Cr SS RBC's and killed during hypoxia when compared to that of hyperoxic animals. These studies suggest that a minor population of sickle cells is removed from circulation during hypoxia and circulates again upon reoxygenation of the animals. Erythrocyte aging does not appear to be responsible for this phenomenon. The oxygen-depdendent circulation of a population of SS RBC's in this animal system is probably due to reversible sickling and trapping of sickled cells in the microcirculation.