OXYGEN-DEPENDENT CIRCULATION OF SICKLE ERYTHROCYTES

  • 1 January 1976
    • journal article
    • research article
    • Vol. 88  (5) , 732-744
Abstract
The effects of in vivo hyperoxia and hypoxia on the intravascular survival of 51Cr-labeled human sickle erythrocytes (SS RBC) 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, allowing extension of the survival of the heterologous human RBC. In the blood of rats breathing ambient air the 51Cr half-life survival of RBC from 11 patients with sickle-cell anemia (mean, 7.1 h; range, 2.0-16.5 h) was significantly shorter (P < 0.001) than that of 5 control subjects (mean, 17.5 h; range, 12.0-26.5 h). When rats transfused with sickle RBC were exposed to 100% O2, a mean increment of 16.5% in blood 51Cr activity was observed within the first 15-60 min. of hyperoxia. Subsequent O2 deprivation (7 to 8% O2) resulted in an equally rapid decrease (mean, 35.6%) in blood 51Cr activity. Continuation of hypoxia for up to 17 h did not cause further acceleration of 51Cr 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 breathe room air again, mean 51Cr blood activity increased by 41.7%. Sickle RBC transfused to guinea pigs exhibited similar O2-dependent survival characteristics. The survival of 51Cr RBC from 4 adult control subjects and of unlabeled fetal RBC from 3 human cord blood samples was unaffected by O2 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 from the same patients. There was increase liver and spleen 51Cr activity in animals transfused with 51Cr SS RBC and killed during hypoxia when compared to that of hyperoxic animals. A minor population of sickle cells is apparently 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 O2-dependent circulation of a population of SS RBC in this animal system is probably due to reversible sickling and trapping of sickled cells in the microcirculation.