The Effect of Anemic Anoxia on the Cellular Development of Nucleated Red Cells

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Abstract
The action of an anoxic stimulus on red cell production was studied in rabbits bled 20 ml./Kg., kept anemic for 20 hours and then reinfused with the previously removed blood. This 20-hour period of anemic anoxia was followed by a characteristic reticulocyte response, a response which was modified by nitrogen mustard or colchicine administered immediately after the 20-hour period of anemia, but was not influenced by anoxia or hyperoxia in the postanemic period. When mitotic division was arrested by colchicine during the 20-hour period of anemic anoxia, the onset of the reticulocyte response, though delayed by 1 to 2 days, was otherwise of characteristic magnitude. These observations indicate that (1) the anoxic stimulus operates in the bone marrow by accelerating the differentiation of stem cells into pronormoblasts, and that thereafter (2) the maturation and multiplication of differentiated nucleated red cells proceed at fixed rates independent of the anoxic stimulus.