A mathematical model of erythropoiesis in mice and rats. Part 3: Suppressed erythropoiesis.

A mathematical model of erythropoietic cell production and its regulation process has been proposed in a preceding paper. It is primarily based on the assumption that the number of cell divisions taking place in the CFU-E and erythropoietic precursor stages can be regulated depending on the oxygen supply to the tissue. Here we provide evidence that this model adequately describes situations of suppressed erythropoiesis. In detail this implies a quantitative description of the following processes: (1) changes in tissue oxygen tension (Pto2) due to increase in red cell numbers (red cell transfusion, posthypoxia), decrease in plasma volume (dehydration) or increase in atmospheric oxygen pressure (hyperoxia), (2) Pto2 dependent reduction of erythropoietin (EPO) production, (3) dose-response of reduced EPO-levels on erythropoietic amplification (omission of three to five mitoses). Model simulations are compared to experimental data obtained from red cell transfusion, posthypoxia, hyperoxia and dehydration. A satisfactory agreement suggests that the model adequately describes and correlates different ways to suppress erythropoiesis. It quantifies the role and relative contribution of the haematocrit, haemoglobin concentration, atmospheric oxygen pressure, tissue oxygen pressure and plasma volume as triggers in erythropoietic suppression under various conditions. In conjunction with the preceding two papers it could be shown that one unique set of model parameters is sufficient to describe erythropoiesis in steady state, stimulation and suppression. Limitations of the model are discussed and experiments for a more detailed investigation of the feedback mechanisms are proposed.