Interactions of animal and computer models in investigations of the "anemia" of space flight.

Previous studies in mice deprived of water have suggested that these animals, like men in space, show hemoconcentration due to plasma volume reductions, a weight loss greater than that due to fluid loss alone, and suppression of red blood cell production. To more fully understand the mechanisms responsible for the suppressed erythropoiesis in dehydrated mice, a mathematical model for erythropoietic regulation has been adapted to this rodent. Computer simulations suggested several new experimental studies to more fully understand the erythroid response to dehydration. The investigations were directed to determining whether dehydration was accompanied by: a) a shortened red blood cell survival, b) altered sensitivity of the erythropoietin (Ep)-producing mechanism, c) a shortened red blood cell transit time, d) changes in the Ep serum half-life, e) changes in hemoglobin P50, and f) reduced renal blood flow. All parameters except changes in renal blood flow were investigated in vivo and incorporated into, or omitted from, the mathematical simulations as directed by experimental findings. The mathematical model is able to realistically simulate the in vivo erythroid response to dehydration making only one, experimentally-untested, assumption. Computer simulations confirm conclusions drawn from the animal studies that the primary cause of the suppressed erythropoiesis in dehydrated mice is the reduced food intake, with hemoconcentration playing a relatively minor role. The interaction between computer simulations and animal experiments is shown to be a powerful approach for formulating and testing hypotheses, designing new experiments, and achieving a clearer understanding of the factors controlling erythropoiesis.