The proposed studies are designed to explore the dynamics and control of blood volume in the chronically catheterized sheep fetus. The long-term objective is to generate an integrated understanding of the various factors which are important in determining fetal blood volume under normal as well as aberrant conditions. The background to the proposed studies is that the regulation of blood volume in fetus appears dramatically different from that in the adult because fluid movements within the fetus (eg, transcapillary, swallowing, urine flow, lymph flow) are roughly an order of magnitude greater than in the adult (relative to body weight). In addition, fluids move by 3 pathways which are not present in the adult (ie, across the placenta, out of the fluid filled lungs, and across the intramembranous pathway) so blood volume regulation in the fetus is more complex than in the adult. Our proposed studies are aimed at exploring cardiovascular, renal and placental mechanisms which control the movement of fluid into and out of the fetal vascular compartment. We will test the following hypotheses: 1) the fetus, when subjected to a long-term loss of blood, can produce only a minor augmentation of its red cell production rate but can rapidly produce large quantities of new plasma proteins; 2) a 3-5 fold elevation in fetal lactate concentration will elevate blood volume and produce severe fetal edema and/or polyhydramnios; and 3) elevations in plasma lactate will produce more extensive fetal edema and/or hydramnios in anemic fetuses. These studies will help us understand disease states such as erythroblastosis fetalis, polyhydramnios, and hydrops fetalis in humans. We will determine the mechanisms of isotonic fluid transfer from the fetus to its mother land determine the changes in placental permeability which occur with short-term vascular volume loading of isotonic fluid into the fetus. In addition, we will explore the developmental changes in the filtration coefficient of the placenta and determine whether selected hormones alter this placental permeability parameter. These studies will provide fundamental information which is needed in order to understand what factors are involved in the control of the distribution of fluid between the fetus and its mother and may provide a basis for the treatment of oligohydramnios. Collectively, results generated from the proposed studies will significantly contribute to our understanding of the regulation of blood volume in the ovine fetus. This, in turn, may lead to better treatment of fetal and neonatal disorders, thereby reducing fetal and neonatal morbidity and mortality.
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