The proposed studies are designed to answer the question """"""""How is fetal blood volume controlled?"""""""" To do this, we propose to use the chronically catheterized fetal sheep as the experimental model, together with improved methods to measure fetal blood volume in utero. We will follow the changes in blood volume after slow and rapid fetal hemorrhage and after intravascular infusions of saline and determine the role of autonomic nervous system and hormonal controls in these responses. We will measure left thoracic duct lymph flow, thracheal secretion, swallowing and urinary output rates under normal, hypovolemic, and hypovolemic conditions. We will also measure the 4 transcapillary Starling pressures and determine their changes under various experimental conditions. We will measure blood volume changes in response to hypoxia and to exogenous hormones. Net transcapillary movement of the plasma proteins for each of these maneuvers will also be determined. Finally, we will measure the osmotic shift of water between the mother, fetus, and amniotic fluid following injection of a hypertonic bolus into each of these spaces. From the experimental data we will determine fetal vascular and interstitial compliances, placental and fetal whole-body capillary filtration coefficients and permeability coefficients, and function curves for lymph flow, urinary output, tracheal secretion, swallowing, and protein osmotic pressures. We will use computer techniques to synthesize the data into a mathematical model of fetal fluids in an effort to better integrate the control of blood volume. The proposed studies should help decrease fetal and neonatal mortality through an improved understanding of basic fetal cardiovascular physiology.
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