The long-term objective of the proposed studies is to understand the detail mechanisms involved in the regulation of amniotic fluid volume under normal as well as abnormal conditions. The studies will be conducted in chronically catheterized pregnant sheep during the last 50 days of gestation. Advanced methods will be used for measuring amniotic fluid volume, fetal urinary output into the amniotic space, and fetal swallowing of amniotic fluid. In addition, the movement of fluid and electrolytes across the fetal membranes will be explored under a number of conditions. The first study is designed to determine to what extent the large daily variations in amniotic fluid volume are related to variations in fetal urine flow rate and swallowing. To determine whether changes in fetal hydration lead to alterations in amniotic fluid volume, physiological saline will be infused intravenously into the fetus over a period of days. Amniotic and allantoic fluid volume regulation will be explored separately by infusing isotonic fluids into these spaces over a period of days and correlating the associated volume and composition changes with the infusion, urine flow, and swallowing rates. The relative contribution of swallowing and transmembrane movements of fluid and electrolytes to amniotic fluid volume regulation will be determined by correlating the amniotic volume changes with urine flow following esophageal and tracheal ligation. The exent to which the placenta is involved in regulating amniotic fluid volume will be determined fetal urine and amniotic fluid for a period of days and relating the net volume and electrolyte loss to the changes in transplacental osmotic and electrolyte concentration gradients. finally, the contribution of individual hormones to regulation will be determined by infusing arginine vasopressin, prolactin, cortisol, or angiotensin II into the amniotic fluid and relating the associated changes in volume and composition to the hormone concentrations in amniotic fluid. Collectively, the proposed studies are important because they will greatly expand our understanding of the regulation of amniotic fluid volume. Because aberrations in amniotic fluid volume are associated with fetal death or poor perinatal outcome, the proposed studies may lead to a decreased fetal and neonatal morbidity and mortality.
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