EXPERIMENTAL POLYHYDRAMNIOS

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The purpose of the project is to evaluate the physiological mechanisms that cause polyhydramnios and hydrops fetalis when fetal sheep are infused with angiotensin I. Under general anesthesia, fetal sheep will be instrumented with indwelling catheters in the umbilical vein, the jugular vein, a pedal artery and vein and the amniotic and allantoic fluids. Maternal catheters will be placed in a femoral artery and uterine vein. In some animals inflatable occluders will be placed on the fetal or maternal venous drainages of the placenta and flow meters on the fetal or maternal terminal aorta. Hypotheses to be tested are that the development of polyhydramnios depends on a change in the placental permeabilities and reflection coefficients for Na and Cl, that an intermediate step is the conversion from angiotensin I to angiotensin II, that there is no second system of water filtration channels across the placental barrier, that the hypertensive effect of angiotensin I is not a direct cause of water disease, that the same placental changes that cause polyhydramnios in intact fetuses cause hydrops fetalis in nephrectomized fetuses and that extraplacental transfer of solutes is not a significant contributor to the process that produces water disease. Elucidation of the pathophysiology of these common diseases of pregnancy will help lead to rational therapy.