Intrauterine growth retardation (IUGR) occurs in approximately 10% of all pregnancies and is associated with significant risk of perinatal death, asphyxia and neonatal acidosis. IUGR is thought to result from inadequate transfer of oxygen and nutrients to the fetus. This may occur as a result of reduced uteroplacental perfusion, altered placental transport or maternal malnourishment. The present proposal will investigate the affects of chronic reduction in uteroplacental blood flow on fetal growth. The following questions will be addressed: 1) Is fetal growth dependent on gestationally related increases in uterine blood flow? 2) When limited oxygen and nutrients are available to the fetus does the fetus alter its oxygen, glucose and/or lactate consumption? 3) does altered uterine blood flow cause changes to occur in umbilical blood flow? Sheep with singleton pregnancies will be instrumented at 105 days gestation (term 145 days) with a vascular occluder on the common internal iliac artery, flow probes on both internal iliac arteries and catheters in the maternal femoral artery and veins, a lateral branch of the uterine artery, uterine vein, fetal hindlimb artery and vein, and the umbilical vein. Using the vascular occluder, uteroplacental blood flow will be held constant in Group II from day 110 to day 138 of gestation or in Group III from day 120 to 138 of gestation. Blood flow will be allowed to increase normally in control animals (Group I). Based on previous studies, holding blood flow constant from day 110-138 will produce a 50% decrease in uteroplacental blood blow at term, while occlusion from day 120-138 will result in a 30% reduction. In each of these groups fetal consumption of oxygen, glucose and lactate will be determined on days 110, 117, 124, 131, and 138 of gestation. On day 138 of gestation pregnant ewes and their fetuses will be sacrificed and fetal growth retardation will be determined by measuring fetal body weight, length, ponderal index, brain and liver weights plus calculated ratios (i.e. brain to liver ratio). In the second portion of the proposal umbilical blood flow will be measured for periods of 1-2 hours three times a week to determine if reduced uteroplacental blood flow alters the normal gestationally related increases in umbilical blood flow; i.e. does uterine and umbilical perfusion matching occur. These combined studies will provide us with valuable insight into the mechanism of fetal growth retardation.
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