458 PERINATAL GLUCOSE TOLERANCE AFTER INTRAUTERINE GROWTH RESTRICTION INTHE LATE-GESTATION OVINE FETUS PHILIPPE DERUELLE1, IVA GUEORGUIEVA2,BERENGERE SICOT DE JENLIS3, SOPHIE JAILLARD4, JACQUES WEILL2,VERONIQUE DEBARGE4, LAURENT STORME4, 1CHRU de Lille, Lille, France,2CHRU de Lille, Pediatric endocrinology unit, Lille, France, 3CHRU de Lille,Department of perinatology, Lille, France, 4CHRU de Lille, France,Department of perinatology, Lille, France

OBJECTIVE: Newborns with Intrauterine-Growth Restriction (IUGR) are atincreased risk to develop a metabolic syndrome later in life, namely obesity,cardiovascular disease, impaired glucose tolerance. Whereas these facts havebeen largely studied during childhood or adult life, little is known about theconsequences of IUGR on glucose tolerance during the perinatal period. Thepurpose of this study was to determine whether chronic placental embolizationin the late gestation ovine fetus induce insulin resistance during the perinatalperiod.

STUDY DESIGN: IUGR was induced by umbilico-placental embolizationduring late gestation in chronically catheterized sheep. Umbilico-placentalembolization was performed between 130 and 140 d of gestation (terme = 147d) during which fetuses were hypoxemic relative to controls. Euglycemic,hyperinsulinemic glucose clamp experiments were performed in utero and duringthe first three weeks after birth in order to measure the effect of fetal insulinconcentration on fetal glucose uptake at a constant glucose concentration. Fetalcoricotropin, cortisol and catecholamines concentrations were measured daily.

RESULTS: Chronic placental embolization produced asymmetrically IUGRfetuses and increased vascular resistance in umbilical artery (P ! .05). Theexogenous glucose infusion rate necessary to maintain constant glycemia wassignificantly lower in IUGR relative to control fetuses at 140 d of gestation(IUGR vs. control, 2.5 G .5 mg/kg/min and 5.0 G 0.5 mg/kg/min, P ! .05) and7 days after birth (IUGR vs. control, 3.5 G .7 mg/kg/min and 5.7 G 1.4 mg/kg/min, P ! .05). Glucose clamps were similar between groups at 2 and 3 weeksafter birth. Cortisol levels were similar between the two groups. In response tochronic fetal hypoxemia, there was a progressive increased in baseline fetal

S132 SMFM Abstracts

456 CHANGES IN AQUAPORIN 1 EXPRESSION AFFECT AMNIOTIC FLUID VOLUMESTEPHANIE MANN1, NATALIA DVORAK2, ROBERT TAYLOR2, 1Phoenix IntegratedResidency in Ob/Gyn, Obstetrics and Gynecology, Phoenix, Arizona,2University of California, San Francisco, Obstetrics, Gynecology andReproductive Sciences, San Francisco, California

OBJECTIVE: Recent work from our laboratory has demonstrated the presenceof aquaporin (AQP) water channels in fetal membranes from pregnancies withnormal amniotic fluid (AF) volume. The objective of this study was toinvestigate changes in AQP 1 mRNA expression from fetal membranes ofpregnancies with polyhydramnios and oligohydramnios.

STUDY DESIGN: Placentas from term pregnancies (37-40 wks) were collectedfrom women who presented with intact membranes and one of the following:(1) idiopathic oligohydramnios (AFI !5.0 cm); (2) polyhydramnios (AFI >24.0cm); and (3) normal amount AF (AFI >5.0 cm and!24.0 cm). The membranes(amnion and chorion) directly overlying the placenta and the free floatingreflected membranes were sampled (total of four samples from each placenta).RNA was isolated from the amnion and chorion of each region. QuantitativeRT-PCR was used to compare expression of AQP1 mRNA in the membranescollected from the above pregnancies. Statistical analysis was performed witha t test. P ! .05 was considered signficant.

RESULTS: As shown in the figure, AQP1 mRNA expression is increased in thereflected amnion from pregnancies with idiopathic polyhydramnios and de-creased in the reflected amnion and chorion from pregnancies with oligohy-dramnios.

CONCLUSION: The expression of the water channel AQP1 is altered in thereflected fetal membranes. These results suggests that there is an adaptiveresponse by the fetal membranes in situations of either decreased or increasedAF volume to prevent excessive loss or accumulation of fluid, respectively. Wespeculate that therapies focused on regulating AQP1 expression may be usefulfor treating oligohydramnios and polyhydramnios.

457 EFFECTS OF PHOSPHODIESTERASE 5 INHIBITOR ON PULMONARY VASCULARREACTIVITY IN THE FETAL LAMB PHILIPPE DERUELLE1, BENOIT LARRUE1,THAMEUR RAKZAH1, SOPHIE JAILLARD1, GHAZWAN BUTROUS2, LAURENT STORME1,1CHRU de Lille, France, Department of Perinatology, Lille, France, 2SandwichLaboratories, Pfizer Limited, Sandwich, Kent, United Kingdom

OBJECTIVE: Nitric oxide (NO) released by pulmonary vascular endotheliumis a potent vasodilator related to increased cGMP content. Hydrolysis of cGMPis achieved predominately by cGMP-specific phosphodiesterases (PDEs). Silde-nafil (SILD) is a selective phosphodiesterase-5 (PDE-5) inhibitor. The purpose ofthe study is to assess the effects of sildenafil on pulmonary vascular circulationduring the perinatal period.

STUDY DESIGN: 12 pregnant ewes were operated on between 128 and 130 daysgestation (term = 145 d). Catheters were placed into the ascending aorta,superior vena cava, main pulmonary artery and left atrium. An ultrasonic flowtransducer was placed around left pulmonary artery (LPA). An inflatablevascular occluder was placed around ductus arteriosus (DA). Fetal lambs weredivided in two groups: (1) a SILD group infused continuously by SILD at 0.3mg/kg/h (n = 6) and; 2/control group (CONT) infused with saline (n = 6).After 24 hrs of infusion, we compared the response of PA hemodynamic to: (1)to increased fetal PaO2, and (2) to increased in vascular shear-stress.

RESULTS: PAP, Q and PVR were similar in both groups before and after 24 hof infusion. Despite similar baseline values, PVR during maternal O2 inhalationwas lower in SILD than in CONT group (0.23 G 0.01 vs 0.27 G 0.01 mm Hg/mL.min respectively) (P ! .01). Furthermore, drop in PVR during acute DAcompression was greater in the SILD group (from 0.54 G 0.03 to 0.26 G 0.02mm Hg/mL.min) than in the CONT group (from 0.55G 0.04 to 0.39G 0.02 mmHg/mL.min) (P ! .01).

CONCLUSION: Although no difference was found in the basal pulmonaryvascular tone, sildenafil increases PVR in the ovine fetus. These data suggest thatPDE-5 is involved in the regulation of pulmonary vascular reactivity during theperinatal period. We further speculate that specific inhibitor of PDE-5 maypotentiate birth related pulmonary vasodilator stimuli and could improveconditions associated with failure to circulatory adaptation at birth.

plasma epinephrine, norepinephrine and dopamine concentrations (P ! .01).CONCLUSION: We concluded that chronic fetal hypoxemia induces insulin

resistance during the perinatal period. We speculate that this change could berelated to an increase in fetal catecholamines levels.

459 WITHDRAWN