242 SPO Abstracts

ATRIAL NATRIURETIC PEPTIDE: A REGULATOR OF THE FETOPLACENTAL ORCULATION? J.C P.Kingdom; Creg Ryan, M.]. Whittle, Jackie Doyle', j.M C Connell*. Perinatal Vascular Research Group The Queen Mother's Hospital &: MRC Blood Pressure Umt" Umversity of Glasgow, SCOTLAND

It IS possible that atnal natrIuretIc peptIde (ANP) may have a vas(xhlator role which allows the fetus to adjust to acute Intravascular loadmg We have mvestIgated this by measunng It at the time of rntravascular transfusIon for Rhesus dISease Paned maternal and fetal pre-transfuslOn samples (1m1) were collected. In 51 cases a post­transfusion sample was collected In 34 Paired donor, pre- and post­transfusion samples (0.1 mD were also collected for pH and p02 measurements m 10 Pulsed doppler SID ratIo measurements were made from the umbilIcal artery (VA), mlddle cerebral artery (MeA) and aorta (AO) before, 15 mms, 3-4 hours and 20-24 hours followmg transfuSIon m 18 cases Plasma ANP was measured usmg a pre-extracted RIA method (recovery 85%,coeffiaent of vanahon 8%) Pre-transfUSIon ANP was sIgnifIcantly hIgher than maternal values (mean 155 pg/ml vs 41 pg/ml, p< 0001) Pre-transfUSIOn ANP was mversly aSSOCIated (by stepWIse multIple regreSSIOn analYSIS) Wlth hematocnt (p< ~OS), but not albwnm (pc: 057) or gestatIOnal age (pc: 992) Post-transfusion ANP was sigruficantly hIgher than pre-transfuSIOn ANP (216 pg/ml vs 155 pgl mt p< 02 WIlcoxon rank sum test) The change In ANP could not be predicted from any transfUSIOn parameter Though donor blood IS aCidotic (mean pH=6 9) there was no change m pH (or p02) followmg transfUSIon An acute reduction m SID raho of the UA was seen In 12/18 fetuses at 15 mms, which tended to return to pre-transfUSIon values at 3-4 hours A regresSIOn analysIS of %change UA SID rabo With % change m fetal ANP m all 18 fetuses Just faIled to achIeve slgmfIcance (p= 058) CorrectIOn of SID for mdIVldual heart rates did not unprove thIS assOClalion A slml1ar, but less ObVIOUS trend was seen In the MCA and AO These data support eVidence from adult and ammal work that ANP has a dynamIc role In the fetus The assOClatlOn between change In

ANP and UA SID suggests thIS peptIde may dIlate the fetoplacental arculahon so provIdmg a mechamsm whIch allows a phYSIOlogICal response to mtravascular loadmg

2 RELATIONSHIPS AMONG CYTOKINES (IL-1, TNF and IL-S) AND HISTOLOGIC MARKERS OF ACUTE ASCENDING INTRAUTERINE INFECTION. Nicholas PotterX,Linda Kosudax,Pierluigl BigazzlX,Alfred Fleming, Anthony M. Vintzileos, Carol Homonx, and Carolyn M. Salafiax. University of Connecticut Health Center, Farmington, CT 06030

Amniotic fluid levels of interleukin-1-~ (IL-1-~), tumor necrosis factor-a (TNF-a) and interleukin-S (IL-S) were determined in a series of pregnancies presenting with preterm spontaneous membrane rupture, and were compared to the placental histology. 25 amniotic fluids taken at 16-20 weeks in the course of routine genetic amniocentesis in which outcome was known, were used to determine lower limits of assay sensitivijies. Quantitative IL-1-~ and TNF-a levels in amniotic flUids were determined by ELISA (Cistron Biotechnology, Pine Brook, New Jersey). A 100 pg/ml was used as the lower limit of assay sensitivity. IL-S levels were determined by radioimmunoassay with elevated levels (> 10 ng/ml) substantiated by IL-S receptor binding competition. All cases in which elevated cytokine levels were identified also had histologic evidence of acute inflammation. While elevated levels of both IL-1-~ and TNF-a were not uniformly observed in amniotic fluid, all

cases with either elevated IL-1-~ or TNF-a had elevated levels of IL-S. Amniotic fluid levels of all three cytokines were directly correlated with the presence and the severity of maternal inflammatory responses in choriodecidua and chorionic plate. Intraamniotic levels of all three cytokines were also correlated with the presence but not the seventy of fetal inflammatory responses, as observed in umbilical and chorionic vessels. We suggest that one aspect of the functional immaturity of the fetal polymorphonuclear leukocyte may be related to responses to IL-S. In addition, IL-S may be the best indicator of intraamniotic infection.

Januan 1991 Am J Ob,tet GvnelOl

3 ENHANCED ENDOTHELIUM-DERIVED RELAXING FACTOR ACTIVITY IN PREGNANT SPONTANEOUSLY HYPERTENSIVE RATS. Robert A. Ahokas" Brian M. Mercer' and Baha M. Sibai, Univ. of Tenn., Memphis, TN

Pregnancy is associated with vasodliation which, m spontaneously hypertensive rats (SHR), causes a profound decrease in blood pressure. Increased prostacyclin (PGI z) production IS thought to cause pregnancy vasodilation, but, endothelium-derived relaxing factor (EDRF) may also be involved. To test this hypotheSIS, we measured changes in mean arterial pressure (MAP) and heart rate (HR) induced by NG_ monomethyl-L-argmine (L-NMMA; 5-40 mg/kg, l.v.), a speCific EDRF mhibitor, m conscious nonpregnant (NP) and pregnant (PG) normotensive Wlstar-Kyoto (WKY) and SHR rats. L-NMMA caused sustained dose-dependent increases in MAP and bradycardia in all rats indicating that basal EDRF production plays a role in vascular homeostasis. In WKY, MAP was mcreased Similarly in NP and PG rats; HR was decreased significantly more in NP than PG rats. L-NMMA caused significantly greater mcreases in MAP m PG than in NP SHR, but simIlar decreases m HR. Indomethacin pretreatment (5 mg/kg, Lv.) had no effect on L-NMMA induced increases in MAP in either NP or PG WKY or SHR. Thus, pregnancy IS assOCiated with increased EDRF activlty in hypertenSive SHR, but not in normotensive WKY rats. EDRF, not PGI2, may be the "antihypertensive factor" of pregnancy m hypertensive animals.

4 IlillOCEO HYPOGLYCEMIA III PREGIIAIIT 101£11 (IIISULIN CLNIP TECIIIIQUE) AIID THE ASSESSMEIIT OF MATERIIAL AIID FETAL RESPONSES. Reece EA, Oi...oo lIP" , Roberts A', Hagay Z", Caprio S', Kra_r 0', DeGennaro II', 6ill A', Sherwin R', TaIIIborlane 11"; Depts. of OB/6YII, Medicine and Pediatrics, Yale University, !lew Haven, CT

Stringent glyce.ic control of pregnant patients with insulin­dependent diabetes _llitus (100II) has bee.... the standard of care. IIIM!ver, such _geEIIt is frequently COIIp li cated by .. ltiple hypoglyce.ic episodes. Since the cause and consequence r.ahllld Wlknown, we initiated the following study which represents the first to ex.ine hulan .aternal and fetal responses to induced .aternal hypoglyce.ia. We studied 9 intensely treated (1IIAl 6.6 + O.SS; nonsal < lIS) IOOM __ n (White classes B-FR) at 26-34 welts gestation. ""iRe!, continuous insulin (2 .l/kg per .inute) and a variable rate dextrose infusion produced gradual and controlled hypoglyc .. ia. 6lucose was l~red fras fasting levels to 90, 80, 70, 50, SO, and 40 IIg/dl every 40 .inutes. At each step, anti-insulin holWll1eS were deterwined and fetal well-being was assessed. Responses were c~red to seven non-pregnant healthy control .-en. Reductions in glucose fro. 107 :!: 6 to 44 :!: 2 lIg/dl In the pregnant diabetic ... n failed to produce an Increase In glucagon levels (109 :!: 11 to 91 :!: 12 pg/.1). Epinephrine, a key anti-Insulin honoone, was also .arkedly suppressed in the pregnant diabetic patient during the hypoglyce.la (96:!: 29 In diabetics vs. 265 :!: 27 pg/.l in controls; P < 0.01). Fetal well-being was assessed continually. Despite a 7-fold increase In epinephrine, there was no Significant alteration in FHR reactivity or variability or In fetal .,v~ts during hypoglyc .. la. Fetal breathing transiently increased, then significantly decreased especially at glucose levels below 70 IIg/dl. lWIilical artery Doppler Indices n.alned virtually unchanged throughout the entire study. Basal levels of prolactin, IIPl, and 11:6 did not change with hypoglyce.ia. Conclusion: The frequent hypoglyc .. ic episodes experienced by tightly controlled pregnant IDOl! """"'" appear to be due not only to i ntens i ve i nsu lin therapy but also to i npa i red counter regulatory homone secretion. These hypoglycemic epiSodes, ~ver, appear to be well tolerated by the developing fetus.