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Volume 166 :\lumber 1, Part 2 49 UMBILICAL VENOUS PLASMA ENDOTIIEUN IS Naf INCREASED IN PREECLAMPSIA. A.Nova. x J. Barton. x M.D. Mitchell. B.M. Mercer. xB.M. Sibai. University of Tennessee, Memphis. and University of Utah. Salt Lake City. Plasma endothelin (ET) levels are usually increased in conditions characterized by endothelial damage and local tissue hypoxia. We previously reported that women with preeclampsia, particularly those with HELLP syndrome. have significantly higher endothelin levels than women with normotensive pregnancies. The purpose of this investigation is to compare umbilical vein plasma ET levels in preeclampsia and normotensive pregnancies. Methods: The study population included 7 women with preeclampsia and 12 with normotensive pregnancies. All hut one woman delivered vaginally at term. Samples were collected immediately after cord clamping using cold vacutainer tubes containing EDTA and aprotinin. The blood was immediately cold centrifuged and plasma fraction was then stored at - 70·c. Plasma was analyzed for endothelin using an RIA technique (Amersham Corp.). Results: As expected. preeclamptic women had significantly higher systolic blood pressures (152 ± 13 v 118 ± 10 mmHg. p < 0.0001) and higher diastolic pressures (97 ± 9.4 v 69 ± 9.2. p < 0.0001). There were no differences between the two groups regarding either gestational age at time of delivery or cord vein ET levels (Table). However. cord blood ET levels are significantly higher than previous reported maternal levels (preeclamptics 12.87 ± 3.6 v 5.5 ± 0.3. p < 0.001 and normotensive 12.2 ± 2.7 v 3.8 ± 0.3. P < 0.0001). Conclusions: Fetal secretion of ET is not increased in preeclampsia. The increase in umbilical ET at delivery suggests a role for ET in perinatal circulatory adaptation. Gestational age (wk) Umbilical vein ET (fmole/ml) Preeclampsia n=7 37.7 2.6 12.87 3.62 Normotensive n= 12 39.0 1.5 12.21 2.69 50 LOW-DOSE ASPIRIN (ASA) INHIBITS LIPID PEROXIDES (LPO) AND THROMBOXANE (TX). BUT NOT PROSTACYCLIN (PGI). IN PREGNANT WOMEN. SW Walsh,' Y Wang,' HH Kay. MC McCoy: Depts OB/GYN. Medical College of Virginia. Richmond. VA and Duke Univ .. Durham, NC Preeclampsia is associated with an imbalance of increased TX and decreased PGl, and recently reported an abnormal increase of LPO (AJOG. Dec.. 1991). LPO are toxic compounds that damage cells and inhibit PGI synthesis. Low· dose ASA therapy reduces the incidence of preeclampsia, presumably by selective inhibition of TX to restore a balance between TX and PGI. However. the effectiveness of low-dose ASA might also relate to inhibition of LPO. To test this, 10 women at risk of preeclampsia were placed on low-dose ASA therapy (81 mg/day) between 19·33 wks of gestation. Plasma samples were collected before ASA and after 3-4 days and 3-4 wks of ASA. Samples were analyzed for TX and PGI by RIA of their stable metabolites. TXB 2 and 6-keto PGF, •• and for LPO by H 2 0 2 equivalents. Low-dose ASA significantly decreased (P<0.05) both LPO (130 ± 18 vs 92 ± 11 and 68 ± 9 nmolj mI. mean ± SE) and TX (502 ± 67 vs. 138 ± 67 and 8 ± 5 pg/ml). but it did not affect PGI (55 ± 10 vs 41 ± 8 and 40 ± 11 pg/ml). Conclusion: LOW-dose ASA selectively inhibits both LPO and TX without affecting PGI. Speculation: This selective inhibitory action of low-dose ASA may account for its effectiveness in the prevention of preeclampsia. HD 20973. SPO Abstracts 295 51 INSULIN CONCENTRATIONS IN CHRONIC HYPERTENSIVE PREGNANT WOMEN. E. Rey,' A. Bonin,' Dept. Ob/Gyn. Sainte- Justine Hospital. Montreal (Quebec), Canada. In order to investigate the state of insulin resistance of chronic hypertensive pregnant women, we studied glucose and insulin responses to oral glucose loads in these patients. Chronic hypertension was defined as essential hypertension known before pregnancy. Gestational diabetic and treated chronic hypertensive women were excluded. Serum capillary glucose was determined by the glucose oxidase method and insulin levels by radio-immunoassay. One hundred and forty-seven (147) euglycemic lean normotensive pregnant women (Body mass index (BMI) = 21.8 ± 0.2), 30 euglycemic obese normotensive pregnant women (BMI = 32.5 ± 1.0) and 25 euglycemic lean chronic hypertensive pregnant women (BMI = 23.7 ± 0.6) received a 50 gm oral glucose load. Insulin levels and insulin to glucose ratio at one hour were significantly higher in normotensive obese and hypertensive women than in normotensive lean women (p < 0.001 and p < 0.01). Following a 100 gm glucose load, glucose and insulin concentrations were measured for a three-hour period in 26 euglycemic lean normotensive women (BMI = 21.9 ± 0.5), 27 euglycemic lean hypertensive women (BMI = 23.5 ± 0.6) and 57 lean gestational diabetic women (BMI = 23.2 ± 0.5). Hypertensive and gestational diabetic women disclosed significantly higher insulin concentration and insulin to glucose ratio than normotensive women at 2 and 3 hours (p < 0.05). These data suggest that mild hypertensive pregnant women, as obese and gestational diabetic patients, display a state of insulin resistance. 52 DOPPLER EVIDENCE OF RENAL HYPERPERF1JSION IN PRE- ECLAHPSIA. JF Smith, GJ Gilson, GO Del Valle, G Joffe, LA Izquierdo, N Chatterjee, LB Curet. University of Ne\¥ Hexico, Albuquerque, NN To further clarify the renal hemodynamic changes associated with preeclampsia, we initi- ated a prospective study of maternal renal arc- uate artery Doppler velocimetry changes associ- ated with that disease. Twelve preeclamptics were compared to 21 normotensive patients. All preeclamptics had blood pressures of at least 140/90, and proteinuria of at least 300 mgs/24 hours. Renal arcuate arteries were identified at the bases of the renal pyramids in a subcos- tal, transverse view; for consistency, the right kidney was chosen for insonation. A sample vol- ume of 3-5 mm and wall filter setting of 50 Hz was used. FINDINGS: Compared to the norr.1oten- sive patients, the preeclamptics had a signifi- cantly lower mean pulsatility index (0.89 vs 1.18, P=O.Ol) of the maternal renal arcuate artery. We have found that the increase in pulsatility index in the late third trimester that occurs in normotensive pregnancies may not occur in preeclamptics; confirmatory longitudi- nal studies are necessary. The data presented here suggests increased renal blood flow in preeclampsia and is consistent \,ith the renal hyperperfusion model for this disease.

49 Umbilical Venous Plasma Endothelin is Not Increased in Preeclampsia

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Page 1: 49 Umbilical Venous Plasma Endothelin is Not Increased in Preeclampsia

Volume 166 :\lumber 1, Part 2

49 UMBILICAL VENOUS PLASMA ENDOTIIEUN IS Naf INCREASED IN PREECLAMPSIA. A.Nova.x J. Barton.x M.D. Mitchell. B.M. Mercer. xB.M. Sibai. University of Tennessee, Memphis. and University of Utah. Salt Lake City.

Plasma endothelin (ET) levels are usually increased in conditions characterized by endothelial damage and local tissue hypoxia. We previously reported that women with preeclampsia, particularly those with HELLP syndrome. have significantly higher endothelin levels than women with normotensive pregnancies. The purpose of this investigation is to compare umbilical vein plasma ET levels in preeclampsia and normotensive pregnancies. Methods: The study population included 7 women with preeclampsia and 12 with normotensive pregnancies. All hut one woman delivered vaginally at term. Samples were collected immediately after cord clamping using cold vacutainer tubes containing EDT A and aprotinin. The blood was immediately cold centrifuged and plasma fraction was then stored at -70·c. Plasma was analyzed for endothelin using an RIA technique (Amersham Corp.). Results: As expected. preeclamptic women had significantly higher systolic blood pressures (152 ± 13 v 118 ± 10 mmHg. p < 0.0001) and higher diastolic pressures (97 ± 9.4 v 69 ± 9.2. p < 0.0001). There were no differences between the two groups regarding either gestational age at time of delivery or cord vein ET levels (Table). However. cord blood ET levels are significantly higher than previous reported maternal levels (preeclamptics 12.87 ± 3.6 v 5.5 ± 0.3. p < 0.001 and normotensive 12.2 ± 2.7 v 3.8 ± 0.3. P < 0.0001). Conclusions: Fetal secretion of ET is not increased in preeclampsia. The increase in umbilical ET at delivery suggests a role for ET in perinatal circulatory adaptation.

Gestational age (wk) Umbilical vein ET (fmole/ml)

Preeclampsia n=7

37.7 2.6 12.87 3.62

Normotensive n= 12

39.0 1.5 12.21 2.69

50 LOW-DOSE ASPIRIN (ASA) INHIBITS LIPID PEROXIDES (LPO) AND THROMBOXANE (TX). BUT NOT PROSTACYCLIN (PGI). IN PREGNANT WOMEN. SW Walsh,' Y Wang,' HH Kay. MC McCoy: Depts OB/GYN. Medical College of Virginia. Richmond. VA and Duke Univ .. Durham, NC

Preeclampsia is associated with an imbalance of increased TX and decreased PGl, and recently reported an abnormal increase of LPO (AJOG. Dec.. 1991). LPO are toxic compounds that damage cells and inhibit PGI synthesis. Low· dose ASA therapy reduces the incidence of preeclampsia, presumably by selective inhibition of TX to restore a balance between TX and PGI. However. the effectiveness of low-dose ASA might also relate to inhibition of LPO. To test this, 10 women at risk of preeclampsia were placed on low-dose ASA therapy (81 mg/day) between 19·33 wks of gestation. Plasma samples were collected before ASA and after 3-4 days and 3-4 wks of ASA. Samples were analyzed for TX and PGI by RIA of their stable metabolites. TXB2 and 6-keto PGF, •• and for LPO by H20 2 equivalents. Low-dose ASA significantly decreased (P<0.05) both LPO (130 ± 18 vs 92 ± 11 and 68 ± 9 nmolj mI. mean ± SE) and TX (502 ± 67 vs. 138 ± 67 and 8 ± 5 pg/ml). but it did not affect PGI (55 ± 10 vs 41 ± 8 and 40 ±

11 pg/ml). Conclusion: LOW-dose ASA selectively inhibits both LPO and TX without affecting PGI. Speculation: This selective inhibitory action of low-dose ASA may account for its effectiveness in the prevention of preeclampsia. HD 20973.

SPO Abstracts 295

51 INSULIN CONCENTRATIONS IN CHRONIC HYPERTENSIVE PREGNANT WOMEN. E. Rey,' A. Bonin,' Dept. Ob/Gyn. Sainte­Justine Hospital. Montreal (Quebec), Canada.

In order to investigate the state of insulin resistance of chronic hypertensive pregnant women, we studied glucose and insulin responses to oral glucose loads in these patients. Chronic hypertension was defined as essential hypertension known before pregnancy. Gestational diabetic and treated chronic hypertensive women were excluded. Serum capillary glucose was determined by the glucose oxidase method and insulin levels by radio-immunoassay. One hundred and forty-seven (147) euglycemic lean normotensive pregnant women (Body mass index (BMI) = 21.8 ± 0.2), 30 euglycemic obese normotensive pregnant women (BMI = 32.5 ± 1.0) and 25 euglycemic lean chronic hypertensive pregnant women (BMI = 23.7 ± 0.6) received a 50 gm oral glucose load. Insulin levels and insulin to glucose ratio at one hour were significantly higher in normotensive obese and hypertensive women than in normotensive lean women (p < 0.001 and p < 0.01). Following a 100 gm glucose load, glucose and insulin concentrations were measured for a three-hour period in 26 euglycemic lean normotensive women (BMI = 21.9 ± 0.5), 27 euglycemic lean hypertensive women (BMI = 23.5 ± 0.6) and 57 lean gestational diabetic women (BMI = 23.2 ± 0.5). Hypertensive and gestational diabetic women disclosed significantly higher insulin concentration and insulin to glucose ratio than normotensive women at 2 and 3 hours (p < 0.05). These data suggest that mild hypertensive pregnant women, as obese and gestational diabetic patients, display a state of insulin resistance.

52 DOPPLER EVIDENCE OF RENAL HYPERPERF1JSION IN PRE­ECLAHPSIA. JF Smith, GJ Gilson, GO Del Valle, G Joffe, LA Izquierdo, N Chatterjee, LB Curet. University of Ne\¥ Hexico, Albuquerque, NN

To further clarify the renal hemodynamic changes associated with preeclampsia, we initi­ated a prospective study of maternal renal arc­uate artery Doppler velocimetry changes associ­ated with that disease. Twelve preeclamptics were compared to 21 normotensive patients. All preeclamptics had blood pressures of at least 140/90, and proteinuria of at least 300 mgs/24 hours. Renal arcuate arteries were identified at the bases of the renal pyramids in a subcos­tal, transverse view; for consistency, the right kidney was chosen for insonation. A sample vol­ume of 3-5 mm and wall filter setting of 50 Hz was used. FINDINGS: Compared to the norr.1oten­sive patients, the preeclamptics had a signifi­cantly lower mean pulsatility index (0.89 vs 1.18, P=O.Ol) of the maternal renal arcuate artery. We have found that the increase in pulsatility index in the late third trimester that occurs in normotensive pregnancies may not occur in preeclamptics; confirmatory longitudi­nal studies are necessary. The data presented here suggests increased renal blood flow in preeclampsia and is consistent \,ith the renal hyperperfusion model for this disease.