- Email: [email protected]
422 The Effect of Third Trimester Estradiol and Progesterone Levels on Endothelial Cell Prostacyclin Production
SPO Abstracts
Volume 168 l'
421
THE EFFECT OF SECOND TRIMESTER LIPID COMPOSITION ON ENDOTHELIAL CELL PROSTACYCLIN PRODUCTION. "T. O'Leary, W. O'Brien, 'J. Krammer, Dept. Ob/Gyn, Univ. S. Florida, Tampa, Florida OBJECTIVE: Prostacyclin (PG I.) Is an Important prostanoid produced by vascular endothelium with vasodilatory and antiaggregatory properties. Pregnancy is associated with an increase in PG 12 production and this may account for some of the vasodilation associated with pregnancy. Women with preeclampsia demonstrate a deficiency in PG 12 production with a resultant imbalance in the prostacyclin/lhromboxane ratio leading to increased platelet aggregation. Recent studies have suggested that sera from women with preeclampsia can result in endothelial cell dysfunction and consequent deficient PG 12 production. Since pregnancy results in significant alterations in serum lipid concentrations, we sought to investigate the role of lipid composition on in vitro endothelial cell PG 12 production. STUDY DESIGN: Cultured endothelial cells were incubated with medium containing 20% pooled serum from second trimester pregnant women (MS), 20% fetal bovine serum (FBS), or 20% FBS with addition of 100 I'M arachidonic acid (M). Following incubation for 24 hours the concentration of the PG 12 metabolite 6-keto-PG Fla was determined by RIA and lipid concentrations by gas chromatography. RESULTS: Endothelial cells incubated with pooled maternal serum significantly increased prostacyclin production over controls (FBS = 167 pg/O.l ml, MS = 301 pg/O.l ml). Endothelial cells incubated with M raised PG 12 production to > 1000 pg/O.l mi. These were revealed virtually identical concentrations of arachidonic acid in the pooled maternal serum samples and the added arachidonic acid media (MS = 0.95 mgldl, M acid = 0.97 mgldl, FBS = 0.42 mg/dl) as compared to control. CONCLUSION: Pooled second trimester maternal serum stimulates PG 12 production by endothelial cells and appears to do so by providing an Increased amount of substrate. This clearly is not the only important factor in PG 12 synthesis. Cell dysfunction and deficient PG 12 production in preeclampsia may be secondary to aberrations of fatty acid metabolism.
423 PER.IPARroM
422
THE EFFECT OF THIRD TRIMESTER ESTRADIOL AND PROGESTERONE LEVELS ON ENDOTHELIAL CELL PROSTACYCLIN PRODUCTION. 'T. O'Leary, W. O'Brien, 'J. Krammer, Dept. Ob/Gyn, Univ. S. Florida, Tampa, Florida. OBJECTIVE: Prostacyclin (PG I.) is an important prostanoid produced by the vascular endothelium with vasodilatory and antiaggregatory properties. The effects of estrogen, both positive and negative, on the cardiovascular system are well known. Pregnancy is associated with very high levels of estrogen and significantly increased PG 12 production. We sought to investigate this association by determining the effect of term pregnancy levels of estrogen and progesterone on in vitro endothelial cell PG 12 production. STUDY DESIGN: Cultured human endothelial cells were incubated with 20% fetal bovine serum (FBS)along, FBS plus estradiol at 25 nglml or 50 nglml, FBS plus progesterone at 100 nglml or 200 nglml, and FBS plus E2 + Prog in combination. Following incubations x 24 hours, the concentration of 6-keto-PG Fla was determined by RIA. RESULTS: There were no significant differences seen in PG 12 production with the addition of estradiol or progesterone Mean 6-keto-PG Fla concentrations in pg/O.l ml were: E2 25 nglml 147 E2 50 nglml 160 p. 100 nglml 181 p. 200 nglml 141 Control 148
424 PREGNANCY OUTCOME IN PATIENTS WITH
CONCLUSION: The high levels of estradiol and progesterone found during pregnancy do not appear to be directly responsible for the increase in endothelial cell PG 12 production or the consequent vasodilation observed in the normal gravid state.
CARDIOMYOPA11IY: AN UNPREDlCfABLE COMPLICATION OF PREGNANCY. B. Rosenn. M. Mlodovnik, S. Cox, C.A. Combs, T.A. Siddiqi. DepL Ob,'Gyn, Unlv. or Cinti~ CincinnatI, on. OBJECTIVE: Peripartum cardiomyopathy (PPCM) is classically described as a postpartum complication affecting older, multiparous, Black women. The purpose of this report is to describe our experience with PPCM which has been different than this classical description and to identify indicators of prognostiC value. SroDY DESIGN: The charts of all patients at our institution with a diagnosis of PPCM from 1979-1988 were reviewed. RESULTS: Twelve women were diagnosed with PPCM; 3 presented antepartum and 5 presented within a month after delivery. Ave women had a viral prodrome during the month preceding the diagnosis. Six of the women were Black, and 6 were White. Ave women were under 25 years of age, only 3 were over 30 and 3 were primiparous. Initial evaluation included EKG, chest x-ray, and eChocardiography. Mean left ventricular end diastolic and end systolic dimensions and left ventricular ejection fractions were significantly abnormal. At 6-12 months followup, 4 women continued to have significant left ventricular dysfunction and 5 women had recovered. Three women died at 6-25 weeks after initial diagnosis. Initial echocardiographic left ventricular ejection fractions were lower and end diastolic dimensions were higher in the patients that died, although these differences did not attain statistical significance. CONCLUSION: PPCM continues to be a rare but serious complication of pregnancy with an unknown etiology and inconsistently reported risk factors. Initial echocardiographic findings may provide useful information on long-term prognosis in these patients.
MECHANICAL AORTIC VALVE REPLACEMENT: A REVIEW. C. Graves", F. Boehm, Dept. Ob/Gyn., Vanderbilt University, Nashville, TN. OBJECTIVE: Pregnancy after mechanical valve replacement has been considered hazardous secondary to maternal and fetal complications. Oral anticoagulation is contraindicated secondary to ita teratogenic effects. The purpose of the study is to review our experience from 1985 to the present with mechanical aortic valve replacement using subcutaneous Heparin as the anticoagulant. STUDY DESIGN: Seven patienta were reviewed in our institution during this time period. All of the patienta were caucasian with mean age 27 ± 3 (range 24-30). All patients had mechanical valve replacements secondary to aortic stenosis. New York Heart Association Classification ranged from Class II to Class IV. All patients had Bjork-Shivley valve replacements except for one patient with a StarrEdwards valve. In all patients Coumadin was discontinued and the patients were anticoagulated with subcutaneous Heparin to maintain a PTI' between 2-2.5 times greater than control. The Heparin was discontinued in labor. RESULTS: All pregnancies were carried to term. There were no complications at the time of delivery related to anticoagulation therapy. No valve thromboses were noted in this group. Two patients underwent cesarean section: one for an abruption, the other for PIH. All infants went to the Normal Nursery with no complications. There was one maternal death secondary to a myocardial infarction two days after delivery. CONCLUSION: Although this is a small series, we conclude that patients with mechanical valve replacement can safely be managed with subcutaneous Heparin with a low incidence of complications related to anticoagulant therapy.
413
Volume 168 l'
421
THE EFFECT OF SECOND TRIMESTER LIPID COMPOSITION ON ENDOTHELIAL CELL PROSTACYCLIN PRODUCTION. "T. O'Leary, W. O'Brien, 'J. Krammer, Dept. Ob/Gyn, Univ. S. Florida, Tampa, Florida OBJECTIVE: Prostacyclin (PG I.) Is an Important prostanoid produced by vascular endothelium with vasodilatory and antiaggregatory properties. Pregnancy is associated with an increase in PG 12 production and this may account for some of the vasodilation associated with pregnancy. Women with preeclampsia demonstrate a deficiency in PG 12 production with a resultant imbalance in the prostacyclin/lhromboxane ratio leading to increased platelet aggregation. Recent studies have suggested that sera from women with preeclampsia can result in endothelial cell dysfunction and consequent deficient PG 12 production. Since pregnancy results in significant alterations in serum lipid concentrations, we sought to investigate the role of lipid composition on in vitro endothelial cell PG 12 production. STUDY DESIGN: Cultured endothelial cells were incubated with medium containing 20% pooled serum from second trimester pregnant women (MS), 20% fetal bovine serum (FBS), or 20% FBS with addition of 100 I'M arachidonic acid (M). Following incubation for 24 hours the concentration of the PG 12 metabolite 6-keto-PG Fla was determined by RIA and lipid concentrations by gas chromatography. RESULTS: Endothelial cells incubated with pooled maternal serum significantly increased prostacyclin production over controls (FBS = 167 pg/O.l ml, MS = 301 pg/O.l ml). Endothelial cells incubated with M raised PG 12 production to > 1000 pg/O.l mi. These were revealed virtually identical concentrations of arachidonic acid in the pooled maternal serum samples and the added arachidonic acid media (MS = 0.95 mgldl, M acid = 0.97 mgldl, FBS = 0.42 mg/dl) as compared to control. CONCLUSION: Pooled second trimester maternal serum stimulates PG 12 production by endothelial cells and appears to do so by providing an Increased amount of substrate. This clearly is not the only important factor in PG 12 synthesis. Cell dysfunction and deficient PG 12 production in preeclampsia may be secondary to aberrations of fatty acid metabolism.
423 PER.IPARroM
422
THE EFFECT OF THIRD TRIMESTER ESTRADIOL AND PROGESTERONE LEVELS ON ENDOTHELIAL CELL PROSTACYCLIN PRODUCTION. 'T. O'Leary, W. O'Brien, 'J. Krammer, Dept. Ob/Gyn, Univ. S. Florida, Tampa, Florida. OBJECTIVE: Prostacyclin (PG I.) is an important prostanoid produced by the vascular endothelium with vasodilatory and antiaggregatory properties. The effects of estrogen, both positive and negative, on the cardiovascular system are well known. Pregnancy is associated with very high levels of estrogen and significantly increased PG 12 production. We sought to investigate this association by determining the effect of term pregnancy levels of estrogen and progesterone on in vitro endothelial cell PG 12 production. STUDY DESIGN: Cultured human endothelial cells were incubated with 20% fetal bovine serum (FBS)along, FBS plus estradiol at 25 nglml or 50 nglml, FBS plus progesterone at 100 nglml or 200 nglml, and FBS plus E2 + Prog in combination. Following incubations x 24 hours, the concentration of 6-keto-PG Fla was determined by RIA. RESULTS: There were no significant differences seen in PG 12 production with the addition of estradiol or progesterone Mean 6-keto-PG Fla concentrations in pg/O.l ml were: E2 25 nglml 147 E2 50 nglml 160 p. 100 nglml 181 p. 200 nglml 141 Control 148
424 PREGNANCY OUTCOME IN PATIENTS WITH
CONCLUSION: The high levels of estradiol and progesterone found during pregnancy do not appear to be directly responsible for the increase in endothelial cell PG 12 production or the consequent vasodilation observed in the normal gravid state.
CARDIOMYOPA11IY: AN UNPREDlCfABLE COMPLICATION OF PREGNANCY. B. Rosenn. M. Mlodovnik, S. Cox, C.A. Combs, T.A. Siddiqi. DepL Ob,'Gyn, Unlv. or Cinti~ CincinnatI, on. OBJECTIVE: Peripartum cardiomyopathy (PPCM) is classically described as a postpartum complication affecting older, multiparous, Black women. The purpose of this report is to describe our experience with PPCM which has been different than this classical description and to identify indicators of prognostiC value. SroDY DESIGN: The charts of all patients at our institution with a diagnosis of PPCM from 1979-1988 were reviewed. RESULTS: Twelve women were diagnosed with PPCM; 3 presented antepartum and 5 presented within a month after delivery. Ave women had a viral prodrome during the month preceding the diagnosis. Six of the women were Black, and 6 were White. Ave women were under 25 years of age, only 3 were over 30 and 3 were primiparous. Initial evaluation included EKG, chest x-ray, and eChocardiography. Mean left ventricular end diastolic and end systolic dimensions and left ventricular ejection fractions were significantly abnormal. At 6-12 months followup, 4 women continued to have significant left ventricular dysfunction and 5 women had recovered. Three women died at 6-25 weeks after initial diagnosis. Initial echocardiographic left ventricular ejection fractions were lower and end diastolic dimensions were higher in the patients that died, although these differences did not attain statistical significance. CONCLUSION: PPCM continues to be a rare but serious complication of pregnancy with an unknown etiology and inconsistently reported risk factors. Initial echocardiographic findings may provide useful information on long-term prognosis in these patients.
MECHANICAL AORTIC VALVE REPLACEMENT: A REVIEW. C. Graves", F. Boehm, Dept. Ob/Gyn., Vanderbilt University, Nashville, TN. OBJECTIVE: Pregnancy after mechanical valve replacement has been considered hazardous secondary to maternal and fetal complications. Oral anticoagulation is contraindicated secondary to ita teratogenic effects. The purpose of the study is to review our experience from 1985 to the present with mechanical aortic valve replacement using subcutaneous Heparin as the anticoagulant. STUDY DESIGN: Seven patienta were reviewed in our institution during this time period. All of the patienta were caucasian with mean age 27 ± 3 (range 24-30). All patients had mechanical valve replacements secondary to aortic stenosis. New York Heart Association Classification ranged from Class II to Class IV. All patients had Bjork-Shivley valve replacements except for one patient with a StarrEdwards valve. In all patients Coumadin was discontinued and the patients were anticoagulated with subcutaneous Heparin to maintain a PTI' between 2-2.5 times greater than control. The Heparin was discontinued in labor. RESULTS: All pregnancies were carried to term. There were no complications at the time of delivery related to anticoagulation therapy. No valve thromboses were noted in this group. Two patients underwent cesarean section: one for an abruption, the other for PIH. All infants went to the Normal Nursery with no complications. There was one maternal death secondary to a myocardial infarction two days after delivery. CONCLUSION: Although this is a small series, we conclude that patients with mechanical valve replacement can safely be managed with subcutaneous Heparin with a low incidence of complications related to anticoagulant therapy.
413