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81 Maternal plasma endothelin is increased in preeclampsia
SPO Abstracts
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81 MATERNAL PLASMA ENDOTHELIN IS INCREASED IN PREECLAMPSIA. A1:I2l£a"" BM Sibai" JR Barton"" R Romero 3, U Bellati: 8M Mercer"" MD Mitchell"2, U. of TN, Memphis" U. of Utah, Salt lake City2, Yale University, New Haven, c"(l. Endothelln is the most potent known vasoconstrictor and IS reportedly increased in srtuations of endothelial damage. Since endothehal damage may playa central role in the pathophysiology of preeclampsia, we investigated the maternal plasma endothelin In preeclamptic and normotensive pregnant women. METHODS: The study population included 27 women with demonstrated preeclampsia (22 with preeclampsia, 1 eclampsia and 4 with HEllP syndrome) and 14 normotensive gravidas who served as controls. Samples were collected in the third trimester using cold vacutainer tubes containing EDTA and aprotinin. The blood was cold centr~uged and immediately the plasma Iraction was stored at -70" centigrade. Plasma was analyzed lor endothelin using a radioimmunoassay technique (Amersham Corp.) RESULTS: There was no difference in gestational age between the 2 groups. Plasma endothehn levels expressed as mean ± SEM were significantly higher in the preeclampsia group (Table). There was no correlation between maternal plasma endothelin levels and the severity of hypertension. However, preeclamptic women with HEllP syndrome had a signilicantly higher level of endothelin (p<0.05) than those without HEllP. CONCLUSIONS: These preliminary resu~s indicate that endothelin is increased in the plasma of preeclamptic women. There is no direct correlation of severity of hypertension and the level of endothelin in the preeclamptic patient. The increase is more prolound in patients with HEllP syndrome suggesting widespread endothelial damage in this group. PREECLAMPSIA 5.48 ± 0 3. 0 I mole/ml "P
83 ELEVATED PLASMA CELLULAR FIBRONECTIN
82 INCREASES IN PLASMA ATRIAL NATRIURETIC PEPTIDE CONCENTRATION ANTEDATE CLINICAL EVIDENCE OF PREECLAMPSIA. MP Malee MD, PhD*; RN Taylor, MD, PhD*; JM Roberts , MD. Department ofOb/Gyn & Reproductive Sciences, UCSF, San Francisco, CA. Atrial natriuretic peptide (ANP) concentrations are typically elevated in volume overload states. However, increased ANP levels have been reported III peripartum preeclampsia, a disorder characterized by central hypovolemia . We hypothesized that ANP levels arc elevated in preeclamptic patients prior to clinically evident disease. ANP concentrations were determined in three groups : uncomplicated pregnancies (UC, n=10); pregnancies complicated by preeclampsia (PE, n=10) ; and nonpregnant, reproductive-aged women (NP, n=10). The former groups were matched for nulliparity and gestational ages at plasma sampling and delivery. Plasma samples obtained prospectively from each patient during the lst, 2nd and 3rd trimester (T), and within 72 hours postpartum (PP) were fro zen prior to RIA . Results are given as the means ± SEM for each group. ANP(pg/ml) PP lslT 2nd T 3rd T (37±1 wks) (9±1 wks) (23±1 wks) « 72 hrs) UC 12.1 ±0.9 14.2±0.5 10.9±1.1 17.0±1.3 PE 31.0±4.3 21.8±2.8 12.9±0.9 18.5 ±3 .4 NP 14.2±l.S Significant longitudinal increases in ANP were noted in both pregnancy groups , with 3rd T> lst T levels; PP levels were greater than alI antepartum levels in the UC but not PE group (P
84 AN ASSOCIATION BETWEEN HLA ANTIGENS AND PREECLAMPSIA IN A BLACK POPULATION: A PILOT STUDY. Kee-Hak Lim ,
CONCENTRATIONS IN PREECLAMPSIA CANNOT BE ATTRIBUTED TO HYPERTENSION ALONE, Steven A Friedman MD,' Robert N. Taylor, MD, PhD,' William R, Crombleholme, MD, Lynn A. Jones, MS ,' David C . Casal, PhD,' James M. Roberts, MD. Department of OB/GYN & Reprod. Sci. and Cardiovascular Research Institute, UCSF, San FranCISco, California; and Adeza Biomedical, Sunnyvale, California Numerous studies support the hypothesi s that matern al endothelial cell \Djury is a central pathogenetic feature of preeclampsia [PEl. Evidence of such injury is provided, in part, by elevations in preeclamptic women of plasma cellular fibronec tin [cFN1, an isoform of fibronectin which IS synthesized by endothelial cells. In order to investigate whether elevated cFN is the result of hypertension or of some other feature present in PE, we have measured cFN concentrations prospectively in three carefully selected groups of nulliparae delivered at term. Nineteen women with strictly defined PE (late-onset hypertension, protein una, and hyperuricemia) and 20 women with transient hypertension [THl (late-onset hypertension alone) were compared with 20 normotensive controls [NC1. Plasma samples obtained after the onset of clinical disease and before delivery were assayed for cFN using a sensitive and specific ELISA, Results are expressed as means ± SE and were analyzed by one-way ANOV A with Scheffe's comparisons.
NC.
cFN (I-lg/ml) 3.5 ± 0.4 MAP (mm Hg) 84 ± 2
~
* 9.8 ± 1.0
* 108 ± 2
ill
baI.u.e < .001 * 108 ± 3 < .001 3.7 ± 0.7
We conclude that elevated blood pressure per se is not responsible for the increased plasma cFN concentrations in PE. These data provide additional evidence that PE is more than just pregnancyinduced hypertension.
M..Q.! Thomas C. C, Peng, M,D,! Steven A. Friedman, M.D . ! John T. Queenan, Jr., M,D .,x Lisa L. Paine, C.N.M" Dr.P,H"x John T, Repke, M .D . The Johns Hopkins Medical Institutions , Baltimore, Maryland 21205 We have obtained HLA A, B, C, and DR tissue typing in five black preeclamptic patients and their newborns . Eight normotensive, healthy black patients and their newborns served as controls, This prospective study was designed as a pilot investigation for a larger study. Four out of five preeclamptic patients had infants with the DR2 phenotype , One preeclamptic patient's infant was DR2 negative. In the control group, only one out of eight patients had an infant that was positive for the DR2 antigen. Using Fisher's Exact Test, this difference in the frequency of the DR2 phenotype between control infants and infants of preeclamptic women is significant (P=0 .03). In addition , we have not noted increased HLA antigen sharing between preeclamptic mothers and their infants. This observation is consistent with the growing body of evidence suggesting a possible association between an HLA antigen and preeclampsia. A larger study is warranted to verify the association between the HLA DR2 antigen and preeclampsia described above.
Volu m e lfi.j,
l'\umber l, Part
271
~
81 MATERNAL PLASMA ENDOTHELIN IS INCREASED IN PREECLAMPSIA. A1:I2l£a"" BM Sibai" JR Barton"" R Romero 3, U Bellati: 8M Mercer"" MD Mitchell"2, U. of TN, Memphis" U. of Utah, Salt lake City2, Yale University, New Haven, c"(l. Endothelln is the most potent known vasoconstrictor and IS reportedly increased in srtuations of endothelial damage. Since endothehal damage may playa central role in the pathophysiology of preeclampsia, we investigated the maternal plasma endothelin In preeclamptic and normotensive pregnant women. METHODS: The study population included 27 women with demonstrated preeclampsia (22 with preeclampsia, 1 eclampsia and 4 with HEllP syndrome) and 14 normotensive gravidas who served as controls. Samples were collected in the third trimester using cold vacutainer tubes containing EDTA and aprotinin. The blood was cold centr~uged and immediately the plasma Iraction was stored at -70" centigrade. Plasma was analyzed lor endothelin using a radioimmunoassay technique (Amersham Corp.) RESULTS: There was no difference in gestational age between the 2 groups. Plasma endothehn levels expressed as mean ± SEM were significantly higher in the preeclampsia group (Table). There was no correlation between maternal plasma endothelin levels and the severity of hypertension. However, preeclamptic women with HEllP syndrome had a signilicantly higher level of endothelin (p<0.05) than those without HEllP. CONCLUSIONS: These preliminary resu~s indicate that endothelin is increased in the plasma of preeclamptic women. There is no direct correlation of severity of hypertension and the level of endothelin in the preeclamptic patient. The increase is more prolound in patients with HEllP syndrome suggesting widespread endothelial damage in this group. PREECLAMPSIA 5.48 ± 0 3. 0 I mole/ml "P
83 ELEVATED PLASMA CELLULAR FIBRONECTIN
82 INCREASES IN PLASMA ATRIAL NATRIURETIC PEPTIDE CONCENTRATION ANTEDATE CLINICAL EVIDENCE OF PREECLAMPSIA. MP Malee MD, PhD*; RN Taylor, MD, PhD*; JM Roberts , MD. Department ofOb/Gyn & Reproductive Sciences, UCSF, San Francisco, CA. Atrial natriuretic peptide (ANP) concentrations are typically elevated in volume overload states. However, increased ANP levels have been reported III peripartum preeclampsia, a disorder characterized by central hypovolemia . We hypothesized that ANP levels arc elevated in preeclamptic patients prior to clinically evident disease. ANP concentrations were determined in three groups : uncomplicated pregnancies (UC, n=10); pregnancies complicated by preeclampsia (PE, n=10) ; and nonpregnant, reproductive-aged women (NP, n=10). The former groups were matched for nulliparity and gestational ages at plasma sampling and delivery. Plasma samples obtained prospectively from each patient during the lst, 2nd and 3rd trimester (T), and within 72 hours postpartum (PP) were fro zen prior to RIA . Results are given as the means ± SEM for each group. ANP(pg/ml) PP lslT 2nd T 3rd T (37±1 wks) (9±1 wks) (23±1 wks) « 72 hrs) UC 12.1 ±0.9 14.2±0.5 10.9±1.1 17.0±1.3 PE 31.0±4.3 21.8±2.8 12.9±0.9 18.5 ±3 .4 NP 14.2±l.S Significant longitudinal increases in ANP were noted in both pregnancy groups , with 3rd T> lst T levels; PP levels were greater than alI antepartum levels in the UC but not PE group (P
84 AN ASSOCIATION BETWEEN HLA ANTIGENS AND PREECLAMPSIA IN A BLACK POPULATION: A PILOT STUDY. Kee-Hak Lim ,
CONCENTRATIONS IN PREECLAMPSIA CANNOT BE ATTRIBUTED TO HYPERTENSION ALONE, Steven A Friedman MD,' Robert N. Taylor, MD, PhD,' William R, Crombleholme, MD, Lynn A. Jones, MS ,' David C . Casal, PhD,' James M. Roberts, MD. Department of OB/GYN & Reprod. Sci. and Cardiovascular Research Institute, UCSF, San FranCISco, California; and Adeza Biomedical, Sunnyvale, California Numerous studies support the hypothesi s that matern al endothelial cell \Djury is a central pathogenetic feature of preeclampsia [PEl. Evidence of such injury is provided, in part, by elevations in preeclamptic women of plasma cellular fibronec tin [cFN1, an isoform of fibronectin which IS synthesized by endothelial cells. In order to investigate whether elevated cFN is the result of hypertension or of some other feature present in PE, we have measured cFN concentrations prospectively in three carefully selected groups of nulliparae delivered at term. Nineteen women with strictly defined PE (late-onset hypertension, protein una, and hyperuricemia) and 20 women with transient hypertension [THl (late-onset hypertension alone) were compared with 20 normotensive controls [NC1. Plasma samples obtained after the onset of clinical disease and before delivery were assayed for cFN using a sensitive and specific ELISA, Results are expressed as means ± SE and were analyzed by one-way ANOV A with Scheffe's comparisons.
NC.
cFN (I-lg/ml) 3.5 ± 0.4 MAP (mm Hg) 84 ± 2
~
* 9.8 ± 1.0
* 108 ± 2
ill
baI.u.e < .001 * 108 ± 3 < .001 3.7 ± 0.7
We conclude that elevated blood pressure per se is not responsible for the increased plasma cFN concentrations in PE. These data provide additional evidence that PE is more than just pregnancyinduced hypertension.
M..Q.! Thomas C. C, Peng, M,D,! Steven A. Friedman, M.D . ! John T. Queenan, Jr., M,D .,x Lisa L. Paine, C.N.M" Dr.P,H"x John T, Repke, M .D . The Johns Hopkins Medical Institutions , Baltimore, Maryland 21205 We have obtained HLA A, B, C, and DR tissue typing in five black preeclamptic patients and their newborns . Eight normotensive, healthy black patients and their newborns served as controls, This prospective study was designed as a pilot investigation for a larger study. Four out of five preeclamptic patients had infants with the DR2 phenotype , One preeclamptic patient's infant was DR2 negative. In the control group, only one out of eight patients had an infant that was positive for the DR2 antigen. Using Fisher's Exact Test, this difference in the frequency of the DR2 phenotype between control infants and infants of preeclamptic women is significant (P=0 .03). In addition , we have not noted increased HLA antigen sharing between preeclamptic mothers and their infants. This observation is consistent with the growing body of evidence suggesting a possible association between an HLA antigen and preeclampsia. A larger study is warranted to verify the association between the HLA DR2 antigen and preeclampsia described above.