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Vo lume 164 N umhe r 1 , Pall 89 A LONGITUDINAL STUDY OF ATRIAL NATRIURETIC FACTOR, PLASMA RENIN ACTIVITY, AND ALDOSTERONE IN NORMAL AND PREECLAMPTIC PREGNANCIES Glenn Merkenson, M.D.1, Jerome N Kopelman, M.D., Beau Freund CPT MSC', John R. Claybaugh PhD1, P. H. Yamamoto RN1, G.M. Hashlro1. Tripler Army Medical Center, Honolulu, Hawaii Clinical data concerning atrial natriuretic hormona (ANF) in pregnancy is conflicting, with soma investigators reporting increases during pregnancy, while others heving found no change. Recent studies indicate preeclamptic pregnancies are associatad wlth elevated levels of ANF, elthough it is uncertain when this increase occurs. The purpose of this investiga- tlon was to serially assay, levals of ANF, aldoster- one (ALDO), and plesme renin activity (PRA), in pregnancies at risk for preeclampsia. Longitudinal data was obtained in 42 pregnancies, 7 of which developed preeclampsia. ANF valuas did not change during the course of the non-preeclamptic pregnan- cies. ANF values did increesa significantly in the preeclamptic pragnancies, prior to the clinical diagnosis of preeclampsia. ALOO and PRA values in both the preeclamptic and non-preaclamptic pregnan- cies were consistent with previous published reports. Therefore, ANF assays may provlde a tool to detect the development of preeclampsia in patients at risk for this disorder. 90 OXYGEN FREE RADIfALS IN * Dekker GA NO PhD , Kraayenbrl.nk AA NO Dep. of Obstetrics Free University Hospital Amsterdam The Netherlands. Immunologic mechanism have been suggested to play a role in the etiology of preeclampsia. Oxygen (0 2 ) free radicals and lipid peroxidation might be the link between the hypothetical immu- nologic mechanisms and the disturbance of endo- thelial physiology known to occur in preeclamp- sia. To determine if 02 free radicals are in- volved in the pathophysiology of preeclampsia we studied lipid peroxides, plasma fibronectin levels, and erythrocyte glutathione peroxidase (GSHPx) activity in 28 pregnant women, 14 pre- eclamptic patients and 14 normotensive women. Lipid peroxides were increased in preeclamptic patients (mean 1.7, SO 0.27 nm/ml) as compared to normotensive pregnancies (mean 1.0, SO 0.2). In preeclampsia fibronectin levels were eleva- ted (mean 690 mgll, range 434-1500 mg/l) as com- pared to normotensive pregnancy (mean 282.5 mgll, range 172-366 mg/l). Fibronectin levels showed a correlation with lipid peroxide levels. In preeclampsia GSHPx activity was higher (mean 6.71, SO 1.26 Ulg Hb) as compared to normoten- sive pregnancy (mean 5.92 SO 0.9). These results show that 02 free radical formation is increased in preeclampsia. The increase in lipid peroxi- dation may be involved in causing endothelial injury as shown to occur by the increase in fibronectin levels. Longitudinal studies are needed to support or refute the hypothesis that an increase in O 2 free radical production, is involved in the etiology of preeclampsia. SPO Abstracts 273 91 MAGNESIUM SULFATE VS. PHENYfOIN IN PREGNANCY INDUCED HYPERTENSION - PREUMINARY REPORT M Appleton MD", T Kuehl PhD", M Raebel PharmD", H Adams PhD", J Pickens MD", B Koops MD", A Knight MD, W Gold MD", Texas A&M University, Scott & White Memorial Hospital, Temple, Texas 76508 Issues of fetal safety, maternal tolerance of side effects, labor outcome and phenytoin levels were evaluated in a randomized clinical trial with the hypothesis that no difference would be found. Patients assigned to MgS04 (N=21) received standard therapy. Patients received phenytoin (N = 16) according to the schedule of Ryan et al. Neonatal evaluation included Brazleton neurologic assessment. Mothers and their primary nurses were asked to numerically rank the degree to which they experienced nausea, emesis, visual disturbance, drowsiness, and slurred speech. Groups did not differ clinically. MgS04 Phenytoin ]st/2nd stages (hrs) 14.4/0.5 10.5/0.6 C-section 5121 2/ 16 Dose to Delivery (hrs) 15.7 12 4 Hospital stay (days) 3 .6 2 .7 Apgars (1/5 min) 719 719 Cord pHIBE 7.26/-4.09 7.25/ -2.88 Brazleton score no difference MaternaVNurse survey 23 .9 19.9 Conclusion: 1) No adverse outcomes or neonatal depression were seen. 2) Free phenytOin levels more accurately reflected drug activity. 3) No difference in any outcome parameters was observed. 92 INFANT RENAL FAILURE WITH MATERNAL ACE INHIBITION. Rosa. F. *, Bosco, L. * Food and Drug Administration , Rockville, Md 29 perinatal renal failures with mat- ernal angiotensin converting enzyme (ACE) inhibition are listed by the FDA . 15 were domestic and 14 foreign. 18 were on enalapril, 9 on captopril, and 2 on lisinopril . Two oligohydramios cases subsided when exposure was stopped before delivery and one was stillborn. Monito r- ing amniotic fluid volume may be useful to detect problem onset . FDA has only 4 perinatal renal failure reports with other antihypertensive agents, when ACE inhibition was not used also. Thirteen cases were fatal (12 apparently from renal failure), 9 had overt recovery, and renal manifestations persisted at the time of last report in 8. As 95% of active metab- olites are ordinarily disposed of by renal ex cretion, effects are prolonged unless dialysis is done. Only 2 deaths occured among dialyzed cases. Oligohydramnios sequelae were respiratory hypoplasia and contractures. Limited cohort experience is availble to quantitate risks .

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Page 1: 90 Oxygen free radicals in preeclampsia

Volume 164 Numher 1 , Pall ~

89 A LONGITUDINAL STUDY OF ATRIAL NATRIURETIC FACTOR, PLASMA RENIN ACTIVITY, AND ALDOSTERONE IN NORMAL AND PREECLAMPTIC PREGNANCIES Glenn Merkenson, M.D.1, Jerome N Kopelman, M.D., Beau Freund CPT MSC', John R. Claybaugh PhD1, P. H. Yamamoto RN1, G.M. Hashlro1. Tripler Army Medical Center, Honolulu, Hawaii

Clinical data concerning atrial natriuretic hormona (ANF) in pregnancy is conflicting, with soma investigators reporting increases during pregnancy, while others heving found no change. Recent studies indicate preeclamptic pregnancies are associatad wlth elevated levels of ANF, elthough it is uncertain when this increase occurs. The purpose of this investiga­tlon was to serially assay, levals of ANF, aldoster­one (ALDO), and plesme renin activity (PRA), in pregnancies at risk for preeclampsia. Longitudinal data was obtained in 42 pregnancies, 7 of which developed preeclampsia. ANF valuas did not change during the course of the non-preeclamptic pregnan­cies. ANF values did increesa significantly in the preeclamptic pragnancies, prior to the clinical diagnosis of preeclampsia. ALOO and PRA values in both the preeclamptic and non-preaclamptic pregnan­cies were consistent with previous published reports. Therefore, ANF assays may provlde a tool to detect the development of preeclampsia in patients at risk for this disorder.

90 OXYGEN FREE RADIfALS IN PREE~SIA * Dekker GA NO PhD , Kraayenbrl.nk AA NO Dep. of Obstetrics Free University Hospital Amsterdam The Netherlands.

Immunologic mechanism have been suggested to play a role in the etiology of preeclampsia. Oxygen (02) free radicals and lipid peroxidation might be the link between the hypothetical immu­nologic mechanisms and the disturbance of endo­thelial physiology known to occur in preeclamp­sia. To determine if 02 free radicals are in­volved in the pathophysiology of preeclampsia we studied lipid peroxides, plasma fibronectin levels, and erythrocyte glutathione peroxidase (GSHPx) activity in 28 pregnant women, 14 pre­eclamptic patients and 14 normotensive women. Lipid peroxides were increased in preeclamptic patients (mean 1.7, SO 0.27 nm/ml) as compared to normotensive pregnancies (mean 1.0, SO 0.2). In preeclampsia fibronectin levels were eleva­ted (mean 690 mgll, range 434-1500 mg/l) as com­pared to normotensive pregnancy (mean 282.5 mgll, range 172-366 mg/l). Fibronectin levels showed a correlation with lipid peroxide levels. In preeclampsia GSHPx activity was higher (mean 6.71, SO 1.26 Ulg Hb) as compared to normoten­sive pregnancy (mean 5.92 SO 0.9). These results show that 02 free radical formation is increased in preeclampsia. The increase in lipid peroxi­dation may be involved in causing endothelial injury as shown to occur by the increase in fibronectin levels. Longitudinal studies are needed to support or refute the hypothesis that an increase in O2 free radical production, is involved in the etiology of preeclampsia.

SPO Abstracts 273

91 MAGNESIUM SULFATE VS. PHENYfOIN IN PREGNANCY INDUCED HYPERTENSION - PREUMINARY REPORT M Appleton MD", T Kuehl PhD", M Raebel PharmD", H Adams PhD", J Pickens MD", B Koops MD", A Knight MD, W Gold MD", Texas A&M University, Scott & White Memorial Hospital, Temple, Texas 76508

Issues of fetal safety, maternal tolerance of side effects, labor outcome and phenytoin levels were evaluated in a randomized clinical trial with the hypothesis that no difference would be found. Patients assigned to MgS04 (N=21) received standard therapy. Patients received phenytoin (N = 16) according to the schedule of Ryan et al. Neonatal evaluation included Brazleton neurologic assessment. Mothers and their primary nurses were asked to numerically rank the degree to which they experienced nausea, emesis, visual disturbance, drowsiness, and slurred speech. Groups did not differ clinically.

MgS04 Phenytoin ]st/2nd stages (hrs) 14.4/0.5 10.5/0.6 C-section 5121 2/16 Dose to Delivery (hrs) 15 .7 12 4 Hospital stay (days) 3 .6 2 .7 Apgars (1/5 min) 719 719 Cord pHIBE 7 .26/-4.09 7 .25/-2.88 Brazleton score no difference MaternaVNurse survey 23.9 19.9 Conclusion: 1) No adverse outcomes or neonatal depression were seen. 2) Free phenytOin levels more accurately reflected drug activity. 3) No difference in any outcome parameters was observed.

92 INFANT RENAL FAILURE WITH MATERNAL ACE INHIBITION. Rosa. F.*, Bosco, L.* Food and Drug Administration , Rockville, Md

29 perinatal renal failures with mat­ernal angiotensin converting enzyme (ACE) inhibition are listed by the FDA . 15 were domestic and 14 foreign. 18 were on enalapril, 9 on captopril, and 2 on lisinopril . Two oligohydramios cases subsided when exposure was stopped before delivery and one was stillborn. Monitor­ing amniotic fluid volume may be useful to detect problem onset . FDA has only 4 perinatal renal failure reports with other antihypertensive agents, when ACE inhibition was not used also. Thirteen cases were fatal (12 apparently from renal failure), 9 had overt recovery, and renal manifestations persisted at the time of last report in 8. As 95% of active metab­olites are ordinarily disposed of by renal excretion, effects are prolonged unless dialysis is done. Only 2 deaths occured among dialyzed cases. Oligohydramnios sequelae were respiratory hypoplasia and contractures. Limited cohort experience is availble to quantitate risks .