17 Magnesium Pidolate Infusion Reduces Angiotensin II Pressor Response in Pregnant Women

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280 SPO Abstracts 15 A RANDOMIZED PROSPECTIVE COMPARISON OF NIFEDIPINE AND BED REST VERSUS BED REST ALONE IN THE MANAGEMENT OF PREECLAMPSIA REMOTE FROM TERM, fl.M Sibai JR Barton X , S Akl x , C Sarinoglu X , BM Mercer x , University of Tennessee, Memphis. Two hundred primigravidas with preeclampsia (hypertension plus proteinuria) at 26-36 weeks' gestation were randomly allocated to be managed with bed rest alone or bed rest plus oral nifedipine 40- 120 mg/day. All women had baseline and serial evaluations of maternal and fetal well being. Following hospitalization, patients with adequate blood pressure response and absent proteinuria «300 mg/24 hr) were subsequently managed on an outpatient basis. There were no differences between the two groups in mean systolic and diastolic blood pressures at time of randomization, however, the nifedipine group had significantly lower systolic (p<O.OOOI) and diastolic (p< 0.0001) blood pressures during therapy. There were no differences in number of days of antepartum maternal hospitalization (12.6 ± 7.9 v 12.3 ± 10.3). Table compares the clinical findings in 197 patients (3 were lost to follow-up). The two groups had similar incidences of abruptio placentae (2% v 3%) and HELLP syndrome (2% v 4%). There were no perinatal deaths in either group and no differences in cord gasses between groups. Conclusions: Nifedipine therapy for preeclampsia significantly reduces maternal blood pressure but does not shorten maternal hospitalization or improve perinatal outcome. Mean + SO Control In = 99) Njfedjpjne In - 98) Admission gest age (wks) 33.5 ± 2.3 32.9 ± 2.6 Pregnancy prolongation (days) 22.3 ± 13.5 22.5 ± 15.7 Delivery for severe HTN # (%) "18 (18) 9 (9) Delivered 2: 37 wk # (%) 60 (60) 50 (51) Birth weight (grams) 2509 ± 728 2403 ± 769 IUGR#(%) 13(13) 15(15) Cord pH < 7.20 11(13) 9 (10) Admitted to SeN # (%) 21 (21) 30 (30) SCN = Special Care Nursery, HTN = hypertension, "P < 0.05 16 MAGNESIUM SULFATE INJECTIONS BLOCK NMDA-INDUCED HIPPOCAMPAL SEIZURES_ D.B. Cotton, R.F. Berman: S. Irtenkauf,' Dept_ Ob/Gyn, Wayne State Univ.lHutzel Hasp., Detroit, MI The use of magnesium sulfate in the treatment of seizures and convulsions associated with preeclampsia-eclampsia is well established. However, the mechanism by which magnesium blocks seizures is unknown. Recent evidence has suggested that activation of excitatory amino acid receptors, such as the N- methyl-D-aspartate (NMDA) receptor, can result in seizures and that these receptors are blocked in a voltage dependent manner by magnesium. Thus magnesium sulfate injections may inhibit seizures directly via a magnesium-induced block of NMDA receptors. As a test of this hypothesis, we examined the ability of intraperitoneal injections of magnesium sulfate to block seizures produced by direct injections of 20 j.Jg of NMDA into the dorsal hippocampus of rats, a region enriched in NMDA receptors. NMDA injections into the hippocampus resulted in almost immediate epileptiform activity, with an average onset latency of 40.7 ± 11 sec. and an average initial seizure duration of 19.5 ± 5 sec. These seizures gradually increased in severity and frequency, evolving into status-type seizures after approximately 10-15 min. Animals pretreated with 270 mg/kg magnesium sulfate either failed to seize or showed seizures of greatly reduced severity and duration. Of those magnesium treated animals which did seize, average seizure onset following NMDA was increased to 96 ± 13 sec. and the average duration was reduced to 8.7 ± 4 sec. These data indicate that magnesium can exert marked anticonvulsant effects against NMDA-induced sp.i,ures and suggest a possible link between excitatory amino acid transmitters (e.g., NMDA) in the nervous system and seizures associated with preeclampsia-eclampsia. January 1992 Am J Obstet Gyneco1 17 MAGNESIUM PIDOLATE INFUSION REDUCES ANGIOTENSIN II PRESSOR RESPONSE IN PREGNANT WOMEN_ Tranauilli AL: Mariani ML: Garzetti CG,x Valensie H,x Romanini C! University of Ancona, Italy Circulating eicosanoids and intracellular free calcium (Cai) may contribute in the systemic pressor response to infused angiotensin II (All) in pregnancy. Since magnesium (Mg) may interfere with both those factors, we studied Cai and the pressor response to All in 10 primigravid women (28-32 weeks' gestation) before and after the infusion of 1 gt Mg pidolate. After the effective pressore dose (EPD) (i.e. the Aii infusion rate at which the diastolic blood pressure increased 20 mmHg) was achieved, or a maximum of 64 ng/kg/min rate was reached, we infused 1 gr Mg pidolate and repeated the test. Cai was measured by means of fluorescent probes at the beginning and the end of both tests. Six women were classified as refractory to All and 4 as sensitive (EPD < 10 ng/kg/min). After Mg pidolate infusion, the 4 sensitive women became refractory, and EPD was significantly enhanced in 3 out of the 6 refractory. Cai increased significantly during All infusion, whereas, after Mg pidolate administration, it did not change. From these results, Mg pidolate may therefore enhance the vascular refractoriness, and Cai mediate the pressor response to All, in pregnancy. 18 A PROSPECTIVE STUDY OF BIOIMPEDANCE ANALYSIS IN NORMAL AND HYPERTENSIVE PREGNANCIES_T M Goodwin. S EstradaX, KA Smith", L Bernstein", R Artal. University of Southern. California, Los Angeles, CA Bioelectrical impedance analysis (BIA) has been proposed as a safe and inexpensive method of estimating total body water in normal and pathologic states, 'The formula for the volume of a conductor. V=L2/Z. describes the relationship between bioimpedance (Z), total oody water (V) and height (L). A prospective study was undertaken to test the hypothesis that lower bioimpedance i' (indicative of 600: increased oody water) +1 is detectable prior to c 55(} the time of diagnosis : in women destined to .s develop pregnancy sot). induced hypertension "C (PIH). Six hundred 450: determinations were made on 161 healthy iii _Control "'f ... POH "'I Weeks of gestation nulliparae from 18 to 40 < 23 23-26 27-3031-3435-3839-41 41 weeks gestation. Thirty-six subjects (22%) developed PIH, but only 3 were diagnosed before 36 weeks gestation. Bioimpedance correlated negatively with gestational age among normals(r=.4,p<.OOI) and patients who developed PIH (r=.5,p<.OOI). The data are displayed above as means for arbitrarily defined gestational age intervals. Mean bioimpedance dirrered significantly between normal and PIH subjects beginning as early as 23 weeks gestation_ BIA may be userul in studying the natural history or PIH_

Transcript of 17 Magnesium Pidolate Infusion Reduces Angiotensin II Pressor Response in Pregnant Women

Page 1: 17 Magnesium Pidolate Infusion Reduces Angiotensin II Pressor Response in Pregnant Women

280 SPO Abstracts

15 A RANDOMIZED PROSPECTIVE COMPARISON OF NIFEDIPINE AND BED REST VERSUS BED REST ALONE IN THE MANAGEMENT OF PREECLAMPSIA REMOTE FROM TERM, fl.M Sibai JR BartonX, S Aklx, C SarinogluX, BM Mercerx, University of Tennessee, Memphis.

Two hundred primigravidas with preeclampsia (hypertension plus proteinuria) at 26-36 weeks' gestation were randomly allocated to be managed with bed rest alone or bed rest plus oral nifedipine 40-120 mg/day. All women had baseline and serial evaluations of maternal and fetal well being. Following hospitalization, patients with adequate blood pressure response and absent proteinuria «300 mg/24 hr) were subsequently managed on an outpatient basis. There were no differences between the two groups in mean systolic and diastolic blood pressures at time of randomization, however, the nifedipine group had significantly lower systolic (p<O.OOOI) and diastolic (p< 0.0001) blood pressures during therapy. There were no differences in number of days of antepartum maternal hospitalization (12.6 ± 7.9 v 12.3 ± 10.3). Table compares the clinical findings in 197 patients (3 were lost to follow-up). The two groups had similar incidences of abruptio placentae (2% v 3%) and HELLP syndrome (2% v 4%). There were no perinatal deaths in either group and no differences in cord gasses between groups. Conclusions: Nifedipine therapy for preeclampsia significantly reduces maternal blood pressure but does not shorten maternal hospitalization or improve perinatal outcome.

Mean + SO Control In = 99) Njfedjpjne In - 98) Admission gest age (wks) 33.5 ± 2.3 32.9 ± 2.6 Pregnancy prolongation (days) 22.3 ± 13.5 22.5 ± 15.7 Delivery for severe HTN # (%) "18 (18) 9 (9) Delivered 2: 37 wk # (%) 60 (60) 50 (51) Birth weight (grams) 2509 ± 728 2403 ± 769 IUGR#(%) 13(13) 15(15) Cord pH < 7.20 11(13) 9 (10) Admitted to SeN # (%) 21 (21) 30 (30)

SCN = Special Care Nursery, HTN = hypertension, "P < 0.05

16 MAGNESIUM SULFATE INJECTIONS BLOCK NMDA-INDUCED HIPPOCAMPAL SEIZURES_ D.B. Cotton, R.F. Berman: S. Irtenkauf,' Dept_ Ob/Gyn, Wayne State Univ.lHutzel Hasp., Detroit, MI

The use of magnesium sulfate in the treatment of seizures and convulsions associated with preeclampsia-eclampsia is well established. However, the mechanism by which magnesium blocks seizures is unknown. Recent evidence has suggested that activation of excitatory amino acid receptors, such as the N­methyl-D-aspartate (NMDA) receptor, can result in seizures and that these receptors are blocked in a voltage dependent manner by magnesium. Thus magnesium sulfate injections may inhibit seizures directly via a magnesium-induced block of NMDA receptors. As a test of this hypothesis, we examined the ability of intraperitoneal injections of magnesium sulfate to block seizures produced by direct injections of 20 j.Jg of NMDA into the dorsal hippocampus of rats, a region enriched in NMDA receptors. NMDA injections into the hippocampus resulted in almost immediate epileptiform activity, with an average onset latency of 40.7 ± 11 sec. and an average initial seizure duration of 19.5 ± 5 sec. These seizures gradually increased in severity and frequency, evolving into status-type seizures after approximately 10-15 min. Animals pretreated with 270 mg/kg magnesium sulfate either failed to seize or showed seizures of greatly reduced severity and duration. Of those magnesium treated animals which did seize, average seizure onset following NMDA was increased to 96 ± 13 sec. and the average duration was reduced to 8.7 ± 4 sec. These data indicate that magnesium can exert marked anticonvulsant effects against NMDA-induced sp.i,ures and suggest a possible link between excitatory amino acid transmitters (e.g., NMDA) in the nervous system and seizures associated with preeclampsia-eclampsia.

January 1992 Am J Obstet Gyneco1

17 MAGNESIUM PIDOLATE INFUSION REDUCES ANGIOTENSIN II PRESSOR RESPONSE IN PREGNANT WOMEN_ Tranauilli AL: Mariani ML: Garzetti CG,x Valensie H,x Romanini C! University of Ancona, Italy

Circulating eicosanoids and intracellular free calcium (Cai) may contribute in the systemic pressor response to infused angiotensin II (All) in pregnancy. Since magnesium (Mg) may interfere with both those factors, we studied Cai and the pressor response to All in 10 primigravid women (28-32 weeks' gestation) before and after the infusion of 1 gt Mg pidolate. After the effective pressore dose (EPD) (i.e. the Aii infusion rate at which the diastolic blood pressure increased 20 mmHg) was achieved, or a maximum of 64 ng/kg/min rate was reached, we infused 1 gr Mg pidolate and repeated the test. Cai was measured by means of fluorescent probes at the beginning and the end of both tests. Six women were classified as refractory to All and 4 as sensitive (EPD < 10 ng/kg/min). After Mg pidolate infusion, the 4 sensitive women became refractory, and EPD was significantly enhanced in 3 out of the 6 refractory. Cai increased significantly during All infusion, whereas, after Mg pidolate administration, it did not change. From these results, Mg pidolate may therefore enhance the vascular refractoriness, and Cai mediate the pressor response to All, in pregnancy.

18 A PROSPECTIVE STUDY OF BIOIMPEDANCE ANALYSIS IN NORMAL AND HYPERTENSIVE PREGNANCIES_T M Goodwin. S EstradaX, KA Smith", L Bernstein", R Artal. University of Southern. California, Los Angeles, CA

Bioelectrical impedance analysis (BIA) has been proposed as a safe and inexpensive method of estimating total body water in normal and

pathologic states, 'The formula for the volume of a conductor. V=L2/Z. describes the relationship between bioimpedance (Z), total oody water (V) and height (L). A prospective study was undertaken to test the hypothesis that lower bioimpedance i' (indicative of ~ 600: increased oody water) +1

is detectable prior to c 55(} the time of diagnosis : in women destined to .s develop pregnancy ~ sot). induced hypertension "C

(PIH). Six hundred ~ 450: determinations were .~ made on 161 healthy iii

~ _Control "'f ...

POH "'I Weeks of gestation

nulliparae from 18 to 40 < 23 23-26 27-3031-3435-3839-41 41 weeks gestation. Thirty-six subjects (22%) developed PIH, but only 3 were diagnosed before 36 weeks gestation. Bioimpedance correlated negatively with gestational age among normals(r=.4,p<.OOI) and patients who developed PIH (r=.5,p<.OOI). The data are displayed above as means for arbitrarily defined gestational age intervals. Mean bioimpedance dirrered significantly between normal and PIH subjects beginning as early as 23 weeks gestation_ BIA may be userul in studying the natural history or PIH_