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101 276 spa Abstracts EHDOTHELIAL VAS01!CTIVE MEDIATORS IN PYECLAMPSIA Dekker GA MD PhD , Kraayenbrink AA MD Dep. of Obstetrics Free University Hospital Amsterdam, The Netherlands. The increase in oxygen (02) free radical pro- duction in preeclampsia may cause a disturbance of endothelial physiology. To deteraine the pos- sible consequences of the increase in 0z free ra- dicals we studied urinary excretion of TXB Z and 6-Keto-PGFla, and plasaa endothelin levels in preeclamptic patient. and in control subject •• In addition plasaa levels of calcitonin gene re- lated peptide (CGRP) were aeasured. The TXB 2 /6- Keto-PGFla ratio was significantly higher in preeclampsia (n=lO, mean 1.27, SD 0.38) as coa- pared with normotensive pregnancy (n=15, mean 0.95, SD 0.31). Endothelin levels were extremely elevated in 2 women with severe preeclampsia, women with a less severe disease showed a non- significant increase. CGRP levels showed a wide range. Mean levels were 54.6 pg/ml (SD 43.4) in noraotensive patients (n=15) and 53.2 pg/al (SD 74.8) in preeclamptic patients (n=lO). These results are compatible with the hypothesis that increased 0z free radical production causes a disturbance in TXAZ/PGI z balance. Plasma level. of endothelin suggest tnat it is only involved in severe preeclaapsia. CGRP appears not to be involved in the pathophysiology of preeclaapsia. The hypothesis is put forward that in preeclaap- sia 0z free radicals cause vasoconstriction by decreasing endothelial EDRF release, and that production of PGI Z by the vessel wall and endo- vascular trophoblast is just a pivotal escape mechanism of the uteroplacental circulation. _ 02 GARIS lJRI:-:JE (SI1)IALTlY - A'J ALn' R'JATIVE TO PIA<;MA URATE Jr\ mE MANAGF»xr OF PRF- ECJA'1PSJA, I<lU1>., Y,:-1, UllII 2x , of Obstetrics and and Faculty Statlstkidn 2 , the Chinf'se tJl!ivprsityof HOlle KOllt: , Pl'jllc'p 1)1' WdJ ps n,,, :.kttprnal plasma llrilte nlfY1SllrPlllent is Olle of the (·sl.lld·lsht· \(J t('sts jll thp Il lrl flde,l"fl lt'lI! lH't' , 11KI reflects renal tuhlll"r c lysfu ll cl iOIl F.u'ly III' i I If- (EM(;) C)SllMI].l I i I Y ti('IK'lids "Ii 11,,- I lt'i rN- ('UI ICt'IItl'at ine "hility of l'E'll<ll t ub"lps, Th is study was 1" I'!'ol1l.·d 10 S,,· jf 1M) uSllu)"lily "wl1'I"I .. s willl 1'1 clsllk I uralp CUllC'.t' ntrot jon in Iwp-eC'1amptic \I.UI1lf'n, Finy "illg l f, lorl JlI'P' I'('J;11111' 1 ii ' (IIIXr; l'I'ilc'o'i<l) i!' lll>-. h"d l.JltKlt l drawll fell' pla,111)(1 l,U 'rltp pst illk 1tiull lilieS 1 d t f' llld hod ClS i lie t hAmp[ i 1:.111 MOll i I I l' ki t on thp Pm"lll el Annlyt leal Systf'm) "rtf'/' ."Imissiull all<l d sdmpl.., "I' rn: was SPill 1'01' oSlllulajjly nK'rlS l,U'ement (freezing point dpprpssioll lllf'thud) 011 the r"llowin£ EMt : OHm),,) ily (lIk ·.1I\ _ sn r,on,2 ..:.. nDsm/kg ) was signifiC'i1ntly cntTel,1tpll (1' - () 492, p< 0 0(1) wi I h w ,,,(, , (0 41 _ 0 10 as well as with hirth weigiJt (2931.:::. 663 g) (I' ; 0 ,:\06, IK<l.(4 ) A similarly sip,ni/,ic:a!ll iOIl ( [' - 0436, p<O,O(2 ) exists bPtweE'JI FMl ; oSlIloldl ity amI plasnlil c ('I\I( i llil K' (70:;..:.. 21 2 l !I1k,] / I) hul I N.1 wil t! I[l'Pd (t' " - O,2flO), Since co]lecUoJl of EMI; cloes nol I'f'{]ulrp d!ld Ihe aHsClciaj pd hazi1rds, dllll is IlSUdll y dOJ](' dS it I'outine fol' lU'ine tE' Stillg jll inpatients, this j ps l can II(' a lIsd\rl "l11:rnalj vp fur f UlI!' t jnn in prp--eclamptic patients, Januar y 1 99 1 Am J Obslet Gvnecol 103 :'RT:-:JARY PRm'FIN A'ID rNZYME EXCRETION IN PRE-ECLA'lPSIA T T idl"»' C,K ChPllIlg2x , R of ;. md i-Uld I-ht> Chillt,SP (If }kmg KOllg, Pl'ill CP .. f Hospi1.tl, HOlle l\()lIe, pX(]I>Lion "r r't'lId] tllbulal' PI1Z,,11.'S, ill ,1dolil iOIl III <lllnuuill, h"s IX> "[l ill PI'P ,'I slll!'p ,I s jgllif icdllt jfllTPdSP 1n Pl'utPiIl and I'IlZyJl. ! .. xI,!,,.1 iOIl is INll'fll<111y fmllK! ill Ihi,,! t:t'illlPstt'j' , th is study Wi l" l('I'f Cll'll lt'd tll t:lJIlipilI't' Px( n'l ion of .dhulIlin (1\ 110 ) "lid 1I',rIIS!- "/'I',[: (';'J\F) (ill¥ll111ll. LLU'h ilIIJIIPl l'iI), tllldl 1W(,lf'ill (c!yC' ,,- tlf 1'1 yl -R glll"osdlH;llidd'':;\' ("\AG) ilklSP (.MP) ,11l" (C',(;l')(I< i1If'1io'), lx'lwl'(,11 pr'oll'illllJ'i !' ,'cldlllptic itlld IlUrllk1] t h: I'll t ri nl..,;;! t'l' (1l<11) / liS i ng ii ]',llIdom III i". ' "dill!,]" 1111' I"",lllh (111">111 .:.. sr' JII) "1'1' I'XPl'!'"Sc·.! <IS j1E' l'mol of CTf',ltinjIlP alld thf' Whiln .. y C t.pst W"S liSP" r'IW iSII" 1'1'" c 'e l'llll!,l iI ' \>I"IM!II It.ld hi g)!" l' ' Il'jllwy PXI ' I,..,llun of Alb (838 .:. 1:; ,2 vs 2...! .:::. 0,:1 g,.'IIIl,l Cr), 1,,1,,] pl'ol .. ill (11;g R , _ 44,J vs 7,2 -=- D,S Cr') d lld 11{F (10,2.:::. J,-l 2,0 _-=- 1,:'\ me/ Illol (I')(p< 0,0001): .IS .1S NJ\G (125,0..:.. 21,3 vs ()''3 7 -=- (l,R l<C/ IIM.t c:'), AAF' t:; 8.:::.:: 4 vs 1,5.:. 0,1 kt: !m ul Cl'), allll C,Dr (R,3.:::. () I) vs 6, 2,:: O,R kC ! ,"o) Cr) (p<O,()()f» 11\1-' r'I'sn1ts : neli Cd It' thdl sigll_ifi cant ren<tl glolllt'l'l llc11' illlel tuhule,r d.tllklB<-' OCCII[' ill [J['P-PC1,Ylll'"i d, " wI t'dlllirMn urin," is CP 1 iabl ... fur lhp aSSeS8Jllf'lJt uf reml fUllction in pre- eC)dlllpsin 104 EFFECT OF MAGNESIUM SULFATE (MgS0 4 ) ON CIRCULATING PROSTANOID LEVELS IN PATIENTS WITH PREGNANCY-INDUCED HYPERTENSION (PIH). WW Andrews, NF Gant, RR Magness x Depts, of Ob!Gyn and Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas The mechanism of action of MgS0 4 in women with PIH remains uncertain. Recent in vitro studies indicate that MgS0 4 enhances prostacyclin (PGI 2 ) production from cultured umbilical vein endothelial cells , Since PGI is decreased in patients with PIH, we measured the effect of MgS0 4 in vivo (2gm/hr IV after a 4gm loading dose) on circulating PGI 2 and other prostanoids in 11 patients with PIH (28-40 wks. gestation). Plasma 6-keto-PGF, (6kPGF, ), thromboxane (Tx)B 2 (metabolites of PGI 2 ana TxA 2 , respectively), prostaglandins E2 and F2a. were measured by RIA, Plasma TxB 2 and PGE 2 levels remained unchanged by MgS0 4 therapy. Plasma 6kPGF'a and the 6kPGF, /TxB 2 ratio were decreased from control (Ohr) Jalues (220±38pg/ml, mean±SEMj 1.41±0,35, respectively) at 2hrs (77±17pg/ml,p<,Q03j 0,47±0.13,p<,01) but rebounded by 4 hrs (316±122pg/mlj 1 ,93±0. 74). Compared to Ohr (131±26pg/ml), MgS0 4 also decreased plasma PGF 2 at 2hrs (90±21pg/ml,p<.025) and 4hr (87±'16pg/ml,p<.05). In conclusion, these in vivo data obtained from patients with PIH are not consistent with the in vitro observation that MgS04, stimulates PGI 2 production from endothelial cells. However, MgS0 4 action may be partially mediated via a reduction in PGF 2 production. a

104 Effect of magnesium sulfate (MgSO4) on circulating prostanoid levels in patients with pregnancy-induced hypertension (PIH)

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Page 1: 104 Effect of magnesium sulfate (MgSO4) on circulating prostanoid levels in patients with pregnancy-induced hypertension (PIH)

101

276 spa Abstracts

EHDOTHELIAL VAS01!CTIVE MEDIATORS IN PYECLAMPSIA Dekker GA MD PhD , Kraayenbrink AA MD Dep. of Obstetrics Free University Hospital Amsterdam, The Netherlands.

The increase in oxygen (02) free radical pro­duction in preeclampsia may cause a disturbance of endothelial physiology. To deteraine the pos­sible consequences of the increase in 0z free ra­dicals we studied urinary excretion of TXBZ and 6-Keto-PGFla, and plasaa endothelin levels in preeclamptic patient. and in control subject •• In addition plasaa levels of calcitonin gene re­lated peptide (CGRP) were aeasured. The TXB2/6-Keto-PGFla ratio was significantly higher in preeclampsia (n=lO, mean 1.27, SD 0.38) as coa­pared with normotensive pregnancy (n=15, mean 0.95, SD 0.31). Endothelin levels were extremely elevated in 2 women with severe preeclampsia, women with a less severe disease showed a non­significant increase. CGRP levels showed a wide range. Mean levels were 54.6 pg/ml (SD 43.4) in noraotensive patients (n=15) and 53.2 pg/al (SD 74.8) in preeclamptic patients (n=lO). These results are compatible with the hypothesis that increased 0z free radical production causes a disturbance in TXAZ/PGIz balance. Plasma level. of endothelin suggest tnat it is only involved in severe preeclaapsia. CGRP appears not to be involved in the pathophysiology of preeclaapsia. The hypothesis is put forward that in preeclaap­sia 0z free radicals cause vasoconstriction by decreasing endothelial EDRF release, and that production of PGIZ by the vessel wall and endo­vascular trophoblast is just a pivotal escape mechanism of the uteroplacental circulation.

_02 GARIS :'vDRNI~ lJRI:-:JE (SI1)IALTlY - A'J ALn'R'JATIVE TO PIA<;MA URATE Jr\ mE MANAGF»xr OF PRF- ECJA'1PSJA, '~T , I<lU1>., Y,:-1, UllII2x , ~~lJ<ll't lllent of Obstetrics and r.YJl'iP('oh~~ and Faculty Statlstkidn2 , the Chinf'se tJl!ivprsityof HOlle KOllt: , Pl'jllc'p 1)1' WdJ ps lIospit.l~, n,,,

:.kttprnal plasma llrilte nlfY1SllrPlllent is Olle of the (·sl.lld·lsht·\(J t('sts jll thp Il lrl flde,l"fl lt'lI! lI~ lH't' t>t'ldJH1J~ i.J

,11KI reflects renal tuhlll"r clysfullc l iOIl F.u'ly lI~orlllng III' i I If- (EM(;) C)SllMI].l I i I Y ti('IK'lids "Ii 11,,- I lt'i rN-

('UIICt'IItl'a t ine "hility of l'E'll<ll t ub"lps, This study was 1" I ' !'ol1l. ·d 10 S,,· jf 1M) uSllu)"lily "wl1'I"I .. s willl 1'1 clsllk I uralp CUllC'.t'ntrot jon in Iwp-eC'1amptic \I.UI1lf'n, Finy "illg lf, lorl JlI'P' I'('J;11111'1 ii ' (IIIXr; l'I'ilc'o'i<l) 1~1l i!'lll>-. h"d l.JltKltl drawll fell' pla,111)(1 l,U 'rltp pst illk1tiull

(l,hC)~;phoj lilieS 1 d t f' llld hod ClS i lie t hI· Amp[ i 1:.111 MOll i I I l' Rl~il£f'llt ki t on thp Pm"lllel Annlyt leal Systf'm) "rtf'/' ."Imissiull all<l d sdmpl.., "I' rn: was SPill 1'01' oSlllulajjly

nK'rlSl,U'ement (freezing point dpprpssioll lllf'thud) 011 the r"llowin£ 1Il0!'fljl~, EMt: OHm),,) ily (lIk ·.1I\ _ sn r,on,2 ..:.. ~fl7 , l nDsm/kg) was signifiC'i1ntly cntTel,1 tpll (1' ~ -() 492, p< 0 0(1) wi I h [l1i1sn~t w ,,,(, , (0 41 _ 0 10 1l1l~'1. ' 1;

as well as with hirth weigiJt (2931.:::. 663 g) (I' ; 0 ,:\06, IK<l.(4 ) A similarly sip,ni/,ic:a!ll C~lI'I't'lal iOIl ( [' -

0436, p<O,O(2 ) exists bPtweE'JI FMl; oSlIloldl ity amI plasnlil c ('I\I( i llilK' (70:;..:.. 21 2 l !I1k,] / I) hul IN.1 wil t! I[l'Pd (t ' " -O,2flO), Since co]lecUoJl of EMI; cloes nol I'f'{]ulrp \lPI\C'I~Il'lllT'" d!ld Ihe aHsClciaj pd hazi1rds, dllll is IlSUdll y

dOJ](' dS it I'outine fol' lU'ine tE'Stillg jll inpatients, this j ps l can II(' a lIsd\rl "l11:rnalj vp fur nK)I[ill)rill!~ n~nal

f UlI!' t jnn in prp--eclamptic patients,

January 199 1 Am J Obslet Gvnecol

103 :'RT:-:JARY PRm'FIN A'ID rNZYME EXCRETION IN PRE-ECLA'lPSIA T T idl"»' C,K ChPllIlg2x , R ~'w'lIl1 l Jl,jllliIll2x, nf'l)r1rtmpnh~ of Obst~t[~jl's ;.md r.YlldPt:olo~;1. i-Uld r.llf~lHic,,; f'.\lh"llJ~':?' I-ht> Chillt,SP l'lIivt-'I'~,i ty (If }kmg KOllg, Pl'illCP .. f \\1d lc~~ Hospi1.tl, HOlle l\()lIe,

~III'1'PosPtllU'illd),y pX(]I>Lion "r r't'lId] tllbulal' PI1Z,,11.'S,

ill ,1dolil iOIl III <lllnuuill, h"s IX>"[l t'p[l(lT'I. ~d ill PI'P ,'I l,~u}J"i'1. slll!'p ,I s jgllif icdllt jfllTPdSP 1n Pl'utPiIl and I'IlZyJl. ! .. xI,!,,.1 iOIl is INll'fll<111y fmllK! ill tll~ Ihi,,!

t:t'illlPst t ' j' , th is study Wil" l('I' f Cll'lllt'd tll t:lJIlipilI't' lll'i(~u'y

Px( n'l ion of .dhulIlin (1\ 110 ) "lid 1I',rIIS!-"/'I',[: (';'J\F) (ill¥ll111ll. LLU'h ilIIJIIPl l'iI), tllldl 1W(,lf'ill (c!yC' -h illf.lillt~), ,,-tlf 1'1 yl -R glll"osdlH;llidd'':;\' ("\AG) (ltd'JI'jll~~tr'j(), rt],·udlu~

,UllinC)I~ 'vt ilklSP (.MP) ,11l" !?-'llIll1~I - ':?.hltdlllyltFmsft-'I'elS'"

(C',(;l')(I< i1If'1io'), lx'lwl'(,11 pr'oll'illllJ'i !' pl'~ ,'cldlllptic (\,~27)

itlld IlUrllk1] t h: I'll t ri nl..,;;! t'l' (1l<11) \\~ "IIPI / liS i ng ii ]',llIdom

III i".' "dill!,]" 1111' I"",lllh (111">111 .:.. sr'JII) "1'1' I'XPl'!'"Sc·.! <IS

j1E'l'mol of CTf',ltinjIlP alld thf' ~1i\llll Whiln .. y C t.pst W"S

liSP" r'IW "C~lll'" iSII" 1'1'" c'e l'llll!,l iI ' \>I"IM!II It.ld hig)!" l' ' Il'jllwy PXI 'I,..,llun of Alb (838 .:. 1:; ,2 vs 2...! .:::. 0,:1 g,.'IIIl,l Cr), 1,,1,,] pl'o l .. ill (11;g R , _ 44,J vs 7,2 -=- D,S !~!nul Cr') d lld 11{F (10,2.:::. J,-l v~' 2,0 _-=- 1,:'\ me/ Illol (I')(p< 0,0001): .IS t.II'~ll .1S NJ\G (125,0..:.. 21,3 vs ()''3 7 -=- (l,R l<C/ IIM.t c: ' ) , AAF' t:; 8.:::.:: 4 vs 1,5.:. 0,1 kt: ! mul Cl'), allll C,Dr (R,3.:::. () I) vs 6 ,2,:: O,R kC! ,"o) Cr) (p<O,()()f» 11\1-' r'I'sn1ts

: neli Cd It' thdl sigll_ifi cant ren<tl glolllt'l'l llc11' illlel tuhule,r d.tllklB<-' OCCII[' ill [J['P-PC1,Ylll'"i d, " wI t'dlllirMn urin," Sdlllplil~

is CP 1 iabl ... fur lhp aSSeS8Jllf'lJt uf reml fUllction in pre­eC)dlllpsin

104 EFFECT OF MAGNESIUM SULFATE (MgS04 ) ON CIRCULATING PROSTANOID LEVELS IN PATIENTS WITH PREGNANCY-INDUCED HYPERTENSION (PIH). WW Andrews, NF Gant, RR Magnessx • Depts, of Ob!Gyn and Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas

The mechanism of action of MgS04 in women with PIH remains uncertain. Recent in vitro studies indicate that MgS04 enhances prostacyclin (PGI2 ) production from cultured umbilical vein endothelial cells , Since PGI is decreased in patients with PIH, we measured the effect of MgS04 in vivo (2gm/hr IV after a 4gm loading dose) on circulating PGI2 and other prostanoids in 11 patients with PIH (28-40 wks. gestation). Plasma 6-keto-PGF, (6kPGF, ), thromboxane (Tx)B2 (metabolites of PGI2 ana TxA2, respectively), prostaglandins E2 and F2a. were measured by RIA, Plasma TxB2 and PGE2 levels remained unchanged by MgS04 therapy. Plasma 6kPGF'a and the 6kPGF, /TxB2 ratio were decreased from control (Ohr) Jalues (220±38pg/ml, mean±SEMj 1.41±0,35, respectively) at 2hrs (77±17pg/ml,p<,Q03j 0,47±0.13,p<,01) but rebounded by 4 hrs (316±122pg/mlj 1 ,93±0. 74). Compared to Ohr (131±26pg/ml), MgS04 also decreased plasma PGF2 at 2hrs (90±21pg/ml,p<.025) and 4hr (87±'16pg/ml,p<.05). In conclusion, these in vivo data obtained from patients with PIH are not consistent with the in vitro observation that MgS04, stimulates PGI2 production from endothelial cells. However, MgS04 action may be partially mediated via a reduction in PGF2 production. a