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Placental prostaglandin levels in pre-eclampsia
CURRENT INVESTIGATION
This section offers prompt first announcement of new observations or discoveries. Articles should be limited to 1,500 words and 6 references. Illustrations or additional references require a proportionate reduction in total words.
Placental prostaglandin levels in pre-eclampsia
Pw-c~clamfi.tia i.5 cha ractv riwl by uteroplacental &hernia. Prostaglnndiru cat/ aitc’r sv.rtrmic blood pr~.ww as wll as wgulatu blood j?ow to the frtoplnrrntal unit. Ire the fiwwnt \tudr. 1~7~4~ o/‘prostaRlandin E z(rere sign$icantly derreased in $arrrrtal tissue tram fwc-xkamptic, pntic,nts. Prostaglandin F, a potent ~;aasoconstrictor. ~‘a.5 mnrkld(y c$mv&tl. ‘l%~.rc~ obserzutior~.s indicate that altered place,ltal metabolism of p~o.stnglrrnrlit~.s IF an important factor in tbc pthophysiology of p-r-eclampsia.
Materials and methods
PRE-ECLAMI-*SIA is a major cause of morbidity and death for the pregnant patient and her fetus. Although the etiology of this disorder is not fully understood, most investigators agree that uteroplacental ischemia plays an important role. ’ Prostaglandins, CzO unsaturated hydroxy-fatty acids, are known to regulate placental carbohydrate and steroid metabolism. They may also alter uteroplacental blood flow.’ We have determined prostaglandin levels in placental specimens liom normal and pre-eclamptic patients to assess the role these compounds might play in the pathophysiology of prr-eclampsia.
Randomly selected pieces of fresh plar-ental tissue obtained at delivery were immediately frozen with the use of Freon* and dry ice. Approximately 400 mg. of‘ tissue was collected. The study included 20 women who had undergone normal term spontaneous vaginal delivery. They had not demonstrated hypertension. proteinuria, or edema during gestation. Twenty-two patients with pre-eclampsia were investigated. All wer(A being monitored in the Fetal Intensive. Care Unit and demonstrated hypertension-a systolic pressure of 140 mm. Hg (or a rise of greater than 30 mm. Hg) and ;I diastolic pressure of 90 mm. Hg (or a rise of greater than 20 mm. Hg). Nineteen were found to havt. proteinuria. and most exhibited edema an&or hyperreflexia. Eight patients met the blood pressure criteria for severe pre-eclampsia. Keview of rhr charts of the
137
138
Demers and Gabbe
25
30 20
15
I 0
\E” z
i
I I
20
I
-IIO
F E
I
I
0
I I
0
I
0
I
0
I
0
I
10
5
i
:
& 0
I I
I
NORMAL n=20 S.D. 2 5 7
l
PRE-ECLAMPSIA n=22 S.D. k 0.71
NORMAL n=20 S.D. + 3.2
PRE-ECLAMPSIA n=22 S.D. ziz 6.5
Fig.
1. PGE levels in placental tissue from 20 control patients and 22 patients with pre-ectampsia. Results are expressed as picograms per milligram of wet tissue weight. The solid line across the data points indicates the mean value. Standard deviations are listed at the bottom of the figure.
Fig.
2. PGF levels in placental tissue taken from 20 control subjects and 22 patients with pre-eclampsia. Results are expressed as picograms per milligram of wet tissue weight.
pre-eclamptic women revealed no previous history of hypertension, renal disease, or diabetes mellitus. Newborn weight, gestational age, Apgar scores at one and five minutes, and placental weight were recorded for both normal and pre-eclamptic patients. Prostaglandin (PC) radioimmunoassays were performed with the use of antiserum prepared in rabbits against the albumin conjugate of PGF2, and PGEI. The PGF antiserum used in these studies had 100
per cent cross-reactivity with PGF,,, 42 per cent crossreactivity with PGF,,, and less than 1 per cent crossreactivity with PC’s of the E, A, and B series as well as the 13,14 dihydro, 15 keto Fza. Cross-reactivity studies with the PGE antiserum indicated 100 per cent crossreaction with PGEI, 70 per cent cross-reactivity with PGEe, 88 per cent reactivity with PGA,, 51 per cent reactivity with PGA2, 14 per cent reactivity with PGBt, 6 per cent reactivity with PGFea, and less than%rie per
Placental prostaglandins
cent cross-reactivity with other related PG compounds including the 13,14-dihydro, 15-keto PGE metabolite. Placental tissue was thawed and extracted initially with ethyl acetate : isopropanol : 0.1 M hydrochloric acid (3 : 3 : 1). Following a saline wash step, the ethyl acetate layer containing the PG’s was removed and applied to a Silicic acid column for chromatographic separation of the individual PC, series. PGE was eluted from the column with a 60 : 40 : 2 benzene-ethyl acetatemethanol solvent front, while PG’s of the F series were &ted with a 60 : 40 : 20 benzene-ethyl acetateInethanol solvent front. The elutions were evaporated and reconstituted with 1 ml. of ethanol in preparation for the radioimmunoassay. Radioimmunoassay was performed as previously described with results exper milligram of wet tissue pressed as picograms weight.” Data were analyzed statistically by analysis of variance. Significance between two groups was determined by the method of least significant differences. A P value of 0.05 or less was considered to be significant.
Results PGE levels were markedly decreased (P < 0.05) in pre-eclamptic placental tissue, as shown in Fig. 1. In contrast, PGF concentrations were significantly elevated (P < 0.05). (Fig. 2). PG levels did not correlate with the severity of the pre-eclampsia.
Comment Uteroplacental ischemia observed in pre-eclampsia could be clue to an alteration in PG metabolism. Speroff has proposed that the development of precclampsia may represent defective PG production, loss
in pre-eclampsla
139
of response to PC;, or a combination 01. thvzc, abnormalities.’ Placental levels of PGF were found to be siqificantl\ increased in pre-eclampsia. These
REFERENCES 1. Speroff,
L: Toxemia
of pregnancy,
Am.
J. Cardiol.
32:
332. 1972. 2. Pulkkinen,
M. O.,
Pitkanen,
H.: Decrease of uteroplacental glandin
FzCr induced
abortion,
Y., Ojala,
A., and Hannelin,
blood flow during prostaProstaglandins
9: 61, 1975.
3. Demers, L. M., Yoshinaga, K., and Creep, R. 0.: Prostaglandin F in uterine fluild during the menstrual cycle and followine steroid treatment. Prostaelandins 5: 513. 1974. 4. Novp. G. J,, Piasecki, G., and Jacukson, B. T.: Effect of prostagkdndins EP and Fa, on umbilical blood flow and fetal hemodynamirs. Prostaglandins 5: 543, 1974.
5. Kyan. W. L.. Coronel. vasodepressor substance OBswr. GYNECOL. 105:
D. M., of the
al,d Johtwn. K. J,: A human placrnta. Ah%. J.
1201, 196l). 6. ,41am, N. A., Clary. P., and Russell, P. L’.: Depressed placental prostaglandin Et metabolism in towtnia of pregnancy, Prostaglandins 4: 363, 1973. 7. Alam, N. A., Clary. P., Shade, A. R.. and Russell, P. ‘I’.: Absence of prostaglandin E, metabolism ill hydatidiform mole, ,4w. J, OBSTET. GYNECOI.. 119: I I3 I 1974.
This section offers prompt first announcement of new observations or discoveries. Articles should be limited to 1,500 words and 6 references. Illustrations or additional references require a proportionate reduction in total words.
Placental prostaglandin levels in pre-eclampsia
Pw-c~clamfi.tia i.5 cha ractv riwl by uteroplacental &hernia. Prostaglnndiru cat/ aitc’r sv.rtrmic blood pr~.ww as wll as wgulatu blood j?ow to the frtoplnrrntal unit. Ire the fiwwnt \tudr. 1~7~4~ o/‘prostaRlandin E z(rere sign$icantly derreased in $arrrrtal tissue tram fwc-xkamptic, pntic,nts. Prostaglandin F, a potent ~;aasoconstrictor. ~‘a.5 mnrkld(y c$mv&tl. ‘l%~.rc~ obserzutior~.s indicate that altered place,ltal metabolism of p~o.stnglrrnrlit~.s IF an important factor in tbc pthophysiology of p-r-eclampsia.
Materials and methods
PRE-ECLAMI-*SIA is a major cause of morbidity and death for the pregnant patient and her fetus. Although the etiology of this disorder is not fully understood, most investigators agree that uteroplacental ischemia plays an important role. ’ Prostaglandins, CzO unsaturated hydroxy-fatty acids, are known to regulate placental carbohydrate and steroid metabolism. They may also alter uteroplacental blood flow.’ We have determined prostaglandin levels in placental specimens liom normal and pre-eclamptic patients to assess the role these compounds might play in the pathophysiology of prr-eclampsia.
Randomly selected pieces of fresh plar-ental tissue obtained at delivery were immediately frozen with the use of Freon* and dry ice. Approximately 400 mg. of‘ tissue was collected. The study included 20 women who had undergone normal term spontaneous vaginal delivery. They had not demonstrated hypertension. proteinuria, or edema during gestation. Twenty-two patients with pre-eclampsia were investigated. All wer(A being monitored in the Fetal Intensive. Care Unit and demonstrated hypertension-a systolic pressure of 140 mm. Hg (or a rise of greater than 30 mm. Hg) and ;I diastolic pressure of 90 mm. Hg (or a rise of greater than 20 mm. Hg). Nineteen were found to havt. proteinuria. and most exhibited edema an&or hyperreflexia. Eight patients met the blood pressure criteria for severe pre-eclampsia. Keview of rhr charts of the
137
138
Demers and Gabbe
25
30 20
15
I 0
\E” z
i
I I
20
I
-IIO
F E
I
I
0
I I
0
I
0
I
0
I
0
I
10
5
i
:
& 0
I I
I
NORMAL n=20 S.D. 2 5 7
l
PRE-ECLAMPSIA n=22 S.D. k 0.71
NORMAL n=20 S.D. + 3.2
PRE-ECLAMPSIA n=22 S.D. ziz 6.5
Fig.
1. PGE levels in placental tissue from 20 control patients and 22 patients with pre-ectampsia. Results are expressed as picograms per milligram of wet tissue weight. The solid line across the data points indicates the mean value. Standard deviations are listed at the bottom of the figure.
Fig.
2. PGF levels in placental tissue taken from 20 control subjects and 22 patients with pre-eclampsia. Results are expressed as picograms per milligram of wet tissue weight.
pre-eclamptic women revealed no previous history of hypertension, renal disease, or diabetes mellitus. Newborn weight, gestational age, Apgar scores at one and five minutes, and placental weight were recorded for both normal and pre-eclamptic patients. Prostaglandin (PC) radioimmunoassays were performed with the use of antiserum prepared in rabbits against the albumin conjugate of PGF2, and PGEI. The PGF antiserum used in these studies had 100
per cent cross-reactivity with PGF,,, 42 per cent crossreactivity with PGF,,, and less than 1 per cent crossreactivity with PC’s of the E, A, and B series as well as the 13,14 dihydro, 15 keto Fza. Cross-reactivity studies with the PGE antiserum indicated 100 per cent crossreaction with PGEI, 70 per cent cross-reactivity with PGEe, 88 per cent reactivity with PGA,, 51 per cent reactivity with PGA2, 14 per cent reactivity with PGBt, 6 per cent reactivity with PGFea, and less than%rie per
Placental prostaglandins
cent cross-reactivity with other related PG compounds including the 13,14-dihydro, 15-keto PGE metabolite. Placental tissue was thawed and extracted initially with ethyl acetate : isopropanol : 0.1 M hydrochloric acid (3 : 3 : 1). Following a saline wash step, the ethyl acetate layer containing the PG’s was removed and applied to a Silicic acid column for chromatographic separation of the individual PC, series. PGE was eluted from the column with a 60 : 40 : 2 benzene-ethyl acetatemethanol solvent front, while PG’s of the F series were &ted with a 60 : 40 : 20 benzene-ethyl acetateInethanol solvent front. The elutions were evaporated and reconstituted with 1 ml. of ethanol in preparation for the radioimmunoassay. Radioimmunoassay was performed as previously described with results exper milligram of wet tissue pressed as picograms weight.” Data were analyzed statistically by analysis of variance. Significance between two groups was determined by the method of least significant differences. A P value of 0.05 or less was considered to be significant.
Results PGE levels were markedly decreased (P < 0.05) in pre-eclamptic placental tissue, as shown in Fig. 1. In contrast, PGF concentrations were significantly elevated (P < 0.05). (Fig. 2). PG levels did not correlate with the severity of the pre-eclampsia.
Comment Uteroplacental ischemia observed in pre-eclampsia could be clue to an alteration in PG metabolism. Speroff has proposed that the development of precclampsia may represent defective PG production, loss
in pre-eclampsla
139
of response to PC;, or a combination 01. thvzc, abnormalities.’ Placental levels of PGF were found to be siqificantl\ increased in pre-eclampsia. These
REFERENCES 1. Speroff,
L: Toxemia
of pregnancy,
Am.
J. Cardiol.
32:
332. 1972. 2. Pulkkinen,
M. O.,
Pitkanen,
H.: Decrease of uteroplacental glandin
FzCr induced
abortion,
Y., Ojala,
A., and Hannelin,
blood flow during prostaProstaglandins
9: 61, 1975.
3. Demers, L. M., Yoshinaga, K., and Creep, R. 0.: Prostaglandin F in uterine fluild during the menstrual cycle and followine steroid treatment. Prostaelandins 5: 513. 1974. 4. Novp. G. J,, Piasecki, G., and Jacukson, B. T.: Effect of prostagkdndins EP and Fa, on umbilical blood flow and fetal hemodynamirs. Prostaglandins 5: 543, 1974.
5. Kyan. W. L.. Coronel. vasodepressor substance OBswr. GYNECOL. 105:
D. M., of the
al,d Johtwn. K. J,: A human placrnta. Ah%. J.
1201, 196l). 6. ,41am, N. A., Clary. P., and Russell, P. L’.: Depressed placental prostaglandin Et metabolism in towtnia of pregnancy, Prostaglandins 4: 363, 1973. 7. Alam, N. A., Clary. P., Shade, A. R.. and Russell, P. ‘I’.: Absence of prostaglandin E, metabolism ill hydatidiform mole, ,4w. J, OBSTET. GYNECOI.. 119: I I3 I 1974.