Catecholamines during therapeutic abortion induced with intra-amniotic prostaglandin F2α

Catecholamines during therapeutic abortion induced with intra-amniotic prostaglandin FZcw WILLIAM PAUL

E. BRENNER, L. OGBURN,

JAMES

R. DINGFELDER,

LINDA

G. STAUROVSKY,

FREDERICK

M.D.

JR.,

M.D.* M.D. C.N.M.

P. ZUSPAN,

Chapel HiU, North Carolina,

M.D.

and Columbus, Ohio

Serial plasma, amniotic fluid, and urine samples were analyzed for epinephrine (E) and norepinephrine (NE) in eight subjects during midtrimester abortion induced by intra-amniotic prostaglandin Fza (PGF,d. After PGF,, administration, plasma E increased and there was no change in plasma NE levels. Amniotic fluid levels of E and NE decreased initially. During the course of abortion the mean level of E in the amniotic fluid increased after fetal distress and decreased after fetal death, indicating that the midtrimester fetus may respond to stress by the urinary excretion of E. The maternal urinary excretion rates of both E and NE increased following PGFP,. The observation that mean plasma levels and urinary excretion rat@ changes correlated better with the course of abortion and uterine contractility rather than with the time of PGF- administration was consistent with the hypothesis that the catecholamine response may be due to the stress of labor rather than to the PGF2, per se. (AM. J. OBSTET. GYNECOL. 130: 178, 1978.)

THE INTRA-AMNIOTIC administration of prostaglandin F,, (PGF,o) is a common method of inducing artificial midtrimester abortion in the United States. Although the method appears to be relatively safe,’ PGF20 affects the autonomic nervous system. Endogenous prostaglandins have been implicated in sympathetic and parasympathetic neuroeffector and ganglionic transmission.2* 3 Prostaglandins appear to act at pre- and post-junctional sites and alter transmitter release.4 Feedback of sympathetic neuroeffector transmission may be modulated by prostaglandins.5 Administration of appropriate amounts of specific PG’s

to animals effected neuroeffector transmission in the heart, blood vessels, spleen, vas deferens, and adipose tissue.6-10 Intravenous infusion of PGF2o in abortifacient doses to gravidas resulted in an increase in circulating norepinephrine (NE) without rapidly altering the plasma concentration of epinephrine (E) or dopamine+hydroxylase.” To evaluate the changes in E and NE that occur during PGFzQ-induced abortion, serial plasma, amniotic fluid, and urine samples were analyzed for E and NE in eight midtrimester subjects after they had received 40 mg. of PGF2~ intra-amniotically.

Material and methods

From the Departments of Obstetrics and Gynecology, University of North Carolina and Ohio State University.

Eight physically healthy gravidas from 18 to 2 1 years of age and 18 to 21 menstrual weeks’ gestation were aborted in the Clinical Research Unit of the University of North Carolina. A single dose of 40 mg. of PGFzo as the Tham salt in a concentration of 5 mg. per milliiiter was administered intra-amniotically through a transabdominally placed catheter by a previously described and course of technique. ** The specific characteristics each patient are portrayed in Table I. All subjects were managed and monitored in a similar manner (Fig. 1). The patients had nothing by

Supported in part by grants from the International Fer[ility Research Program, Research Triangle Park, No& Carolina (AIDlcsd 2979), and the Ford Foundation (Grant No. 690-0108). Received for publication Accepted July

May

2 7, 1977.

13, 1977.

Reprint requests: Dr. William E. Brenner, Department Obstetrics and Gynecology, Old Clinic Bug. 226 H, Chapel Hill, North Carolina 27514.

of

*Present address: Universig of Minnesota, Department Obstetrics and Gynecology, Minneapolis, Minnesota.

of

178

Volume Number

Catechoiamines

130

‘L

mouth for nine hours before induction. Intrauterine catheters for monitoring and injecting PGF~Q and brachial venous catheters for obtaining blood specimens were inserted a minimum of four hours prior to PGFZa injections, which were all performed sometime between 9:00 and 1O:OO A.M. Following administration of PC, the patients ate a regular diet, excepting that no caffeine was ingested. Heart rate, respiratory rate, indirect brachial blood pressure, fetal heart rate, and oral temperature were recorded every hour from four hours prior to the administration of PGFzcv until a minimum of four hours after completion of the abortion. All subjects were continuously observed and monitored in duplicate for intra-amniotic pressure by the open-end catheter technique I3 from four hours prior to administration until abortion of the fetus. Total urinary output for quantitative analysis of E and NE was collected in the following time periods: Four hours prior until immediately before PGFZa administration, from PGFza administration (time 0) to 4 hours, four to eight hours, eight to 16 hours, and 16 to 24 hours. Urine samples were refrigerated and preserved with sodium metabisulfite (50 mg. for <50 ml., 100 mg. for 5 1 to 100 ml.) and 4N perchloric acid (2.5 ml. for <50 ml., 5 ml. for 51 to 100 ml.). Samples were stored at temperatures less than -4” C. Amniotic fluid samples (10 ml.) for quantitative analysis of E and NE were obtained immediately prior to PGF2a administration and at four, eight, 16, and 24 hours thereafter and at the time of fetal distress. Samples were preserved with 0.5 ml. of 4N perchloric acid and 20 mg. of sodium metabisulfite and stored at -4” c;. Brachial venous blood samples for quantitative analysis of E and NE were obtained in heparinized syringes immediately prior to the administration of PGF,*, and four, eight, 16, and 24 hours thereafter, and at the time of fetal distress. The results of fatty acid and coagulation studies which were conducted concomitantly are not included in this report. The 30 ml. heparinized blood sample was immediately centrifuged in a refrigerated atmosphere, sodium metabisulfite (20 mg.) was added to the supernatant plasma, and the sample was stored at -4” C. Samples from two patients (Cases 3 and 7) were lost. The methods of quantitative analysis of E and NE in urine. amniotic fluid, and plasma have been described.‘” Samples of various body fluids were all analyzed on the same day when possible. Definitions were standardized. Gestational age was the number of completed weeks from the last normal menstrual period to the time of PGF,a administration.

during abortion with PGF,,

HEART RATE Bux)D PRESSURE REStVRATORY RATE FETAL HEART RATE

..*.........**.....*..

INTRAAMNtOTK: PRESSURE

I

COAGULATION PARAMETERS AMNIOTH:

FLUID-E.

PLASMA-E, URINE-E. NE

NE

NE .

179

.

.

.

.

.

.

.

.

.

.

.

.

.

.

=

e

=

l

Abortions were classified as “complete” when both the fetus and placenta were completely expelled from the uterus and “incomplete” when the fetus was completely expelled and part of the placenta was not completely expelled from the uterus. The time of fetal distress (F.D.) was defined as the time at which a minimum change of 20 beats per minute was noted in the fetal heart rate. When calculating uterine activity, only contractions of more than 5 mm. Hg were considered. Montevideo units equal the number of contractions in 10 minutes times the mean intensity in millimeters of mercury of these contractions. A Torr-minute is equivalent to a pressure of 1 mm. Hg for one minute’s duration and is calculated by multiplying the intrauterine pressure in millimeters of mercury by the duration in minutes the pressure is maintained. The areas of the uterine contractility records were calculated with a hand planimeter. Cumulative Torrminutes were calculated only from the time of PGF2, administration. Chi square tests of homogeneity were used to analyze the data, and only the significance level (the p level) of these tests is presented. Results Abortion, All subjects aborted between 9.8 and 32.6 hours (mean 18.8 hours) after PGFZQ, administration (Table I). One patient (No. 2) aborted incompletely and underwent curettage five hours after abortion of the fetus. The only complication or side effect in these patients was emesis, which occurred in seven patients. The fetal heart was no longer detectable by ultrasound as early as the one-hour examination and as late as the 16 hour examination. The time of fetal death did not appear to be related to the induction-to-abortion time. Plasma catecholamine. There was no one time after

180

Brenner et al.

January

15, 1978

Am. J. Obstet. Gynecol.

Table

I.

Overview

of the subjects and their clinical

course after intra-amniotic

CaSV NO.

‘4ge

Ra&F+

Marital statwst

Grauidity

Parity

Height (in.)

1

21

N

s

2

1

66.7

2

21

c

M

1

1

3

18

N

S

1

4

19

N

S

5

18

C

6

18

7 8

Weight (Kg.)

administration

of 40 mg. of PGF,,

Gestation (wk.)

Typeof abortionS

Stage 3 curettage

49.06

18

C

No

64.7

51.1

18

I

Yes

0

64.4

71.9

18

C

No

1

0

60.1

48.1

18

c

No

M

1

0

65.4

71.2

18

C

No

N

s

1

0

61.4

48.7

21

C

No

18

N

S

2

1

64.4

71.9

18

C

No

18

C

S

1

0

56.0

57.9

20

C

No

Mean

62.7

58.8

S.D.

k3.738

a 11.073

*N = Negro, C = Caucasian. tS = Single, M = married. $C = Complete, I = incomplete. PGFza! administration when all of the six patients who had plasma catecholamine determinations had plasma concentrations of E and NE (Fig. 2) greater than the preinjection range. Compared to the preinjection value, four of the six patients had an increase in plasma E and all six subjects had at least a small increase in plasma NE at some time after PGF*(u administration. Mean plasma concentration of E and NE increased after PGFfa administration. The mean E concentration at eight hours after PGF2a administration was significantly higher (P < 0.05) than the mean preinjection value. None of the mean values for plasma NE was significantly different (P < 0.1) from control values. Amniotic fluid. Only three of the E and none of the NE (Fig. 2) specimens in the eight subjects were above the range observed in the preinjection specimens. The mean E and NE values decreased after PGF, administration and were lower at the time of fetal distress. None of the means was significantly different (P < 0.1) from the mean of the control values. No consistent decline was observed in individual patients. Amniotic fluid E levels appeared to be related to the times of fetal distress and death (Fig. 3). In four patients the events of fetal distress and fetal death occurred at times that resulted in samples having been obtained (1) prior to fetal distress, (2) at fetal distress, (3) after fetal distress and before fetal death, and (4)

after death. At the time of fetal distress the mean amniotic fluid of E was low. After the time of distress but before death of the fetus the mean E concentration increased. After fetal death the mean E concentration was significantly (P < 0.05) lower than after fetal distress. Fetal ‘urine. Urine was obtained from the 20 week fetus delivered by patient number 8. The concentration of E was 0.7 pg per liter and NE was 0.0 pg per liter, indicating the ability of the fetus to excrete amines. Urine. Following PGFza administration urinary output of E and NE (Fig. 4) was elevated in most specimens as compared to the excretion rate prior to induction. All subjects had increased rates of E and NE excretion at some time after PGFSa administration when compared to their preinduction excretion rate. However, there were wide ranges of catecholamine excretion and only the mean level of E and NE at eight to 16 hours was significantly different (P < 0.05) from the preinjection rates. Excretion rates at the time of abortion were usually low when compared to those of laboring patients. Overview. T&e mean plasma and amniotic fluid levels and mean rates of urinary excretion of E and NE after PGFm administration are portrayed in Fig. 5. Following PGFzcr administration, mean plasma E and uri-

Volume

130

Number

2

Catecholamines

No. of Time r&j&al dt\tru.u (hr.)

dosesof meperidine

No. of doses of prochlorpe-rau’ne

No. of emesrs

Time until rupture of membranes

abortion

Time until plncmtal 6+uision

Time until

frtcll

during

abortion

Fetal wt. (Cl%/

PioCent/ll ill. (Grn.)

with PGF,,

Maximum temp. PF.)

7 hr. 40 min.

3

0

1

7 hr. 40 min.

31 hr. 45 min.

32 hr. 40 min.

129

IO3

99.2

5 hr. 43 min.

4

1

2

16 hr. 23 min.

1X hr. 50 min.

24 hr. IO min.

244

155

99.8

2 hr. 45 min.

4

0

1

13 hr. 30 min.

13 hr. 30 min.

13 hr. 30 min.

293

198

99

1 hr. 40 min.

5

1

2

15 hr. 0 min.

22 hr. 7 min.

24 hr. 35 min.

138

90

99.4

1 hr. 38 min.

6

1

2

20 hr. 38 min.

25 hr. 8 min.

28 hr. 38 min.

268

136

98.6

2 hr. 19 min.

2

1

1

9 hr. 50 min.

9 hr. 50 min.

9 hr. 50 min.

315

153

99.6

2 hr. 10 min.

3

1

1

10 hr. 15 min.

10 hr. 15 min.

IO hr. I5 min.

287

139

98.2

3 hr. 50 min.

4

0

0

16 hr. 5 min.

16 hr. 20 min.

16 hr. 20 min.

597

262

99.2

3 hr. 25 min.

3.875

0.5125

1.250

14 hr. 1 min.

18 hr. 49 min.

20 hr. 20 min.

283.7

154.6

99.125

0

0

23 hr. 59 min.

I7 hr. 13 min.

t8

-t2 hr. 10 min.

nary E excretion increased for a minimum of 8 hours. By 16 hours after PGFza administration pla’sma and amniotic fluid E levels had decreased and the urinary excretion rate declined thereafter. Mean NE concentration in the plasma did not appear to change, whereas amniotic fluid levels appeared to decrease and urinary excretion rate increased until 16 hours after PGF2~ administration. Mean amniotic fluid levels at the time of fetal distress were lower than the mean amniotic E and NE levels prior to PGF2, administration. To better determine correlations with the course of abortion, mean plasma and amniotic f7uid catecholamine levels and urinary excretion rates were portrayed as proportions of the abortion time, since each patient aborted at a different time after PGF2~ administration (Fig. 6). Obviously the time from PGFZa instillation and the proportion of abortion time are not variables that are independent of one another. Since mean plasma levels of catecholamines correlated better with mean urinary catecholamine excretion rates when means were plotted over the course of abortion (Fig. 6) than with times after PGFz~ administration (Fig. 5), it appears that catecholamine excretion correlates better with the course of abortion than with the time of PGFza administration. Mean plasma E concentration and urinary excretion rates of E increased early in labor,

181

hr. 9 min.

reached a plateau, and then decreased prior to delivery of the fetus. Postabortal levels and rates were low. In contrast, mean amniotic fluid E and NE levels decreased in early labor. After the mean time of fetal distress mean amniotic fluid E concentration increased transiently and then decreased late in the course of abortion when many of the fetuses were dead. Mean plasma and amniotic fluid levels of NE did not appear to change, whereas the urinary excretion rate increased early in labor, reached a plateau, and then decreased late in the course of abortion. The mean postaborrion NE excretion rate was higher than preinduction levels. Uterine contractility. Following PGFza administration uterine activity evolved in a consistent manner. In individual patients (Fig. 7) after a short period, frequent 10~. intensity contractions and a rising tonus were observed. Later contractions were less frequent and of higher intensity and longer duration. Uterine activity, as measured in Torr minutes and Montevideo Units, initially increased. Mean uterine activity as measured in Torr minutes and Montevideo Units and uterine tonus increased rapidly initially and then reached a plateau after PGF,, administration (Fig. 8) and over the course of abortion (Fig. 9). Frequency increased initially and then decreased, whereas intensity of uterine c.ontractions in-

182

Brenner et al.

January Am. J.

Il. AMNIOTIC

I. PLASMA A. EPINEPHRINE

28 26

.

24 22

FLUID

A. EPINEPHRINE.

. . .

.

15, 1978

Obstet. Gynerol.

.

i

. .

B. NOREPlNEitiRlNE . INDIVIDUAL 0 MEAN

.

VALUES

P

MEAN AND RANGE OF PRRINJKTION VALUES

. l

.

.

9. NOREPINEPHRINE

VALUES

Q 1.43 @A 1.2F

!D I 0 0

0

0

0 z z

1.0.B-

’4

.6-

g

.4.2 -

I

-4

4

8

16.

24

0

. FGFRE

TIME I liRS.1

TIME ( HRS.1

Fig. 2. Plasma and amniotic fluid catecholamines after intra-amniotic administration of PGFza. The plasma E and NE for six subjects and the amniotic fluid E and NE for eigh’t midtrimester subjects over the time after the intra-amniotic administration of 40 mg. of PGFm as detailed in the text are graphed. Values at the time of fetal distress (FD) are plotted at the mean time of FD. creased rapidly over the initial 2 hours and then increased at a slower rate. Parameters of uterine activity were calculated for only 90 per cent of the abortion time since the values immediately prior to abortion were often not valid because the monitoring catheters often prolapsed into the vagina or were obstructed at this time.

Comment Following the intra-amniotic administration of an abortifacient dose of PGFza and over the course of abortion it appears that there is an increased release of E and NE. Increased plasma levels of E were detectable in all subjects, increased levels of NE were detected in most subjects, and increased rates of urinary excretion of E and NE occurred in all patients. Following abor-

tion all of these parameters ofincreased catecholamine release decreased to levels similar to those observed prior to PGF*a administration. Catecholamine release in patients undergoing abortion induced with intra-amniotically administered PGFza appears to differ from that of patients undergoing abortion induced with intravenous PGF2a and patients having spontaneous term labor. Among patients undergoing therapeutic abortion induced with intravenously administered PGFza, plasma NE increased significantly, whereas plasma E levels did not change significantly. I1 Although patients in term labor did not have increased rates of E and NE excretion during labor, elevated rates of catecholamine excretion were observed on the day after delivery.” In contrast. eclamptic patients in labor” and patients undergoing

Volume

130

Number

2

Catecholamines

during abortion with PGF,,

183

2.62.4 2

2.2 -

%

2.0 -

$1 z

1.8-

pt $ i

l6

f’

:-:-

B

1.0 0.8 -

Fig. 3. Mean amniotic fluid catecholamines related to fetal distress and death. The mean amniotic fluid concentrations of E and NE among four subjects in whom “fetal distress” as defined in the text and fetal death occurred at times that allowed for amniotic fluid samples to be drawn at times (I) prior to distress, (2) of fetal distress, (3) after distress and before death, and (4) after death, according to the protocol detailed in the text. abortion induced with intra-amniotic PGFm appear to have increased E and NE excretion during labor. The significance of this increased catecholamine release is unknown. Although these increases in E and NE plasma levels are enough to effect fatty acid metabolism,16 they are probably not enough to effect observable cardiovascular parameters since abortion induced with intravenously administered PGFza failed to cause significant changes in heart rate, direct arterial blood pressure, central venous pressure, cardiac output, or electrocardiogram. ” However, regional blood flow may be altered by such small increases in circulating E and NE. Thus, although these changes in catecholamine metabolism do not appear to be large enough to cause maternal stress reactions, they may be important in maintaining homeostasis. The intra-amniotic administration of PGFpa in abortifacient doses does not appear to inhibit maternal sympathetic nerve function. Numerous studies have demonstrated the many prostaglandins inhibit neurally induced release of NE in several organs.” Since there were no significant changes in cardiovascular parameters and there was evidence of increased release of both E and NE in these patients receiving intraamniotic PGFza, there is no evidence in this study to indicate that there was any alteration of sympathetic response after PGF2a administration. Although the etiology of the increased E and NE release in the study patients cannot be determined with certainty, there are reasons to believe the increased re-

A. EPINEPHRINE .

25

.

20

8. NOREPINEPHRINE 20

I

r

TIME

(HRS.)

Fig. 4. Urinary E and NE after PGFm. The urinary excretion rates of E and NE over time in eight subjects after the intraamniotic administration of 40 mg. of PG F,a as detailed in the text are graphed. Squares are next to the values obtained in patients who aborted during that time period. lease was related to labor and side effects of PGFm rather than being a direct effect of PGFm. Following the intra-amniotic administration of PGFza the amniotic fluid half life is usually less than 12 hours. Although the blood levels remain very iow, PGFza is detectable in the blood within one hour after intraamniotic administration and the blood concentration

184

Brenner et al.

16-

January 15, 1978 Am. J. Obstet. Gynecol.

A. PLASMA

I6 14

I

14 -

A. PLASMA

2. O-

*I

l-

-EPINEPHRINE HNOREPtNEPHRtNE

w -

EPtNEPHRtNE NOREPtNEPHRtNE

, s C. URINE 17 -

q n

T

16 -

C. URINE

EPtNEPHRtNE

IS-

NOREPlNEPHRtNE

17 -

15 -

16 -

14 -

15 -

I3 -

14 -

12 -

13 -

I, -

q l

EPtNEPHRtNE NOREPtNEPHRtNE

Tr .

‘TIME

IHRi.)

Fig. 5. Mean E and NE levels after PGFza. The mean plasma level of E and NE f 1 S.D. among six subjects, the amniotic fluid levels among eight subjects, and the urinary excretion rate + SD. in eight subjects over the time after the intraamniotic administration of 40 mg. of PGF, as detailed in the text are graphed. The mean values of plasma and amniotic fluid catecholamines are graphed at the mean time of fetal distress and are not joined to the line connecting the other means.

appears to be related to the intrauterine concentration.rg Following intravenous administration, the effects of PGF2~ are within a few minutes. Thus, if the increase in plasma E and NE and excretion rate were a direct effect of the PGFzo, one would anticipate that the maximum E and NE blood levels and urinary excretion would be noted within 4 hours of PGF& ad-

Fig. 6. Mean E and NE levels over course of abortion. The mean plasma level of E and NE among six subjects, the amniotic fluid levels among eight subjects, and the urinary excretion rate in eight subjects over the course of abortion as proportion of the abortion time after induction with the intra-amniotic administration of 40 mg. of PGFm as detailed in the text are graphed.

ministration rather than at eight hours as they were in this studv. E appeared to increase more than NE after intruamniotic administration. In contrast, during abortion induced with intrauenow infusions of PGF2a:, NE was noted to be increased more than E.” If the increase in catecholamines were a direct effect of circulating

Volume Number

Catecholamines

130 2

during

abortion

with PGF,,,

A.P.

18 y.o. Gl PO 18 wks. gestation Ab Time IO hrs. 15min *O” IOOo

0 &+

PGF2a

PGF2a *5mg. -“-,.I ,,,,,,rrr,

HzI”

MEPERtDlNE

75 mg - I.M. f

,)35mg. ’

0

r

I

I

20

IO

30

TC g sg200 100 5

IN MINUTES

Fig. 7. Initial

intrauterine pressure and uterine activity in one subject after intra-amniotic administration of 40 mg. of PGF,,. The record of direct intra-amniotic pressure as measured by the openend catheter technique in one subject during and after the intra-amniotic administration of prostaglandin is photographed. The calculated uterine activity and uterine activity units are portraved in A and the cumulative uterine activity is portrayed in B.

A. MEAN 700

Fig. 8. Mean

0

2

4

6

2

4

6

6

IO

-

32*ooo

- E. CUMULATIVE

6

1012

0

W 2 24.000 5I 20,000

-

b

16,000

-

e

I2,OOO

-

6,000

-

4,000

-

-

12

0

0. INENSITY

C. FREQUENCY

0

-

=,m

ul 28,oMl-

’

m 16r

40m

2

4 TIME

2

ANDTONUS

6 8 WIRS.)

IO

4

6

6

IO

E. UTERINE

I2

0

2

I2

ACTIVITY

4

6

6

IO

12

uterine activity after the intra-amniotic administration of 40 mg. of PGFm. The mean uterine activity, cumulative uterine activity, frequency in contractions, intensity, tonus, and utei-ine activity over the time after the intra-amniotic administration of 40 mg. of PGFm in eight subjects as detailed in the text are graphed. Only preabortion values are included.

185

166

Brenner et al.

January Am. J. Obstet.

15, 1978 Gynecol.

Fig. 9. Mean uterine activity over the course of abortion induced by the intra-amniotic administration of 40 mg. of PGF,. The mean uterine activity, cumulative uterine activity, frequency in contractions, intensity, tonus, and uterine activity over the course of abortion in per cent of abortion time after the intra-amniotic administration of 40 mg. of PGFzo in eight subjects as detailed in the text are graphed. Values at the time of abortion (100 per cent) were not graphed because they were often not valid because of mechanical problems.

PGFm, one might anticipate a more consistent effect. If the increase in catecholamines were a direct effect of the PGFza!, one might also expect the increase in catecholamines to occur in all patients within a relatively short period of time rather than at various times after PGF20 administration as they did in this study. It appears that the increase in mean E plasma values and rates of urinary excretion correlated better with the course of labor (Fig. 6) than the time of PGFra administration (Fig. 5), and that the maximum catecholamine output occurred at a time after labor was established in that uterine activity had reached a plateau and patients were frequently having pain and on occasion were vomiting. Thus, the rise in plasma catecholamine and increase in the rate of excretion was probably not due to a direct action of PC on the sympathetic nervous system but rather a secondary sympathetic response to the induction of labor and/or the side effects of labor and PGFzcr. The amniotic fluid levels of E may be dependent upon fetal excretion. Relatively high levels of catecholamines were present in the fetal urine. The

pre-PGF= injection levels may have been relatively high in some patients because samples were obtained shortly after intra-amniotic catheter placement, which may have stressed the fetus. The mean amniotic fluid concentration of E increased after fetal distress and decreased after fetal death. It is doubtful that the increase in amniotic fluid concentration of E and NE was secondary to the increased maternal plasma levels since amniotic fluid levels of E and NE decreased early in the course of abortion when plasma levels of E were increasing. Three observations appear to be pertinent: (1) second-trimester fetuses appear to be capable of producing E and NE, (2) second-trimester fetuses appear to secrete increased quantitites of E in response to stress, and (3) increased amniotic fluid levels of E may reflect a fetus that has been stressed. Further studies will be necessary to determine the types of stress, the associated changes, and the practicability of using amniotic

fluid

catecholamine

chronic and acute In summary, it intra-amniotically in a small increase

levels

as

indicators

of

fetal stress. appears that abortion induced with administered PGFzo usually results in maternal catecholamine secretion

Volume Number

130 2

which

appears

labor,

side

the tration

P(;F2a.

to be related

effects, There

attenuates

and

to the stress

abortion

process

is no evidence the

maternal

that or

fetal

imposed rather PGFm

by the than

to

adminis-

response centration excretion

Catecholamines

during

to stress.

increased

of

The

E appears

by the

fetus

abortion

to result in response

187

with PGF,,

amniotic from

fluid an

con-

increased

to stress.

catecholamine

REFERENCES 1. Brenner, W. E.: The current status of prostaglandins as abortifacients, AM. J. OBSTET. GYNECOL. 123: 306: 1975. 2. Hedqvist, P.: Prostaglandin induced inhibition of vascular tone and reactivity in the cat’s hind leg in vivo, Eur. J. Pharmacol. 17: 157, 1972. 3. Hedqvist, P.: Prostaglandin induced inhibition of neurotransmission in the isolated guinea pig seminal vesicle, Acta Physiol. Stand. 84: 506, 1972. 4. Swedin, G.: Endogenous inhibition of the mechanical response of the isolated rat and guinea pig vas deferens to pre- and postganglionic nerve stimulation, Acta Physiol. Stand. 83: 473, 1971. 5. Hedqvist, P.: Studies on the effect of prostaglandins E, and Ez on the sympathetic neuromuscular transmission in some animal tissues. Acta Physiol. Stand. 79(Suppl. 345): 1. 1970. 6. Wennmalm, A., and Hedqvist, P.: Prostaglandin Et as inhibitor of the sympathetic neuroeffector system in the rabbit heart, Life Sci. S(Part 1): 931, 1970. 7. Weiner, R., and Kaley, G.: Influence of prostaglandin E, on the terminal vascular bed, Am. J. Physiol. 217: 563, 1969. 8. Davies, B. N., and Withrington, P. G.: Actions of Prostaglandins A,, AB, E,. Es, Fio, F20 on Splenic Vascular and Capsular Smooth Muscle and Their Interactions with Sympathetic Nerve Stimulation, Catecholamines and Angiotensin, in Mantegazza, P., and Horton, E. W.. editors: Prnstaglandins, Peptides and Amines, London and New York, 1969, Academic Press, Inc., pp. 53-56. 9. Naimzada, M. K.: Effects of some naturally occurring prostaglandins on the isolated hypogastric nerve seminal vesicle preparation of the guinea pig, Life Sci. 8: 49, 1969h. 10. Berti. F., and Usardi. M. M.: Investigations on a new inhibitor of free fatty acid mobilization, G. Ital. Arteriosclerosi 2: 261. 1964.

11. Mueller, R. A., Fishburne, J. I.. Brenner, W. E., Braaksma, J. T., Staurovsky, L. G., Hoffer, J. L., and C. H.: Changes in human plasma Hendricks, catecholamines and dopamine-beta-hydroxylase produced by prostaglandin Fso, Prostaglandins 2: 219, 1972. 12. Staurovsky, L. G., Brenner, W. E., Dingfelder, J. R., Kumarasamy, T., and Grimes, D.: Transabdominal amniocentesis for intraamniotic administration of prostaglandin, University of North Carolina Consortium, 1973. 13. Alvarez, H., and Caldeyro, R.: Contractility of the human uterus recorded by new methods, Surg. Gynecol. Obstet. 91: 1, 1950. 14. Zuspan, F. P., and Cooley, M. A.: Semi-automated fluorometric trihydroxy indole method for determining epinephrine (E) and norepinephrine (NE), Adv. Auto. Anal. 1: 351, 1970. (Proceedings of Technicon International Congress, New York, 1969.) 15. Zuspan, F. P.: Adrenal gland and sympathetic nervous system response in eclampsia, AM. J. OBSTET. GYNECOL. 114: 304, 1972.

16. Ogburn, P. L., Jr., Brenner, W. E., Reitz, R. C., Zuspan, F. P., Staurovsky, L. G., and Dingfelder, J. R.: Arachidonic acid and other free fatty acid changes during ahornon induced by prostaglandin Fza, AM. J. OBSTET. GYNECOL. 130: 188, 1978.

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1, Plenum Press, Inc., chap. 4, pp. 101-131. 19. Green, K.: Personal communication. Karolinska stitutet, Stockholm, Sweden.

Medical and Surgical Diseases in Pregnancy The Department of Obstetrics and Gynecology of the University of Iowa College of Medicine announces a postgraduate course, entitled “Medical and Surgical Diseasesin Pregnancy,” to be held in Iowa City, Iowa, May 15-16, 1978. Topics covered wiII include management of pregnant patients with cardiovascular, renal, respiratory, gastrointestinal, autoimmune, and neurological diseases,as well as diabetes, anemia, obesity, and malignant neoplasms. Guest speakers will include William Spellacy, M.D., John Queenan, M.D., and Robert Resnik, M.D. Registration fee is $150 ($75 for residents and fellows). For registration and information contact: Office of Continuing Medical Education, The University of Iowa, College of Medicine, 285 Med Labs, Iowa City, Iowa 52240. Telephone: (319) 353-5763.

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