Production of prostacyclin, 6-keto-PGF1 alpha and thromboxane B2 by human umbilical vessels increases from the placenta towards the fetus

The aim of this study was to investigate the production of prostacyclin (PGI2) and thromboxane B2 (TXB2) by incubated samples of umbilical arteries and veins taken at different distances (2, 10, 20, 30 cm) from the placenta to provide additional information relevant to the haemodynamics of umbilical blood flow. The production of PGI2, and 6-keto-PGF1 alpha (the stable metabolite of PGI2), was higher in both veins and arteries as the distance from the placenta at which the vessels were sampled was increased. A similar correlation between production by venous rings and distance from the placenta was observed for TXB2, but there was no apparent gradient of TXB2 production by the samples of arterial rings. No statistically significant variations were discernible in the ratio of 6-keto-PGF1 alpha:TXB2 (approximately 50 in the veins and approximately 20 in the arteries) in relation to the sampling distance. The significance of these high ratios is discussed in relation to umbilical blood flow and fetal well-being and development.     

Effect of vacuum curettage on the concentrations of plasma 6-keto-prostaglandin Flα and serum thromboxane B2

Summary. Serial plasma samples collected before and after vacuum curettage followed by methylergometrine injection in 10 women were assayed for 6-keto-prostaglandin F_lα (6-keto-PGF^1α). The mean 6-keto-PGF_lα concentration was 97.2 (SE 8.8) pg/ml before cervical dilatation. The concentration rose to 128.2 (SE 13.5) pg/ml (P < 0.10) immediately and to 133.3 (SE 17.8) pg/ml (P < 0.05) 1 h after curettage and returned to the initial value within 5 h. Neither methylergometrine nor anaesthesia, nor non-gynaecological surgery, caused changes in the level of plasma 6-keto-PGF_lα. The capacity of the platelets to produce thromboxane A² during spontaneous clotting of blood did not change during vacuum curettage, anaesthesia and non-gynaecological surgery, nor after methylergometrine. The evidence suggests that the pregnant myometrium and/or intrauterine tissues capable of generating prostacyclin (PGI₂) in vitro may release PG1₂ also in vivo .     

Vaginal and abdominal delivery increases maternal urinary 6-keto-prostaglandin F1α excretion

Summary. To study the role of the antiaggregatory and vasodilatory prostacyclin (PGI₂) during human delivery, serial urine samples collected from 13 women delivered vaginally and from eight delivered abdominally were assayed for 6-keto-prostaglandin F_1α (6-keto-PGF_1α a breakdown product of PGI₂) by high-performance-liquid-chromatography and radioimmunoassay. In women delivered vaginally the mean urinary 6-keto-PGF_1α concentration was 41.9 (SE 8.3) ng/mmol creatinine, before the onset of labour and increased progressively to a maximum of 186.5 (SE 47.6) ng/mmol creatinine 2 h after delivery irrespective of the use of oxytocin and epidural analgesia. In women delivered by caesarean section under epidural anaesthesia, the urinary 6-keto-PGF_1α rose from 33.4 (SE 4.2) ng/mmol creatinine to 2153 (SE 314) ng/mmol creatinine 2 h after section. In both groups the increased levels had fallen by 24 h postpartum to levels below those found before delivery. In neonatal urine 6-keto-PGF_1α concentrations were some 12–30 times higher than those in postpartum urine. Thus, vaginal and abdominal delivery is accompanied by significant increases in maternal PGI₂ release, perhaps in the myometrium and/or intrauterine tissues. This may be of significance in the regulation of fetoplacental blood flow and in the prevention of intra- and postpartum thrombosis.     

Amniotic fluid concentrations of secreted pregnancy-associated endometrial α1 and α2-globulins (α1- and α2-PEG)

Summary. The levels of pregnancy-associated endometrial α₁- and α₂-globulins (α₁- and α₂-PEG), the two major proteins synthesized and secreted by the endometrium in vitro have been assayed in 210 amniotic fluid specimens obtained at termination of pregnancy or by amniocentesis, or at delivery. α₁-PEG was undetectable until week 10 and thereafter rose to peak levels between weeks 20 and 24. Levels fell 15-fold by week 35 but substantial amounts were still present at parturition. α₂-PEG was present at highest levels during early pregnancy, at weeks 6–15, but thereafter levels rapidly fell until during weeks 31–42 α₂-PEG was detectable in only 3 of 25 specimens. During weeks 15–20, when α₂-PEG levels fell and α₁-PEG levels rose, a high correlation was observed between the week of gestation and the log of the ratios of the concentration of these proteins. These observations provide the opportunity to assess the role of endometrial and decidual dysfunction in the aetiology of pregnancy disorders.     

Primary dysmenorrhoea: the importance of both prostaglandins E2 and F2α

Summary. Menstrual fluid was collected in a contraceptive diaphragm from 16 women with primary dysmenorrhoea and 12 matched control subjects without dysmenorrhoea. Prostaglandins F_2α (PGF_2α), E₂ (PGE₂) and 6-oxo-prostaglandin F_1α (6-oxo-PGF_lα) were extracted and measured using gas-chromatography: mass spectrometry (GC:MS). The concentrations of both PGF_2α and PGE₂ were higher on days 1 and 2 in the dysmenorrhoea group than in the control group and the concentration of PGF_2α was higher on day 1 than on day 2 in the dysmenorrhoea group. The concentrations of 6-oxo-PGF_1α (the stable metabolite of PGI₂) were low in both groups. These results confirm suggestions that PGF_2α is important in the aetiology of dysmenorrhoea and also indicate that PGE₂ may be involved.     

Termination of Pregnancy by Intra-uterine Prostaglandin F2α

Summary: Fourteen pregnancies between the 12th and 19th weeks of gestation were terminated by intra-uterine administration of prostaglandin F_2α. In 7 patients the method of administration was transcervically into the extra-ovular space; in the other 7, administration was directly into the amniotic sac. The methods of administration, the doses used, the side effects and results are discussed. The findings indicate that intra-amniotic administration is the procedure of choice: firstly, because of the incidence of genital tract infection after transcervical administration; secondly, because 3 patients in the transcervical group had incomplete abortions and required anaesthesia for curettage; and finally, the induction-abortion interval was significantly less when the drug was administered into the uterine cavity.     

Thromboxane A2 and prostacyclin levels in molar pregnancy

Summary. Plasma levels of thromboxane (TX) A₂ and prostacyclin (PGI₂), as measured by radioimmunoassay of their respective stable metabolites TXB₂ and 6–keto PGF_1α, were studied in six molar pregnancies immediately before, immediately following and 24 h after evacuation of the uterus. The mean (SD) levels for TXB₂ were 150 (41), 137 (32) and 125 (25) pg/ml respectively, and for 6–keto PGF_1α the respective values were 225 (52), 226 (127) and 213 (49) pg/ml. There was no significant difference in the levels of prostanoids between the samples taken at the various time intervals. The concentration of these prostanoids in molar intravesicular fluid was also determined. Their respective mean (SD) pg/ml values were 3682 (760) for TXB₂ and 2969 (744) for 6–keto PGF_1α. In 15 normal pregnancies of equivalent gestation, the mean amniotic fluid levels of TXB₂ and 6–keto PGF_lα were 34 (17) and 146 (86) pg/ml respectively. The ability of molar trophoblast to generate the prostanoids from [¹⁴C]arachidonic acid in vitro was also demonstrated. Mean (SD) values for TXB₂ and 6-keto PGF_1α were 12.2 (2.6) and 13.2 (1.8) pg/mg protein/min, respectively. It is likely that the high concentrations of prostanoids in vesicular fluid reflect the synthesizing ability of the villus vesicles. The mole contributes little to the circulatory prostanoids possibly because its villi are deficient in blood circulation.     

Complex formation of pregnancy-specific α2–glycoprotein (SP1α) and heparin

Summary. The Schwangerschaftsprotein 1 (SP₁,)α values in blood measured by rocket immunoelectrophoresis are affected by the addition of anticoagulants. When compared with values in serum, those in heparin plasma were much higher, while those in sequestrene ethylenediaminetetra acetic acid), sodium citrate and fluoride oxalate were lower. On the other hand, SP₁ and SP₁β concentrations were not significantly affected in heparin or sequestrene and were only slightly depressed in sodium citrate and flouride oxalate. The effect of heparin on SP₁α in serum was dosedependent. We surmise that SP₁α forms a complex with heparin and that it may be involved in the coagulation system in pregnancy.