Maternal ingestion of acetylsalicylic acid inhibits fetal and neonatal prostacyclin and thromboxane in humans

Ylikorkala, Olavi; Mäkilä, U.-M.; Kääpä, Pietari; Viinikka, Lasse

doi:10.1016/0002-9378(86)90823-9

Cited by 52 publications

(14 citation statements)

References 14 publications

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“…In the present study, we further examined if apical exposure of aspirin could attenuate AA-induced apical/basal releases of TX by normal and/or preeclamptic trophoblasts. The concentrations of aspirin used in this study (10μM and 100μM) were relatively compatible to the concentrations of aspirin measured in the umbilical circulation after maternal ingestion of aspirin of 100 mg or 500 mg (23,24) and similar to the previously published in vitro works (22,23). Our results showed that neither apical nor basal release of PGI2 was affected in cultured trophoblasts with apical exposure of aspirin, although previous reports showed that the same concentration of aspirin 100μM exhibited an inhibitory effect on PGI2 production (22,23).…”

Section: Discussionsupporting

confidence: 73%

Predominant Basal Directional Release of Thromboxane, but not Prostacyclin, by Placental Trophoblasts from Normal and Preeclamptic Pregnancies

Zhao

Lewis

et al. 2008

Placenta

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Objective-To investigate apical and basal releases of thromboxane (TX) and prostacyclin (PGI2) by trophoblasts (TCs) from normal and preeclamptic (PE) placentas.Methods-TCs isolated from normal and PE placentas were incubated in cell culture inserts for 48hrs. Medium from the upper (apical) and the lower (basal) chambers were then collected separately and measured for TX and PGI2 by their stable metabolites of TXB2 and 6-keto PGF1α by ELISA. Apical and basal releases of TX and PGI were also examined with apical exposure of TCs to arachidonic acid (AA)+/-aspirin at different concentrations. Villous tissue expressions for PGI synthase, TX synthase and TX (TP) receptor were examined by immunohistochemistry.Results-1) TXB2, but not 6-keto PGF1α, concentrations were significantly higher in the lower than in the upper chambers with both normal and PE TCs (p<0.01); 2) apical exposure of TCs to AA resulted in a significant increase in TX releases towards both the upper and the lower chambers in normal TCs (p<0.01), but only a significant increase in the upper chamber in PE TCs (p < 0.01); 3) aspirin could attenuate AA-induced TX release both in the upper and the lower chambers in normal, but not in PE, TCs (p<0.01), respectively; 4) there were no differences in 6-keto PGF1α productions both in normal and PE TCs treated with AA +/− aspirin; 5) intense staining of TX synthase and TP receptor was seen in syncytiotrophoblast layer, villous core vessels and stromal cells in preeclamptic placental tissue sections.Conclusion-Predominant basal release of TX together with intense staining of TX synthase and TP receptor in trophoblasts, stromal cells and villous core vessels are found in placentas from PE. We speculate if predominant basal release of TX by TCs occurs in vivo as we found in our in vitro culture condition, basal released TX may play a significant role in increased placental vasoconstriction such as in PE.

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Section: Discussionsupporting

confidence: 73%

Predominant Basal Directional Release of Thromboxane, but not Prostacyclin, by Placental Trophoblasts from Normal and Preeclamptic Pregnancies

Zhao

Lewis

et al. 2008

Placenta

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“…The side effect most commonly considered in association with ASA treatment during pregnancy is excess bleeding. A 100 mg single dose of ASA did not affect umbilical artery PGI 2 production, whereas 500 mg significantly inhibited production as well as tending to suppress urinary excretion of 6‐keto by newborns (Yli‐korkala et al 1986). In the present study, long term treatment with 50 mg of ASA daily prolonged bleeding time in mothers, but it was clinically insignificant since no bleeding‐related complications, such as placental abruption, appeared and bleeding during delivery was normal.…”

Section: Discussionmentioning

confidence: 95%

Low dose aspirin in hypertensive pregnant women: effect on pregnancy outcome and prostacyclin‐thromboxane balance in mother and newborn

Viinikka

Hartikainen‐Sorri

Lumme

et al. 1993

BJOG

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Objective To study the effect of daily treatment with 50 mg of aspirin (ASA) on the hypertensive pregnancy complications and on the production prostacyclin (PGI2) and thromboxane A2 (TxA2) in high risk pregnant women and their infants. Design Placebo controlled prospective study. Setting Departments of Obstetrics and Gynaecology, University of Helsinki, University of Oulu and Central Hospital of Middle Finland, Finland. Subjects Two hundred and eight pregnant women with pre‐existing hypertension or a history of severe preeclampsia in their previous pregnancy. Prostanoids were studied in a subgroup of 18 women. Interventions The women were randomised to receive ASA (50 mg/day, n= 103) or placebo (n= 105) from the mean of 15 weeks gestational age to delivery. The exacerbation of pre‐existing hypertension or the appearance of hypertension in previously normotensive women, the appearance of proteinuria and fetal growth were the main end points, but some other clinical characteristics were also recorded. Urinary excretion of PGI2 and TxA2 metabolites by mothers and infants and their production in umbilical arteries in vitro were also studied. Results Two women (one in both groups) had miscarriages, and one pregnancy was terminated for fetal anencephaly (ASA group). In addition, seven women discontinued the treatment due to urticaria (two women in ASA group), increased activity of aspartate amino tranferase in serum (one woman in both groups), or increased bleeding time (one woman in ASA group, two women in placebo group), and one woman in the placebo group was lost from follow‐up. Thus the end points could be assessed in 97 women taking ASA and 100 women taking placebo. ASA did not diminish the rate of the rise of blood pressure without (12 vs 14, respectively) or with proteinuria (9 vs 11), but fetal haemodynamic disturbances as assessed by Doppler equipment (1/44 vs 6/45 women studied, P= 0.05) and need for treatment in neonatal intensive care unit (10 vs 21, P= 0.04) were more rare in ASA group. ASA tended to increase the birthweight of the newborn (3348 ± 707 g vs 3170 ± 665 g, mean ± SD, P= 0.07), but two perinatal deaths occurred in ASA group. ASA prolonged the bleeding time of the mother (435 s, 210–998 s (geometric mean, range) vs 349 s, 210–690 s, P= 0.02), but caused no extra blood loss during delivery, nor affected neonatal hemostasis. In a subgroup of mothers (ASA, n = 10; placebo, n = 8), ASA inhibited more than 90% of platelet TxA2‐production, and caused a 65 to 80% decrease in the urinary excretion of TxA2 metabolites, but no decrease in the urinary excretion of PGI2 metabolites. Conclusions ASA did not prevent the rise of maternal hypertension, but improved fetal haemodynamic performance and reduced the need of intensive neonatal care. It inhibited strongly maternal thromboxane A2 but not PGI2 production and thus shifted the balance between PGI2/TxA2 to the dominance of the vasodilatory, anti‐aggregatory side.

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“…The ratio between prostacyclin and thromboxane (a powerful vasoconstrictor and inducer of platelet aggregation) is thought to be important in the regulation of platelet and vascular function. Low‐dose aspirin (100 mg) has minimal effect on prostacyclin production, but is a potent inhibitor of thromboxane 6 . It therefore alters the ratio of prostanoids in favour of improved perfusion and could enhance fetal growth.…”

Section: Introductionmentioning

confidence: 99%

Administration of low‐dose aspirin to mothers with small for gestational age fetuses and abnormal umbilical Doppler studies to increase birthweight: a randomised double‐blind controlled trial

McCowan

Harding

et al. 1999

BJOG

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Objective To determine whether antenatal treatment (for 2 14 days) with 100 mg aspirin daily, given to mothers with small for gestational age fetuses and abnormal umbilical Doppler, will increase birthweight. DesignSetting A tertiary referral centre.Participants Ninety-nine women, of whom 65 were treated for 2 14 days (32 with aspirin and 33 with placebo) and comprised the study group. The entry criteria were: singleton pregnancy with ultrasound evidence of a small for gestational age fetus (abdominal circumference < 10%); previous anatomy scan c 20 weeks and no evidence of fetal abnormality; gestation between 24 and 36 weeks; umbilical artery Doppler resistance index > 95% for gestation; no previous aspirin treatment in pregnancy; and no contra-indication to aspirin treatment. ResultsThe mean duration of treatment was 30 days for aspirin treated, and 29 for placebo. No difference was found in birthweight or other measures of fetal growth or newborn morbidity between those treated with aspirin or placebo. Compliance, assessed by thromboxane B2 analysis, showed almost complete suppression of thromboxane B, in aspirin treated women.Conclusion Low-dose aspirin did not increase birthweight in pregnancies where the fetus has abnormal umbilical Doppler and is thought to be small for gestational age.Randomised, double-blind placebo controlled trial.

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Maternal ingestion of acetylsalicylic acid inhibits fetal and neonatal prostacyclin and thromboxane in humans

Cited by 52 publications

References 14 publications

Predominant Basal Directional Release of Thromboxane, but not Prostacyclin, by Placental Trophoblasts from Normal and Preeclamptic Pregnancies

Predominant Basal Directional Release of Thromboxane, but not Prostacyclin, by Placental Trophoblasts from Normal and Preeclamptic Pregnancies

Low dose aspirin in hypertensive pregnant women: effect on pregnancy outcome and prostacyclin‐thromboxane balance in mother and newborn

Administration of low‐dose aspirin to mothers with small for gestational age fetuses and abnormal umbilical Doppler studies to increase birthweight: a randomised double‐blind controlled trial

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