Inhibition of prostaglandin synthesis and its effect on uterine activity during established premature labor in sheep

Jennifer E. Scott, Peta L. Grigsby, Jonathan J. Hirst, Graham Jenkin

    Research output: Contribution to journalArticle

    11 Scopus citations

    Abstract

    Objective: Continuous infusion of the selective prostaglandin synthase type-2 inhibitor nimesulide, together with the oxytocin receptor antagonist atosiban, inhibits glucocorticoid induction of labor in sheep. We evaluated the effectiveness of this treatment commencing after the onset of premature labor when prostaglandin concentrations are already significantly elevated. Methods: Premature labor was induced in chronically cannulated fetuses by constant fetal dexamethasone infusion. After the onset of active labor in each ewe, defined as uterine electromyographic (EMG) activity twice basal levels, ewes received combined nimesulide and atosiban (20.0 and 4.12 mg/kg per day, respectively; n = 6) or vehicle (n-methyl-2-pyrrolidone and saline each 1 mL/hour; n = 4) infusions for 48 hours. Maternal and fetal plasma PGFM (13, 14-dihydro-15-keto PGF, the stable metabolite of prostaglandin (PG) F) and PGE2 concentrations were measured before, during, and after infusions. Results: Four nimesulide- and atosiban-treated ewes successfully completed the 48-hour infusion period with no deliveries occurring during inhibitor treatment, or up to 6 hours after inhibitor treatment. Delivery was delayed in two other ewes, compared with control animals. Uterine EMG activity in nimesulide- and atosiban-treated ewes (n = 4) was significantly reduced during the 48-hour inhibitor treatment period. Maternal and fetal prostaglandin concentrations were significantly decreased in inhibitor-treated ewes during and after the infusions. Conclusions: The combination of nimesulide and atosiban treatment for 48 hours successfully inhibited the progression of active premature labor to delivery. This study further supports the potential value of this treatment regime for the inhibition of premature labor.

    Original languageEnglish (US)
    Pages (from-to)266-276
    Number of pages11
    JournalJournal of the Society for Gynecologic Investigation
    Volume8
    Issue number5
    DOIs
    StatePublished - Sep 10 2001

    Keywords

    • Atosiban
    • Nimesulide
    • Preterm labor
    • Prostaglandins

    ASJC Scopus subject areas

    • Obstetrics and Gynecology

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