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

OBJECTIVE: Continuous infusion of the selective prostaglandin synthase type -2 inhibitor nimesulide, together with the oxytocin receptor antagonist ato siban, inhibits glucocorticoid induction of labor in sheep. We evaluated th e effectiveness if this treatment commencing after the onset of premature l abor when prostaglandin concentrations are already significantly elevated. METHODS: Premature labor was induced in chronically cannulated fetuses by c onstant fetal dexamethasone infusion. After the onset of active labor in ea ch ewe, defined as uterine electromyographic (EMG) activity twice basal lev els, elves 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 P GFM (13, 14-dihydro-15-keto PGF(2 alpha), the stable metabolite of prostagl andin (PG) F-2 alpha) and PGE(2) concentrations were measured before, durin g, and after infusions. RESULTS: Four nimesulide- and atosiban-treated ewes successfully completed the 48-hour infusion period with no deliveries occurring dining inhibitor t reatment, or np to 6 hours after inhibitor treatment. Delivery tvas delayed in two other elves, compared with control animals. Uterine EMG activity in nimesulide- and atosiban-treated elves (n = 4) was significantly reduced d uring the 48-hour inhibitor treatment period. Maternal and fetal prostaglan din concentrations were significantly decreased in inhibitor-treated ewes d uring and after the infusions. CONCLUSIONS: The combination of nimesulide and atosiban treatment for 48 ho urs successfully inhibited the progression of active premature labor to del ivery. This study further supports the potential value of this treatment re gime for the inhibition of premature labor. Copyright (C) 2001 by the Socie ty for Gynecologic Investigation.