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Inhibition of Prostaglandin Synthesis and Its Effect on Uterine Activity During Established Premature Labor in Sheep

Fetal and Neonatal Research Group, Department of Physiology, Monash University, Clayton, Victoria, Australia

Peta L. Grigsby, BS

Fetal and Neonatal Research Group, Department of Physiology, Monash University, Clayton, Victoria, Australia; Department of Physiology, Monash University, Clayton, Victoria, 3800, Australia; p.grigsby{at}med.monash.edu.au

Jonathan J. Hirst, PhD

Graham Jenkin, PhD

Fetal and Neonatal Research Group, Department of Physiology, Monash University, Clayton, Victoria, Australia

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 PGF₂, the stable metabolite of prostaglandin (PG) F₂) 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 treatmenmt 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.

Key Words: Prostaglandins • nimesulide • atosiban • preterm labor

Journal of the Society for Gynecologic Investigation, Vol. 8, No. 5, 266-276 (2001)
DOI: 10.1177/107155760100800503


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