title: Vaginal versus oral indomethacin in a rabbit model for non-infection-mediated preterm birth: an alternate tocolytic approach.
abstract: OBJECTIVE
  We examined the hypotheses that vaginal indomethacin is more effective for prolonging gestation, and mediates its tocolytic actions via changes in cervical matrix metalloproteinase (MMP) activity, compared to oral.
  
  
  METHODS
  Pregnant rabbits induced with mifepristone received oral or vaginal indomethacin; or oral or vaginal vehicle once daily for 2 days. Premature delivery, fetal ductus arteriosus, and cervical MMP activity were assessed.
  
  
  RESULTS
  Vaginal indomethacin delayed delivery >72 hours in 100% of the rabbits, extending gestation to 28.2 +/- 0.5 (P < .01) versus 26.4 +/- 0.3, 25.8 +/- 0.5, and 26.5 +/- 0.3 days, for vaginal placebo, oral indomethacin, and oral vehicle, respectively. Fetal ductus arteriosus was patent in all groups. Vaginal indomethacin decreased MMP-1, -8, and -9 activities and increased TIMP-1 levels in the cervix.
  
  
  CONCLUSIONS
  Vaginal indomethacin is more effective than oral for prolonging gestation in the rabbit. Its tocolytic effects may be mediated, in part, by alterations in cervical MMP activity.
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Miller Children's Hospital, Women's Pavilion, Long Beach, CA, USA. nostrof@gmail.com
authors.forename: Wilbert
authors.initials: W
authors.lastname: Fortson
authors.forename: Kay D A
authors.initials: KD
authors.lastname: Beharry
authors.forename: Stephen
authors.initials: S
authors.lastname: Nageotte
authors.forename: Jeremy H
authors.initials: JH
authors.lastname: Sills
authors.forename: Yuri
authors.initials: Y
authors.lastname: Stavitsky
authors.forename: Tamerou
authors.initials: T
authors.lastname: Asrat
authors.forename: Houchang D
authors.initials: HD
authors.lastname: Modanlou
mesh_terms: D000282:Administration, Intravaginal; D000284:Administration, Oral; D000818:Animals; D002584:Cervix Uteri / Q000201:enzymology; D005260:Female; D007213:Indomethacin / Q000008:administration & dosage* / Q000009:adverse effects; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D011247:Pregnancy; D047928:Premature Birth / Q000517:prevention & control*; D011817:Rabbits; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis; D015145:Tocolysis
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1; D007213:Indomethacin