Vaginal versus oral indomethacin in a rabbit model for non-infection-mediated preterm birth: an alternate tocolytic approach.
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.
Fortson
Wilbert
W
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Miller Children's Hospital, Women's Pavilion, Long Beach, CA, USA. nostrof@gmail.com
Beharry
Kay D A
KD
Nageotte
Stephen
S
Sills
Jeremy H
JH
Stavitsky
Yuri
Y
Asrat
Tamerou
T
Modanlou
Houchang D
HD
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
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