TY - JOUR
T1 - Vaginal versus oral indomethacin in a rabbit model for non-infection-mediated preterm birth
T2 - An alternate tocolytic approach
AU - Fortson, Wilbert
AU - Beharry, Kay D.A.
AU - Nageotte, Stephen
AU - Sills, Jeremy H.
AU - Stavitsky, Yuri
AU - Asrat, Tamerou
AU - Modanlou, Houchang D.
N1 - Funding Information:
This work was made possible through a grant from the Memorial Medical Center Foundation, Long Beach, CA.
PY - 2006/10
Y1 - 2006/10
N2 - 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. Study design: 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. Conclusion: 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.
AB - 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. Study design: 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. Conclusion: 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.
KW - Indomethacin
KW - Matrix metalloproteinases
KW - Mifepristone
KW - Preterm birth
UR - http://www.scopus.com/inward/record.url?scp=33748759599&partnerID=8YFLogxK
U2 - 10.1016/j.ajog.2006.06.037
DO - 10.1016/j.ajog.2006.06.037
M3 - Article
C2 - 17000239
AN - SCOPUS:33748759599
SN - 0002-9378
VL - 195
SP - 1058
EP - 1064
JO - American journal of obstetrics and gynecology
JF - American journal of obstetrics and gynecology
IS - 4
ER -