Inhibition of cervical ripening by local application of cyclooxygenase 2 inhibitor.
OBJECTIVE
Our goal was to test the hypothesis that the previously demonstrated progesterone-independent prolongation of pregnancy in rats treated with cervical application of the cyclooxygenase 2 inhibitor nimesulide is the result of inhibition of cervical ripening.


METHODS
Timed-pregnant Sprague-Dawley rats were randomly allocated to treatment with 50 mg nimesulide or vehicle, applied daily on the cervix for 5 days (days 14-18). On day 19 the animals were humanely killed and the cervices were removed. In the first series of experiments the cervices of animals treated with nimesulide (n = 10) or vehicle (n = 10) were examined with a cervimeter, which stretches the cervical tissues in incremental steps of 0.2 mm at 1-minute intervals. A steeper slope through the linear portion of the resulting force-versus-displacement curve indicates more resistance to stretch. In the second series of experiments the cervices of animals treated with nimesulide (n = 11) or vehicle (n = 11) were examined with the Collascope optical device. The cervical content of cross-linked collagen was measured with light-induced fluorescence. The fluorescence spectrum at 390 nm (peak wavelength of the collagen spectrum) was determined. For standardization, the ratio of counts of collagen peak over reference counts was used in the final analyses as an indicator of cross-linked collagen content.


RESULTS
Animals treated with cervical application of nimesulide had significantly higher resistance to stretch than controls (slope: 0.2564 +/- 0.1213 vs 0.1387 +/- 0.0652; P =.019). The cervical content of cross-linked collagen was not significantly different between nimesulide-treated animals and controls (light-induced fluorescence ratios: 3.2134 +/- 0.7390 vs 2.7892 +/- 0.8518; P =.227).


CONCLUSIONS
Treatment with cervical application of the cyclooxygenase 2 inhibitor nimesulide prevents the physiologic process of cervical ripening in late pregnancy. The inhibition is not the result of changes in cross-linked collagen content. Inhibition of cervical ripening with locally administered cyclooxygenase 2 inhibitor may be a potentially valuable treatment for patients at risk for preterm delivery.
Bukowski
R
R
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston 77555-0587, USA.
Mackay
L
L
Fittkow
C
C
Shi
L
L
Saade
G R
GR
Garfield
R E
RE
D000287:Administration, Topical; D000818:Animals; D020070:Cervical Ripening / Q000187:drug effects*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D005260:Female; D007527:Isoenzymes / Q000009:adverse effects*; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013449:Sulfonamides / Q000494:pharmacology*
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C012655:nimesulide