Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2000-7-6
pubmed:abstractText
Nonselective cyclooxygenase (COX) inhibitors are potent tocolytic agents; however, they also have adverse fetal effects such as constriction of the fetal ductus arteriosus. Recently, selective COX-2 inhibitors have been used in the management of preterm labor in the hope of avoiding fetal complications. However, both COX-1 and -2 are expressed by cells of the ductus arteriosus. We used fetal lambs (0.88 gestation) to assess the ability of selective COX-2 inhibitors celecoxib and NS398 to affect the ductus arteriosus. Both selective COX-2 inhibitors decreased PGE(2) and 6ketoPGF(1alpha) production in vitro; both inhibitors constricted the isolated ductus in vitro. The nonselective COX-1/COX-2 inhibitor indomethacin produced a further reduction in PG release and an additional increase in ductus tension in vitro. We used a prodrug of celecoxib to achieve 1.4 +/- 0.6 microg/ml, mean +/- standard deviation, of the active drug in vivo. This concentration of celecoxib produced both an increase in pressure gradient and resistance across the ductus; celecoxib also decreased fetal plasma concentrations of PGE(2) and 6ketoPGF(1alpha). Indomethacin (0.7 +/- 0.2 microg/ml) produced a significantly greater fall in ductus blood flow than celecoxib and tended to have a greater effect on ductus resistence in vivo. We conclude that caution should be used when recommending COX-2 inhibitors for use in pregnant women, because COX-2 appears to play a significant role in maintaining patency of the fetal ductus arteriosus.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/6-Ketoprostaglandin F1 alpha, http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 1, http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2, http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2 Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Dinoprostone, http://linkedlifedata.com/resource/pubmed/chemical/Epoprostenol, http://linkedlifedata.com/resource/pubmed/chemical/Indomethacin, http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes, http://linkedlifedata.com/resource/pubmed/chemical/N-(2-cyclohexyloxy-4-nitrophenyl)met..., http://linkedlifedata.com/resource/pubmed/chemical/Nitrobenzenes, http://linkedlifedata.com/resource/pubmed/chemical/Nitroprusside, http://linkedlifedata.com/resource/pubmed/chemical/Oxygen, http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandin-Endoperoxide Synthases, http://linkedlifedata.com/resource/pubmed/chemical/Pyrazoles, http://linkedlifedata.com/resource/pubmed/chemical/Sulfonamides, http://linkedlifedata.com/resource/pubmed/chemical/Vasodilator Agents, http://linkedlifedata.com/resource/pubmed/chemical/celecoxib
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0363-6119
pubmed:author
pubmed:issnType
Print
pubmed:volume
278
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
R1496-505
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:10848516-6-Ketoprostaglandin F1 alpha, pubmed-meshheading:10848516-Animals, pubmed-meshheading:10848516-Cyclooxygenase 1, pubmed-meshheading:10848516-Cyclooxygenase 2, pubmed-meshheading:10848516-Cyclooxygenase 2 Inhibitors, pubmed-meshheading:10848516-Cyclooxygenase Inhibitors, pubmed-meshheading:10848516-Dinoprostone, pubmed-meshheading:10848516-Ductus Arteriosus, pubmed-meshheading:10848516-Epoprostenol, pubmed-meshheading:10848516-Female, pubmed-meshheading:10848516-Hemodynamics, pubmed-meshheading:10848516-Indomethacin, pubmed-meshheading:10848516-Isoenzymes, pubmed-meshheading:10848516-Nitrobenzenes, pubmed-meshheading:10848516-Nitroprusside, pubmed-meshheading:10848516-Oxygen, pubmed-meshheading:10848516-Pregnancy, pubmed-meshheading:10848516-Prostaglandin-Endoperoxide Synthases, pubmed-meshheading:10848516-Pulmonary Artery, pubmed-meshheading:10848516-Pyrazoles, pubmed-meshheading:10848516-Sheep, pubmed-meshheading:10848516-Sulfonamides, pubmed-meshheading:10848516-Vasoconstriction, pubmed-meshheading:10848516-Vasodilator Agents
pubmed:year
2000
pubmed:articleTitle
Cyclooxygenase-2 inhibitors constrict the fetal lamb ductus arteriosus both in vitro and in vivo.
pubmed:affiliation
Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California 94143-0544, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't