Abstract
CORRIGENDACorrigendumPublished Online:01 Dec 2000https://doi.org/10.1152/ajpregu.2000.279.6.Ca3Original articleMoreSectionsPDF (48 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmail Volume 279, June 2000Volume 48, June 2000Pages R1496–R1505: Yasushi Takahashi, Christine Roman, Sylvain Chemtob, Mary M. Tse, Emil Lin, Michael A. Heymann, and Ronald I. Clyman. “Cyclooxygenase-2 inhibitors constrict the fetal lamb ductus arteriosus both in vitro and in vivo.”The accepted version of the In Vitro Studies section of methods is shown below instead of the earlier version that was published.In Vitro StudiesThe purpose of the in vitro studies was to show that inhibitors of COX-2, celecoxib and NS-398, were capable of inhibiting prostaglandin production and contractile tone in the ductus itself. They complement the in vivo studies where the effects of the COX-2 inhibitor could be attributed to systemic effects that are independent of the drug's direct action on the ductus.Nineteen fetal lambs (between 125 and 137 days) were delivered by cesarean section. The ewe was anesthetized with a constant intravenous infusion of ketamine HCl and diazepam throughout the procedure. The fetus was given ketamine HCl (30 mg/kg im) before rapid exsanguination. The ductus arteriosus was dissected free of loose adventitial tissue and divided into 1-mm-wide rings that were placed in separate 10-ml organ baths and kept in a dark room, as we described previously (7). Tissue oxygen concentration is significantly lower in isolated ductus rings incubated in bath solutions containing “fetal Po2” when compared with the fetal ductus in vivo. In vivo, the fetal lamb ductus relies on vasa vasorum that perfuse 60–70% of the muscle media. The measured average tissue O2 concentration in the late gestation fetal lamb ductus in vivo is 1.5–2% O2 (Po2 = 10–14 mmHg) (H. Kajino, C. Koch, and R. Clyman, unpublished results). In vitro, the ductus wall receives oxygen only from the lumen and adventitial surface (as well as the 2 cut faces). Average tissue O2 concentrations in rings of fetal lamb ductus incubated with bath solutions containing fetal Po2 (4% O2, Po2 = 28 mmHg) is only 0.6% (Po2 = 4 mmHg). An average tissue O2 concentration of 1.5–2% (as observed in the fetal ductus in vivo) is not achieved in vitro until the oxygen concentration of the organ bath solution is increased to 30% O2 (Kajino et al., unpublished results). Therefore, we equilibrated our bath solution with 30% O2 to mimic average fetal tissue O2 concentration in vivo. Although there are different absolute tensions that develop in ductus rings that are incubated in bath solution equilibrated with 30% O2 compared with those incubated at 4% O2 (because of differences in oxygen-induced tension), the contractile response to nonselective (indomethacin) and selective COX-2 inhibitors is the same at these two bath oxygen concentrations. This is consistent with our unpublished observations that PGE2 or 6-keto-PGF1α(6ketoPGF1α) production rates are similar at these two bath solution oxygen concentrations (Kajino et al., unpublished results).This article has no references to display. Previous Back to Top Next FiguresReferencesRelatedInformationRelated articlesCyclooxygenase-2 inhibitors constrict the fetal lamb ductus arteriosus both in vitro and in vivo 01 Jun 2000American Journal of Physiology-Regulatory, Integrative and Comparative Physiology More from this issue > Volume 279Issue 6December 2000Pages Ca3-Ca3 Copyright & PermissionsCopyright © 2000 the American Physiological Societyhttps://doi.org/10.1152/ajpregu.2000.279.6.Ca3History Published online 1 December 2000 Published in print 1 December 2000 PDF download Metrics Downloaded 64 times
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