Indomethacin activity in the fetal vasculature of normal and meconium exposed human placentae

Objective: To study the effect of indomethacin on the vasculature of isolat ed perfused human placental cotyledon in normal and meconium pretreated pla centae. Study design: Isolated placental cotyledons were dually perfused an d fetal perfusion pressure was used as an index of vascular resistance. Mec onium-stained amniotic fluid (MSAF) was collected from patients after artif icial rupture of membranes, diluted 1:2. 1:4. 1:16 and 1:32 and a spectroph otometric determination of meconium concentration in amniotic fluid was per formed. Only MSAF with an optical density of 20.0 units per gram was used i n this study. In five placentae. the effect of indomethacin (100 mug/ml con tinuous perfusion from the fetal site) on basal pressure of the fetal-place ntal vasculature was established. In five more placentae. the effect of ind omethacin on MSAF-induced vasoconstriction was established when a bolus inj ections of 1 mi MSAF was made into the fetal circulation, The statistical s ignificance of response to MSAF injection was determined by paired I-test a nd ANOVA repeated measurements. Results: A significant vasoconstrictor resp onse to MSAF was achieved in normal placentae. Bolus injections of MSAF int o the fetal circulation resulted in a significant increase in perfusion pre ssure (P = 0.0026). Indomethacin was capable of significantly reducing the basal perfusion pressure (P = 0.03). Significant attenuation of vasoconstri ctor response to MSAF occurred in the presence of indomethacin (P = 0.0016) . Conclusion: Indomethacin causes a significant reduction in basal pressure of fetal placental vasculature in the human placental circulation in vitro and is capable of attenuating the vasoconstrictory activity of MSAF. The m echanism of such activity may be explained partially by the inhibitory effe ct of indomethacin on the pc-mediated pathways. (C) 2001 Elsevier Science I reland Ltd. All rights reserved.