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

Objective: To study the effect of indomethacin on the vasculature of isolated perfused human placental cotyledon in normal and meconium pretreated placentae. Study design: Isolated placental cotyledons were dually perfused and fetal perfusion pressure was used as an index of vascular resistance. Meconium-stained amniotic fluid (MSAF) was collected from patients after artificial rupture of membranes, diluted 1:2, 1:4, 1:16 and 1:32 and a spectrophotometric determination of meconium concentration in amniotic fluid was performed. Only MSAF with an optical density of 20.0 units per gram was used in this study. In five placentae, the effect of indomethacin (100 μg/ml continuous perfusion from the fetal site) on basal pressure of the fetal-placental vasculature was established. In five more placentae, the effect of indomethacin on MSAF-induced vasoconstriction was established when a bolus injections of 1 ml MSAF was made into the fetal circulation. The statistical significance of response to MSAF injection was determined by paired t-test and ANOVA repeated measurements. Results: A significant vasoconstrictor response to MSAF was achieved in normal placentae. Bolus injections of MSAF into the fetal circulation resulted in a significant increase in perfusion pressure (P=0.0026). Indomethacin was capable of significantly reducing the basal perfusion pressure (P=0.03). Significant attenuation of vasoconstrictor 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 mechanism of such activity may be explained partially by the inhibitory effect of indomethacin on the PG-mediated pathways.