The Ratio of Thromboxane to Prostacyclin is Increased by Peroxide in a Dose-Dependent Manner, Along with Increased Vasoconstriction in the Human Placenta

Abstract

Objective: To determine if perfusion of the human placenta with increasing doses of exogenous peroxide will result in a dose-dependent increase in the ratio of thromboxane to prostacyclin, and a progressive increase in placental vasoconstriction.Methods: Isolated human placental cotyledons (n = 7) were perfused serially for 20-min intervals with control Krebs-Ringer-bicarbonate (KRB) buffer gassed with 95% O2 and 5% CO2, and then KRB buffer containing progressively increasing concentrations of f-butyl hydroperoxide (10, 25, 50, and 100 μmol/L). Control KRB buffer was perfused between each dose of t-butyl hydroperoxide. Perfusion pressure was continually monitored and maternal and fetal effluent samples were collected and analyzed for thromboxane and prostacyclin by their stable metabolites, TXB2 and 6-keto PGF1α.Results: Compared to control KRB buffer, perfusion with t-butyl hydroperoxide at concentrations of 25, 50, and 100 μmol/L resulted in a progressive and significant increase in the fetal secretion rate ratio of thromboxane to prostacyclin (22.9 ± 7.9 vs. 29.1 ± 7.3, 38.8 ± 2.3, and 52.4 ± 8.9, respectively). Peroxide significantly increased the thromboxane secretion rate on the fetal side (0.52 ± 0.2 ng/min vs. 1.3 ± 0.38 ng/min, 1.4 ± 0.31 ng/min, and 1.9 ± 0.24 ng/min), as well as on the maternal side (3.3 ± 0.75 ng/min vs. 5.4 ± 0.82 ng/min, 6.1 ± 0.96 ng/min, and 7.5 ± 1.2 ng/min) for the 25, 50, and 100 μmol/L concentrations, respectively. Peroxide perfusion did not have a significant effect on the fetal secretion rate of prostacyclin, and maternal secretion of prostacyclin was nondetectable. Coincident with the increase in the thromboxane to prostacyclin ratio, peroxide also increased the perfusion pressure (PP) and vascular resistance (VR) in a dose-dependent manner for the 25, 50, and 100 μmol/L concentrations (PP: 32.9 ± 2.5 mm Hg for control vs. 39.0 ± 5.6 mm Hg, 39.7 ± 2.5 mm Hg, and 50.4 ± 2.9 mm Hg; VR: 13.8 ± 1.9 mm Hg±min/mL vs. 16.2 ± 2mm Hg±min/mL, 16.6 ± 1.8mm Hg-min/mL, and 21.7 ± 2.2 mm Hg±min/mL, respectively). The increases in perfusion pressure and vascular resistance were highly correlated with the increase in the thromboxane to prostacyclin ratio (r = 0.826 and r = 0.848, respectively).Conclusions: Perfusion of the isolated human placental cotyledon with progressively increasing concentrations of peroxide resulted in a progressive increase in the ratio of thromboxane to prostacyclin. The increase in the ratio was due to the stimulation of thromboxane. There were also progressive increases in perfusion pressure and vascular resistance that were highly correlated with the increase in the thromboxane to prostacyclin ratio.