THE RATIO OF THROMBOXANE TO PROSTACYCLIN IS INCREASED BY PEROXIDE IN A DOSE-DEPENDENT MANNER, ALONG WITH INCREASED VASOCONSTRICTION IN THE HUMAN PLACENTA

Objective: To determine if perfusion of the human placenta with increa sing doses of exogenous peroxide will result in a dose-dependent incre ase in the ratio of thromboxane to prostacyclin, and a progressive inc rease in placental vasoconstriction. Methods: Isolated human placental cotyledons (n = 7) were perfused serially for 20-min intervals with c ontrol Krebs-Ringer-bicarbonate (KRB) buffer gassed with 95% O-2 and 5 % CO2,, and then KRB buffer containing progressively increasing concen trations of t-butyl hydroperoxide (10, 25, 50, and 100 mu mol/L). Cont rol 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 prost acyclin by their stable metabolites, TXB2, and 6-keto PGF(1 alpha). Re sults: Compared to control KRB buffer, perfusion with t-butyl hydroper oxide at concentrations of 25, 50, and 100 mu mol/L resulted in a prog ressive 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 +/- 0.8 2 ng/min, 6.1 +/- 0.96 ng/min, and 7.5 +/- 1.2 ng/min) for the 25, 50, and 100 mu mol/L concentrations, respectively. Peroxide perfusion did not have a significant effect on the fetal secretion rate of prostacy clin, and maternal secretion of prostacyclin was nondetectable. Coinci dent with the increase in the thromboxane to prostacyclin ratio, perox ide also increased the perfusion pressure (PP) and vascular resistance (VR) in a dose-dependent manner for the 25, 50, and 100 mu mol/L conc entrations (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.mi n/mL vs. 16.2 +/- 2 mm Hg.min/mL, 16.6 +/- 1.8 mm Hg.min/mL, and 21.7 +/- 2.2 mm Hg.min/mL, respectively), The increases in perfusion pressu re and vascular resistance were highly correlated with the increase in the thromboxane to prostacyclin ratio (r = 0.826 and r = 0.848, respe ctively). Conclusions: Perfusion of the isolated human placental cotyl edon 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 vascu lar resistance that were highly correlated with the increase in the th romboxane to prostacyclin ratio.