MATERNAL PERFUSION WITH LOW-DOSE ASPIRIN PREFERENTIALLY INHIBITS PLACENTAL THROMBOXANE WHILE SPARING PROSTACYCLIN

Objective: Production sites of thromboxane and prostacyclin are compar tmentalized within the human placenta. Thromboxane is produced primari ly by the trophoblast cells closest to the maternal circulation, where as prostacyclin is produced primarily by the endothelial cells closest to the fetal circulation. Theoretically, this arrangement allows for a selective inhibition of placental thromboxane by maternally derived aspirin because according to Fick's Second Law of Diffusion, the conce ntration of aspirin would decline as it crossed from the maternal to t he fetal side, thereby sparing prostacyclin on the fetal side. We hypo thesized that perfusion of aspirin on the maternal side of the placent a would result in inhibition of thromboxane with a sparing of prostacy clin. Study Design: To test this, we perfused human placental cotyledo ns in vitro with low doses of aspirin (5 x 10(-5) mol/L and 1 x 10(-4) mol/L) from the maternal side and measured the secretion rates of the stable metabolites of thromboxane and prostacyclin (TXB2 and 6-keto-P GF(1 alpha), respectively). We also determined the transport of aspiri n across the placenta. Results: Only 34% of the aspirin perfused on th e maternal side crossed to the fetal side, providing proof of Pick's S econd Law of Diffusion for the transport of aspirin across the human p lacenta. Compared to the control, perfusion of aspirin on the maternal side of the placenta preferentially inhibited the secretion of thromb oxane while sparing prostacyclin. The total placental secretion rate o f TXB2 was decreased by 48.8% by aspirin at a concentration of 5 x 10( -5) mol/L and by 80.2% at a concentration of 1 x 10(-4) mol/L. In cont rast, the secretion rate of 6-keto-PGF(1 alpha) was decreased by only 4.2% and 21.5% by these concentrations of aspirin. The placental secre tion rate ratio of TXB2 to 6-keto-PGF(1 alpha), decreased from 14.9 fo r the control to 7.9 and 3.8 with each dose of aspirin, respectively. There were no changes over time in maternal or fetal secretion rates o f thromboxane or prostacyclin for placental cotyledons perfused withou t aspirin. Conclusions: The compartmentalization of thromboxane and pr ostacyclin synthesis within the human placenta provides an arrangement whereby low doses of maternally derived aspirin can preferentially in hibit thromboxane because as aspirin crosses from the maternal to the fetal side, the higher concentrations of aspirin on the maternal side inhibit thromboxane in the trophoblast cells, but as aspirin crosses, its concentrations decline, so prostacyclin synthesis by the endotheli al cells on the fetal side is spared. This is a beneficial effect of l ow-dose aspirin therapy for the prevention of preeclampsia.