![Sample our Medicine, Dentistry, Nursing & Allied Health journals, sign in here to start your FREE access for 14 days]({"type":"image" , "src" : "/sda/5944/TOC-Subject-Sample-2021-Medicine-Dentistry-Nursing-Allied-Health.jpg"})
Abstract
Objective: Production sites of thromboxane and prostacyclin are compartmentalized within the human placenta. Thromboxane is produced primarily by the trophoblast cells closest to the maternal circulation, whereas 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 concentration of aspirin would decline as it crossed from the maternal to the fetal side, thereby sparing prostacyclin on the fetal side. We hypothesized that perfusion of aspirin on the maternal side of the placenta would result in inhibition of thromboxane with a sparing of prostacyclin.
Study Design: To test this, we perfused human placental cotyledons in vitro with low doses of aspirin (5 × 10−-5 mom and 1 × 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-PGF1α respectively). We also determined the transport of aspirin across the placenta.
Results: Only 34% of the aspirin perfused on the maternal side crossed to the fetal side, providing proof of Fick's Second Law of Diffusion for the transport of aspirin across the human placenta. Compared to the control, perfusion of aspirin on the maternal side of the placenta preferentially inhibited the secretion of thromboxane while sparing prostacyclin. The total placental secretion rate of TXB2 was decreased by 48.8% by aspirin at a concentration of 5 × 10−-5 mom and by 80.2% at a concentration of 1 × 10−-4 mom. In contrast, the secretion rate of 6–keto-PGF1α was decreased by only 4.2% and 21.5% by these concentrations of aspirin. The placental secretion rate ratio of TXB, to 6–keto-PGF1α decreased from 14.9 for 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 of thromboxane or prostacyclin for placental cotyledons perfused without aspirin.
Conclusions: The compartmentalization of thromboxane and prostacyclin synthesis within the human placenta provides an arrangement whereby low doses of maternally derived aspirin can preferentially inhibit 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 endothelial cells on the fetal side is spared. This is a beneficial effect of low-dose aspirin therapy for the prevention of preeclampsia.