Transfer of aspirin across the perfused human placental cotyledon

Pregnancy-induced hypertension is associated with a reduction in prostacyclin synthesis that is relative to normotensive pregnancy, whereas thromboxane A₂ synthesis is unchanged or increased. The net effect is a decreased prostacyclin/thromboxane ratio that may result in the reduced fetal-placental blood flow seen in pregnancy-induced hypertension because thromboxane is known to constrict this circulation. Low-dose aspirin (acetylsalicylic acid), which is used to treat pregnancy-induced hypertension, selectively inhibits thromboxane synthesis and therefore may alter fetal-placental blood flow. We have investigated the transfer of acetylsalicylic acid in the perfused human placental cotyledon and its effects on fetal-placental perfusion pressure. Human placental cotyledons were perfused with tissue culture medium 199 plus 5% polyvinylpyrrolidone that was gassed with 95% oxygen/5% carbon dioxide at flow rates of 10 ml/min (maternal) and 4 ml/min (fetal). Acetylsalicylic acid (10^-5 mol/L) was added to the maternal circuit, and cotyledons were perfused for 1 hour with aliquots taken from a closed fetal circuit every 5 minutes. Acetylsalicylic acid was assayed by spectrofluorometry at 306 412 nm. Our data indicate an initial rapid transfer of ascetylsalicylic acid during the first 5 minutes into the fetal-placental circulation, the concentration then decreased to a steady state at 0.4 × 10^-5 mol/L. Resting perfusion pressure of both maternal and fetal circulation did not change after the addition of acetylsalicylic acid to maternal perfusate and transfer to the fetal circulation.