[Modification of transplacental digoxin transfer in the isolated placental lobule]

Digoxin is widely used in the transplacental therapy of fetal tachyarrhythmia. Unfortunately, in cases with severe cardiac insufficiency and hydrops fetalis, transplacental passage of digoxin is often hampered and therapy therefore ineffective. The present study was designed to establish the isolated placental lobule to quantify transplacental digoxin passage under different experimental conditions. Ten human placentas were obtained immediately after delivery, and a lobule was dually perfused after cannulating a small artery and vein of the chorionic plate and piercing four catheters through the corresponding basal plate. Flow rates were 12 ml/min in the maternal circuit and 6 (I) respectively 3 ml/min (II) in the fetal circuit. The maternal circuit was spiked with digoxin to 6.18 +/- 0.40 ng/ml, and transplacental passage was calculated from repeated fetal and maternal perfusate samples (Fluorescence-Polarization-Immunoassay; TDx, Abbott Laboratories). Within three hours of recirculating perfusion with a fetal flow rate of 6 ml/min (I), digoxin concentrations in the maternal circuit (400 ml) declined to 3.56 +/- 0.09 ng/ml, whereas digoxin levels in the fetal compartment (200 ml) increased to 2.58 +/- 0.37 ng/ml. With a fetal perfusion rate of 3 ml/min (II), the efflux of digoxin out of the maternal circuit was lower (p < 0.05) and the influx in the total compartment was reduced (fetal digoxin concentrations reached only 26.9 +/- 10.6% vs. 39.1 +/- 5.5% of the initial maternal digoxin concentrations). These data suggest that severe fetal cardiac insufficiency with reduced placental perfusion may be in part responsible for the decrease of transplacental digoxin passage in fetuses with hydrops.