FACTORS INFLUENCING THE TRANSPLACENTAL DI GOXIN PASSAGE IN THE ISOLATED PLACENTAL LOBULE

Digoxin is widely used in the transplacental therapy of fetal tachyarr hythmia. 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 e stablish the isolated placental lobule to quantify transplacental digo xin passage under different experimental conditions. Ten human placent as were obtained immediately after delivery, and a lobule was dually p erfused after cannulating a small artery and vein of the chorionic pla te and pierting four catheters through the corresponding basal plate. Flow rates were 12 ml/min in the maternal circuit and 6 (I) respective ly 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 c alculated from repeated fetal and maternal perfusate samples (Fluoresc ence-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 t o 3.56 +/- 0.09 ng/ml, whereas digoxin levels in the fetal compartemen t (200 ml) increased to 2.58 +/- 0.37 ng/ml. With a fetal perfusion ra te 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 redu ced (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 transplacent al digoxin passage in fetuses with hydrops.