Fetal uptake of intraamniotic digoxin in sheep

To explore the possibility that intraamniotic administration of digoxin is an effective treatment regimen for fetal tachyarrhythmia, we injected digoxin into the amniotic fluid cavity of pregnant sheep and examined the time course of digoxin distribution to the fetal and maternal plasma compartments. Animals were studied in two groups according to digoxin dosage: 0.7-1.8 nmol/kg fetal body wt in the high-dose group (n = 6) and 0.1-0.6 nmol/kg fetal body wt in the low-dose group (n = 14). Within 1 h, plasma digoxin concentrations in the high-dose and low-dose groups were 18.2 +/- 15.0 nmol/L and 2.7 +/- 0.8 nmol/L, respectively (values are expressed as mean +/- SD). At 6 h digoxin concentrations were 13.8 +/- 7.0 and 3.1 +/- 0.9 nmol/L, and at 24 h they were 2.3 nmol/L (n = 1) and 1.8 +/- 1.2 nmol/L, respectively. Peak maternal digoxin levels were about one-tenth fetal values in the high-dose group and undetectable in the low-dose group. Fetal digoxin concentrations were significantly greater in the descending aorta than in the umbilical vein (p less than 0.02). Fetal arterial blood pressure and heart rate were not significantly different from control at any time after digoxin administration. These results demonstrate that digoxin is rapidly taken up into the fetal circulation from the maternal amniotic cavity. The exact mechanism whereby this occurs is unknown, but transplacental transfer from the maternal circulation is not involved. Our findings suggest that intraamniotic administration of digoxin may be an alternative treatment for fetal tachyarrhythmias when direct administration of antiarrhythmic agents is ineffective or produces maternal toxicity.