Potential route for fetal therapy: intramembranous absorption of intraamniotically injected furosemide

Our purpose was to determine whether intraamniotically injected furosemide could be absorbed directly into fetal circulation by the ovine intramembranous pathway.

Nine chronically catheterized fetal sheep, five with an intact and four with a surgically ligated esophagus, were studied for 7 hours on 2 consecutive days. Day 1 was a control day in which the fetal parameters of arterial, venous, and amniotic fluid pressures; heart rate; and urine flow were measured continuously. Fetal and maternal blood, amniotic fluid, and fetal urine were sampled for osmolality, electrolytes, blood gases, and pH twice during the first hour and hourly thereafter. On day 2, 15 mg of furosemide was injected into the amniotic cavity after 1 hour and fetuses were monitored in the same fashion as on the control day.

On day 2, both intact and ligated fetuses demonstrated a rapid and prolonged increase in urine flow (p < 0.01) compared with control day fetuses. Esophageal ligation decreased, but did not eliminate, the diuresis. Free water clearance increased equally (p < 0.05) in both groups compared with control fetuses. Sodium and chloride excretion increased significantly in intact (sodium 591% +/- 220% and chloride 763% +/- 295%) and ligated fetuses (sodium 234% +/- 70% and chloride 409% +/- 74%) compared with control fetuses.

Diuresis after esophageal ligation demonstrates that furosemide is absorbed by the ovine intramembranous pathway.