Effects of Indomethacin on Fetal Rat Lungs: A Possible Cause of Persistent Fetal Circulation (PFC)

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Abstract
Summary: Indomethacin, because of its prostaglandin inhibition, may cause constriction of the ductus arteriosus and affect the pulmonary circulation. To study this possibility, we gave indomethacin daily by gavage to two groups of pregnant rats from the 17th day of pregnancy through delivery (group 1, 2 mg/kg/day; group 2, 4 mg/kg/day). Group 3, untreated control pregnant rats, received saline. The pups were killed 30 min after birth and heart-lung preparations were perfused with glutaraldehyde. Appropriate blocks were processed for quantitative morphometry of the pulmonary arteries and arterioles. For analysis, the vessels were grouped by external diameter, i.e., P < 0.05). Muscularized arterioles, P < 0.05). These results show that the fetal pulmonary circulation's response to indomethacin comprises the appearance of medial hypertrophy and newly muscularized arterioles. When these changes occur in lungs with immature, thick saccular walls, there is a decreased surface for oxygen exchange and an increased pulmonary vascular resistance resulting in a persistent fetal circulation. Speculation: Indomethacin, during pregnancy, may cause constriction of the ductus arteriosus and induce a persistent fetal circulation in the newborn. Inasmuch as salicylates also may be causative agents of persistent fetal circulation, their use by pregnant women should be carefully examined.