Delayed closure of the ductus arteriosus after birth has been observed in newborn infants with critical
pulmonic stenosis and in newborn lambs with experimental
pulmonic stenosis. This delayed ductal closure may be caused by a decreased ability of the muscle to contract when exposed to
oxygen or to an increased production of or sensitivity to
prostaglandin (PG) E2, the endogenous ductus arteriosus
vasodilator. To determine whether the abnormal hemodynamic pattern during fetal life associated with
pulmonic stenosis alters the responsiveness of the ductus arteriosus, we operated on 10 fetal lambs of gestational ages 70 to 77 days (term is 148 days) and placed a band around the pulmonary artery. Catheterization at 137 to 142 days showed severe
pulmonic stenosis. We then studied isolated rings of ductus arteriosus from these lambs. The
oxygen-induced increase in tension in rings of ductus arteriosus from lambs with
pulmonic stenosis was significantly decreased (2.55 +/- 0.38; n = 10) compared with rings from control lambs (4.03 +/- 0.51; n = 6, p less than .03). There was no difference between the two groups in either the amount of
PGE2 released by the rings or in the sensitivity (expressed as median effective dose) of the rings to
PGE2. There was also no difference in the increase in tension when endogenous
PGE2 was inhibited by
indomethacin. We conclude that delayed closure of the ductus arteriosus in lambs with experimental
pulmonic stenosis is not caused by increased sensitivity to or production of
PGE2 in the ductus arteriosus (as it is in premature lambs) but rather is the result of a diminished ability of the ductus arteriosus to contract when exposed to
oxygen.