Decreased contractility of the ductus arteriosus in experimental pulmonic stenosis.
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.
D000818:Animals; D015232:Dinoprostone; D004195:Disease Models, Animal; D004373:Ductus Arteriosus / Q000503:physiopathology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D010100:Oxygen / Q000494:pharmacology; D011247:Pregnancy; D011458:Prostaglandins E / Q000378:metabolism / Q000494:pharmacology; D011666:Pulmonary Valve Stenosis / Q000503:physiopathology*; D012756:Sheep
D011458:Prostaglandins E; D015232:Dinoprostone; D010100:Oxygen; D007213:Indomethacin