Factors that increase the contractile tone of the ductus arteriosus also regulate its anatomic remodeling

Permanent closure of the full-term newborn ductus arteriosus (DA) occurs on ly if profound hypoxia develops within the vessel wall during luminal oblit eration. We used fetal and newborn baboons and lambs to determine why the i mmature DA fails to remodel after birth. When preterm newborns were kept in a normoxic range (PaO2 : 50-90 mmHg), 86% still had a small patent DA on t he sixth day after birth; in addition, the preterm DA wall was only mildly hypoxic and had only minimal remodeling. The postnatal increase in PaO2 nor mally induces isometric contractile responses in rings of DA; however, the excessive inhibitory effects of endogenous prostaglandins and nitric oxide, coupled with a weaker intrinsic DA tone, make the preterm DA appear to hav e a smaller increment in tension in response to oxygen than the DA near ter m. We found that oxygen concentrations, beyond the normoxic range, produce an additional increase in tension in the preterm DA that is similar to the contractile response normally seen at term. We predicted that preterm newbo rns, kept at a higher PaO2, would have increased DA tone and would be more likely to obliterate their lumen. We found that preterm newborns, maintaine d at a PaO2 >200 mmHg, had only a 14% incidence of patent DA. Even though D A constriction was due to elevated PaO2, obliteration of the lumen produced profound hypoxia of the DA wall and the same features of remodeling that w ere observed at term. DA wall hypoxia appears to be both necessary and suff icient to produce anatomic remodeling in preterm newborns.