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

Hiroki Kajino, Yao Qi Chen, Steven R. Seidner, Nahid Waleh, Françoise Mauray, Christine Roman, Sylvain Chemtob, Cameron J. Koch, Ronald I. Clyman

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Fermanent closure of the full-term newborn ductus arteriosus (DA) occurs only if profound hypoxia develops within the vessel wall during luminal obliteration. We used fetal and newborn baboons and lambs to determine why the immature 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 the sixth day after birth; in addition, the preterm DA wall was only mildly hypoxic and had only minimal remodeling. The postnatal increase in Pao2 normally 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 have a smaller increment in tension in response to oxygen than the DA near term. 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 newborns, kept at a higher Pao2, would have increased DA tone and would be more likely to obliterate their lumen. We found that preterm newborns, maintained at a Pao2 >200 mmHg, had only a 14% incidence of patent DA. Even though DA constriction was due to elevated Pao2, obliteration of the lumen produced profound hypoxia of the DA wall and the same features of remodeling that were observed at term. DA wall hypoxia appears to be both necessary and sufficient to produce anatomic remodeling in preterm newborns.

Original languageEnglish (US)
Pages (from-to)R291-R301
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume281
Issue number1 50-1
DOIs
StatePublished - 2001

Keywords

  • Hypoxia
  • Newborn
  • Nitric oxide
  • Oxygen
  • Prostaglandins

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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