Combined prostaglandin and nitric oxide inhibition produces anatomic remodeling and closure of the ductus arteriosus in the premature newborn baboon

Steven R Seidner, Yao Qi Chen, Patricia R. Oprysko, Francoise Mauray, Mary M. Tse, Emil Lin, Cameron Koch, Ronald I. Clyman

Research output: Contribution to journalArticle

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Abstract

After birth, the full-term ductus arteriosus actively constricts and undergoes extensive histologic changes that prevent subsequent reopening. These changes are thought to occur only if a region of intense hypoxia develops within the ductus wall after the initial active constriction. In preterm infants, indomethacin-induced constriction of the ductus is often transient and is followed by reopening. Prostaglandins and nitric oxide both play a role in inhibiting ductus closure in vitro. We hypothesized that combined inhibition of both prostaglandin and nitric oxide production (with indomethacin and N-nitro-L-arginine (L-NA), respectively) may be required to produce the degree of functional closure that is needed to cause intense hypoxia. We used preterm (0.67 gestation) newborn baboons that were mechanically ventilated for 6 d: 6 received indomethacin alone, 7 received indomethacin plus L-NA, and 16 received no treatment (control). Just before necropsy, only 25% of control ductus and 33% of indomethacin-treated ductus were closed on Doppler examination; in contrast, 100% of the indomethacin-plus-L-NA-treated ductus were closed. Control and indomethacin-treated baboons developed negligible-to-mild ductus hypoxia (EF5 technique). Similarly, there was minimal evidence of ductus remodeling. In contrast, indomethacin-plus-L-NA-treated baboons developed intense hypoxia in regions where the ductus was most constricted. The hypoxic muscle strongly expressed vascular endothelial growth factor, and proliferating luminal endothelial cells filled and occluded the lumen. In addition, cells in the most hypoxic regions were undergoing DNA fragmentation. In conclusion, preterm newborns are capable of remodeling their ductus, just like the full-term newborn, if they can reduce their luminal blood flow to a point that produces intense ductus wall hypoxia. Combined prostaglandin and nitric oxide inhibition may be necessary to produce permanent closure of the ductus and prevent reopening in preterm infants.

Original languageEnglish (US)
Pages (from-to)365-373
Number of pages9
JournalPediatric Research
Volume50
Issue number3
StatePublished - 2001
Externally publishedYes

Fingerprint

Ductus Arteriosus
Papio
Indomethacin
Prostaglandins
Nitric Oxide
Premature Infants
Constriction
Newborn Infant
DNA Fragmentation
Vascular Endothelial Growth Factor A
Arginine
Endothelial Cells
Hypoxia
Parturition
Pregnancy
Muscles

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Seidner, S. R., Chen, Y. Q., Oprysko, P. R., Mauray, F., Tse, M. M., Lin, E., ... Clyman, R. I. (2001). Combined prostaglandin and nitric oxide inhibition produces anatomic remodeling and closure of the ductus arteriosus in the premature newborn baboon. Pediatric Research, 50(3), 365-373.

Combined prostaglandin and nitric oxide inhibition produces anatomic remodeling and closure of the ductus arteriosus in the premature newborn baboon. / Seidner, Steven R; Chen, Yao Qi; Oprysko, Patricia R.; Mauray, Francoise; Tse, Mary M.; Lin, Emil; Koch, Cameron; Clyman, Ronald I.

In: Pediatric Research, Vol. 50, No. 3, 2001, p. 365-373.

Research output: Contribution to journalArticle

Seidner, SR, Chen, YQ, Oprysko, PR, Mauray, F, Tse, MM, Lin, E, Koch, C & Clyman, RI 2001, 'Combined prostaglandin and nitric oxide inhibition produces anatomic remodeling and closure of the ductus arteriosus in the premature newborn baboon', Pediatric Research, vol. 50, no. 3, pp. 365-373.
Seidner, Steven R ; Chen, Yao Qi ; Oprysko, Patricia R. ; Mauray, Francoise ; Tse, Mary M. ; Lin, Emil ; Koch, Cameron ; Clyman, Ronald I. / Combined prostaglandin and nitric oxide inhibition produces anatomic remodeling and closure of the ductus arteriosus in the premature newborn baboon. In: Pediatric Research. 2001 ; Vol. 50, No. 3. pp. 365-373.
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AU - Chen, Yao Qi

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AU - Mauray, Francoise

AU - Tse, Mary M.

AU - Lin, Emil

AU - Koch, Cameron

AU - Clyman, Ronald I.

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