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Updated: Jul 17, 2026

A Swine Model of Neonatal Asphyxia
Published on: October 11, 2011
The paradoxical patent ductus arteriosus
Kathryn N Ivey1, Deepak Srivastava
1Gladstone Institute of Cardiovascular Disease, University of California San Francisco, San Francisco, California 94158, USA.
Insights
Patent ductus arteriosus (PDA) in premature infants often requires intervention. New research reveals prostaglandins have dual roles in ductus arteriosus (DA) closure, impacting COX inhibitor effectiveness and suggesting improved treatments for PDA.
Area of Science:
- Cardiovascular physiology
- Neonatal medicine
- Developmental biology
Background:
- Patent ductus arteriosus (PDA) is a common complication in preterm infants, necessitating closure for survival.
- Current treatments like COX inhibitors are limited by birth weight and often require surgical intervention in premature infants.
- Paradoxical PDA in mice with targeted COX pathway deletions suggests complex roles for prostaglandins.
Discussion:
- Prostaglandins play a dual role in both the development and closure of the ductus arteriosus (DA).
- Understanding these dual roles is crucial for interpreting the paradoxical effects of COX inhibitors observed in PDA.
- This research sheds light on why COX inhibitors may be less effective in severely premature infants.
Key Insights:
- Prostaglandins are essential for normal ductus arteriosus (DA) development and timely postnatal closure.
- COX inhibitors, while used to close PDA, may disrupt DA development due to their impact on prostaglandin synthesis.
- Genetic evidence in mice highlights the critical, multifaceted role of the COX pathway in DA patency.
Outlook:
- New therapeutic strategies targeting prostaglandin pathways could improve PDA treatment outcomes in preterm infants.
- Further research may elucidate specific prostaglandin mediators and receptors involved in DA closure.
- This study paves the way for more personalized and effective interventions for neonatal cardiovascular conditions.
Abstract:
The ductus arteriosus (DA) is a vessel whose patency is required for fetal survival but is incompatible with postnatal life. Because of developmental insufficiency, the DA in preterm infants often fails to close in a condition known as patent DA (PDA). Although COX inhibitors can be used to close the PDA by lowering circulating prostaglandin levels, their effectiveness is correlated with birth weight, and severely premature infants often require surgical repair. Paradoxically, targeted deletion of COX pathway components in mice results in PDA. In this issue of the JCI, Yokoyama et al. describe dual roles for prostaglandins in DA development and closure, offering new insights into the mechanism of negative effects of COX inhibitors that may influence the treatment of severely premature infants with PDA and lead to improvement of their outcomes (see the related article beginning on page 3026).
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