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This Article Full Text Full Text (PDF) All Versions of this Article: 290/2/R359    most recent 00629.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Levin, M. Articles by Clyman, R. I. Search for Related Content PubMed PubMed Citation Articles by Levin, M. Articles by Clyman, R. I.

DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

Postnatal constriction, ATP depletion, and cell death in the mature and immature ductus arteriosus

¹Cardiovascular Research Institute and Department of Pediatrics, University of California, San Francisco; ²Wallenberg Laboratory for Cardiovascular Research, Göteborg University, Göteborg, Sweden, Departments of ³Pediatrics and ⁴Pathology, University of Texas Health Science Center, San Antonio, Texas; ⁵SRI International, Menlo Park, California

Submitted 30 August 2005 ; accepted in final form 9 October 2005

After birth, constriction of the full-term ductus arteriosus induces oxygen, glucose and ATP depletion, cell death, and anatomic remodeling of the ductus wall. The immature ductus frequently fails to develop the same degree of constriction or anatomic remodeling after birth. In addition, the immature ductus loses its ability to respond to vasoconstrictive agents, like oxygen or indomethacin, with increasing postnatal age. We examined the effects of premature delivery and postnatal constriction on the immature baboon ductus arteriosus. By 6 days after birth, surrogate markers of hypoxia (HIF1/VEGF mRNA) and cell death [dUTP nick-end labeling (TUNEL)-staining] increased, while glucose and ATP concentrations (bioluminescence imaging) decreased in the immature ductus. TUNEL-staining was significantly related to the degree of glucose and ATP depletion. Glucose and ATP depletion were directly related to the degree of ductus constriction; while TUNEL-staining was logarithmically related to the degree of ductus constriction. Extensive cell death (>15% TUNEL-positive cells) occurred only when there was no Doppler flow through the ductus lumen. In contrast, HIF1/VEGF expression and ATP concentrations were significantly altered even when the immature ductus remained open after birth. Decreased ATP concentrations produced decreased oxygen-induced contractile responses in the immature ductus. We hypothesize that ATP depletion in the persistently patent immature newborn ductus is insufficient to induce cell death and remodeling but sufficient to decrease its ability to constrict after birth. This may explain its decreasing contractile response to oxygen, indomethacin, and other contractile agents with increasing postnatal age.

baboon; hypoxia; glucose; glycogen; HIF1

This article has been cited by other articles:

				J. Reese Death, dying, and exhaustion in the ductus arteriosus: prerequisites for permanent closure Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2006; 290(2): R357 - R358. [Full Text] [PDF]