title: In utero indomethacin alters O2 delivery to the fetal ductus arteriosus: implications for postnatal patency.
abstract: Indomethacin produces constriction and hypoxia of the fetal ductus arteriosus. This is associated with death of smooth muscle cells in the ductus wall and an increased incidence of patent ductus arteriosus in the newborn period. We used fetal sheep to determine which factors are responsible for indomethacin-induced hypoxic cell death. Cell death in the ductus wall is directly related to the degree of indomethacin-induced ductus constriction and is present at both moderate and marked degrees of constriction. Both moderate and marked degrees of ductus constriction reduce vasa vasorum flow to the ductus (moderate = 69 +/- 25%; marked = 30 +/- 16% of preinfusion values) and increase the thickness of the ductus wall. In contrast, ductus luminal blood flow is not affected by moderate degrees of constriction and is reduced only after marked constriction. Although indomethacin increases ductus tone, it has no effect on ductus oxygen consumption. These findings suggest that the hypoxic cell death that occurs during the early stages of indomethacin-induced constriction is primarily due to changes in vasa vasorum blood flow and muscle media thickness.
authors.affiliation: Cardiovascular Research Institute, University of California, San Francisco, California 94143-0544, USA.
authors.forename: Seth H
authors.initials: SH
authors.lastname: Goldbarg
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Carolyn
authors.initials: C
authors.lastname: Cruz
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kajino
authors.forename: Christine
authors.initials: C
authors.lastname: Roman
authors.forename: Bao Mei
authors.initials: BM
authors.lastname: Liu
authors.forename: Yao Qi
authors.initials: YQ
authors.lastname: Chen
authors.forename: Françoise
authors.initials: F
authors.lastname: Mauray
authors.forename: Ronald I
authors.initials: RI
authors.lastname: Clyman
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D004373:Ductus Arteriosus / Q000502:physiology*; D004374:Ductus Arteriosus, Patent / Q000503:physiopathology; D005260:Female; D020287:In Situ Nick-End Labeling; D007213:Indomethacin / Q000494:pharmacology*; D008863:Microspheres; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012756:Sheep; D015145:Tocolysis; D014651:Vasa Vasorum / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D010100:Oxygen; D007213:Indomethacin