Effects of indomethacin in utero on the pulmonary vasculature of the newborn lambs.
Exposure of the fetus to indomethacin and the resultant closure of the ductus arteriosus in utero has been suggested to be one possible cause of persistent pulmonary hypertension of the newborn (PPHN). We examined whether or not closing the ductus arteriosus of fetal lambs by the administration of in-domethacin to the fetus and ewe could produce the functional and structural changes of PPHN. Three treated and four non-treated lambs were delivered by cesarean section. Postnatal hemodynamics were studied in two of the treated lambs. Pulmonary arterial pressure gradually decreased after delivery and did not reveal features compatible with PPHN, while the blood gases remained within the physiological range. However, acute hypoxemia produced a re-elevation in pulmonary arterial pressure. Morphometric analysis showed the medial thickening of normally fully-muscularized pulmonary arteries, but there was no abnormal extension of fully-muscularized arteries to the intraacinar level in the treated lambs. In conclusion, we could not reproduce functional and structural changes of PPHN in newborn lambs by the administration of indomethacin in utero. However, our experimental animal model with excessive muscularization of the pulmonary vasculature appears to be useful for studying vasoconstriction in response to hypoxemia.
Department of Pediatrics, Tohoku University School of Medicine, Sendai.
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Ohara
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Ogata
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Tezuka
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004373:Ductus Arteriosus / Q000502:physiology; D005260:Female; D005333:Fetus / Q000378:metabolism; D005865:Gestational Age; D006339:Heart Rate / Q000187:drug effects; D007213:Indomethacin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D008168:Lung / Q000033:anatomy & histology; D011247:Pregnancy; D011652:Pulmonary Circulation / Q000187:drug effects*; D012756:Sheep
D007213:Indomethacin