ArticlePediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies2009
Milrinone enhances relaxation to prostacyclin and iloprost in pulmonary arteries isolated from lambs with persistent pulmonary hypertension of the newborn.
Article in Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 79 citations in OpenAlex.
- Milrinone relaxes pulmonary veins in guinea pigs and humans.PloS one · 2014Trial
- Evidence-Based Guidelines for Acute Stabilization and Management of Neonates with Persistent Pulmonary Hypertension of the Newborn.American journal of perinatology · 2023Article
- Effects of Neonatal Caffeine Administration on Vessel Reactivity in Adult Mice.American journal of perinatology · 2021Article
- Pathophysiology and Management of Persistent Pulmonary Hypertension of the Newborn.Clinics in perinatology · 2021Review
- Life-threatening PPHN refractory to nitric oxide: proposal for a rational therapeutic algorithm.European journal of pediatrics · 2021Review
- Management of systemic hypotension in term infants with persistent pulmonary hypertension of the newborn: an illustrated review.Archives of disease in childhood. Fetal and neonatal edition · 2021Review
- Nitric oxide activates AMPK by modulating PDE3A in human pulmonary artery smooth muscle cells.Physiological reports · 2020Article
- The Natural-Mineral-Based Novel Nanomaterial IFMC Increases Intravascular Nitric Oxide without Its Intake: Implications for COVID-19 and beyond.Nanomaterials (Basel, Switzerland) · 2020Article
- Persistent Pulmonary Hypertension of the Newborn: Pathophysiological Mechanisms and Novel Therapeutic Approaches.Frontiers in pediatrics · 2020Review
- Intravenous epoprostenol improves oxygenation index in patients with persistent pulmonary hypertension of the newborn refractory to nitric oxide.Journal of perinatology : official journal of the California Perinatal Association · 2018Article
- Surgery for partial atrioventricular septal defect with pulmonary hypertension in an adult dog.The Journal of veterinary medical science · 2018Article
- Response to pulmonary vasodilators in infants with congenital diaphragmatic hernia.Pediatric surgery international · 2018Article
- Milrinone in congenital diaphragmatic hernia - a randomized pilot trial: study protocol, review of literature and survey of current practices.Maternal health, neonatology and perinatology · 2017Review
- Congenital Diaphragmatic hernia - a review.Maternal health, neonatology and perinatology · 2017Review
- Pharmacologic strategies in neonatal pulmonary hypertension other than nitric oxide.Seminars in perinatology · 2016Review
- Treatment of premature infants with pulmonary hypertension and right ventricular dysfunction with milrinone: a case series.Journal of perinatology : official journal of the California Perinatal Association · 2015Article
- Altered prostanoid metabolism contributes to impaired angiogenesis in persistent pulmonary hypertension in a fetal lamb model.Pediatric research · 2015Article
- Persistent pulmonary hypertension of the newborn.Maternal health, neonatology and perinatology · 2015Article
- A comprehensive study of clinical biomarkers, use of inotropic medications and fluid resuscitation in newborns with persistent pulmonary hypertension.Pediatric cardiology · 2015Article
- Update on PPHN: mechanisms and treatment.Seminars in perinatology · 2014Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
unlabelledProstacyclin is a pulmonary vasodilator and is produced by prostacyclin synthase and stimulates adenylate cyclase (AC) via the prostacyclin receptor (IP) to produce cAMP. Forskolin is a direct stimulant of AC. Phosphodiesterase 3 hydrolyzes cAMP and is inhibited by milrinone.
objectiveTo characterize the prostacyclin-AC-cAMP pathway in the ovine ductal ligation model of persistent pulmonary hypertension of the newborn (PPHN).
settingUniversity-based laboratory animal facility. SUBJECTS: Lambs delivered to time-dated pregnant ewes.
interventionsFifth generation pulmonary arteries (PA) and lung parenchyma were isolated from control fetal lambs (n = 8) and fetal lambs with PPHN induced by antenatal ductal ligation (n = 9). We studied relaxation responses to various agonists (milrinone, forskolin, prostacyclin, and iloprost, a prostacyclin analog) that increase cAMP in PA after half-maximal constriction with norepinephrine and pretreatment with propranolol +/- indomethacin. Lung protein levels of prostacyclin synthase, IP, AC2, and phosphodiesterase 3A were analyzed by Western blot and cAMP by enzyme-linked immunoassay. MAIN
resultsMilrinone relaxed control and PPHN PA and pretreatment with indomethacin significantly impaired this response. Relaxation to milrinone, prostacyclin, and iloprost were significantly impaired in PA from PPHN lambs. Pretreatment with milrinone markedly enhanced relaxation to prostacyclin and iloprost in PPHN PA, similar to relaxation in control PA. Relaxation to forskolin was similar in control and PPHN PAs indicating normal AC activity. Protein levels of prostacyclin synthase and IP were decreased in PPHN lungs compared with control, but AC2, cAMP, and phosphodiesterase 3A remained unchanged.
conclusionsProstacyclin and iloprost are dilators of PAs from PPHN lambs and their effect is enhanced by milrinone. This combination therapy may be an effective strategy in the management of patients with PPHN.
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