Steroid therapy for meconium aspiration syndrome in newborn infants

Ward, Meredith C.; Sinn, John

doi:10.1002/14651858.cd003485

Cited by 49 publications

(21 citation statements)

References 16 publications

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“…They are potent anti-inflammatory agents that have been reported to decrease hospital stay and duration of oxygen dependence in meconium aspiration syndrome, a disease often associated with the development of PPHN (34,39). Recent evidence from animal models of PPHN also suggests a potential role for glucocorticoids in restoring normal pulmonary vascular function.…”

mentioning

confidence: 99%

Hydrocortisone normalizes oxygenation and cGMP regulation in lambs with persistent pulmonary hypertension of the newborn

Perez

Lakshminrusimha

Wedgwood

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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In the pulmonary vasculature, cGMP levels are regulated by soluble guanylate cyclase (sGC) and phosphodiesterase 5 (PDE5). We previously reported that lambs with persistent pulmonary hypertension of the newborn (PPHN) demonstrate increased reactive oxygen species (ROS) and altered sGC and PDE5 activity, with resultant decreased cGMP. The objective of this study was to evaluate the effects of hydrocortisone on pulmonary vascular function, ROS, and cGMP in the ovine ductal ligation model of PPHN. PPHN lambs were ventilated with 100% O(2) for 24 h. Six lambs received 5 mg/kg hydrocortisone every 8 h times three doses (PPHN-hiHC), five lambs received 3 mg/kg hydrocortisone followed by 1 mg·kg(-1)·dose(-1) times two doses (PPHN-loHC), and six lambs were ventilated with O(2) alone (PPHN). All groups were compared with healthy 1-day spontaneously breathing lambs (1DSB). O(2) ventilation of PPHN lambs decreased sGC activity, increased PDE5 activity, and increased ROS vs. 1DSB lambs. Both hydrocortisone doses significantly improved arterial-to-alveolar ratios relative to PPHN lambs, decreased PDE5 activity, and increased cGMP relative to PPHN lambs. High-dose hydrocortisone also increased sGC activity, decreased PDE5 expression, decreased ROS, and increased total vascular SOD activity vs. PPHN lambs. These data suggest that hydrocortisone treatment in clinically relevant doses improves oxygenation and decreases hyperoxia-induced changes in sGC and PDE5 activity, increasing cGMP levels. Hydrocortisone reduces ROS levels in part by increasing SOD activity in PPHN lambs ventilated with 100% O(2.) We speculate that hydrocortisone increases cGMP by direct effects on sGC and PDE5 expression and by attenuating abnormalities induced by oxidant stress.

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mentioning

confidence: 99%

Hydrocortisone normalizes oxygenation and cGMP regulation in lambs with persistent pulmonary hypertension of the newborn

Perez

Lakshminrusimha

Wedgwood

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…İnhale budenosid ile yapılan başka çalışmada ise budenosidin enflamatuar hücreleri azalttığı ve akciğer fonksiyonları üzerinde olumlu etkileri olduğu saptanmıştır. Ancak sonuç olarak şu an için MAS tedavisinde glukokortikoidlerin rutin kullanımı halen önerilmemek-tedir (36).…”

Section: Antinflamatuar Tedaviunclassified

Meconium Aspiration Syndrome (MAS)

Uslu¹,

Dursun²,

Bülbül³

2015

Sisli Etfal

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Derleme / Review ÖZET:Mekonyum Aspirasyon Sendromu (MAS) Mekonyum aspirasyonu, tipik olarak fetal hipoksik iskemik stresin intestinal peristaltizme yol açarak, amniyotik sıvının mekonyum ile kontaminasyonu ve gasping sonucu akciğerin derin dokularına kadar nüfuz etmesi ile ortaya çıkar. Tüm doğumların %10-15'inde amniyotik sıvı mekonyum ile kontamine iken bu bebeklerin %5-10'unda mekonyum aspirasyonu ve solunum yetersizliği gelişir. Bu derlemede, MAS klinik bulguları, tanısal ve tedavisel yaklaşımı ile ilgili güncel bilgiler sunulmaktadır. GİRİŞMeconium kelimesi eski Yunanca'da opiuma benzer anlamına gelmektedir. Aristoteles, amnion sıvısında mekonyumla doğan bebeklerin uykuya eği-limli ve depresif olduklarını gözlemlemesi nedeniyle bu maddeye mekonyum ismini vermiştir (1). Mekonyumla boyalı amniyotik sıvı (MBAS) ile doğan bebeklerin bir kısmında görülen mekonyum aspirasyon sendromu (MAS), sıklıkla term ve postterm yenidoğanlarda hipoksemik solunum yetmezliği ile seyreden ve solunum yetmezliği bulgularına yol açacak diğer faktörlerin eşlik etmediği bir durumdur (2). Term ve postterm yenidoğanlarda yoğun bakım gereksinimine yol açan solunum sıkıntısı nedenlerinin başında gelmektedir. Neonatoloji alanındaki gelişmelere rağmen günümüzde hala ciddi morbidite ve mortaliteye sahiptir. Sıklık ve Risk FaktörleriMekonyumla boyalı amniyotik sıvı normal gebeliklerin %5-24'ünde (ortalama %13) görülür (pretermde %5.1, termde %16.5, posttermde %27.1) ve olası bir fetal distres göstergesidir. Amniyotik sıvıda mekonyum ve anormal kalp hızı paterni olan hastalarda perinatal mortalite %3-22.2, neonatal mortalite ise %7-50'dir. Mekonyum aspirasyon sendromu ise MBAS ile doğan bebeklerin %2-10'unda görülmekte-dir. Son çalışmalara göre 37. gebelik haftasından büyük bebeklerde MAS sıklığı %0.4-1.8'dir. Gebelik haftası (GH) arttıkça risk artmaktadır ve 41-42. gebelik haftasından sonra sıklık %1.2-1.4'e yükselmekte-dir (1,3,4).Mekonyum aspirasyon sendromu sıklığı, postmatürite (GH>42), gebelik haftasına göre düşük doğum ağırlığına (SGA) sahip olma ve fetusu sıkıntıya soka-

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“…In case reports from human neonates, steroids have been reported to decrease hospital stay and duration of oxygen use after meconium aspiration. [26][27][28] More recently, new data have emerged on the use of steroids in animal models of PPHN. Prenatally administered betamethasone attenuated oxidative stress and improved in vitro PA response to vasodilators in a fetal lamb model of pulmonary hypertension.…”

Section: Persistent Pulmonary Hypertension Of the Newborn (Pphn)mentioning

confidence: 99%

Hydrocortisone Normalizes Phosphodiesterase‐5 Activity in Pulmonary Artery Smooth Muscle Cells from Lambs with Persistent Pulmonary Hypertension of the Newborn

et al. 2014

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Phosphodiesterase-5 (PDE5) is the primary phosphodiesterase in the pulmonary vasculature. It degrades cyclic guanosine monophosphate (cGMP) and inhibits cGMP-mediated vasorelaxation. We previously reported that hydrocortisone treatment decreased hyperoxia-induced PDE5 activity and markers of oxidative stress in lambs with persistent pulmonary hypertension of the newborn (PPHN) ventilated with 100% O 2 . The objective of our study was to determine the molecular mechanism by which hydrocortisone downregulates PDE5 and oxidative stress in fetal pulmonary artery smooth muscle cells (FPASMCs) from PPHN lambs. PPHN FPASMC were incubated for 24 hours in either 21% or 95% O 2 . Some cells were treated with 100 nM hydrocortisone and/or AE1 μM helenalin, an inhibitor of nuclear factor κ B (NFκB), a redox-sensitive transcription factor. Exposure to hyperoxia led to increased PDE5 activity, oxidative stress, and NFκB activity. Pretreatment of PPHN FPASMC with hydrocortisone normalized PDE5 activity, decreased cytosolic oxidative stress, increased expression of extracellular superoxide dismutase and NFκB inhibitory protein, and decreased NFκB activity. Similarly, treatment with NFκB inhibitor, helenalin, decreased PDE5 activity. These data suggest that hyperoxia activates NFκB, which in turn induces PDE5 activity in PPHN FPASMC, whereas treatment with hydrocortisone attenuates these changes by blocking reactive oxygen species-induced NFκB activity.

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Steroid therapy for meconium aspiration syndrome in newborn infants

Abstract: Steroid therapy for meconium aspiration syndrome in newborn infants.

Cited by 49 publications

References 16 publications

Hydrocortisone normalizes oxygenation and cGMP regulation in lambs with persistent pulmonary hypertension of the newborn

Hydrocortisone normalizes oxygenation and cGMP regulation in lambs with persistent pulmonary hypertension of the newborn

Meconium Aspiration Syndrome (MAS)

Hydrocortisone Normalizes Phosphodiesterase‐5 Activity in Pulmonary Artery Smooth Muscle Cells from Lambs with Persistent Pulmonary Hypertension of the Newborn

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