Antenatal Corticosteroids Increase Fetal, But Not Postnatal, Pulmonary Blood Flow in Sheep

Crossley, Kelly J.; Morley, Colin J; Allison, Beth J.; Davis, Peter G; Polglase, Graeme R.; Wallace, Megan Jane; Zahra, Valerie; Hooper, Stuart B.

doi:10.1203/pdr.0b013e3181b1bc5d

Cited by 25 publications

(41 citation statements)

References 36 publications

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“…Crossley et al [26] had similar results to ascertain that in sheep fetuses using prenatal GCs that significantly increased blood flow in the immature fetal lung, due to a decrease in pulmonary vascular resistance that occurs in response to vasodilator stimuli.…”

Section: Discussionmentioning

confidence: 78%

Effect of corticosteroids and lung ventilation in the VEGF and NO pathways in congenital diaphragmatic hernia in rats

et al. 2014

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Section: Discussionmentioning

confidence: 78%

Effect of corticosteroids and lung ventilation in the VEGF and NO pathways in congenital diaphragmatic hernia in rats

et al. 2014

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“…Lung tissue was also collected from fetal sheep with decreased cortisol levels induced by fetal adrenalectomy (ADX) and increased glucocorticoid levels induced by fetal cortisol infusion or maternal betamethasone treatment (7,12,60).…”

Section: Ovine Experimental Groupsmentioning

confidence: 99%

“…A bolus dose of betamethasone (11.4 mg im in 2 ml; Celestone Chronodose, Schering-Plough) was administered to pregnant ewes at 36 h and again at 24 h prior to euthanasia at 124 days GA (n ϭ 6) (12). The dose and timing are similar to dose and timing used clinically to mature the human fetal lung in women at risk of preterm delivery.…”

Section: Ovine Experimental Groupsmentioning

confidence: 99%

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The oncogeneTrop2regulates fetal lung cell proliferation

McDougall

Hooper

Zahra

et al. 2011

American Journal of Physiology-Lung Cellular and Molecular Phys

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The factors regulating growth of the developing lung are poorly understood, although the degree of fetal lung expansion is critical. The oncogene Trop2 (trophoblast antigen 2) is upregulated during accelerated fetal lung growth, and we hypothesized that it may regulate normal fetal lung growth. We investigated Trop2 expression in the fetal and neonatal sheep lung during accelerated and delayed lung growth induced by alterations in fetal lung expansion, as well as in response to glucocorticoids. Trop2 expression was measured using real-time PCR and localized spatially using in situ hybridization and immunofluorescence. During normal lung development, Trop2 expression was higher at 90 days gestational age (GA; 4.0 ± 0.8) than at 128 days GA (1.0 ± 0.1), decreased to 0.5 ± 0.1 at 142 days GA (full term ∼147 days GA), and was positively correlated to lung cell proliferation rates (r = 0.953, P < 0.005). Trop2 expression was regulated by fetal lung expansion, but not by glucocorticoids. It was increased nearly threefold by 36 h of increased fetal lung expansion (P < 0.05) and was reduced to ∼55% of control levels by reduced fetal lung expansion (P < 0.05). Trop2 expression was associated with lung cell proliferation during normal and altered lung growth, and the TROP2 protein colocalized with Ki-67-positive cells in the fetal lung. TROP2 was predominantly localized to fibroblasts and type II alveolar epithelial cells. Trop2 small interfering RNA decreased Trop2 expression by ∼75% in cultured fetal rat lung fibroblasts and decreased their proliferation by ∼50%. Cell viability was not affected. This study demonstrates that TROP2 regulates lung cell proliferation during development.

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“…Despite this, the ability of steroids to improve ventilation parameters may assist in maintaining haemodynamic stability. Studies in sheep have shown that betamethasone treatment decreases fetal pulmonary vascular resistance and subsequently increases pulmonary blood flow, leading to an improved cardiopulmonary transition at birth in preterm lambs [22]. Other studies have found significant vasoconstriction in the near-term brain despite hypercapnia, potentially protecting against fluctuations in the cerebral blood flow [23].…”

Section: Prenatal Therapiesmentioning

confidence: 99%

Ventilation-Induced Brain Injury in Preterm Neonates: A Review of Potential Therapies

Barton

Tolcos²,

Miller

et al. 2016

Neonatology

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Mechanical ventilation is a risk factor for cerebral inflammation and brain injury in preterm neonates. The risk increases proportionally with the intensity of treatment. Recent studies have shown that cerebral inflammation and injury can be initiated in the delivery room. At present, initiation of intermittent positive pressure ventilation (IPPV) in the delivery room is one of the least controlled interventions a preterm infant will likely face. Varying pressures and volumes administered shortly after birth are sufficient to trigger pathways of ventilation-induced lung and brain injury. The pathways involved in ventilation-induced brain injury include a complex inflammatory cascade and haemodynamic instability, both of which have an impact on the brain. However, regardless of the strategy employed to deliver IPPV, any ventilation has the potential to have an impact on the immature brain. This is particularly important given that preterm infants are already at a high risk for brain injury simply due to immaturity. This highlights the importance of improving the initial respiratory support in the delivery room. We review the mechanisms of ventilation-induced brain injury and discuss the need for, and the most likely, current therapeutic agents to protect the preterm brain. These include therapies already employed clinically, such as maternal glucocorticoid therapy and allopurinol, as well as other agents, such as erythropoietin, human amnion epithelial cells and melatonin, already showing promise in preclinical studies. Their mechanisms of action are discussed, highlighting their potential for use immediately after birth.

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Antenatal Corticosteroids Increase Fetal, But Not Postnatal, Pulmonary Blood Flow in Sheep

Cited by 25 publications

References 36 publications

Effect of corticosteroids and lung ventilation in the VEGF and NO pathways in congenital diaphragmatic hernia in rats

Effect of corticosteroids and lung ventilation in the VEGF and NO pathways in congenital diaphragmatic hernia in rats

The oncogeneTrop2regulates fetal lung cell proliferation

Ventilation-Induced Brain Injury in Preterm Neonates: A Review of Potential Therapies

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