Corticosteroids, Thyrotropin-Releasing Hormone, and Antioxidant Enzymes in Preterm Lamb Lungs

Walther, Frans J.; Ikegami, Machiko; Warburton, David; Polk, Daniel H.

doi:10.1203/00006450-199112000-00004

Cited by 32 publications

(12 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In preterm infants, two doses of prenatal corticosteroids doubled endogenous surfactant synthesis from plasma [U- 13 C]glucose [48]. In summary, prenatal corticosteroids enhance surfactant PC synthesis in vivo but de novo synthesis rates remain low and alveolar pool sizes are not increased within 48 h. In preterm animals with RDS, prenatal corticosteroids improve pulmonary compliance within 15 h [49] accompanied by stimulated structural development [50,51,52]. Therefore, the pathophysiology of improved lung function after prenatal corticosteroids remains controversial.…”

Section: Effects Of Prenatal Corticosteroids On Surfactant Synthesis mentioning

confidence: 99%

Neonatal Respiratory Diseases in the Newborn Infant: Novel Insights from Stable Isotope Tracer Studies

et al. 2016

View full text Add to dashboard Cite

Respiratory distress syndrome is a common problem in preterm infants and the etiology is multifactorial. Lung underdevelopment, lung hypoplasia, abnormal lung water metabolism, inflammation, and pulmonary surfactant deficiency or disfunction play a variable role in the pathogenesis of respiratory distress syndrome. High-quality exogenous surfactant replacement studies and studies on surfactant metabolism are available; however, the contribution of surfactant deficiency, alteration or dysfunction in selected neonatal lung conditions is not fully understood. In this article, we describe a series of studies made by applying stable isotope tracers to the study of surfactant metabolism and lung water. In a first set of studies, which we call ‘endogenous studies', using stable isotope-labelled intravenous surfactant precursors, we showed the feasibility of measuring surfactant synthesis and kinetics in infants using several metabolic precursors including plasma glucose, plasma fatty acids and body water. In a second set of studies, named ‘exogenous studies', using stable isotope-labelled phosphatidylcholine tracer given endotracheally, we could estimate surfactant disaturated phosphatidylcholine pool size and half-life. Very recent studies are focusing on lung water and on the endogenous biosynthesis of the surfactant-specific proteins. Information obtained from these studies in infants will help to better tailor exogenous surfactant treatment in neonatal lung diseases.

show abstract

Section: Effects Of Prenatal Corticosteroids On Surfactant Synthesis mentioning

confidence: 99%

Neonatal Respiratory Diseases in the Newborn Infant: Novel Insights from Stable Isotope Tracer Studies

et al. 2016

View full text Add to dashboard Cite

show abstract

“…In addition, they stimulate lamellar body development in type II cells, and increase both tissue and alveolar content of surfactant (32). Finally, they also increase levels of the surfactant-associated proteins A, B, C, and D. In addition to these positive effects on surfactant production, glucocorticoids also stimulate antioxidant enzyme activity (33). Although still not completely defined, some of these effects appear to result largely from increased production of fibroblast-pneumonocyte factor by the fetal lung fibroblasts (34).…”

Section: Mechanisms Of Glucocorticoid Actionmentioning

confidence: 93%

Tracheal Ligation and Corticosteroids in Congenital Diaphragmatic Hernia: For Better for Worse?

2001

View full text Add to dashboard Cite

C ongenital diaphragmatic hernia (CDH) continues to frustrate clinicians for several reasons: it is not possible to predict accurately the extent of pulmonary hypoplasia in the individual fetus and the postnatal response to treatment modalities such as inhalational nitric oxide (NO) is variable. Moreover, the use of extra corporeal membrane oxygenation (ECMO) carries a high morbidity and sometimes profound long-term sequelae.Analysis of the literature reveals a myriad of treatment modalities proposed as "solutions" for the problem pulmonary hypoplasia in CDH. They range from termination of pregnancy following prenatal ultrasound to gentle handling of the lung postnatally to diminish iatrogenic damage of the fragile hypoplastic lungs (1). The fetal sheep model of CDH opened the way to fetal intervention and endoscopic fetoscopic procedures (FETENDO) such as tracheal ligation/occlusion in the human (2-7). Others have studied the basic mechanisms of pulmonary growth in a drug-induced CDH model (the Nitrofen rodent model) with or without the evaluation of additional treatment modalities such as corticosteroids and/or TSH releasing hormone (TRH) (8 -14).The supposed "lung growth" resulting from tracheal ligation is not founded on clean concepts of underlying mechanisms, although a variety of factors has been suggested (15-17).Intriguing are recent observations from different laboratories of the negative effects of tracheal ligation, in fetal sheep, on type II cell differentiation, as nicely evaluated by Kay et al. in this issue (18). The question of whether we will end up with a combined approach of tracheal ligation/occlusion and maternal betamethasone therapy to rescue type II cell differentiation as optimal treatment of CDH in humans is therefore still open.We have to bear in mind that the experiments described in the paper of Kay et al. were not conducted in a CDH model. As a consequence, we can only assume that the response will be the same in the hypoplastic lungs of CDH. However, no research data are available to support this assumption. Other questions are unanswered too, because the authors only assessed certain structural features of Type II cell density and markers of mRNA for two surfactant proteins. Whether steroids do more than up-regulate mRNA for the surfactant proteins or enhance function remains controversial. The study by Kay et al. involved no physiologic assessment of lung function, gas exchange or the development of pulmonary hypertension.Before we apply the results of the experimental approach of Kay et al. in a clinical setting, we have to analyze the arguments for the use of corticosteroids to enhance lung development in prenatally diagnosed CDH, because the few reports on the use of corticosteroids in human CDH consist of personal communications, individual case reports, and anecdotal small series. However prenatal steroids are used to enhance lung development in premature infants.

show abstract

“…Because prenatal administration of dexamethasone has been shown to result in improved survival and increased antioxidant enzyme activities [35,36], we hypothesized that antioxidant enzyme activities would be higher in our postnatally dexamethasone-treated, O 2 -exposed rats. However, while antioxidant enzyme activities were significantly higher in both O 2 exposure groups, no differences between the saline and dexamethasonetreated groups were observed.…”

Section: Discussionmentioning

confidence: 99%

Effects of Postnatal Dexamethasone on Oxygen Toxicity in Neonatal Rats

Dallas

Keeney²,

Mathews³

et al. 2004

Neonatology

View full text Add to dashboard Cite

We investigated the effect of timing of early postnatal dexamethasone on survival of hyperoxia-exposed neonatal rats. Pups <24 h old were treated with a tapering course of dexamethasone or saline beginning either prior to exposure (day 0), or after 2, 4, or 6 days of ≧98% O₂ (n = 11–14) or air (n = 8–11). Exposures were continued for 14 days. By day 14, day 0 pups had poor survival regardless of the exposure (14% in O₂, 13% in air). Survival of pups treated with dexamethasone after 2, 4 and 6 days of O₂ exposure was significantly higher at 14 days (50, 86 and 79%, respectively) compared to saline O₂ controls (9%, p < 0.001 for each). Pulmonary biochemical analyses were conducted after exposure for 7 days in rat pups treated with dexamethasone or saline beginning after 4 days of exposure to air or O₂(n = 11–12 for each group). While pups treated with dexamethasone showed greatly improved survival compared to O₂ controls, there was no decrease in neutrophil influx into the lung as measured by lung myeloperoxidase and neutrophil counts in histologic specimens and lavage fluid. Catalase, glutathione peroxidase, total and manganese superoxide dismutase activities as well as manganese superoxide dismutase (MnSOD) mRNA expression were elevated in both O₂ groups after 7 days compared to the air groups (p < 0.05) and MnSOD mRNA expression was elevated in the O₂/dexamethasone group, but there were no differences between dexamethasone and saline groups in O₂. Thus, this study indicates that the timing of dexamethasone administration is crucial. Mechanisms other than increases in antioxidant enzymes or decreases in lung neutrophils underlie the ability of dexamethasone to improve survival of these neonatal rats.

show abstract

Corticosteroids, Thyrotropin-Releasing Hormone, and Antioxidant Enzymes in Preterm Lamb Lungs

Cited by 32 publications

References 28 publications

Neonatal Respiratory Diseases in the Newborn Infant: Novel Insights from Stable Isotope Tracer Studies

Neonatal Respiratory Diseases in the Newborn Infant: Novel Insights from Stable Isotope Tracer Studies

Tracheal Ligation and Corticosteroids in Congenital Diaphragmatic Hernia: For Better for Worse?

Effects of Postnatal Dexamethasone on Oxygen Toxicity in Neonatal Rats

Contact Info

Product

Resources

About