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

Gonçalves, Frances Lilian Lanhellas; Figueira, Rebeca Lopes; Simões, Ana Leda Bertoncini; Gallindo, Rodrigo Melo; Coleman, A. C.; Peiró, José Luis; Sbragia, Lourenço

doi:10.1007/s00383-014-3610-y

Cited by 9 publications

(16 citation statements)

References 41 publications

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“…If the previously published time points of plasma VEGF measurements are hypothetically merged with our results, one can speculate on the trajectory of VEGF appearance in tissues and blood after the onset of hyperoxic exposure: the VEGF‐release from cell‐associated stores might start immediately after oxygen exposure, with VEGF protein being primarily undetectable in lung tissue at 30 min (Gonçalves et al. ), then being detectable and reaching significantly increased concentrations in blood plasma at 120 min, as in our study, and persistently elevated up to 48 h and more (Sato et al. ).…”

Section: Discussionsupporting

confidence: 76%

“…Yet, Gonçalves et al. () did not observe an immunohistochemical VEGF protein increase in lung tissues of newborn rat pups after 30 min of hyperoxic MV (FiO 2 1.0, V T 9 mL/kg, PEEP 0 cmH 2 O). If the previously published time points of plasma VEGF measurements are hypothetically merged with our results, one can speculate on the trajectory of VEGF appearance in tissues and blood after the onset of hyperoxic exposure: the VEGF‐release from cell‐associated stores might start immediately after oxygen exposure, with VEGF protein being primarily undetectable in lung tissue at 30 min (Gonçalves et al.…”

Section: Discussionmentioning

confidence: 93%

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Mechanical ventilation strategies alter cardiovascular biomarkers in an infant rat model

et al. 2018

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Mechanical ventilation (MV) is routinely used in pediatric general anesthesia and critical care, but may adversely affect the cardiocirculatory system. Biomarkers are increasingly measured to assess cardiovascular status and improve clinical treatment decision‐making. As the impact of mechanical ventilation strategies on cardiovascular biomarkers in ventilated infants is largely unknown, we conducted this retrospective study in a healthy in vivo infant rat ventilation model using 14‐days old Wistar rats. We hypothesized that 2 h of mechanical ventilation with high and low positive end‐expiratory pressure (PEEP), hyperoxemia, hypoxemia, hypercapnia, and hypocapnia would significantly impact B‐type natriuretic peptide (BNP), vascular endothelial growth factor (VEGF), and endothelin‐1 (ET‐1). We found BNP to be driven by both high (9 cmH2O) and low (1 cmH2O) PEEP compared to ventilated control animals (P < 0.05). VEGF concentrations were associated with high PEEP, hyperoxemia, hypoxemia, and hypocapnia (P < 0.05), whereas ET‐1 levels were changed only in response to hypoxemia (P < 0.05). In conclusion, the mode of mechanical ventilation alters plasma biomarker concentrations. Moreover, BNP and VEGF might serve as surrogate parameters for ventilation induced cardiovascular compromise and lung tissue damage. Furthermore, our data support the hypothesis, that sudden onset of hyperoxemia may trigger a quick VEGF release as a possible cellular survival reflex.

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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 93%

Mechanical ventilation strategies alter cardiovascular biomarkers in an infant rat model

et al. 2018

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“…There was no significant improvement in LBWR in any study, with two studies reporting an improvement in airway histology (increased sacular volume) . Steroids upregulated VEGF‐r expression but failed to upregulate mRNA SP‐A and SP‐B in single studies . In rabbits two studies delivered steroids IA, immediately following CDH creation.…”

Section: Resultsmentioning

confidence: 89%

“…36,63 Steroids upregulated VEGF-r expression but failed to upregulate mRNA SP-A and SP-B in single studies. 36,63,59 In rabbits two studies delivered steroids IA, immediately following CDH creation. This was reported to show improvement in histology (alveolar and septal density) in one study without increase in LBWR.…”

Section: Steroidsmentioning

confidence: 94%

Medical interventions to reverse pulmonary hypoplasia in the animal model of congenital diaphragmatic hernia: A systematic review

Eastwood

Russo

Toelen

et al. 2015

Pediatric Pulmonology

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We aimed to systematically review all published pre-clinical research on prenatal medical treatment of pulmonary hypoplasia in congenital diaphragmatic hernia (CDH). Background The neonatal mortality due to isolated CDH remains high. Whether fetal endoscopic tracheal occlusion (FETO) reduces mortality is still to be demonstrated. Therefore more potent preferentially medical therapy would be welcomed. Methods We searched MEDLINE (Pubmed), Embase and the Web of Science including all studies from the earliest date (1951) to December 2013. Article quality was assessed using the modified CAMRADES checklist. Inclusion criteria were those animal studies addressing prenatal medical interventions and principal variables were confirmation of a diaphragmatic defect, lung to body weight ratio (LBWR), formal airway morphometry or DNA/protein content. Results In total 983 articles were identified. Following abstract review, 96 articles were assessed by two authors in agreement with a third for eligibility. Of these, 43 were included in the final analysis. The median number of study quality checklist items (maximum 10) scored was 4 (IQ range: 2-5). Thirty (69.8%) of studies were in the nitrofen rat. The majority were treated with vitamins or glucocorticoids. Single studies reported some improvement in lung morphology with alternative therapies. It was impossible to identify a pattern in animal model selection or creation, mode, time point or duration of treatment and readouts. Only one study reported a sample size calculation. Conclusion Comparison in pre-clinical studies in CDH is challenging due to methodological variation. Agreed standardized methods need to be applied in future investigation of new medical therapies.

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“…The efficacy of antenatal corticosteroids for CDH was first established in successful rat, [51][52][53][54] rabbit, [55][56][57] and sheep 58,59 models (►Table 1). These animal studies predominantly investigated betamethasone and dexamethasone, fluorinated synthetic corticosteroids that cross the placenta from maternal to fetal circulation, have minimal mineralocorticoid activity and are weak immunosuppressants.…”

Section: Pharmacokinetics and Bioavailabilitymentioning

confidence: 99%

Antenatal Medical Therapies to Improve Lung Development in Congenital Diaphragmatic Hernia

et al. 2018

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Congenital diaphragmatic hernia (CDH) is a birth defect characterized by failed closure of the diaphragm, allowing abdominal viscera to herniate into the thoracic cavity and subsequently impair pulmonary and vascular development. Despite improving standardized postnatal management, there remains a population of severe CDH for whom postnatal care falls short. In these severe cases, antenatal surgical intervention (fetoscopic endoluminal tracheal occlusion [FETO]) may improve survival; however, FETO increases the risk of preterm delivery, is not widely offered, and still fails in half of cases. Antenatal medical therapies that stimulate antenatal pulmonary development are therefore interesting alternatives. By presenting the animal research underpinning novel antenatal medical therapies for CDH, and considering the applications of these therapies to clinical practice, this review will explore the future of antenatal CDH management with a focus on the phosphodiesterase-5 inhibitor sildenafil.

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

Abstract: The use of prenatal dexamethasone added to ventilation alters the VEGF and NO pathways.

Cited by 9 publications

References 41 publications

Mechanical ventilation strategies alter cardiovascular biomarkers in an infant rat model

Mechanical ventilation strategies alter cardiovascular biomarkers in an infant rat model

Medical interventions to reverse pulmonary hypoplasia in the animal model of congenital diaphragmatic hernia: A systematic review

Antenatal Medical Therapies to Improve Lung Development in Congenital Diaphragmatic Hernia

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