Neonatal cardiopulmonary transition in an ovine model of congenital diaphragmatic hernia

ObjectiveInfants with a congenital diaphragmatic hernia (CDH) are at high risk of developing pulmonary hypertension after birth, but little is known of their physiological transition at birth. We aimed to characterise the changes in cardiopulmonary physiology during the neonatal transition in an ovine model of CDH.MethodsA diaphragmatic hernia (DH) was surgically created at 80 days of gestational age (dGA) in 10 fetuses, whereas controls underwent sham surgery (n=6). At 138 dGA, lambs were delivered via caesarean section and ventilated for 2 hours. Physiological and ventilation parameters were continuously recorded, and arterial blood gas values were measured.ResultsDH lambs had lower wet lung-to-body-weight ratio (0.016±0.002vs0.033±0.004), reduced dynamic lung compliance (0.4±0.1mL/cmH2O vs1.2±0.1 mL/cmH2O) and reduced arterial pH (7.11±0.05vs7.26±0.05), compared with controls. While measured pulmonary blood flow (PBF) was lower in DH lambs, after correction for lung weight, PBF was not different between groups (4.05±0.60mL/min/gvs4.29±0.57 mL/min/g). Cerebral tissue oxygen saturation was lower in DH compared with control lambs (55.7±3.5vs67.7%±3.9%).ConclusionsImmediately after birth, DH lambs have small, non-compliant lungs, respiratory acidosis and poor cerebral oxygenation that reflects the clinical phenotype of human CDH. PBF (indexed to lung weight) was similar in DH and control lambs, suggesting that the reduction in PBF associated with CDH is proportional to the degree of lung hypoplasia during the neonatal cardiopulmonary transition.

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Effects of tracheal occlusion on the neonatal cardiopulmonary transition in an ovine model of diaphragmatic hernia

Archives of Disease in Childhood - Fetal and Neonatal Edition ◽

10.1136/archdischild-2018-316047 ◽

2019 ◽

Vol 104 (6) ◽

pp. F609-F616 ◽

Cited By ~ 1

Author(s):

Philip L J DeKoninck ◽

Kelly J Crossley ◽

Aidan J Kashyap ◽

Sasha M Skinner ◽

Marta Thio ◽

...

Keyword(s):

Pulmonary Vascular Resistance ◽

Vascular Resistance ◽

Diaphragmatic Hernia ◽

Weight Ratio ◽

Lung Compliance ◽

Ovine Model ◽

Lung Weight ◽

Tracheal Occlusion ◽

Arterial Blood Gas ◽

Arterial Blood

ObjectiveFetoscopic endoluminal tracheal occlusion (FETO) aims to reverse pulmonary hypoplasia associated with congenital diaphragmatic hernia (CDH) and mitigate the associated respiratory insufficiency and pulmonary hypertension after birth. We aimed to determine whether FETO improves the cardiopulmonary transition at birth in an ovine model of CDH.MethodsIn 12 ovine fetuses with surgically induced diaphragmatic hernia (DH; 80 dGA), an endotracheal balloon was placed tracheoscopically at ≈110 dGA and removed at ≈131 dGA (DH+FETO), while 10 were left untreated (DH). At ≈138 dGA, all lambs (survival at delivery: 67% [DH+FETO], 70% [DH]) were delivered via caesarean section and ventilated for 2 hours. Physiological and ventilation parameters were continuously recorded, and arterial blood-gas values were measured.ResultsCompared with DH, DH+FETO lambs had increased wet lung-to-body-weight ratio (0.031±0.004 vs 0.016±0.002) and dynamic lung compliance (0.7±0.1 vs 0.4±0.1 mL/cmH2O). Pulmonary vascular resistance was lower in DH+FETO lambs (0.44±0.11 vs 1.06±0.17 mm Hg/[mL/min]). However, after correction for lung weight, pulmonary blood flow was not significantly different between the groups (4.19±0.57 vs 4.05±0.60 mL/min/g). Alveolar–arterial difference in oxygen tension was not significantly different between DH+FETO and DH (402±41mm Hg vs 401±45 mm Hg).ConclusionsFETO accelerated lung growth in fetuses with CDH and improved neonatal respiratory function during the cardiopulmonary transition at birth. However, despite improved lung compliance and reduced pulmonary vascular resistance, there were less pronounced benefits for gas exchange during the first 2 hours of life.

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Fetal tracheal occlusion in the rat model of nitrofen-induced congenital diaphragmatic hernia

Journal of Applied Physiology ◽

10.1152/jappl.1999.87.2.769 ◽

1999 ◽

Vol 87 (2) ◽

pp. 769-775 ◽

Cited By ~ 39

Author(s):

Yoshihiro Kitano ◽

Paul Davies ◽

Daniel von Allmen ◽

N. Scott Adzick ◽

Alan W. Flake

Keyword(s):

Congenital Diaphragmatic Hernia ◽

Diaphragmatic Hernia ◽

Rat Model ◽

Weight Ratio ◽

Lung Parenchyma ◽

Lung Hypoplasia ◽

Lung Growth ◽

Lung Weight ◽

Pregnant Rats ◽

Tracheal Occlusion

Prenatal tracheal occlusion (TO) consistently accelerates lung growth in the sheep model of congenital diaphragmatic hernia (CDH). However, significant variability in lung growth has been observed in early clinical trials of TO. We hypothesized that lung hypoplasia created at relatively late stages of lung development may not be equivalent to human CDH-induced lung hypoplasia, which begins early in gestation. To test this hypothesis, we performed TO in the rat model of nitrofen-induced CDH. Left-sided CDH was induced by administering 100 mg of nitrofen to timed pregnant rats on day 9 of gestation. On day 19 of gestation, four to five fetuses per dam underwent surgical ligation of the trachea. At death ( day 21.5), lungs from non-CDH (non-CDH group), left-CDH (CDH group), and trachea-occluded left-CDH fetuses (CDH-TO group) were harvested and compared by weight, DNA and protein content, and stereological morphometry. Wet and dry lung weight-to-body weight ratio, total lung DNA and protein contents, the volume of lung parenchyma, and the total saccular surface area of the CDH-TO group were significantly increased relative to the CDH group and were either greater than or comparable to the non-CDH controls. We conclude that TO accelerates lung growth and increases lung parenchyma in an early-onset model of CDH-induced lung hypoplasia.

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Prevention of pulmonary hypoplasia and pulmonary vascular remodeling by antenatal simvastatin treatment in nitrofen-induced congenital diaphragmatic hernia

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00345.2014 ◽

2015 ◽

Vol 308 (7) ◽

pp. L672-L682 ◽

Cited By ~ 20

Author(s):

Martine Makanga ◽

Hidekazu Maruyama ◽

Celine Dewachter ◽

Agnès Mendes Da Costa ◽

Emeline Hupkens ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Body Weight ◽

Congenital Diaphragmatic Hernia ◽

Diaphragmatic Hernia ◽

Weight Ratio ◽

The Body ◽

Lung Hypoplasia ◽

External Diameter ◽

Pathological Features ◽

Pulmonary Vessel

Congenital diaphragmatic hernia (CDH) has a high mortality rate mainly due to lung hypoplasia and persistent pulmonary hypertension of the newborn (PPHN). Simvastatin has been shown to prevent the development of pulmonary hypertension (PH) in experimental models of PH. We, therefore, hypothesized that antenatal simvastatin would attenuate PPHN in nitrofen-induced CDH in rats. The efficacy of antenatal simvastatin was compared with antenatal sildenafil, which has already been shown to improve pathological features of PPHN in nitrofen-induced CDH. On embryonic day (E) 9.5, nitrofen or vehicle was administered to pregnant Sprague-Dawley rats. On E11, nitrofen-treated rats were randomly assigned to antenatal simvastatin (20 mg·kg−1·day−1 orally), antenatal sildenafil (100 mg·kg−1·day−1 orally), or placebo administration from E11 to E21. On E21, fetuses were delivered by cesarean section, killed, and checked for left-sided CDH. Lung tissue was then harvested for further pathobiological evaluation. In nitrofen-induced CDH, simvastatin failed to reduce the incidence of nitrofen-induced CDH in the offspring and to increase the body weight, but improved the lung-to-body weight ratio and lung parenchyma structure. Antenatal simvastatin restored the pulmonary vessel density and external diameter, and reduced the pulmonary arteriolar remodeling compared with nitrofen-induced CDH. This was associated with decreased lung expression of endothelin precursor, endothelin type A and B receptors, endothelial and inducible nitric oxide synthase, together with restored lung activation of apoptotic processes mainly in the epithelium. Antenatal simvastatin presented similar effects as antenatal therapy with sildenafil on nitrofen-induced CDH. Antenatal simvastatin improves pathological features of lung hypoplasia and PPHN in experimental nitrofen-induced CDH.

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Changes in the Expression of Vascular Endothelial Growth Factor after Fetal Tracheal Occlusion in an Experimental Model of Congenital Diaphragmatic Hernia

Critical Care Research and Practice ◽

10.1155/2013/958078 ◽

2013 ◽

Vol 2013 ◽

pp. 1-6

Author(s):

E. Sanz-López ◽

E. Maderuelo ◽

D. Peláez ◽

P. Chimenti ◽

R. Lorente ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Congenital Diaphragmatic Hernia ◽

Diaphragmatic Hernia ◽

Weight Ratio ◽

Angiogenic Factor ◽

Vascular Endothelial ◽

Lung Weight ◽

Tracheal Occlusion ◽

Endothelial Growth Factor

Introduction. Vascular endothelial growth factor (VEGF), an angiogenic factor secreted by type II pneumocytes, could play a role in congenital diaphragmatic hernia (CDH) pathogenesis. Animal studies suggest that VEGF accelerates lung growth.Aim. To quantify VEGF on fetal lungs in a nitrofen rat model for CDH and to analyze the effect of tracheal occlusion (TO) in VEGF in fetal lung rats after nitrofen and in control rats not exposed to nitrofen.Methods. Pregnant rats received nitrofen on day 9.5 of gestation. Fetuses were divided into 2 groups: those that underwent TO on day 20 and those that did not. On day 21, fetuses were delivered, and the lungs were dissected for subsequent VEGF quantification.Results. CDH was detected in 43% of the fetuses that received nitrofen. Fetuses with CDH showed significantly reduced lung weight/fetal weight ratio and lower VEGF levels than the remainder. A higher VEGF value was observed after TO.Conclusions. VEGF protein was significantly lower in fetuses with CDH. TO induced a significant increase in VEGF compared to the fetuses that did not undergo TO. Although not statistically significant, we observed higher VEGF levels in fetuses with CDH and TO compared to fetuses with CDH and no further intervention.

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The co-occurrence of congenital diaphragmatic hernia, esophageal atresia/tracheoesophageal fistula, and lung hypoplasia

Birth Defects Research Part A Clinical and Molecular Teratology ◽

10.1002/bdra.20098 ◽

2005 ◽

Vol 73 (1) ◽

pp. 53-57 ◽

Cited By ~ 15

Author(s):

Marieke van Dooren ◽

Dick Tibboel ◽

Claudine Torfs

Keyword(s):

Congenital Diaphragmatic Hernia ◽

Esophageal Atresia ◽

Diaphragmatic Hernia ◽

Tracheoesophageal Fistula ◽

Lung Hypoplasia

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Possibility of application of prenatal ultrasound indexes in congenital diaphragmatic hernia in fetus to determine postnatal outcomes

10.21516/2413-1458-2021-20-1-17-24 ◽

2021 ◽

Author(s):

N.V. Mashinets

Keyword(s):

Congenital Diaphragmatic Hernia ◽

Diaphragmatic Hernia ◽

Pleural Cavity ◽

Prenatal Ultrasound ◽

Lung Hypoplasia ◽

Prenatal Period ◽

Compression Index ◽

Disease Group ◽

Group I ◽

Group Ii

Objectives. To assess the effectiveness of the use of prenatal ultrasound indexes in congenital diaphragmatic hernia of the fetus to determine the postnatal prognosis. Materials. The analysis of 95 observations of left-sided congenital diaphragmatic hernia of the fetus was carried out. In the prenatal period, the composition of organs displaced into the pleural cavity was determined, the heart compression index (HCI), O/E LHR according to Jani and DeKoninck, and QLI were calculated. Results. Survival rate of newborns was 57.9%, mortality rate was 42.1%. The newborns were divided into two groups depending on the outcome of the disease. Group I — surviving newborns (n = 55), group II — deceased patients (n = 40). In the analyzed groups, there were no statistical differences in the timing of delivery, birth weight of newborns, the severity of asphyxia after birth and the type of hernia. In group I, the intestinal loops and stomach were significantly more often identified in the pleural cavity in isolation, less often the liver. HCI corresponded to 1.3, Jani O/E LHR 45.7%, DeKoninck O/E LHR 38.7%, QLI 0.7. In group II, concomitant malformations, polyhydramnios and displacement of the liver into the pleural cavity were significantly more frequent. HCI was 1.5, Jani O/E LHR 38.6%, DeKoninck O/E LHR 32.0%, QLI 0.6. Conclusions. In predicting the outcome of the disease for a newborn, the most effective is a comprehensive assessment of the location of the liver, the heart compression index and the index of lung hypoplasia (O/E LHR according to Jani). The diagnostic accuracy of the method is 80%, the sensitivity is 74.4%, and the specificity is 83.3%.

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Prenatal Diagnosis and Management of a Rare Central Tendon Defect Type of Congenital Diaphragmatic Hernia with a Massive Pericardial Effusion

Case Reports in Obstetrics and Gynecology ◽

10.1155/2020/6798253 ◽

2020 ◽

Vol 2020 ◽

pp. 1-5

Author(s):

Inas Babic ◽

Haifa Al-Jobair ◽

Osama Al Towaijri ◽

Huda Al-Shammary ◽

Merna Atiyah ◽

...

Keyword(s):

Pericardial Effusion ◽

Congenital Diaphragmatic Hernia ◽

Diaphragmatic Hernia ◽

Neonatal Morbidity ◽

Lung Hypoplasia ◽

Defect Type ◽

Tendon Defect ◽

Prenatal Diagnostic ◽

Large Pericardial Effusion ◽

Prenatal Intervention

The central tendon defect type of congenital diaphragmatic hernia (CDH) is extremely rare and usually associated with a significant pericardial effusion. Prenatal diagnostic ultrasound features of this quite rare entity remain often overlooked or misdiagnosed. There is a dearth of literature about the role of prenatal intervention, often through an elective pericardiocentesis, for the prevention of lung hypoplasia and to decrease the overall neonatal morbidity and mortality. To the best of our knowledge, till date, there is only one case that was subjected to a prenatal intervention. Here, we present a second case of a central tendon defect type of CDH with a large pericardial effusion that was subjected to a prenatal transthoracic pericardiocentesis. Although smooth intubation and ventilation were performed immediately after birth, the infant suffered for several months from respiratory instability. Laparoscopic central tendon hernia repair was performed, and neonate was discharged home at seven months of age. Although prenatal pericardiocentesis may facilitate smoother postnatal intubation and ventilation, its broader effect on respiratory function is uncertain and still remains elusive.

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Cellular Origin(s) of Congenital Diaphragmatic Hernia

Frontiers in Pediatrics ◽

10.3389/fped.2021.804496 ◽

2021 ◽

Vol 9 ◽

Author(s):

Gabriëla G. Edel ◽

Gerben Schaaf ◽

Rene M. H. Wijnen ◽

Dick Tibboel ◽

Gabrielle Kardon ◽

...

Keyword(s):

Congenital Diaphragmatic Hernia ◽

Diaphragmatic Hernia ◽

Birth Defect ◽

Congenital Disorder ◽

Diaphragmatic Defect ◽

Lung Hypoplasia ◽

Cellular Origin ◽

Recent Developments ◽

Mechanical Factors

Congenital diaphragmatic hernia (CDH) is a structural birth defect characterized by a diaphragmatic defect, lung hypoplasia and structural vascular defects. In spite of recent developments, the pathogenesis of CDH is still poorly understood. CDH is a complex congenital disorder with multifactorial etiology consisting of genetic, cellular and mechanical factors. This review explores the cellular origin of CDH pathogenesis in the diaphragm and lungs and describes recent developments in basic and translational CDH research.

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Tetralogy of Fallot with congenital diaphragmatic hernia and left lung hypoplasia: assessment of the adequacy of the peripheral pulmonary vascular growth after hernia repair

Cardiology in the Young ◽

10.1017/s104795111100134x ◽

2011 ◽

Vol 22 (2) ◽

pp. 235-238 ◽

Cited By ~ 3

Author(s):

Hong Ju Shin ◽

Won Kyoung Jhang ◽

Tae Jin Yun

Keyword(s):

Congenital Diaphragmatic Hernia ◽

Tetralogy Of Fallot ◽

Diaphragmatic Hernia ◽

Left Lung ◽

Lung Hypoplasia ◽

Vascular Growth ◽

Threatening Condition ◽

Central Pulmonary Artery ◽

Life Threatening ◽

Vascular Beds

AbstractCongenital diaphragmatic hernia is a life-threatening condition frequently associated with various congenital cardiac diseases. In congenital diaphragmatic hernia associated with tetralogy of Fallot, central pulmonary artery size of the affected side may not reflect the capacitance of peripheral pulmonary vascular beds. We report a case of congenital diaphragmatic hernia associated with tetralogy of Fallot, which was repaired after assessing the adequacy of the pulmonary vascular beds by intra-operative pulmonary blood flow study.

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