Cardiac Adaptation to Severe Congenital Diaphragmatic Hernia

Pelizzo, Gloria; Bussani, Rossana; Zandonà, Lorenzo; Custrin, Ana; Bellieni, Carlo V.; Silvestri, Annalisa De; Calcaterra, Valeria

doi:10.3109/15513815.2015.1122125

Cited by 13 publications

(13 citation statements)

References 25 publications

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“…Abnormal lung development, which accompanies this condition, is considered the most crucial clinically relevant characteristic. However, the role of structural problems in other internal organs, such as the liver and heart, should not be underestimated on CDH prognosis 13,16–18 …”

Section: Discussionmentioning

confidence: 99%

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Liver pathological alterations in fetal rabbit model of congenital diaphragmatic hernia

Pelizzo

Peiró

Villanacci

et al. 2022

Congenital Anomalies

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To date, fetal liver implication is not a well-understood phenomenon in congenital diaphragmatic hernia (CDH). We evaluated the fetal morphologic changes on liver growth after surgical procedure in CDH experimental model. A diaphragmatic defect at gestational day E25 and tracheal occlusion (TO) at E27 were surgically created in rabbit fetuses. Five experimental groups were assessed: control group, left CDH, right CDH, CDH + TO, and TO alone. Body and organ growth were measured. For histological evaluation of the CDH effect, liver sections were collected. Left-CDH group had livers with increased leukocyte infiltration in comparison with controls (p = 0.02). Increased capillary sinusoid congestion and hepatocyte vacuolation were greater in left-CDH compared with the right-CDH group (p = 0.05). Capillary sinusoid congestion and interstitial edema were more evident in the left-CDH compared with CDH + TO group (p = 0.05). Increases in sinusoid congestion, hepatocyte vacuolation, and interstitial edema were also greater in the CDH + TO compared with controls (p ≤ 0.02). Intrathoracic liver weight was higher in right-CDH compared with left-CDH group (p < 0.001). Total lung weights (TLW) were significantly lower in both left-CDH compared with controls (p < 0.001), CDH + TO (p = 0.01), and TO (p < 0.01) and in right-CDH compared with CDH + TO (p < 0.01) and TO (p < 0.01).Decreased kidney and heart weights were also recorded. Hemodynamics and structural fetal liver changes in laterality were noted in CDH model. Regulation of intrathoracic liver weights seems to be disturbed by the absence of diaphragmic contact.Pulmonary injury is supported by the effect of a first hit, while the growth of internal organs suggests a multisystemic remodeling related to the fetal adaptation.

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Section: Discussionmentioning

confidence: 99%

“…The hypothesis that reduced mRNA expression levels are responsible for the morphological changes affecting the function of liver lipid droplet expression has been postulated 16–20 . However, the role of hemodynamic changes on metabolic impairment of the hepatic cellular component should be not excluded.…”

Section: Discussionmentioning

confidence: 99%

Liver pathological alterations in fetal rabbit model of congenital diaphragmatic hernia

Pelizzo

Peiró

Villanacci

et al. 2022

Congenital Anomalies

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“…Both rates of IUGR and left-sided CHD are high among newborns with intrathoracic masses, also in our study, therefore it is not clear if heterogeneity of ventricular repolarization is ascribable to these variables or is due to hypoxemic severe RDS. Data from histology and cellular immunophenotyping support the cardiovascular remodeling hypothesis which consists of an inhomogeneous distribution of ventricular growth factors and muscle proteins [ 39 ]. Subtle ECG repolarization disorders could be attributed to these non-homogenous cardiac muscle alterations.…”

Section: Discussionmentioning

confidence: 98%

Clinical cardiac assessment in newborns with prenatally diagnosed intrathoracic masses

et al. 2018

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BackgroundCongenital space-occupying thoracic malformations and diaphragmatic hernia have in common pulmonary hypoplasia. Our study aims to assess cardiac involvement during post-natal adaptation.MethodsA retrospective study was carried out on newborns with prenatally diagnosed intrathoracic mass. Gathering for respiratory distress syndrome (RDS), 35 neonates were compared for clinical course, cardiovascular enzymes, ECG, and ultrasound.ResultsThe analysis revealed a high left heart defect rate in patients with severe RDS, without being influenced by the laterality. Ultrasound or laboratory assessment did not detect altered cardiac dimension or cardiomyopathy. Solely ECG signs of right ventricular strain were found. Increased QT-dispersion, T-wave and cardiac variability alterations in the first hours were all expression of non-specific cardiac repolarization disorders but predict worse outcome.ConclusionsAlthough RDS is the predominant symptom, slight cardiac dysfunctions should be recognized for prompt treatment. Conventional examinations for postnatal adaption should be integrated by complementary investigations.

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“…In particular, when left-sided cardiac underdevelopment is detected prenatally, this is considered a poor prognostic factor since at delivery the heart is less compliant and unable to maintain normal cardiac function [8, 34, 35]. Additionally, in animal models [4] and human CDH [5], histological and immunohistochemical alterations support structural cardiac impairment.…”

Section: Discussionmentioning

confidence: 99%

“…The first hit affects the heart before and apart from diaphragm development on a background of genetic and environmental factors (in this animal model the pathogenetic mechanism is represented by nitrofen toxicity; however, in humans the exact cause of CDH has not been unidentified) [5]. The second hit results from direct heart compression exerted by the herniated intrathoracic organs, with subsequent cardiac adaptations [5]. …”

Section: Discussionmentioning

confidence: 99%

Effects of Simvastatin on Fetal Cardiac Impairment in the Diaphragmatic Experimental Hernia Model

Pelizzo¹,

Bussani

Mazzon

et al. 2018

Fetal Diagn Ther

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Background: Statins and sildenafil have been shown to exert beneficial effects in cardiac injury. We hypothesized that antenatal maternal administration of simvastatin and/or sildenafil might also promote benefits in cardiac remodeling of congenital diaphragmatic hernia (CDH). Therefore, we performed micro-CT image analysis and histology of the heart after antennal treatment in experimental nitrofen-induced CDH. Methods: At 9.5 days post conception (dpc), pregnant rats were exposed to nitrofen. At 16 and 20 dpc fetuses were treated with simvastatin and/or sildenafil. At 21 dpc postmortem micro-CT and autopsy were performed. Results: All nitrofen-treated fetuses had a lower birth weight compared to controls; in the simvastatin-treated group, a significant improvement in CDH was noted. Impairment of the lung and liver was also noted in CDH. Compared to controls, CDH rats showed lower ventricular mass, with greater left ventricular thickness; simvastatin decreased the ventricular mass and improved wall thickness. CDH rats exhibited myocardial hypotrophy, severe vascular depression in the left ventricle, and intense interstitial edema compared to controls and nitrofen-exposed animals without CDH. In CDH, the cardiac morphology appeared deformed with left ventricular wall verticalization. Simvastatin improved cardiac myocyte appearance and heart morphology. Conclusion: The potential to treat CDH with antenatal simvastatin may improve the management of this malformation.

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Cardiac Adaptation to Severe Congenital Diaphragmatic Hernia

Abstract: Left ventricle immaturity seems to be a cardiac adaptive response of severe CDH in utero.

Cited by 13 publications

References 25 publications

Liver pathological alterations in fetal rabbit model of congenital diaphragmatic hernia

Liver pathological alterations in fetal rabbit model of congenital diaphragmatic hernia

Clinical cardiac assessment in newborns with prenatally diagnosed intrathoracic masses

Effects of Simvastatin on Fetal Cardiac Impairment in the Diaphragmatic Experimental Hernia Model

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