Lung Pathology in Patients with Congenital Diaphragmatic Hernia Treated with Fetal Surgical Intervention, Including Tracheal Occlusion

2003 ◽  
Vol 6 (6) ◽  
pp. 536-546 ◽  
Author(s):  
Amy E. Heerema ◽  
Joseph T. Rabban ◽  
Roman M. Sydorak ◽  
Micheal R. Harrison ◽  
Kirk D. Jones
Keyword(s):  
Body Weight ◽  
Congenital Diaphragmatic Hernia ◽  
Diaphragmatic Hernia ◽  
Pulmonary Hypoplasia ◽  
Weight Ratio ◽  
Lung Pathology ◽  
Body Weight Ratio ◽  
Fetal Intervention ◽  
Tracheal Occlusion ◽  
Significant Difference

Fetal intervention for congenital diaphragmatic hernia was developed to lessen the high morbidity and mortality of pulmonary hypoplasia. Lung pathology and morphometry in patients treated with fetal intervention have not been described. We report clinical and autopsy findings, as well as basic lung morphometry in 16 cases of congenital diaphragmatic hernia with fetal intervention (12 cases tracheal occlusion; 4 cases hernia repair), and 19 cases of congenital diaphragmatic hernia without fetal intervention. All patients who underwent fetal intervention were born premature. Lung enlargement with increased lung-to-body weight ratio was observed with fetal tracheal occlusion, accompanied by lower than normal radial alveolar counts and increased alveolar size. Patients treated with tracheal occlusion also had early alveolar development (at 29.8, 30.6, and 30.9 wk postconceptual age) as well as mucous fluid pooling in airways and alveoli. All cases showed severe alveolar septal widening, more extensive in patients without fetal intervention. When grouped by postconceptual age, no statistically significant difference was found between patients with and without fetal intervention with respect to lung-to-body weight ratio, radial alveolar count, mean alveolar length, and relative arteriolar media thickness. Lung enlargement has been observed with fetal tracheal occlusion sonographically; our studies suggest that this is due in part to emphysema and mucous fluid pooling. The lung remains abnormal with low radial alveolar counts and increased alveolar size. Tracheal occlusion did not prevent development of lung pathology associated with pulmonary hypoplasia.

A study on the safety evaluation of buphrenorphine administered through an autoinjector compared with manual injection using haematological and biochemical variables in rats

2016 ◽  
Vol 36 (9) ◽  
pp. 901-909 ◽  
Author(s):  
D Sheela ◽  
R Vijayaraghavan ◽  
S Senthilkumar
Keyword(s):  
Body Weight ◽  
Research Work ◽  
Safety Evaluation ◽  
Weight Ratio ◽  
The Body ◽  
Control Group ◽  
Body Weight Ratio ◽  
Significant Difference ◽  
Manual Group ◽  
Significant Change

Buprenorphine drug cartridge was made for autoinjector device for use in emergency and critical situations to reduce the morbidity and mortality. Water-filled cartridges were prepared and buprenorphine was injected aseptically in the cartridge, to make 0.05 and 0.10 mg/mL. Rats were injected intraperitoneally, buprenorphine (0.3 and 0.6 mg/kg), repeatedly with the autoinjector and compared with manual injection (7 days and 14 days) using various haematological and biochemical parameters. No significant change was observed in the body weight, organ to body weight ratio and haematological variables in any of the experimental groups compared with the control group. Except serum urea and aspartate aminotransferase, no significant change was observed in glucose, cholesterol, triglycerides, bilirubin, protein, albumin, creatinine, uric acid, alanine aminotransferase, gamma glutamyltransferase and alkaline phosphatase. The autoinjectors deliver the drugs with spray effect and force for faster absorption. In the present study, the autoinjector meant for intramuscular injection was injected intraperitoneally in rats, and the drug was delivered with force on the vital organs. No significant difference was observed in the autoinjector group compared to the manual group showing tolerability and safety of the buphrenorphine autoinjector. This study shows that buprenorphine autoinjector can be considered for further research work.

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

2015 ◽  
Vol 308 (7) ◽  
pp. L672-L682 ◽  
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.

scholarly journals Congenital Diaphragmatic Hernia: Review of Current Concept in Surgical Management

ISRN Surgery ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Emeka B. Kesieme ◽  
Chinenye N. Kesieme
Keyword(s):  
Congenital Diaphragmatic Hernia ◽  
Surgical Management ◽  
Diaphragmatic Hernia ◽  
Minimal Invasive Surgery ◽  
Pulmonary Hypoplasia ◽  
Open Repair ◽  
Minimal Invasive ◽  
Fetal Intervention ◽  
Prosthetic Devices ◽  
Diaphragmatic Hernias

Congenital diaphragmatic hernias (CDHs) occur mainly in two locations: the foramen of Morgagni and the more common type involving the foramen of Bochdalek. Hiatal hernia and paraesophageal hernia have also been described as other forms of CDH. Pulmonary hypertension and pulmonary hypoplasia have been recognized as the two most important factors in the pathophysiology of congenital diaphragmatic hernia. Advances in surgical management include delayed surgical approach that enables preoperative stabilization, introduction of fetal intervention due to improved prenatal diagnosis, the introduction of minimal invasive surgery, in addition to the standard open repair, and the use of improved prosthetic devices for closure.

Vitamin A decreases the incidence and severity of nitrofen-induced congenital diaphragmatic hernia in rats

1999 ◽  
Vol 277 (2) ◽  
pp. L423-L429 ◽  
Author(s):  
Bernard Thébaud ◽  
Dick Tibboel ◽  
Caroline Rambaud ◽  
Jean-Christophe Mercier ◽  
Jacques R. Bourbon ◽  
...  
Keyword(s):  
Vitamin A ◽  
Congenital Diaphragmatic Hernia ◽  
Diaphragmatic Hernia ◽  
Weight Ratio ◽  
Treated Group ◽  
Control Group ◽  
Lung Growth ◽  
Body Weight Ratio ◽  
Pregnant Rats ◽  
Antenatal Treatment

Congenital diaphragmatic hernia (CDH) is a major cause of refractory respiratory failure in the newborn. Pulmonary hypoplasia often limits survival. Vitamin A (Vit A) is an important signal for lung growth. We hypothesized that antenatal treatment with Vit A would stimulate lung growth and decrease mortality in experimental CDH induced in rats by ingestion of the herbicide nitrofen (2,4-dichlorophenyl- p-nitrophenyl ether). Nitrofen was administered to pregnant rats on day 12 of gestation (term 22 days). Rats were assigned to five groups: three groups received one dose of oral antenatal Vit A (15,000 IU) before ( day 10), concomitant with ( day 12), or after ( day 14) nitrofen administration; one group received only nitrofen; and a control group received vehicle (olive oil). The incidence of CDH was markedly lower in all groups receiving Vit A ( day 10, 44%; day 12, 20%; and day 14, 40%) compared with the nitrofen-treated group (84%; P < 0.05). The 72-h survival was higher in all 3 Vit A-treated groups ( day 10, 40%; day 12, 58%; and day 14, 70%) compared with the nitrofen-treated group (16%; P< 0.05). Lung-to-body weight ratio and radial saccular count were significantly increased by Vit A. Antenatal treatment with Vit A lowers the incidence and severity of experimental CDH and increases lung growth and maturation.

Lungs’ size in different anatomical variant of fetal congenital diaphragmatic hernia

2018 ◽  
pp. 40-44
Author(s):  
G.O. Grebinichenko ◽  
◽  
I.Yu. Gordienko ◽  
Keyword(s):  
Congenital Diaphragmatic Hernia ◽  
Diaphragmatic Hernia ◽  
Pulmonary Hypoplasia ◽  
Differential Analysis ◽  
Early Assessment ◽  
Anatomical Variant ◽  
Anatomical Variants ◽  
Chamber View ◽  
Significant Difference ◽  
Liver Herniation

The objective: to compare lung indices in fetuses with different anatomical variants of left-sided congenital diaphragmatic hernia, determined by two-dimensional ultrasound examination. Materials and methods. Data from 157 ultrasound examinations in 136 fetuses as patients with the most typical anatomical variants of left-sided diaphragmatic hernia were analyzed. The area of the lungs and the herniated liver were measured in the standard cross section of fetal thorax, at the level of a four-chamber view, with following calculation of prognostic indices. Comparison of indices’ means in groups depending on the abdominal organs herniated into fetal chest was performed using Student’s t-test. Results. The most numerous group in our study was one with herniation of the liver, stomach and intestines (62.5%). Significantly lower values of all lung indices were found in this group (p≤0.0001). In particular, observed-to-expected area ratio equaled to 35.59±8.8 and 31.73±10.51 in these fetuses in II and III trimesters respectively. In fetuses with intestines herniation, this index was 60.67±10.93 and 57.37±7.98, in fetuses with stomach and intestines herniation – 53.20±7.02 and 51.77±9.57 in II and III trimesters, respectively. Differential analysis of lung indices depending on the degree of liver herniation showed the presence of statistically highly significant difference in both second and third trimesters. In the group with mild liver herniation, the largest lung sizes and indices were determined, which were similar to values registered in groups without hepatic herniation. The lowest values of all lung indices were registered in the group with severe liver herniation. Conclusions. The anatomical variant of left diaphragmatic hernia with herniation of liver, stomach and intestines into thorax was the most common among our study population; in this group the lowest values of term-independent lung indices were observed. However, this group turned out to be heterogeneous: with different degrees of liver herniation, different degrees of pulmonary hypoplasia were found. Significant differences in lung indices found in II trimester can become a basis for early assessment of the severity of pathology and prediction of postnatal outcome. Keywords: congenital diaphragmatic hernia, liver herniation, pulmonary hypoplasia, lung size, prenatal diagnosis.

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

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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