Hypoplastic Lungs Research Articles

Effect of lung hypoplasia on the cardiorespiratory transition in newborn lambs.

Newborns with lung hypoplasia (LH) commonly have limited respiratory function and often require ventilatory assistance after birth. We aimed to characterize the cardiorespiratory transition and respiratory function in newborn lambs with LH. LH was induced by draining fetal lung liquid in utero [110-133 days (d), term = 147d, n = 6]. At ~133d gestation, LH and Control lambs (n = 6) were instrumented and ventilated for 3 h to monitor blood-gas status, oxygenation, ventilator requirements, and hemodynamics during the transition from fetal to newborn life. Lambs with LH had significantly reduced relative wet and dry lung weights indicating hypoplastic lungs compared with Control lambs. LH lambs experienced persistent hypercapnia and acidosis during the ventilation period, had lower lung compliance, and had higher alveolar-arterial differences in oxygen and oxygenation index compared with Control lambs. As a result, LH lambs required greater respiratory support and more supplemental oxygen. Following delivery, LH lambs experienced periods of significantly lower pulmonary artery blood flow and higher carotid artery blood flow in association with the lower oxygenation levels. The detrimental effects of LH can be attributed to a reduction in lung size and poorer gas exchange capabilities. This study has provided greater understanding of the effect of LH itself on the physiology underpinning the transition from fetal to newborn life. Advances in this area is the key to identifying improved or novel management strategies for babies with LH starting in the delivery room, to favorably alter the fetal-to-newborn transition toward improved outcomes and reduced lifelong morbidity.NEW & NOTEWORTHY Current clinical management of newborns with lung hypoplasia (LH) is largely based on expert opinion rather than scientific evidence. We have generated physiological evidence for detrimental effects of LH on hemodynamics and respiratory function in newborn lambs, which mimics the morbidity observed in LH newborns clinically. The unfavorable consequences of LH can be attributed to a reduction in lung size and poorer gas exchange capabilities.

Prenatal microRNA miR-200b Therapy Improves Nitrofen-induced Pulmonary Hypoplasia Associated With Congenital Diaphragmatic Hernia.

We aimed to evaluate the use of miR-200b as a prenatal transplacental therapy in the nitrofen rat model of abnormal lung development and congenital diaphragmatic hernia (CDH). Pulmonary hypoplasia (PH) and pulmonary hypertension determine mortality and morbidity in CDH babies. There is no safe medical prenatal treatment available. We previously discovered that higher miR-200b is associated with better survival in CDH babies. Here, we investigate the role of miR-200b in the nitrofen rat model of PH and CDH and evaluate its use as an in vivo prenatal therapy. We profiled miR-200b expression during nitrofen-induced PH using RT-qPCR and in situ hybridization in the nitrofen rat model of PH and CDH. The effects of nitrofen on downstream miR-200b targets were studied in bronchial lung epithelial cells using a SMAD luciferase assay, Western blotting and Immunohistochemistry. We evaluated miR-200b as a lung growth promoting therapy ex vivo and in vivo using lung explant culture and transplacental prenatal therapy in the nitrofen rat model. We show that late lung hypoplasia in CDH is associated with (compensatory) upregulation of miR-200b in less hypoplastic lungs. Increasing miR-200b abundance with mimics early after nitrofen treatment decreases SMAD-driven TGF-β signaling and rescues lung hypoplasia both in vitro and in vivo. Also, prenatal miR-200b therapy decreases the observed incidence of CDH. Our data indicate that miR-200b improves PH and decreases the incidence of CDH. Future studies will further exploit this newly discovered prenatal therapy for lung hypoplasia and CDH.

Scimitar sign in the absence of anomalous pulmonary venous drainage: a case report.

BackgroundScimitar syndrome consists of anomalous pulmonary vein drainage to the inferior vena cava. Its name derives from the image this anomalous pulmonary vein creates on a chest radiograph. We describe a case of normal venous pulmonary vein drainage that also presented the scimitar sign due to an aorto-collateral vessel.Case summaryA 15-month-old girl presented with mild dyspnoea and fever. Control chest X-ray showed an image of cardiac dextroposition, hypoplastic right lung, and the ‘scimitar sign’. Although the transthoracic echocardiogram confirmed the initial suspicion of anomalous pulmonary venous drainage, the computed tomography (CT) scan showed normal right pulmonary veins connected to the left atrium and revealed that an aorto-collateral vessel caused the scimitar sign.DiscussionAlthough the patient had several typical alterations of the scimitar syndrome, the pulmonary venous connection was normal, and the scimitar sign was due to an aorto-collateral vessel. It might be difficult to describe venous pulmonary connections on the basis of echocardiography, so an angio CT scan proved to be a valuable tool in this scenario.

The proportion of alveolar type 1 cells decreases in murine hypoplastic congenital diaphragmatic hernia lungs.

BackgroundPulmonary hypoplasia, characterized by incomplete alveolar development, remains a major cause of mortality and morbidity in congenital diaphragmatic hernia. Recently demonstrated to differentiate from a common bipotent progenitor during development, the two cell types that line the alveoli type 1 and type 2 alveolar cells have shown to alter their relative ratio in congenital diaphragmatic hernia lungs.ObjectiveWe used the nitrofen/bisdiamine mouse model to induce congenital diaphragmatic hernia and accurately assess the status of alveolar epithelial cell differentiation in relation to the common bipotent progenitors.Study designPregnant Swiss mice were gavage-fed with nitrofen/bisdiamine or vehicle at embryonic day 8.5. The administered dose was optimized by assessing the survival, congenital diaphragmatic hernia and facial abnormality rates of the exposed mouse pups. NanoCT was performed on embryonic day 11.5 and 16.5 to assess the embryonic and early canalicular stages of lung development. At embryonic day 17.5 corresponding to late canalicular stage, congenital diaphragmatic hernia lungs were characterized by measuring the lung weight/body weight ratio, morphometry, epithelial cell marker gene expression levels and alveolar cell type quantification.ResultsNitrofen/bisdiamine associated congenital diaphragmatic hernia lungs showed delayed development, hypoplasia with morphologic immaturity and thickened alveolar walls. Expression levels of distal epithelial progenitor marker Id2 increased, alveolar type 1 cell markers Pdpn and Hopx decreased, while type 2 cell markers pro-SPC and Muc1 remained constant during the canalicular stage. The number of Pdpn+ type 1 alveolar cells also decreased in congenital diaphragmatic hernia lungs.ConclusionThe mouse nitrofen/bisdiamine model is a potential model allowing the study of congenital diaphragmatic hernia lung development from early stages using a wide array of methods. Based on this model, the alveolar epithelium showed a decrease in the number of alveolar type 1 cell in congenital diaphragmatic hernia lungs while type 2 cell population remains unchanged.

Expression of fibroblast growth factor-10 during histogenesis of human lung in prenatal period

Introduction: The developing human lung has five stages. Many important signaling molecules have been identified at each stage of the developing lung. Fibroblast growth factor (FGF) signaling, mainly FGF10, is a key molecule in airway branching. Failure of the expression of FGF10 may lead to hypoplastic lung and blunted tracheal end. In this view, the expression of FGF10 was studied in each stage of human lung development. Material and Methods: In the present study, ten aborted fetuses of gestational age 14–26 weeks were procured from the Department of Obstetrics and Gynaecology, LNH, New Delhi, after ethical clearance. After fixation in 10% formalin, serial sections of each lung tissue were stained with hematoxylin and eosin, and immunostaining was done to see the expression of FGF10. Results: The amount of mesenchymal tissue decreased and condensed with advancing gestational age. At 14-week gestation, the first expression of FGF10 was seen in mesenchyme by immunostaining. Discussion and Conclusion: As the gestational age advances, the amount of mesenchymal tissue decreases and gradual diminution of the height of epithelium was seen. By the 26th week of intrauterine life, fetal lung attains morphological maturity so as to support the extrauterine life of a growing fetus.

992: Physiologically based cord clamping improves pulmonary hemodynamics during neonatal transition in lambs with diaphragmatic hernia

Many infants with congenital diaphragmatic hernia (CDH) develop pulmonary hypertension during the neonatal period, due to underdeveloped lung vessels and an increased sensitivity to vasoactive triggers. The abnormal pulmonary vascular bed is not equipped to adapt to the rapid cardiovascular changes that occur immediately after umbilical cord clamping, exposing these lungs to increased arterial pressures. We hypothesised that delaying umbilical cord clamping until these hypoplastic lungs are fully aerated and optimally vasodilated could protect the vascular bed from these high pressures. A diaphragmatic hernia (DH) was surgically created at ≈80 days gestational age (GA; term≈147d) in 17 ovine fetuses. At ≈138d GA, all lambs were instrumented and then delivered via caesarean section. The umbilical cord was clamped either immediately prior to ventilation onset (immediate cord clamping, DH-ICC; n=6) or after achieving a target tidal volume of 4 mL/kg, with a maximum delay of 10 min (physiologically based cord clamping, DH-PBCC; n=11). Lambs were ventilated for a total of 120 min with real-time monitoring of physiological parameters. Pulmonary blood flow (PBF) gradually increased following ventilation onset in both groups, however to a greater degree in DH-PBCC lambs (Figure 1a). PBF was 2-fold greater in DH-PBCC compared to DH-ICC lambs at 15 min following ventilation onset (45 ± 9 vs. 22 ± 3 mL/min/kg; p=0.005), and by the end of the 120 min ventilation period was 3-fold greater (23 ± 4 vs 8 ± 2 mL/min/kg; p=0.048). Pulmonary arterial pressure increased more gradually and to a lesser degree in DH-PBCC lambs, reaching a maximum of 77 ± 5 mmHg in DH-ICC lambs at 10 min, and a maximum of 64 ± 3 mmHg in DH-PBCC lambs at 17 min (Figure 1b). Pulmonary vascular resistance (PVR) dramatically decreased following lung aeration in both groups, however subsequently increased in DH-ICC lambs after 60 min of ventilation (Figure 2). By the end of the 120 min ventilation period, PVR was 3-fold lower in DH-PBCC compared to DH-ICC lambs (2.2 ± 0.6 vs. 0.6 ± 0.1 mmHg/(L/min); p<0.001). In lambs with DH, PBCC reduced pulmonary arterial pressure during the initial neonatal transition and was associated with lower PVR and greater PBF throughout the first 120 min of neonatal life. These findings suggest that delaying cord clamping may improve the neonatal transition of infants with CDH.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Anesthetic considerations for cesarean section in a parturient complicated by Scimitar syndrome-like pathophysiology

BackgroundPre-existing poor respiratory function is a significant challenge for women to successfully continue pregnancy and accomplish delivery.CasePregnancy and delivery were successfully managed without any maternal or neonatal complications, in a 26-year-old woman with severely impaired respiratory function, due to a unilateral hypoplastic lung, accompanying Scimitar syndrome-like circulation. Hyperventilation, normally observed even at the first trimester, was absent by the end of the second trimester. This would indicate her ventilation must have reached utmost capacity. Premature delivery by the mode of elective cesarean section delivery was, therefore, the most reasonable option. General anesthesia, combined with a continuous epidural infusion of low-concentrate local anesthetics, containing opioid, was sufficient to avoid the need for unexpected mechanical ventilation in intra- and early postoperative periods and to provide excellent post-partum analgesia.ConclusionThis combination can be a potent alternative in tailoring anesthesia for cesarean section in women with extremely impaired pulmonary reserve.

Endoplasmic reticulum stress response is activated in pulmonary hypoplasia secondary to congenital diaphragmatic hernia, but is decreased by administration of amniotic fluid stem cells

Pulmonary hypoplasia secondary to congenital diaphragmatic hernia (CDH) is characterized by impaired epithelial homeostasis. Recently, amniotic fluid stem cells (AFSCs) have been shown to promote growth in hypoplastic lungs of rat fetuses with CDH. Herein, we investigated whether CDH hypoplastic lungs mount an endoplasmic reticulum (ER) stress response and whether AFSCs could re-establish pulmonary epithelial homeostasis. Primary epithelial cells were isolated from fetal rat lungs at E14.5 from control and nitrofen-exposed dams at E9.5. Nitrofen-exposed epithelial cells were grown in medium alone or co-cultured with AFSCs. Epithelial cell cultures were compared for apoptosis (TUNEL), cytotoxicity (LIVE/DEAD assay), proliferation (5'EdU), and ER stress (CHOP, Bcl-2) using one-way ANOVA (Dunn's post-test). Compared to control, nitrofen-exposed epithelial cells had increased cytotoxicity and apoptosis, reduced proliferation, and activated ER stress. AFSCs restored apoptosis, proliferation, and ER stress back to control levels, and significantly reduced cytotoxicity. This study shows for the first time that ER stress-induced apoptosis is activated in the pulmonary epithelium of hypoplastic lungs from fetuses with CDH. AFSC treatment restores epithelial cellular homeostasis by attenuating the ER stress response and apoptosis, by increasing proliferation and migration ability, and by reducing cytotoxicity.

MicroRNA 200b is upregulated in the lungs of fetal rabbits with surgically induced diaphragmatic hernia.

Profiling of miR-200b expression and its targets (transforming growth factor [TGF]-β2 and ZEB2) in the surgical rabbit congenital diaphragmatic hernia (DH) model before and after tracheal occlusion (TO). Thirty-eight timed-pregnant rabbits had left DH creation on gestational day (GD) 23. On GD28, 17 randomly selected fetuses had TO. We harvested fetuses at GD23, GD28, or GD30. We calculated lung-to-body weight ratios, processed lungs for miR-200b in situ hybridization and real-time quantitative polymerase chain reaction, and evaluated effects on downstream targets TGF-β2 or ZEB2. We obtained 16 DH fetuses (n=7 GD28 and n=9 GD30), 13 TO fetuses (GD30), and 38 control fetuses (n=15 GD23, n=11 GD28, and n=12 GD30). Diaphragmatic hernia lungs were hypoplastic, and TO resulted in control lung-to-body weight ratio levels. Term miR-200b-3p levels were significantly upregulated in the hypoplastic compared with control ipsilateral lung (1.906±0.90 vs 0.7429±0.44) (P<.01). Fetal TO ipsilateral lungs displayed a variable miR-200b response on in situ hybridization and polymerase chain reaction, with levels similar to control and congenital DH lungs. The TGF-β2 was unchanged in hypoplastic and TO lungs, and ZEB2 tended to be reduced in TO compared with DH lungs (1.79 [0.4-2.9] vs 0.73 [0.5-1.4]). Hypoplastic fetal rabbit lungs display upregulation of miR-200b expression although downstream targets are not different from controls. Following TO, fetal rabbit lungs display a variable miR-200b response.

Heparin impairs angiogenic signaling and compensatory lung growth after left pneumonectomy.

Children with hypoplastic lung diseases, such as congenital diaphragmatic hernia, can require life support via extracorporeal membrane oxygenation and systemic anticoagulation, usually in the form of heparin. The role of heparin in angiogenesis and organ growth is inconclusive, with conflicting data reported in the literature. This study aimed to investigate the effects of heparin on lung growth in a model of compensatory lung growth (CLG). Compared to the absence of heparin, treatment with heparin decreased the vascular endothelial growth factor (VEGF)-mediated activation of VEGFR2 and mitogenic effect on human lung microvascular endothelial cells in vitro. Compared to non-heparinized controls, heparinized mice demonstrated impaired pulmonary mechanics, decreased respiratory volumes and flows, and reduced activity levels after left pneumonectomy. They also had lower lung volume, pulmonary septal surface area and alveolar density on morphometric analyses. Lungs of heparinized mice displayed decreased phosphorylation of VEGFR2 compared to the control group, with consequential downstream reduction in markers of cellular proliferation and survival. The use of bivalirudin, an alternative anticoagulant that does not interact with VEGF, preserved lung growth and pulmonary mechanics. These results demonstrated that heparin impairs CLG by reducing VEGFR2 activation. These findings raise concern for the clinical use of heparin in the setting of organ growth or regeneration.

Short rib-polydactyly syndrome (Saldino-Noonan type) undetected by standard prenatal genetic testing

Abstract Short rib-polydactyly syndrome (SRPS) is an extremely rare lethal skeletal dysplasia characterized by organ abnormalities, polydactyly, shortened tubular bones and a constricted thoracic cage [Saldino RM. Lethal short-limbed dwarfism: achondrogenesis and thanatophoric dwarfism. Am J Roentgenol. 1971;112:185–97]. In this case, we describe a neonate born with Type I SRPS (Saldino-Noonan type). Prenatal ultrasounds were suspicious for skeletal dysplasia, but prenatal genetic testing was negative. Postnatally, the infant was found to have severely hypoplastic lungs, a large patent ductus arteriosus, hydrops fetalis, polydactyly and a saddle nose. Postnatal DNA sequencing confirmed the diagnosis of SRPS and revealed a compound heterogeneous mutation in a gene involved in primary cilia synthesis. Ultimately, the infant was withdrawn from life support at 7 days due to severe respiratory decompensation from the lung hypoplasia.

Lower Distending Pressure Improves Respiratory Mechanics in Congenital Diaphragmatic Hernia Complicated by Persistent Pulmonary Hypertension

To investigate the effects of distending pressures on respiratory mechanics and pulmonary circulation in newborn infants with congenital diaphragmatic hernia (CDH) and persistent pulmonary hypertension (PPHN). In total, 17 consecutive infants of ≥37 weeks of gestational age with CDH and PPHN were included in this prospective, randomized, crossover pilot study. Infants were assigned randomly to receive 2 or 5 cmH2O of positive end-expiratory pressure (PEEP) for 1 hour in a crossover design. The difference between peak inspiratory pressure and PEEP was kept constant. Respiratory mechanics, lung function, and hemodynamic variables assessed by Doppler echocardiography were measured after each study period. At 2 cmH2O of PEEP, tidal volume and minute ventilation were greater (P < .05), and respiratory system compliance was 30% greater (P < .05) than at 5 cmH2O. PaCO2 and ventilation index were lower at 2 cmH2O than at 5 cmH2O (P < .05). Although preductal peripheral oxygen saturation was similar at both PEEP levels, postductal peripheral oxygen saturation was lower (median [range]: 81% [65-95] vs 91% [71-100]) and fraction of inspired oxygen was greater (35% [21-70] vs 25% [21-60]) at 5 cmH2O. End-diastolic left ventricle diameter, left atrium/aortic root ratio, and pulmonary blood flow velocities in the left pulmonary artery were lower at 5 cmH2O. After surgical repair, lower distending pressures result in better respiratory mechanics in infants with mild-to-moderate CDH. We speculate that hypoplastic lungs in CDH are prone to overdistension, with poor tolerance to elevation of distending pressure.

Diagnostic accuracy of low-dose dual-source cardiac computed tomography as compared to surgery in univentricular heart patients

BackgroundTo evaluate the ability of low radiation dose dual-source computed tomography (DSCT) to depict the features of morphological univentricular heart and to define accuracy by comparing findings with surgery.MethodsLow radiation dose dual-source cardiac computed tomography (CCT) of 33 cases of functional univentricular heart preliminary diagnosis by echocardiography compared with the results of surgery were retrospectively analyzed (aged 1 day to 4 years, median 5 months). The appropriate dose reduction strategies and iterative reconstruction were applied.ResultsThirty three univentricular heart patients were classified into three types according to Anderson’s classification method, including 16 cases (48.5%) univentricular of right ventricular type with rudimentary chamber of left ventricle, 11 cases (33.3%) univentricular of left ventricular type with rudimentary chamber of right ventricle and 6 cases (18.2%) univentricular heart of indeterminate type without rudimentary chamber. The extracardiac malformation such as hypoplastic aortic arch, coronary artery fistula, total anomalous pulmonary venous returns or hypoplastic lung were presented frequently. The overall sensitivity and specification of cardiac CT was 100% compared to the results of surgery. The procedural dose-length product was 18 ± 5 mGy-cm, and unadjusted and adjusted radiation doses were 0.25 and 0.64 mSv, respectively.ConclusionCardiac CT can diagnose accurately and be performed with a low radiation exposure in patients with the functional univentricular heart disease. The aorta, pulmonary artery and lung can be evaluated completely and simultaneously as well. Cardiac CT is an effective advanced non-invasive imaging modality to comprehensive evaluation the functional univentricular heart patients, particularly if cardiac MRI poses a high risk or is contraindicated.

Prenatal intervention for the management of congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) is the result of incomplete formation of the diaphragm that occurs during embryogenesis. The defect in the diaphragm permits the herniation of abdominal organs into the thoracic cavity contributing to the impairment of normal growth and development of the fetal lung. In addition to the hypoplastic lung, anomalies of the pulmonary arterioles worsen the pulmonary hypertension that can have detrimental effects in severe cases. Most cases of CDH can be effectively managed postnatally. Advances in neonatal and surgical care have resulted in improved outcomes over the years. When available, extracorporeal membrane oxygenation can provide temporary cardiorespiratory support for those not effectively supported by mechanical ventilation. In spite of these advances, very severe cases of CDH still carry a very high mortality and morbidity rate. Advances in imaging and evaluation now allow for early and accurate prenatal diagnosis of CDH, thereby identifying those at greatest risk who may benefit from prenatal intervention. This review article discusses some of the surgical and non-surgical prenatal interventions in the management of isolated severe congenital diaphragmatic hernia.

Vascular endothelial growth factor accelerates compensatory lung growth by increasing the alveolar units.

BackgroundDeficiency of vascular endothelial growth factor (VEGF) is associated with hypoplastic lung diseases such as congenital diaphragmatic hernia (CDH). Provision of VEGF has been demonstrated to be beneficial in hyperoxia-induced bronchopulmonary dysplasia and thus could induce lung growth and improve outcome in hypoplastic lung diseases. We aimed to determine the effects of exogenous VEGF in a rodent model of compensatory lung growth after left pneumonectomy.MethodsEight-ten-week-old C57Bl6 male mice underwent left pneumonectomy followed by daily intra-peritoneal injections of saline or VEGF (0.5 mg/kg). Lung volume measurement, pulmonary function tests, and morphometric analyses were performed on post-operative day (POD) 4 and 10. Pulmonary expression of angiogenic factors was analyzed by quantitative polymerase chain reaction and western blot.ResultsLung volume on POD 4 was higher in the VEGF-treated mice (P = 0.03). On morphometric analyses, VEGF increased parenchymal volume (P = 0.001), alveolar volume (P = 0.0003), and alveolar number (P < 0.0001) on POD 4. The VEGF group displayed higher levels of phosphorylated-VEGFR2/VEGFR2 (P = 0.03) and epidermal growth factor (EGF) mRNA (P = 0.01).ConclusionVEGF accelerated compensatory lung growth in mice by increasing alveolar units. These changes may be mediated by VEGFR2 and EGF-dependent mechanisms.

Scimitar syndrome: Anaesthetic management for pulmonary resection of the unaffected lung

Abstract Scimitar syndrome is a rare congenital anomaly characterised by anomalous drainage of the right pulmonary veins in the inferior vena cava, frequently associated with right lung and pulmonary artery hypoplasia, dextrocardia and abnormal systemic arterial supply to the lower lobe. Pulmonary resection surgery on healthy lung is exceptional, and there are no published records of it, as far as we know. A man with scimitar syndrome diagnosed with a lung nodule with malignant features in the contralateral lung. This situation implies huge anaesthetic complexity, mainly for intraoperative ventilation. Although spirometry and stress test did not contraindicate the planned lobectomy, scintigraphy showed a hypoplastic right lung with an uptake of 15%. From an anaesthetic point of view we discarded selective ventilation of the right lung, since the shunt made it functionally non-existent. In consequence we proposed four anaesthetic possibilities. After the placement of an epidural catheter and left selective intubation, thoracoscopy with intermittent apnoeas was our first choice, and we could complete the extirpation and avoid excessive complexity.

Decreased Expression of Integrin Subunits α3, α6, and α8 in the Branching Airway Mesenchyme of Nitrofen-Induced Hypoplastic Lungs.

Pulmonary hypoplasia (PH), characterized by smaller lung size and reduced airway branching, remains a major cause of neonatal mortality in newborns with congenital diaphragmatic hernia (CDH). Integrin-mediated cell-matrix interactions play an essential role in the fetal lung mesenchyme by stimulating branching morphogenesis. Mice lacking integrin subunits α3 (Itga3) and α6 (Itga6) exhibit severe PH. Furthermore, Itga8-knockout mice show defective airway branching, suggesting that Itga3, Itga6, and Itga8 are crucial for fetal lung development. We hypothesized that expression of Itga3, Itga6, and Itga8 is decreased in the branching airway mesenchyme of hypoplastic rat lungs in the nitrofen-induced CDH model. Time-mated rats received nitrofen or vehicle on gestational day 9 (D9). Fetuses were sacrificed on D15, D18, and D21, and dissected lungs were divided into control and nitrofen-exposed specimens (n = 12 per time-point and group, respectively). Pulmonary gene expression of Itga3, Itga6, and Itga8 was analyzed by quantitative real-time polymerase chain reaction. Immunofluorescence double-staining for Itga3, Itga6, and Itga8 was combined with the mesenchymal marker Fgf10 to evaluate protein expression and localization in branching airway tissue. Relative mRNA expression of Itga3, Itga6, and Itga8 was significantly decreased in lungs of nitrofen-exposed fetuses on D15, D18, and D21 compared with controls. Confocal laser scanning microscopy showed markedly diminished immunofluorescence of Itga3, Itga6, and Itga8 mainly in mesenchymal cells surrounding branching airways of nitrofen-exposed fetuses on D15, D18, and D21 compared with controls. Decreased expression of Itga3, Itga6, and Itga8 in the pulmonary mesenchyme may lead to disruptions in airway branching morphogenesis, thus contributing to PH in the nitrofen-induced CDH model.

Lung hypoplasia in newborn rabbits with a diaphragmatic hernia affects pulmonary ventilation but not perfusion

BackgroundA congenital diaphragmatic hernia (DH) can result in severe lung hypoplasia that increases the risk of morbidity and mortality after birth; however, little is known about the cardiorespiratory transition at birth.MethodsUsing phase-contrast X-ray imaging and angiography, we examined the cardiorespiratory transition at birth in rabbit kittens with DHs. Surgery was performed on pregnant New Zealand white rabbits (n=18) at 25 days’ gestation to induce a left-sided DH. Kittens were delivered at 30 days’ gestation, intubated, and ventilated to achieve a tidal volume (Vt) of 8 ml/kg in control and 4 ml/kg in DH kittens while they were imaged.ResultsFunctional residual capacity (FRC) recruitment and Vt in the hypoplastic left lung were markedly reduced, resulting in a disproportionate distribution of FRC into the right lung. Following lung aeration, relative pulmonary blood flow (PBF) increased equally in both lungs, and the increase in pulmonary venous return was similar in both control and DH kittens.ConclusionThese findings indicate that nonuniform lung hypoplasia caused by DH alters the distribution of ventilation away from hypoplastic and into normally grown lung regions. During transition, the increase in PBF and pulmonary venous return, which is vital for maintaining cardiac output, is not affected by lung hypoplasia.

Hydrops fetalis secondary to supradiaphragmatic extrapulmonary sequestration with congenital cystic adenomatoid malformation

Congenital cystic adenomatoid malformation is a hamartomatous lesion. A 30 year old woman, G2P1L1, in the 29th week of gestation presented with pain abdomen, chest pain, cough with expectoration, fever and inability to appreciate fetal movements of 2 days duration. Clinically, she had pneumonia. An ultrasound revealed a single fetus in breech presentation with features of hydrops fetalis, hypoplastic left lung, mediastinal shift to the left and poor diastolic and systolic flow in the umbilical artery.A still born male baby delivered subsequently was found at autopsy to have hydrops fetalis, supradiaphragmatic right sided extralobar sequestration with associated congenital cystic adenomatoid malformation.The right lung also showed congenital cystic adenomatoid malformation. There were no other associated anomalies. We present a rare case of extralobar sequestrationwith congenital cystic adenomatoid malformation.

Non-Immune Hydrops Foetalis due to Congenital Toxoplasmosis: a rare case report with review of literature.

Non-Immune Hydrops Foetalis (NIHF) implies an excess of total body water which manifests as extracellular accumulation of fluid in serous cavities and soft tissues of foetus without any detectable circulating antibody against RBC antigen. Toxoplasmosis is an important congenitally acquired infectious cause of NIHF.Mother had complaints of fever, reduced foetal movements, USG showed hydrops foetalis and she tested positive for Toxoplasma IgG antibodies. On autopsy, foetus had generalised subcutaneous oedema, bilateral hypoplastic lungs with pleural effusion and oedema of brain with ventriculomegaly suggestive of hydrocephalus. We report a rare case of NIHF due to congenital toxoplasmosis with bilateral hypoplastic lungs, with emphasis on epidemiology and prevention of toxoplasmosis. DOI: 10.21276/APALM.1077