Signaling between the epicardium and underlying myocardium is crucial for proper heart development. The complex molecular interactions and regulatory networks involved in this communication are not well understood. In this study, we integrated mass spectrometry with bioinformatics to systematically characterize the secretome of embryonic chicken EPDC-heart explant (EHE) co-cultures. The 150-protein secretome dataset established greatly expands the knowledge base of the molecular players involved in epicardial-myocardial signaling. We identified proteins and pathways that are implicated in epicardial-myocardial signaling for the first time, as well as new components of pathways that are known to regulate the crosstalk between epicardium and myocardium. The large size of the dataset enabled bioinformatics analysis to deduce networks for the regulation of specific biological processes and predicted signal transduction nodes within the networks. We performed functional analysis on one of the predicted nodes, NF-κB, and demonstrate that NF-κB activation is an essential step in TGFβ2/PDGFBB-induced cardiac epithelial-to-mesenchymal transition. In summary, we have generated a global perspective of epicardial-myocardial signaling for the first time, and our findings open exciting new avenues for investigating the molecular basis of heart development and regeneration.
Congenital chylothorax is a rare and often severe anomaly without well-established medical therapies. Previously, propranolol use in patients with lymphatic malformations and secondary chylothorax was associated with improvement in clinical signs. We hypothesized that propranolol treatment would be beneficial for severe congenital chylothorax. We reviewed medical records of neonates born from 2015 to 2019 at our tertiary center with a prenatal diagnosis of congenital chylothorax for whom either prenatal or postnatal propranolol therapy was initiated. Inclusion was limited to fetuses diagnosed with severe congenital chylothorax without significant genetic, infectious, or cardiac anomalies, and who underwent prenatal interventions to mitigate consequences of the condition. Propranolol was administered orally to pregnant women at 20 mg 4 times daily and increased to a maximum dose of 40 mg 4 times daily, or to infants at 0.3 mg/kg/d and increased to 1 to 2 mg/kg/d. Primary outcomes were the time course of resolution of ultrasonographical, clinical, and/or radiologic signs of chylothorax after treatment with propranolol. Four neonates met the inclusion criteria. In 2 cases, prenatal initiation of propranolol led to resolution of the chylothoraxes before delivery (38 and 32 days after treatment) on a dose of 40 mg/day 4 times daily. Neonates had a normal postnatal course. Postnatal propranolol was initiated in 2 neonates with respiratory failure when chylothoraces were refractory to standard management. Stabilization and improvement of their pleural effusion was observed by imaging at 29 and 13 days after initiation of propranolol. There were no significant maternal or neonatal complications from prenatal or postnatal propranolol use. Propranolol may be efficacious in treating severe fetal congenital chylothorax.
Objective: Extracorporeal membrane oxygenation (ECMO) is a lifesaving measure for patients in cardiac or respiratory failure. Extracorporeal cardiopulmonary resuscitation (ECPR) is emergent ECMO cannulation during cardiac arrest. All ECMO patients are at high risk for neurologic complications, but the degree of risk of ECPR relative to ECMO without CPR in progress (non-ECPR ECMO) is not well documented in infants. The goal of the present study is to compare neurologic complication rates between infants who underwent ECPR and those who underwent non-ECPR ECMO. Methods: We performed a retrospective chart review on all patients admitted between 2009 and 2020 to the neonatal intensive care unit (NICU) in our quaternary children's hospital. We separated patients by ECPR vs. non-ECPR ECMO cannulation. We compared rates of death and used neuroimaging and video electroencephalogram (vEEG) to determine incidence of stroke, intracranial hemorrhage, and seizure. Chi-square and Fisher's exact tests were used to compare these categorical variables among groups.Results: A total of 181 infants were cannulated onto ECMO. Of these, 40 received ECPR, 56 received non-ECPR ECMO for a cardiac indication, and 85 received non-ECPR ECMO for a respiratory indication. After excluding patients currently admitted (n=1, ECPR), 180 patients were subjected to analysis. ECPR patients were less likely to survive to hospital discharge than patients who underwent non-ECPR ECMO for respiratory indications, and less likely to survive without any neurologic complication compared with infants who underwent non-ECPR ECMO for cardiac or respiratory indications. Interpretation: Significantly fewer ECPR patients survived without experiencing a neurologic complication, compared with non-ECPR ECMO patients.
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