Background Current right ventricular (RV) volume overload (VO) is established in adult mice. There are no neonatal mouse VO models and how VO affects postnatal RV development is largely unknown. Methods and Results Neonatal VO was induced by the fistula between abdominal aorta and inferior vena cava on postnatal day 7 and confirmed by abdominal ultrasound, echocardiography, and hematoxylin and eosin staining. The RNA‐sequencing results showed that the top 5 most enriched gene ontology terms in normal RV development were energy derivation by oxidation of organic compounds, generation of precursor metabolites and energy, cellular respiration, striated muscle tissue development, and muscle organ development. Under the influence of VO, the top 5 most enriched gene ontology terms were angiogenesis, regulation of cytoskeleton organization, regulation of vasculature development, regulation of mitotic cell cycle, and regulation of the actin filament‐based process. The top 3 enriched signaling pathways for the normal RV development were PPAR signaling pathway, citrate cycle (Tricarboxylic acid cycle), and fatty acid degradation. VO changed the signaling pathways to focal adhesion, the PI3K‐Akt signaling pathway, and pathways in cancer. The RNA sequencing results were confirmed by the examination of the markers of metabolic and cardiac muscle maturation and the markers of cell cycle and angiogenesis. Conclusions A neonatal mouse VO model was successfully established, and the main processes of postnatal RV development were metabolic and cardiac muscle maturation, and VO changed that to angiogenesis and cell cycle regulation.

Background: Emerging evidence suggests that gut microbiota dysbiosis plays a role in sepsis. Recent advances in sequencing technology enable the characterization of the gut microbiota and can provide clues for the pathogenesis of sepsis, which may help develop biomarkers for diagnosis or prognosis prediction in children with sepsis.Methods: The gut microbiota from 25 children with sepsis and 15 age-and sex-matched healthy controls were extracted and sequenced by high-throughput Illumina Hiseq, targeting the 16S rDNA genes. The differences of gut microbiota between the two groups were analyzed to assess if the gut microbiota can be used as an auxiliary prognostic marker for sepsis. Results:The diversity of gut microbiota in children with sepsis was significantly lower than that of healthy controls (P<0.001). The overall community structure of gut microbiota was also altered considerably. On the genus level, children with sepsis had more opportunistic pathogens, such as Acinetobacter and Enterococcus, while fewer beneficial bacterial, such as Roseburia, Bacteroides, Clostridia, Faecalibacterium, and Blautia, were detected. Further analysis of the association between the gut microbiota and clinical features revealed that the pathogens from bacteria culture correlated to the dominant bacteria genus detected in the intestinal flora.Furthermore, the gut microbiota diversity was negatively associated with the antibiotic therapy duration, but did not correlate with type of antibiotics used. Finally, gut microbiota disturbance was correlated with increased mortality rate.Conclusions: Overall, we confirmed that gut microbiota disturbance occurred in the children with sepsis, and changes in the fecal microbiota were closely related to clinical characteristics. Elucidation of such dysbiosis could improve our understanding of sepsis pathogenesis and help develop microbiota-based diagnosis, monitoring, and therapy for sepsis.

The molecular atlas of postnatal mouse ventricular development has been made available and cardiac regeneration is documented to be a downregulated process. The right ventricle (RV) differs from the left ventricle. How volume overload (VO), a common pathologic state in children with congenital heart disease, affects the downregulated processes of the RV is currently unclear. We created a fistula between the abdominal aorta and inferior vena cava on postnatal day 7 (P7) using a mouse model to induce a prepubertal RV VO. RNAseq analysis of RV (from postnatal day 14 to 21) demonstrated that angiogenesis was the most enriched gene ontology (GO) term in both the sham and VO groups. Regulation of the mitotic cell cycle was the second-most enriched GO term in the VO group but it was not in the list of enriched GO terms in the sham group. In addition, the number of Ki67-positive cardiomyocytes increased approximately 20-fold in the VO group compared to the sham group. The intensity of the vascular endothelial cells also changed dramatically over time in both groups. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the downregulated transcriptome revealed that the peroxisome proliferators-activated receptor (PPAR) signaling pathway was replaced by the cell cycle in the top-20 enriched KEGG terms because of the VO. Angiogenesis was one of the primary downregulated processes in postnatal RV development, and the cell cycle was reactivated under the influence of VO. The mechanism underlying the effects we observed may be associated with the replacement of the PPAR-signaling pathway with the cell-cycle pathway.

Objectives: To investigate whether respiratory variations in aortic blood flow by echocardiography can accurately predict volume responsiveness in ventilated children with leukemia and neutropenic septic shock. Design: A prospective study. Setting: A 25-bed PICU of a tertiary hospital. Patients: Mechanically ventilated children with leukemia who had been exposed to anthracyclines and exhibited neutropenic septic shock were enrolled. Interventions: Transthoracic echocardiography was performed to monitor the aortic blood flow before and after fluid administration. Measurements and Main Results: After volume expansion, left ventricular stroke volume increased by greater than or equal to 15% in 16 patients (responders) and less than 15% in 14 patients (nonresponders). The performance of respiratory variation in velocity time integral of aortic blood flow and respiratory variation in peak velocity of aortic blood flow for predicting volume responsiveness, as determined by the area under the receiver operating characteristic curve, was 0.74 (95% CI, 0.55–0.94; p = 0.025) and 0.71 (95% CI, 0.53–0.90; p = 0.048), respectively. Positive end-expiratory pressure was higher in nonresponders than in responders (p = 0.035). Conclusions: Respiratory variation in velocity time integral of aortic blood flow and respiratory variation in peak velocity of aortic blood flow derived from transthoracic echocardiography showed only a fair reliability in predicting volume responsiveness in ventilated children with leukemia and neutropenic septic shock.

Background: Pulmonary regurgitation caused by the correction or palliation of pediatric tetralogy of Fallot (TOF) leads to chronic right ventricular (RV) volume overload (VO), which induces adolescent RV dysfunction. A better understanding of the molecular mechanism by which VO initiates neonatal RV remodeling may bring new insights into the post-surgical management of pediatric TOF.Methods and Results: We created a fistula between the abdominal aorta and inferior vena cava on postnatal day 1 (P1) using a rat model to induce neonatal VO. Echocardiography revealed that the velocity and velocity- time-integral of the pulmonary artery (PA) were significantly elevated, and hematoxylin and eosin (H&amp;E) staining showed that the diameter of the RV significantly increased. RNA-seq analysis of the RV on P7 indicated that the top 10 enriched Gene Ontology (GO) terms and the top 20 enriched terms in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were associated with immune responses. Flow-cytometric analysis demonstrated that the number of CD4+and CD8+ immune cells were significantly augmented in the VO group compared with the sham group.Conclusions: A neonatal cardiac VO rat model on P1 was successfully created, providing a platform for studying the molecular biology of neonatal RV under the influence of VO. VO - induces an immune response at the neonatal stage (from P1 to P7), suggesting that immune responses may be an initiating factor for neonatal RV remodeling under the influence of VO and that immunosuppressants may be used to prevent pediatric RV remodeling caused by VO.

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Clinical observation indicates that exercise capacity, an important determinant of survival in patients with congenital heart disease (CHD), is most decreased in children with reduced pulmonary blood flow (RPF). However, the underlying mechanism remains unclear. Here, we obtained human RPF lung samples from children with tetralogy of Fallot as well as piglet and rat RPF lung samples from animals with pulmonary artery banding surgery. We observed impaired alveolarization and vascularization, the main characteristics of pulmonary dysplasia, in the lungs of RPF infants, piglets, and rats. RPF caused smaller lungs, cyanosis, and body weight loss in neonatal rats and reduced the number of alveolar type 2 cells. RNA-sequencing demonstrated that RPF induced the downregulation of metabolism and migration, a key biological process of late alveolar development, and the upregulation of immune response, which was confirmed by flow cytometry and cytokine detection. In addition, the immunosuppressant cyclosporine A rescued pulmonary dysplasia and increased the expression of the Wnt signaling pathway, which is the driver of postnatal lung development. We concluded that RPF results in pulmonary dysplasia, which may account for the reduced exercise capacity of CHD patients with RPF. The underlying mechanism is associated with immune response activation, and immunosuppressants have a therapeutic effect in CHD-associated pulmonary dysplasia.

Aims The management of heart failure (HF) in young children is challenging. The present study aimed to clarify the effect of left univentricular epicardial pacing on dilated cardiomyopathy with left bundle branch block (LBBB) in children. Methods and results A total of five cases (30.86 ± 16.39 months, three female) of children weighing 5.8–15 kg with dilated cardiomyopathy and LBBB were included in this study. LBBB in one child occurred after device closure of peri‐membranous ventricular septal defects, and the remaining four were idiopathically discovered early after birth. Before implantation, all children suffered from refractory HF and cardiac dilatation; the left ventricular ejection fraction was 33.48 ± 5.84% with Ross Heart Failure Classification III–IV. Electrical and mechanical dyssynchrony were observed in all children with QRS duration >140 ms and prolonged septal‐to‐left posterior wall motion delay. Left univentricular epicardial pacing was successfully implanted via left axillary minithoracotomy in the five children. Sensed atrioventricular delays (83 ± 15 ms) were optimized by velocity time integral of aortic blood flow before discharge. During the follow‐up period (10.8 ± 2.68 months), the dilated failing heart was reversed significantly in terms of decreased left ventricular dimension (55.62 ± 3.46 vs. 38.94 ± 3.69 mm, P = 0.005), while the left ventricular ejection fraction improved to 60.18 ± 8.78% (P = 0.006). Conclusions In young children with low body weight, if HF is caused by or related to LBBB, left ventricular epicardial pacing still has an excellent effect.