Post-interventional Evaluation and Follow-Up in Children With Patent Ductus Arteriosus Complicated With Moderate to Severe Pulmonary Arterial Hypertension: A Retrospective Study.

Background: Transcatheter closure is an important treatment for patent ductus arteriosus (PDA) complicated with moderate and severe pulmonary arterial hypertension (PAH). This report presents our experience with transcatheter closure of PDA complicated with moderate and severe PAH. Methods: The 49 cases of PDA complicated with moderate and severe PAH were collected in the Second Affiliated Hospital and Yuying Children's Hospital from January 2014 to December 2019 with transcatheter closure of PDA and follow-up. All patients were invited for transthoracic echocardiography, electrocardiogram, and thoracic radiography check-up. Results: Device implantation was successful in 48 of 49 patients (98.0%). Among them, 30 cases were in the PAH after defect correction (CD) group, and 19 examples were in the Non-PAH after defect correction (NCD) group. Pulmonary systolic pressure, left atrial diameter, and left ventricular end-diastolic diameter immediately after interventional therapy and 6 months later were lower than the pre-operative levels (p < 0.05). The incidence of the immediate residual shunt (RS) in this study was 34.9%, most of which were minimal amount shunt. RS disappeared in all patients within 1 year of therapy. Four patients had thrombocytopenia and one patient had left pulmonary artery stenosis. No other serious adverse event occurred during the follow-up period. The pressure gradient tricuspid valve regurgitation (PGTI) and the right heart catheterization (RHC) consistency points were 93.75% (15/16) and were within the 95% consistency limit by the Bland-Altman method. The Logistic regression analysis concluded that the pre-operative Pp/Ps and the narrowest diameter of PDA are risk factors for post-operative PAH (p < 0.05). The cut-off point of the pre-operative Pp/Ps and the narrowest diameter of PDA were calculated to be 0.595 and 4.75 mm, respectively. Conclusion: Interventional occlusion in children with PDA complicated with moderate and severe PAH is safe, effective, and has few complications. Targeted drug therapy has a good clinical effect. The narrowest diameter of PDA and the pre-operative Pp/Ps may be one of the risk factors of residual PAH after interventional therapy.

STAT3 Suppresses Cardiomyocytes Apoptosis in CVB3-Induced Myocarditis Via Survivin.

Background: Viral myocarditis (VMC) is a common inflammatory cardiovascular disease with unclear mechanisms, which mainly affects children and adolescents. Apoptosis is the key to CVB3-induced myocarditis, and blocking this process may be beneficial to the therapy of VMC. Hence, this study aimed to explore the protective function of STAT3 on cardiomyocyte apoptosis of VMC and its underlying mechanisms. Methods and Results: In this research, we confirmed that STAT3 was significantly activated in both animal and cell models of VMC. To further clarify what role did STAT3 play in VMC, AG490, an inhibitor of STAT3, was used to suppress p-STAT3. Our results demonstrated that decreased expression of p-STAT3 caused by AG490 significantly aggravated severity of VMC with elevated myocardial inflammation, deteriorative ventricular systolic function and increased mortality. It suggested that STAT3 plays a protective role in VMC. To further identify the anti-apoptosis impact that activated STAT3 made, we constructed lentivirus to regulate the expression of STAT3 in NMCs. We found that up-regulated activated STAT3 attenuated cardiomyocyte apoptosis, but down-regulated one aggravated that, which verified activated STAT3 played an anti-apoptosis role in VMC. Following that, we explored what elements are involved in the anti-apoptotic mechanism of activated STAT3 by using survivin inhibitor YM155. The result showed the anti-apoptotic effect of activated STAT3 does not work in the case of survivin inhibition. Conclusion: Our findings demonstrated STAT3 by targeting survivin alleviated cardiomyocyte apoptosis in CVB3-induced myocarditis.

Nicotinic Agonist Inhibits Cardiomyocyte Apoptosis in CVB3-Induced Myocarditis via α3ß4-nAChR/PI3K/Akt-Dependent Survivin Upregulation.

BACKGROUND: Cardiomyocyte apoptosis is critical for the development of coxsackievirus B3- (CVB3-) induced myocarditis, which is a common cardiac disease that may result in heart failure or even sudden death. Previous studies have associated CVB3-induced apoptosis with the downregulation of antiapoptotic proteins. Here, attempts were made to examine whether nicotinic acetylcholine receptors (nAChRs), especially α3ß4-nAChRs, were a novel therapeutic antiapoptotic target via the activation of survivin, a strong antiapoptotic protein, in viral myocarditis (VMC). METHODS AND RESULTS: In the present study, we demonstrated that nAChRs, α3ß4-nAChR subunits in particular, were present and upregulated in CVB3-infected neonatal rat cardiomyocytes (NRC) and H9c2 cells by RT-qPCR. The function of α3ß4-nAChRs was next examined using its specific blocker α-CTX AuIB in vitro. The results of the TUNEL assay and western blot experiments showed that the block of α3ß4-nAChRs abrogated nicotine-mediated protection of NRC from CVB3-induced apoptosis, and this effect displayed a substantial correlation with the protein expressions of pAkt, survivin, and Cleaved Caspase-3. Hence, the involvement of the PI3K/Akt pathway was further verified by LY294002, a selective inhibitor of PI3K. As a result, nicotine-mediated induction of pAkt and survivin was abolished by LY294002; meanwhile, apoptotic NRC were increased accompanied by an increase of Cleaved Caspase-3 expression. Regarding CVB3-infected BALB/c mice, the α-CTX AuIB- and LY294002-treated groups had a lower survival rate, deteriorative ventricular systolic function, and more severe inflammation than the nicotine-treated group and the modulation of pAkt, survivin, and Cleaved Caspase-3 protein expressions was similar to that in CVB3-infected NRC. In addition, we found that a nicotinic agonist reduced CVB3 replication in a dose-dependent manner in vitro, which indicates that nAChR activation may serve as a possible protection mechanism of CVB3-induced myocarditis. CONCLUSIONS: Our study demonstrated that α3ß4-nAChR subunits are essential in the nicotine-mediated antiapoptotic effect of protecting cardiomyocytes from CVB3-induced apoptosis in vivo and in vitro. This protection correlated with the PI3K/Akt pathway and the inducement of the antiapoptotic protein survivin. A combination of these mechanisms serves as a novel protective response to treat viral myocarditis.