modifications-langendorff-method-for-simultaneous-isolation-atrial

Modifications of the Langendorff Method for Simultaneous Isolation of Atrial and Ventricular Myocytes from Adult Mice

A single cardiomyocyte is a vital tool in the cellular and subcellular level studies of cardiac biology and diseases as a fundamental unit of contraction ...

Capital Medical University

 "Pill-in-the-pocket" (PIP) treatment with type IC drugs for cardioversion of recent-onset atrial fibrillation (AF) has been recommended in guidelines. Major adverse effects have been often reported, and the underlying mechanisms are proposed to be associated with the genetic backgrounds.  A male patient was treated with PIP approach (propafenone 600 mg.po) for the conversion of new onset AF. His symptoms got worse and referred to emergency room; ECG showed a typical Brugada syndrome (BrS) type I ECG pattern with sinus rhythm. Genetic screening identified a common SCN5A polymorphism R1193Q. Propafenone blockade of I was studied in HEK293 cells expressed SCN5A R1193Q channel and WT channel using patch clamp techniques. There was no significant difference in peak current and steady-state gating parameters between R1193Q and WT at baseline. At clinically relevant concentration of 2 μmol/L propafenone, use-dependent block (UDB) of I was more pronounced in R1193Q versus WT (44.2 ± 7.2 versus 24.8 ± 5.7% at the frequency of 2 Hz,  < 0.05); IC of UDB was 2.9 ± 0.7 μmol/L for R1193Q and 8.1 ± 1.8 μmol/L for WT, respectively. Propafenone produced more left shift of steady-state inactivation and slower recovery from inactivation in R1193Q compared with WT.  A common SCN5A polymorphism R1193Q enhances UDB by propafenone and predisposes the patients to drug-induced BrS with PIP treatment. Our data suggest that R1193Q polymorphism is likely to be a genetic marker for the major adverse effects associated with propafenone PIP approach for AF patients' management. Ajmaline challenge to rule out the presence of BrS should be considered prior to propafenone PIP therapy in AF patients who are identified to have R1193Q polymorphism.

"Pill-in-the-Pocket" Treatment of Propafenone Unmasks ECG Brugada Pattern in an Atrial Fibrillation Patient With a Common SCN5A R1193Q Polymorphism.

The outcomes of atrial fibrillation (AF) ablation remain suboptimal. It is important to identify which AF patients will most likely benefit from ablation and who are more likely to show treatment failure, especially in those with structural heart disease such as hypertrophic cardiomyopathy (HCM).

Depolarization and repolarization parameters on ECG predict recurrence after atrial fibrillation ablation in patients with hypertrophic cardiomyopathy.

Cardiac tamponade is a common life-threatening complication during radiofrequency ablation of atrial fibrillation (RAAF) and is mostly managed by pericardiocentesis. Thus far, the optimal timing for drain removal has not been established.

Early versus delayed removal of the pericardial drain in patients with cardiac tamponade complicating radiofrequency ablation of atrial fibrillation.

Interleukin-19 (IL-19) has been shown to be involved in coronary artery diseases and atherosclerosis, while its expression in myocardial infarction is poorly understood. In this study, the dynamic increase in circulating IL-19 in acute ST-segment elevation myocardial infarction (STEMI) patients was detected.

IL-19 as a Biomarker for the Severity of Acute Myocardial Infarction.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a novel class of glucose-lowering agents that significantly improve the prognosis of patients with type 2 diabetes (T2D) and heart failure. SGLT2i has recently been implicated in the treatment of atrial fibrillation (AF) with clinical data demonstrating that these agents decrease the incidence of AF events in patients with T2D. Fundamental findings have suggested that SGLT2i may alleviate atrial electrical and structural remodeling. The underlying mechanisms of SGLT2i are likely associated with balancing the sodium and calcium handling disorders and mitigating the mitochondrial dysfunction in atrial myocytes. This review illustrates the advances in understanding the underlying mechanisms of SGLT2i as an evolving treatment modality for AF.

Sodium-Glucose Cotransporter 2 Inhibitors Potentially Prevent Atrial Fibrillation by Ameliorating Ion Handling and Mitochondrial Dysfunction.

There are distinct results for the relationship between new-onset atrial fibrillation (NOAF) and subsequent incident cancer. To date, no systematic analysis has been conducted on this issue. This study aims to explore the relationship between NOAF and the risk of developing cancer through a meta-analysis with a large sample size.

The Association of New-Onset Atrial Fibrillation and Risk of Cancer: A Systematic Review and Meta-Analysis.

Thrombospondin-2 (TSP-2) is an important extracellular matrix protein that is involved in a variety of cardiovascular diseases, including viral myocarditis and abdominal aortic aneurysm. The present study aimed to investigate TSP-2 expression in patients with aortic dissection (AD). Aortas were obtained from patients with AD and healthy donors, and TSP-2 expression level in all samples was measured by western blotting and immunofluorescence assays. Blood samples were also collected from patients with AD and non-AD (NAD) subjects. Circulating TSP-2, tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels in each sample were detected using ELISAs. In addition, the effect of TSP-2 on angiotensin II (Ang II)-induced smooth muscle cell (SMC) apoptosis was assessed . Compared with healthy donors, aortic TSP-2 expression level was significantly increased in patients with AD. Furthermore, TSP-2 was secreted primarily by SMCs, but also by endothelial cells. TSP-2 plasma expression level was also elevated in patients with AD compared with non-AD subjects. Furthermore, TSP-2 serum expression level was positively correlated with TNF-α and IL-6 expression levels in patients with AD. In addition, recombinant mouse TSP-2 treatment increased Bax mRNA expression and decreased Bcl2 mRNA expression in Ang II-treated SMCs; however, the effects were reversed following treatment with the NF-κB p65 signaling pathway inhibitor JSH-23 or with the anti-TNF-α and anti-IL-6 neutralizing antibodies. The present study demonstrated that TSP-2 expression was increased in the aortic tissues and plasma of patients with AD. These findings suggested that TSP-2 may participate in the progression of AD by activating the NF-κB p65 signaling pathway and amplifying the inflammatory response.

Article	Year
"Pill-in-the-Pocket" Treatment of Propafenone Unmasks ECG Brugada Pattern in an Atrial Fibrillation Patient With a Common SCN5A R1193Q Polymorphism. Frontiers in physiology\| PubMed ID: 30984031	2019
Depolarization and repolarization parameters on ECG predict recurrence after atrial fibrillation ablation in patients with hypertrophic cardiomyopathy. Journal of cardiovascular electrophysiology\| PubMed ID: 31441155	2019
Early versus delayed removal of the pericardial drain in patients with cardiac tamponade complicating radiofrequency ablation of atrial fibrillation. Journal of cardiovascular electrophysiology\| PubMed ID: 31904158	2020
IL-19 as a Biomarker for the Severity of Acute Myocardial Infarction. Archives of medical research\| PubMed ID: 32111500	2020
Sodium-Glucose Cotransporter 2 Inhibitors Potentially Prevent Atrial Fibrillation by Ameliorating Ion Handling and Mitochondrial Dysfunction. Frontiers in physiology\| PubMed ID: 32848857	2020
The Association of New-Onset Atrial Fibrillation and Risk of Cancer: A Systematic Review and Meta-Analysis. Cardiology research and practice\| PubMed ID: 33062319	2020
Thrombospondin-2 is upregulated in patients with aortic dissection and enhances angiotensin II-induced smooth muscle cell apoptosis. Experimental and therapeutic medicine\| PubMed ID: 33093888	2020

Kui Wu

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