Dual calcium-voltage optical mapping of regional voltage and calcium signals in intact murine -R2474S hearts.

Unlabelled: Abnormal regional variations in electrical and calcium homeostasis properties have been implicated in catecholaminergic polymorphic ventricular tachycardias (CPVT) attributable to abnormal RyR2-mediated store Ca release, but their underlying mechanism have not been well explored in intact hearts.

Methods: We performed in vivo and ex vivo studies including high throughput mapping of Ca transients (CaT) and transmembrane voltage (V) in murine wild-type (WT) and heterozygous -R2474S/+ hearts, before and during isoprenaline (ISO) challenge.

Results: ISO-challenged -R2474S/+ showed increased incidence of arrhythmia accompanied by abnormal Ca transients compared to WT.

Brain-to-heart cholinergic synapse-calcium signaling mediates ischemic stroke-induced atrial fibrillation.

Stroke-related cardiovascular diseases have attracted considerable attention, with atrial fibrillation (AF) being among the most frequent complications. Despite increasing clinical evidence, experimental models of stroke-induced AF are still lacking, hindering mechanistic discoveries and the development of adequate therapeutics targeting this stroke-heart syndrome (SHS). This study aims to create a rat model of ischemic stroke-induced AF (ISIAF) and to explore the efficacy and mechanism of Wenxin Keli (WK), an antiarrhythmic Chinese medicine.

Exenatide reduces atrial fibrillation susceptibility by inhibiting hKv1.5 and hNav1.5 channels.

Exenatide, a promising cardioprotective agent, protects against cardiac structural remodeling and diastolic dysfunction. Combined blockade of sodium and potassium channels is valuable for managing atrial fibrillation (AF). Here, we explored whether exenatide displayed anti-AF effects by inhibiting human Kv1.

In Vivo Base Editing of Rescues Type 3 Long QT Syndrome in Mice.

Background: Pathogenic variants in can result in long QT syndrome type 3, a life-threatening genetic disease. Adenine base editors can convert targeted A T base pairs to G C base pairs, offering a promising tool to correct pathogenic variants.

Methods: We generated a long QT syndrome type 3 mouse model by introducing the T1307M pathogenic variant into the gene.

Corrigendum: Acute osimertinib exposure induces electrocardiac changes by synchronously inhibiting the currents of cardiac ion channels.

[This corrects the article DOI: 10.3389/fphar.2023.

Heterogeneities in Ventricular Conduction Following Treatment with Heptanol: A Multi-Electrode Array Study in Langendorff-Perfused Mouse Hearts.

Background: Previous studies have associated slowed ventricular conduction with the arrhythmogenesis mediated by the gap junction and sodium channel inhibitor heptanol in mouse hearts. However, they did not study the propagation patterns that might contribute to the arrhythmic substrate. This study used a multi-electrode array mapping technique to further investigate different conduction abnormalities in Langendorff-perfused mouse hearts exposed to 0.

Molecular Correlates of Early Onset of Diabetic Cardiomyopathy: Possible Therapeutic Targets.

Diabetes mellitus (DM) is associated with mitochondrial dysfunction and oxidative stress that can lead to diabetic cardiomyopathy (DCM), which can often remain undetected until late stages of the disease. However, myocardial injury occurs before the onset of measurable cardiac dysfunction, although its molecular correlates are poorly understood. In this study, we made a DM rat induced by a high-fat diet combined with low and high doses of streptozotocin (STZ) to emulate pre and early DCM.

Measures of repolarization variability predict ventricular arrhythmogenesis in heptanol-treated Langendorff-perfused mouse hearts.

Background: Time-domain and non-linear methods can be used to quantify beat-to-beat repolarization variability but whether measures of repolarization variability can predict ventricular arrhythmogenesis in mice have never been explored.

Methods: Left ventricular monophasic action potentials (MAPs) were recorded during constant right ventricular 8 ​Hz pacing in Langendorff-perfused mouse hearts, in the presence or absence of the gap junction and sodium channel inhibitor heptanol (0.1, 0.

Electrophysiological and Proarrhythmic Effects of Hydroxychloroquine Challenge in Guinea-Pig Hearts.

Hydroxychloroquine (HCQ), clinically established in antimalarial and autoimmune therapy, recently raised cardiac arrhythmogenic concerns when used alone or with azithromycin (HCQ+AZM) in Covid-19. We report complementary, experimental, studies of its electrophysiological effects. In patch clamped HEK293 cells expressing human cardiac ion channels, HCQ inhibited I and I at a therapeutic concentrations (ICs: 10 ± 0.

US-guided percutanous microwave ablation for early-stage hepatocellular carcinoma in elderly patients is as effective as in younger patients: A 10-year experience.

Objective: To compare the overall survival (OS), disease-free survival (DFS) and liver-cancer-specific survival (LCSS) of elderly (≥65 years) and younger patients (< 65 years) with early-stage hepatocellular carcinoma (HCC) using ultrasound-guided percutaneous microwave ablation (US-PMMA).

Materials And Methods: From January 2002 to December 2017, 510 elderly and 1053 younger patients were diagnosed with early-stage HCC according to the Milan criteria. All of these patients were treatment-naïve to US-PMMA.

Percutaneous Microwave Ablation versus Laparoscopic Partial Nephrectomy for cT1a Renal Cell Carcinoma: A Propensity-matched Cohort Study of 1955 Patients.

Background Percutaneous microwave ablation (MWA) and laparoscopic partial nephrectomy (LPN) are two modalities indicated for early-stage renal cell carcinoma (RCC) with low extent of invasion. Purpose To compare the long-term results of percutaneous MWA and LPN in the treatment of cT1a RCC. Materials and Methods This retrospective study included 1955 patients with cT1a RCC treated with percutaneous MWA or LPN between April 2006 and November 2017.

The cardiac sympathetic co-transmitter neuropeptide Y is pro-arrhythmic following ST-elevation myocardial infarction despite beta-blockade.

Aims: ST-elevation myocardial infarction is associated with high levels of cardiac sympathetic drive and release of the co-transmitter neuropeptide Y (NPY). We hypothesized that despite beta-blockade, NPY promotes arrhythmogenesis via ventricular myocyte receptors.

Methods And Results: In 78 patients treated with primary percutaneous coronary intervention, sustained ventricular tachycardia (VT) or fibrillation (VF) occurred in 6 (7.

Sinus node-like pacemaker mechanisms regulate ectopic pacemaker activity in the adult rat atrioventricular ring.

In adult mammalian hearts, atrioventricular rings (AVRs) surround the atrial orifices of atrioventricular valves and are hotbed of ectopic activity in patients with focal atrial tachycardia. Experimental data offering mechanistic insights into initiation and maintenance of ectopic foci is lacking. We aimed to characterise AVRs in structurally normal rat hearts, identify arrhythmia predisposition and investigate mechanisms underlying arrhythmogenicity.

β-Adrenergic Receptor Stimulation and Alternans in the Border Zone of a Healed Infarct: An Study and Computational Investigation of Arrhythmogenesis.

Following myocardial infarction (MI), the myocardium is prone to calcium-driven alternans, which typically precedes ventricular tachycardia and fibrillation. MI is also associated with remodeling of the sympathetic innervation in the infarct border zone, although how this influences arrhythmogenesis is controversial. We hypothesize that the border zone is most vulnerable to alternans, that β-adrenergic receptor stimulation can suppresses this, and investigate the consequences in terms of arrhythmogenic mechanisms.

Quantification of Beat-To-Beat Variability of Action Potential Durations in Langendorff-Perfused Mouse Hearts.

Beat-to-beat variability in action potential duration (APD) is an intrinsic property of cardiac tissue and is altered in pro-arrhythmic states. However, it has never been examined in mice. Left atrial or ventricular monophasic action potentials (MAPs) were recorded from Langendorff-perfused mouse hearts during regular 8 Hz pacing.

Local tumor progression after ultrasound-guided percutaneous microwave ablation of stage T1a renal cell carcinoma: risk factors analysis of 171 tumors.

Purpose: To retrospectively review long-term oncologic outcomes after ultrasound (US)-guided percutaneous microwave ablation (MWA) of T1a renal cell carcinoma (RCC) and to identify the incidence and risk factors that predict local tumor progression (LTP) after MWA of RCC.

Materials And Methods: The present study was approved by the institutional review board. A total of 162 patients with 171 RCC nodules (mean size, 2.

Phosphodiesterase 2A as a therapeutic target to restore cardiac neurotransmission during sympathetic hyperactivity.

Elevated levels of brain natriuretic peptide (BNP) are regarded as an early compensatory response to cardiac myocyte hypertrophy, although exogenously administered BNP shows poor clinical efficacy in heart failure and hypertension. We tested whether phosphodiesterase 2A (PDE2A), which regulates the action of BNP-activated cyclic guanosine monophosphate (cGMP), was directly involved in modulating Ca2+ handling from stellate ganglia (SG) neurons and cardiac norepinephrine (NE) release in rats and humans with an enhanced sympathetic phenotype. SG were also isolated from patients with sympathetic hyperactivity and healthy donor patients.

Comparing the excepted values of atom-bond connectivity and geometric-arithmetic indices in random spiro chains.

The atom-bond connectivity () index and geometric-arithmetic () index are two well-studied topological indices, which are useful tools in QSPR and QSAR investigations. In this paper, we first obtain explicit formulae for the expected values of and indices in random spiro chains, which are graphs of a class of unbranched polycyclic aromatic hydrocarbons. Based on these formulae, we then present the average values of and indices with respect to the set of all spiro chains with hexagons and make a comparison between the expected values of and indices in random spiro chains.

C-type natriuretic peptide and natriuretic peptide receptor B signalling inhibits cardiac sympathetic neurotransmission and autonomic function.

Aims: B-type natriuretic peptide (BNP)-natriuretic peptide receptor A (NPR-A) receptor signalling inhibits cardiac sympathetic neurotransmission, although C-type natriuretic peptide (CNP) is the predominant neuropeptide of the nervous system with expression in the heart and vasculature. We hypothesized that CNP acts similarly to BNP, and that transgenic rats (TGRs) with neuron-specific overexpression of a dominant negative NPR-B receptor would develop heightened sympathetic drive.

Methods And Results: Mean arterial pressure and heart rate (HR) were significantly (P < 0.

Protection against ventricular fibrillation via cholinergic receptor stimulation and the generation of nitric oxide.

Key Points: Animal studies suggest an anti-fibrillatory action of the vagus nerve on the ventricle, although the exact mechanism is controversial. Using a Langendorff perfused rat heart, we show that the acetylcholine analogue carbamylcholine raises ventricular fibrillation threshold (VFT) and flattens the electrical restitution curve. The anti-fibrillatory action of carbamylcholine was prevented by the nicotinic receptor antagonist mecamylamine, inhibitors of neuronal nitric oxide synthase (nNOS) and soluble guanylyl cyclase (sGC), and can be mimicked by the nitric oxide (NO) donor sodium nitroprusside.

CAPON modulates neuronal calcium handling and cardiac sympathetic neurotransmission during dysautonomia in hypertension.

Genome-wide association studies implicate a variant in the neuronal nitric oxide synthase adaptor protein (CAPON) in electrocardiographic QT variation and sudden cardiac death. Interestingly, nitric oxide generated by neuronal NO synthase-1 reduces norepinephrine release; however, this pathway is downregulated in animal models of cardiovascular disease. Because sympathetic hyperactivity can trigger arrhythmia, is this neural phenotype linked to CAPON dysregulation? We hypothesized that CAPON resides in cardiac sympathetic neurons and is a part of the prediseased neuronal phenotype that modulates calcium handling and neurotransmission in dysautonomia.

Efficacy of B-Type Natriuretic Peptide Is Coupled to Phosphodiesterase 2A in Cardiac Sympathetic Neurons.

Elevated B-type natriuretic peptide (BNP) regulates cGMP-phosphodiesterase activity. Its elevation is regarded as an early compensatory response to cardiac failure where it can facilitate sympathovagal balance and cardiorenal homeostasis. However, recent reports suggest a paradoxical proadrenergic action of BNP.

Mkk4 is a negative regulator of the transforming growth factor beta 1 signaling associated with atrial remodeling and arrhythmogenesis with age.

Background: Atrial fibrillation (AF), often associated with structural, fibrotic change in cardiac tissues involving regulatory signaling mediators, becomes increasingly common with age. In the present study, we explored the role of mitogen-activated protein kinase kinase 4 (Mkk4), a critical component of the stress-activated mitogen-activated protein kinase family, in age-associated AF.

Methods And Results: We developed a novel mouse model with a selective inactivation of atrial cardiomyocyte Mkk4 (Mkk4(ACKO)).