Multiple Dynamical Mechanisms of Phase-2 Early Afterdepolarizations in a Human Ventricular Myocyte Model: Involvement of Spontaneous SR Ca2+Release

In this study, dynamical mechanisms of EAD formation in human ventricular myocytes (HVMs) were investigated using the mathematical model developed by ten Tusscher and Panfilov (Am J Physiol Heart Circ Physiol 291, 2006). We explored how the rapid (IKr) and slow (IKs) components of delayed-rectifier K+ channel currents, L-type Ca2+ channel current (ICaL), Na+/Ca2+ exchanger current (INCX), and intracellular Ca2+ handling via the sarcoplasmic reticulum (SR) contribute to initiation, termination and modulation of phase-2 EADs during pacing in relation to bifurcation phenomena in non-paced model cells. Parameter-dependent dynamical behaviors of the non-paced model cell were determined by calculating stabilities of equilibrium points (EPs) and limit cycles, and bifurcation points to construct bifurcation diagrams. Action potentials (APs) and EADs during pacing were reproduced by numerical simulations for constructing phase diagrams of the paced model cell dynamics. Results are summarized as follows: (1) A modified version of the ten Tusscher-Panfilov model with accelerated ICaL inactivation could reproduce bradycardia-related EADs in LQTS type 2 and β-adrenergic stimulation-induced EADs in LQTS type 1. (2) Two types of EADs with different initiation mechanisms, ICaL reactivation–dependent and spontaneous SR Ca2+ release–mediated EADs, were detected. (3) Termination of EADs (AP repolarization) during pacing depended on the slow activation of IKs. (4) Spontaneous SR...
Source: Frontiers in Physiology - Category: Physiology Source Type: research

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Torsade de Pointes arrhythmia is a potentially lethal polymorphic ventricular tachyarrhythmia (pVT) in the setting of long QT syndrome. Arrhythmia susceptibility is influenced by risk factors modifying repolarization.
Source: Heart Rhythm - Category: Cardiology Authors: Source Type: research
General examination – eyes and facial dysmorphism Clinically examination is guided by the symptoms. Unless the history is not correlated with findings, important diagnostic possibilities may be missed. Clinical examination starts off with a focused general examination followed by a detailed examination of the cardiovascular system. Relevant points in other systems like basal crepitations, hepatosplenomegaly and neurological deficits should be looked for. Examination strategy should be fitting to the clinical situation. When a patient presents to the emergency room, it should be a short but focused examination to perm...
Source: Cardiophile MD - Category: Cardiology Authors: Tags: HBC Source Type: blogs
Sudden unexpected death in epilepsy (SUDEP) is the most common cause of premature mortality in individuals with epilepsy. Acute and adaptive changes in heart rhythm in epilepsy implicate cardiac dysfunction as a potential pathogenic mechanism in SUDEP. Furthermore, variants in genes associated with Long QT syndrome (LQTS) have been identified in patients with SUDEP. LQTS is a cardiac arrhythmia condition that causes sudden cardiac death with strong similarities to SUDEP. Here, we discuss the possibility of an additive risk of death due to the functional consequences of a pathogenic variant in an LQTS gene interacting with ...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
A 30-something was in the ED for some minor trauma when he was noted to have a fast heart rate.  He acknowledged that he had palpitations. but only when asked.  He had a history heavy alcohol use.  Blood pressure was normal (109/83).Here is his 12-lead:There is a wide complex tachycardia with a rate of 257, with RBBB and LPFB (right axis deviation) morphology.The Differential Diagnosis is: SVT with aberrancy(#)     [AVNRT vs. WPW (also called AVRT*)]    Atrial flutter with 1:1 conduction, with aberrancy    VT coming from the anterior fascicle (fascicular...
Source: Dr. Smith's ECG Blog - Category: Cardiology Authors: Source Type: blogs
CONCLUSION: Autonomic (HRV) and cardiac repolarization (QTVI) ECG measures differ based on LQTS genotype and history of arrhythmias in LQTS1. SDNN, RMSSD, and pNN50 were each independent markers for LQTS genotype. PMID: 32942226 [PubMed - as supplied by publisher]
Source: Autonomic Neuroscience - Category: Neuroscience Authors: Tags: Auton Neurosci Source Type: research
Long QT-Syndrome (LQTS) patients are at risk of arrhythmias and seizures. We investigated whether autonomic and cardiac repolarization measures differed based on LQTS genotypes, and in LQTS patients with vs. without arrhythmias and seizures.
Source: Autonomic Neuroscience: Basic and Clinical - Category: Neuroscience Authors: Source Type: research
éowski The head-up tilt table test (HUTT) with the upright phase is used to help determine an imbalance of the sympathetic nervous system that is related to abnormal electrocardiographic repolarization in children with vasovagal syncope (VVS) and also in patients with the long QT syndrome (LQTS). The study attempted to evaluate T wave morphology and QT and TpTe (Tpeak–Tend) intervals recorded in ECG during the HUTT for a more accurate diagnosis of children with VVS. The group investigated 70 children with a negative HUTT result: 40 patients with VVS and 30 healthy volunteers without syncope. The RR interval a...
Source: International Journal of Environmental Research and Public Health - Category: Environmental Health Authors: Tags: Article Source Type: research
This study aimed to correlate the  arrhythmia mechanism to pregnancy and early postnatal outcomes in fetal bradycardia. This was retrospective study (May 2013–November 2019). Fetuses with sustained bradycardia (heart rate ≤ 100 per minute) were included. Based on arrhythmia mechanism, patients were categorized into 4 group s:Group 1: blocked atrial ectopics, Group 2: second-degree atrioventricular block (AVB), Group 3: complete AVB and group 4: sinus bradycardia. Clinical presentation, need for transplacental therapy, pregnancy and early postnatal outcomes were analysed. A total of&nbs...
Source: Journal of Fetal Medicine - Category: Perinatology & Neonatology Source Type: research
BackgroundLong QT syndrome 3 (LQT3) is caused by SCN5A mutations. Late sodium current (late INa) inhibitors are current-specific to treat patients with LQT3, but the mechanisms underlying mexiletine (MEX) -sensitive (N1325S and R1623Q) and -insensitive (M1652R) mutations remains to be elucidated.MethodsLQT3 patients with causative mutations were treated with oral MEX following i.v. lidocaine. Whole-cell patch-clamp techniques and molecular remodeling were used to determine the mechanisms underlying the sensitivity to MEX.ResultsIntravenous administration of lidocaine followed by MEX orally in LQT patients with N1325S and R...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
ConclusionsThe present case series reports a new ablation strategy systematically targeting autonomic GPs in LQTS patients. CNA shortens QTc (through sympathetic modulation) and increases heart rate. Although promising, these preliminary results need to be confirmed in the larger prospective study.
Source: Journal of Interventional Cardiac Electrophysiology - Category: Cardiology Source Type: research
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