Antiarrhythmic Mechanisms of Epidural Blockade After Myocardial Infarction.

Background: Thoracic epidural anesthesia (TEA) has been shown to reduce the burden of ventricular tachycardia in small case series of patients with refractory ventricular tachyarrhythmias and cardiomyopathy. However, its electrophysiological and autonomic effects in diseased hearts remain unclear, and its use after myocardial infarction is limited by concerns for potential right ventricular dysfunction.

Methods: Myocardial infarction was created in Yorkshire pigs (N=22) by left anterior descending coronary artery occlusion.

Circulating noradrenaline leads to release of neuropeptide Y from cardiac sympathetic nerve terminals via activation of β-adrenergic receptors.

Cardiac disease is marked by sympathoexcitation and elevated levels of noradrenaline (NA) and cotransmitter neuropeptide Y (NPY). Increased NPY levels are associated with a greater risk of ventricular arrhythmias and mortality. Nonetheless, the factors that cause NPY release remain poorly understood.

High-rate pacing suppresses Torsade de Pointes arrhythmias and reduces spatial dispersion of repolarization in the chronic AV-block dog model.

An electrical storm of Torsade de Pointes arrhythmias (TdP) can be reproducibly induced in the anesthetized chronic AV-block (CAVB) dog by infusion of the I-blocker dofetilide. Earlier studies showed that these arrhythmias 1) arise from locations with high spatial dispersion in repolarization (SDR) and 2) can be suppressed by high-rate pacing. We examined whether suppression of TdP by high-rate pacing is established through a decrease in SDR in the CAVB dog.

Cardiac vagal afferent neurotransmission in health and disease: review and knowledge gaps.

The meticulous control of cardiac sympathetic and parasympathetic tone regulates all facets of cardiac function. This precise calibration of cardiac efferent innervation is dependent on sensory information that is relayed from the heart to the central nervous system. The vagus nerve, which contains vagal cardiac afferent fibers, carries sensory information to the brainstem.

Autonomic control of ventricular function in health and disease: current state of the art.

Purpose: Cardiac autonomic dysfunction is one of the main pillars of cardiovascular pathophysiology. The purpose of this review is to provide an overview of the current state of the art on the pathological remodeling that occurs within the autonomic nervous system with cardiac injury and available neuromodulatory therapies for autonomic dysfunction in heart failure.

Methods: Data from peer-reviewed publications on autonomic function in health and after cardiac injury are reviewed.

Chronically altered ventricular activation causes pro-arrhythmic cardiac electrical remodelling in the chronic AV block dog model.

Aims: Altered ventricular activation (AVA) causes intraventricular mechanical dyssynchrony (MD) and impedes contraction, promoting pro-arrhythmic electrical remodelling in the chronic atrioventricular block (CAVB) dog. We aimed to study arrhythmogenic and electromechanical outcomes of different degrees of AVA.

Methods And Results: Following atrioventricular block, AVA was established through idioventricular rhythm (IVR; n = 29), right ventricular apex (RVA; n = 12) pacing or biventricular pacing [cardiac resynchronization therapy (CRT); n = 10].

I inhibitor JNJ303 prolongs the QT interval and perpetuates arrhythmia when combined with enhanced inotropy in the CAVB dog.

Introduction: Impaired I induced by drugs or due to a KCNQ1 mutation, diagnosed as long QT syndrome type 1 (LQT1) prolongs the QT interval and predisposes the heart to Torsade de Pointes (TdP) arrhythmias. The anesthetized chronic AV block (CAVB) dog is inducible for TdP after remodeling and I inhibitor dofetilide. We tested the proarrhythmic effect of I inhibition in the CAVB dog, and the proarrhythmic role of increased contractility herein.

Autonomic modulation of ventricular electrical activity: recent developments and clinical implications.

Purpose: This review aimed to provide a complete overview of the current stance and recent developments in antiarrhythmic neuromodulatory interventions, focusing on lifethreatening vetricular arrhythmias.

Methods: Both preclinical studies and clinical studies were assessed to highlight the gaps in knowledge that remain to be answered and the necessary steps required to properly translate these strategies to the clinical setting.

Results: Cardiac autonomic imbalance, characterized by chronic sympathoexcitation and parasympathetic withdrawal, destabilizes cardiac electrophysiology and promotes ventricular arrhythmogenesis.

Severe Bradycardia Increases the Incidence and Severity of Torsade de Pointes Arrhythmias by Augmenting Preexistent Spatial Dispersion of Repolarization in the CAVB Dog Model.

Introduction: Torsade de pointes arrhythmias (TdP) in the chronic atrioventricular block (CAVB) dog model result from proarrhythmic factors, which trigger TdP and/or reinforce the arrhythmic substrate. This study investigated electrophysiological and arrhythmogenic consequences of severe bradycardia for TdP.

Methods: Dofetilide (25 μg/kg per 5 min) was administered to eight anesthetized, idioventricular rhythm (IVR) remodeled CAVB dogs in two serial experiments: once under 60 beats per minute (bpm), right ventricular apex paced (RVA60) conditions, once under more bradycardic IVR conditions.

Single-cell transcriptomic profiling of satellite glial cells in stellate ganglia reveals developmental and functional axial dynamics.

Stellate ganglion neurons, important mediators of cardiopulmonary neurotransmission, are surrounded by satellite glial cells (SGCs), which are essential for the function, maintenance, and development of neurons. However, it remains unknown whether SGCs in adult sympathetic ganglia exhibit any functional diversity, and what role this plays in modulating neurotransmission. We performed single-cell RNA sequencing of mouse stellate ganglia (n = 8 animals), focusing on SGCs (n = 11,595 cells).

Point of View: Electrophysiological Endpoints Differ When Comparing the Mode of Action of Highly Successful Anti-arrhythmic Drugs in the CAVB Dog Model With TdP.

In the anaesthetized, chronic atrioventricular block (CAVB) dog, ventricular ectopic beats and Torsade de pointes arrhythmias (TdP) are believed to ensue from an abrupt prolongation of ventricular repolarization and increased temporal dispersion of repolarization, quantified as short-term variability (STV). These TdP stop spontaneously or, when supported by substantial spatial dispersion of repolarization (SDR), degenerate into ventricular fibrillation. However, most studies involving ventricular arrhythmias do not quantify SDR by means of an electrophysiological parameter.

Review of case reports on hyperkalemia induced by dietary intake: not restricted to chronic kidney disease patients.

Hyperkalemia is a metabolic disturbance of the potassium balance that can cause potentially fatal cardiac arrhythmias. Kidney dysfunction and renin-angiotensin-aldosterone system inhibiting drugs are notorious for their tendency to induce hyperkalemia by decreasing the excretion of potassium. The role of dietary potassium intake in inducing hyperkalemia is less clear.