Skin sympathetic nerve activity as a biomarker of fitness.

Background: Exercise stress testing is frequently used to expose cardiac arrhythmias. Aerobic exercise conditioning has been used as a nonpharmacologic antiarrhythmic intervention.

Objective: The purpose of this study was to test the hypothesis that noninvasively recorded skin sympathetic nerve activity (SKNA) is increased during exercise and that SKNA response varies according to fitness levels.

Permissive Modulation of Sphingosine-1-Phosphate-Enhanced Intracellular Calcium on BK Channel of Chromaffin Cells.

Sphingosine-1-phosphate (S1P), is a signaling sphingolipid which acts as a bioactive lipid mediator. We assessed whether S1P had multiplex effects in regulating the large-conductance Ca-activated K channel (BK) in catecholamine-secreting chromaffin cells. Using multiple patch-clamp modes, Ca imaging, and computational modeling, we evaluated the effects of S1P on the Ca-activated K currents () in bovine adrenal chromaffin cells and in a pheochromocytoma cell line (PC12).

Recording Intrinsic Nerve Activity at the Sinoatrial Node in Normal Dogs With High-Density Mapping.

Background: It is known that autonomic nerve activity controls the sinus rate. However, the coupling between local nerve activity and electrical activation at the sinoatrial node (SAN) remains unclear. We hypothesized that we would be able to record nerve activity at the SAN to investigate if right stellate ganglion (RSG) activation can increase the local intrinsic nerve activity, accelerate sinus rate, and change the earliest activation sites.

The frequency spectrum of sympathetic nerve activity and arrhythmogenicity in ambulatory dogs.

Background: Sympathetic nerve activity, heart rate (HR), and blood pressure (BP) all have very low frequency (VLF), low frequency (LF), and high frequency (HF) oscillations.

Objective: The purpose of this study was to test the hypothesis that the frequency spectra of subcutaneous nerve activity (ScNA), stellate ganglion nerve activity (SGNA), HR, and BP are important to cardiac arrhythmogenesis.

Methods: We used radiotransmitters to record SGNA, ScNA, HR, and BP in 6 ambulatory dogs and determined the dominant frequency and paroxysmal atrial tachyarrhythmias (PATs) episodes in 3-minute windows over a 24-hour period.

Complex Arrhythmia Syndrome in a Knock-In Mouse Model Carrier of the N98S Mutation.

Background: Calmodulin mutations are associated with arrhythmia syndromes in humans. Exome sequencing previously identified a de novo mutation in resulting in a p.N98S substitution in a patient with sinus bradycardia and stress-induced bidirectional ventricular ectopy.

New insights into immunomodulation via overexpressing lipoic acid synthase as a therapeutic potential to reduce atherosclerosis.

Atherosclerosis is a systemic chronic inflammatory disease. Many antioxidants including alpha-lipoic acid (LA), a product of lipoic acid synthase (Lias), have proven to be effective for treatment of this disease. However, the question remains whether LA regulates the immune response as a protective mechanism against atherosclerosis.

Sex-specific I activation in rabbit ventricles with drug-induced QT prolongation.

Background: Female sex is a known risk factor for drug-induced long QT syndrome (diLQTS). We recently demonstrated a sex difference in apamin-sensitive small-conductance Ca-activated K current (I) activation during β-adrenergic stimulation.

Objective: The purpose of this study was to test the hypothesis that there is a sex difference in I in the rabbit models of diLQTS.

Advancing Research on the Complex Interrelations Between Atrial Fibrillation and Heart Failure: A Report From a US National Heart, Lung, and Blood Institute Virtual Workshop.

The interrelationships between atrial fibrillation (AF) and heart failure (HF) are complex and poorly understood, yet the number of patients with AF and HF continues to increase worldwide. Thus, there is a need for initiatives that prioritize research on the intersection between AF and HF. This article summarizes the proceedings of a virtual workshop convened by the US National Heart, Lung, and Blood Institute to identify important research opportunities in AF and HF.

Small-conductance Ca-activated K channels promote J-wave syndrome and phase 2 reentry.

Background: Small-conductance Ca-activated potassium (SK) channels play complex roles in cardiac arrhythmogenesis. SK channels colocalize with L-type Ca channels, yet how this colocalization affects cardiac arrhythmogenesis is unknown.

Objective: The purpose of this study was to investigate the role of colocalization of SK channels with L-type Ca channels in promoting J-wave syndrome and ventricular arrhythmias.

Left cardiac sympathetic denervation reduces skin sympathetic nerve activity in patients with long QT syndrome.

Background: Although left cardiac sympathetic denervation (LCSD) is an effective antiarrhythmic therapy for patients with long QT syndrome (LQTS), direct evidence of reduced sympathetic activity after LCSD in humans is limited.

Objective: The purpose of this study was to assess skin sympathetic nerve activity (SKNA) in patients with LQTS undergoing LCSD.

Methods: We prospectively enrolled 17 patients with LQTS who underwent LCSD between 2017 and 2019.

Cardiac resynchronization therapy modulates peripheral sympathetic activity.

Background: Heightened sympathetic nerve activity has been associated with poorer prognosis in patients with reduced left ventricular systolic function (ie, heart failure with reduced ejection fraction [HFrEF]).

Objective: The purpose of this study was to investigate the effects of cardiac resynchronization therapy (CRT) on sympathetic nerve activity, measured by average skin sympathetic nerve activity (aSKNA).

Methods: This prospective study enrolled 36 patients with HFrEF who received CRT.

Subcutaneous nerve stimulation reduces sympathetic nerve activity in ambulatory dogs with myocardial infarction.

Background: Subcutaneous nerve stimulation (ScNS) remodels the stellate ganglion and reduces stellate ganglion nerve activity (SGNA) in dogs. Acute myocardial infarction (MI) increases SGNA through nerve sprouting.

Objective: The purpose of this study was to test the hypothesis that ScNS remodels the stellate ganglion and reduces SGNA in ambulatory dogs with acute MI.

Skin sympathetic nerve activity as a biomarker for syncopal episodes during a tilt table test.

Background: Autonomic imbalance is the proposed mechanism of syncope during a tilt table test (TTT). We have recently demonstrated that skin sympathetic nerve activity (SKNA) can be noninvasively recorded using electrocardiographic electrodes.

Objective: The purpose of this study was to test the hypothesis that increased SKNA activation precedes tilt-induced syncope.

Effects of ondansetron on apamin-sensitive small conductance calcium-activated potassium currents in pacing-induced failing rabbit hearts.

Background: Ondansetron, a widely prescribed antiemetic, has been implicated in drug-induced long QT syndrome. Recent patch clamp experiments have shown that ondansetron inhibits the apamin-sensitive small conductance calcium-activated potassium current (I).

Objective: The purpose of this study was to determine whether ondansetron causes action potential duration (APD) prolongation by I inhibition.

Walk the Line: The Role of Ubiquitin in Regulating Transcription in Myocytes.

The ubiquitin-proteasome offers novel targets for potential therapies with their specific activities and tissue localization. Recently, the expansion of our understanding of how ubiquitin ligases (E3s) specifically regulate transcription has demonstrated their roles in skeletal muscle, complementing their roles in protein quality control and protein degradation. This review focuses on skeletal muscle E3s that regulate transcription factors critical to myogenesis and the maintenance of skeletal muscle wasting diseases.

Effects of anesthetic and sedative agents on sympathetic nerve activity.

Background: The effects of sedative and anesthetic agents on sympathetic nerve activity (SNA) are poorly understood.

Objective: The purpose of this study was to determine the effects of commonly used sedative and anesthetic agents on SNA in ambulatory dogs and humans.

Methods: We implanted radiotransmitters in 6 dogs to record stellate ganglion nerve activity (SGNA), subcutaneous nerve activity (ScNA), and blood pressure (BP).

Characterization of skin sympathetic nerve activity in patients with cardiomyopathy and ventricular arrhythmia.

Background: Heightened sympathetic nerve activity is associated with occurrence of ventricular arrhythmia (VA).

Objective: To investigate the association of skin sympathetic nerve activity (SKNA) and VA occurrence.

Methods: We prospectively enrolled 65 patients with severe cardiomyopathy.

Renal Denervation Update From the International Sympathetic Nervous System Summit: JACC State-of-the-Art Review.

Three recent renal denervation studies in both drug-naïve and drug-treated hypertensive patients demonstrated a significant reduction of ambulatory blood pressure compared with respective sham control groups. Improved trial design, selection of relevant patient cohorts, and optimized interventional procedures have likely contributed to these positive findings. However, substantial variability in the blood pressure response to renal denervation can still be observed and remains a challenging and important problem.

Subcutaneous nerve stimulation for rate control in ambulatory dogs with persistent atrial fibrillation.

Background: Subcutaneous nerve stimulation (ScNS) damages the stellate ganglion and improves rhythm control of atrial fibrillation (AF) in ambulatory dogs.

Objective: The purpose of this study was to test the hypothesis that thoracic ScNS can improve rate control in persistent AF.

Methods: We created persistent AF in 13 dogs and randomly assigned them to ScNS (n = 6) and sham control (n = 7) groups.

Antiarrhythmic and proarrhythmic effects of subcutaneous nerve stimulation in ambulatory dogs.

Background: High output subcutaneous nerve stimulation (ScNS) remodels the stellate ganglia and suppresses cardiac arrhythmia.

Objective: The purpose of this study was to test the hypothesis that long duration low output ScNS causes cardiac nerve sprouting and increases plasma norepinephrine concentration and the duration of paroxysmal atrial tachycardia (PAT) in ambulatory dogs.

Methods: We prospectively randomized 22 dogs (11 males and 11 females) into 5 different output groups for 2 months of ScNS: 0 mA (sham) (n = 6), 0.

Small-conductance calcium-activated potassium current modulates the ventricular escape rhythm in normal rabbit hearts.

Background: The apamin-sensitive small-conductance calcium-activated K (SK) current I modulates automaticity of the sinus node. I blockade by apamin causes sinus bradycardia.

Objective: The purpose of this study was to test the hypothesis that I modulates ventricular automaticity.