Sympathetic nerve fibers and ganglia in canine cervical vagus nerves: localization and quantitation.

Background: Cervical vagal nerve (CVN) stimulation may improve left ventricular ejection fraction in patients with heart failure.

Objectives: To test the hypothesis that sympathetic structures are present in the CVN and to describe the location and quantitate these sympathetic components of the CVN.

Methods: We performed immunohistochemical studies of the CVN from 11 normal dogs and simultaneously recorded stellate ganglion nerve activity, left thoracic vagal nerve activity, and subcutaneous electrocardiogram in 2 additional dogs.

Carvedilol analogue inhibits triggered activities evoked by both early and delayed afterdepolarizations.

Background: Carvedilol and its analogues suppress delayed afterdepolarizations (DADs) and catecholaminergic polymorphic ventricular tachycardias by direct action on the cardiac ryanodine receptor type 2 (RyR2).

Objective: To test a hypothesis that carvedilol analogue may also prevent triggered activities (TAs) through the suppression of early afterdepolarizations (EADs).

Methods: Intracellular Ca(2+) and membrane voltage were simultaneously recorded by using optical mapping technique in Langendorff-perfused mouse and rabbit hearts to study the effect of carvedilol analogue VK-II-36, which does not have significant beta-blocking effects.

Arrhythmias in the muscular dystrophies.

The muscular dystrophies are a group of inherited diseases affecting skeletal muscle that also affect cardiac muscle. Cardiac involvement occurs as a degenerative process with fibrosis and fatty replacement of the myocardium. Electrophysiologists are asked to participate in the care of muscular dystrophy patients because of the risk of atrial arrhythmias, conduction disease, bradycardia, ventricular arrhythmias, and sudden death.

Neural control of ventricular rate in ambulatory dogs with pacing-induced sustained atrial fibrillation.

Background: We hypothesize that inferior vena cava-inferior atrial ganglionated plexus nerve activity (IVC-IAGPNA) is responsible for ventricular rate (VR) control during atrial fibrillation (AF) in ambulatory dogs.

Methods And Results: We recorded bilateral cervical vagal nerve activity (VNA) and IVC-IAGPNA during baseline sinus rhythm and during pacing-induced sustained AF in 6 ambulatory dogs. Integrated nerve activities and average VR were measured every 10 seconds over 24 hours.

Triggered firing and atrial fibrillation in transgenic mice with selective atrial fibrosis induced by overexpression of TGF-β1.

Background: Calcium transient triggered firing (CTTF) is induced by large intracellular calcium (Ca(i)) transient and short action potential duration (APD). We hypothesized that CTTF underlies the mechanisms of early afterdepolarization (EAD) and spontaneous recurrent atrial fibrillation (AF) in transgenic (Tx) mice with overexpression of transforming growth factor β1 (TGF-β1).

Methods And Results: MHC-TGFcys(33)ser Tx mice develop atrial fibrosis because of elevated levels of TGF-β1.

Ryanodine receptor inhibition potentiates the activity of Na channel blockers against spontaneous calcium elevations and delayed afterdepolarizations in Langendorff-perfused rabbit ventricles.

Background: Na channel blockers are effective in suppressing delayed afterdepolarizations (DADs) in isolated Purkinje fibers. However, in isolated mouse ventricular myocytes lacking calsequestrin, only those Na channel blockers that also inhibit type 2 ryanodine receptor channels were effective against spontaneous Ca elevation (SCaE) and DADs.

Objective: To test the hypothesis that combined Na channel and type 2 ryanodine receptor channel blocker ((R)-propafenone) is more effective than a Na channel blocker (lidocaine) in suppressing SCaE and DADs in the intact rabbit ventricles.

Electroanatomic remodeling of the left stellate ganglion after myocardial infarction.

Objectives: The purpose of this study was to evaluate the changes of left stellate ganglionic nerve activity (SGNA) and left thoracic vagal nerve activity (VNA) after acute myocardial infarction (MI).

Background: Whether MI results in remodeling of extracardiac nerve activity remains unclear.

Methods: We implanted radiotransmitters to record the SGNA, VNA, and electrocardiogram in 9 ambulatory dogs.

Heart failure decreases nerve activity in the right atrial ganglionated plexus.

Objective: We tested the hypothesis that heart failure (HF) results in right atrial ganglionated plexus (RAGP) denervation that contributes to sinoatrial node dysfunction.

Background: HF is associated with sinoatrial node dysfunction. However, the detailed mechanisms remain unclear.

Pacemaker and implantable cardioverter-defibrillator use in a US myotonic dystrophy type 1 population.

Introduction: We assessed implant rates, indications, characteristics, and outcomes in patients with the neuromuscular disease, myotonic dystrophy type 1 (DM1) receiving a pacemaker or an implantable cardioverter-defibrillator (ICD).

Methods And Results: Device use was evaluated in a prospective, multicenter registry of 406 genetically confirmed adult patients followed for 9.5 ± 3.

A retrospective analysis of proceduralist-directed, nurse-administered propofol sedation for implantable cardioverter-defibrillator procedures.

Background: There is controversy whether proceduralist-directed, nurse-administered propofol sedation (PDNAPS) is safe.

Objective: To assess the frequency of adverse events when PDNAPS is used for implantable cardioverter-defibrillator (ICD)-related procedures and to determine the patient and procedural characteristics associated with adverse events.

Methods: Consecutive ICD-related procedures using PDNAPS from May 2006 to July 2009 at a tertiary-care hospital were evaluated.

Continuous low-level vagus nerve stimulation reduces stellate ganglion nerve activity and paroxysmal atrial tachyarrhythmias in ambulatory canines.

Background: We hypothesize that left-sided low-level vagus nerve stimulation (LL-VNS) can suppress sympathetic outflow and reduce atrial tachyarrhythmias in ambulatory dogs.

Methods And Results: We implanted a neurostimulator in 12 dogs to stimulate the left cervical vagus nerve and a radiotransmitter for continuous recording of left stellate ganglion nerve activity, vagal nerve activities, and ECGs. Group 1 dogs (N=6) underwent 1 week of continuous LL-VNS.

Survival and CTG repeat expansion in adults with myotonic dystrophy type 1.

Introduction: An association is observed between the severity of myotonic dystrophy type 1 (DM1) and the genetic abnormality of cytosine-thymine-guanine (CTG) repeat expansion. It is unknown whether an association exists between survival and CTG repeat expansion.

Methods: In an adult 406-patient DM1 cohort, the phenotype, including survival age, was evaluated in relation to CTG repeat expansion.

Small-conductance calcium-activated potassium channel and recurrent ventricular fibrillation in failing rabbit ventricles.

Rationale: Fibrillation/defibrillation episodes in failing ventricles may be followed by action potential duration (APD) shortening and recurrent spontaneous ventricular fibrillation (SVF).

Objective: We hypothesized that activation of apamin-sensitive small-conductance Ca(2+)-activated K(+) (SK) channels is responsible for the postshock APD shortening in failing ventricles.

Methods And Results: A rabbit model of tachycardia-induced heart failure was used.

Intracellular calcium and the mechanism of anodal supernormal excitability in langendorff perfused rabbit ventricles.

Background: Anodal stimulation hyperpolarizes the cell membrane and increases the intracellular Ca(2+) (Ca(i)) transient. This study tested the hypothesis that the maximum slope of the Ca(i) decline (-(dCa(i)/dt)(max)) corresponds to the timing of anodal dip on the strength-interval curve and the initiation of repetitive responses and ventricular fibrillation (VF) after a premature stimulus (S(2)).

Methods And Results: We simultaneously mapped the membrane potential (V(m)) and Ca(i) in 23 rabbit ventricles.

Short-term memory and electrical restitution in the canine transmural ventricle.

Cardiac short-term memory is an intrinsic property of paced myocardium that reflects the influence of pacing history. Using an optical mapping method to record membrane voltage and intracellular calcium (Ca(2 +)(i)), this study investigated the properties and mechanisms of short-term memory in isolated and perfused canine wedge preparations. In addition to the dynamic and S1S2 pacing protocols, a perturbed downsweep pacing protocol was used to get a complete overview of the restitution portrait.

Increased mortality with left ventricular systolic dysfunction and heart failure in adults with myotonic dystrophy type 1.

Background: Myotonic dystrophy type 1 (DM1) is a neurologic disorder with known cardiac involvement, including left ventricular systolic dysfunction (LVSD), heart failure (HF), atrioventricular and intraventricular conduction system disease, and sudden death. We studied the prevalence of these conditions and associated findings in a large population with DM1.

Methods: History, physical examination, genetic testing, and electrocardiography were performed on 406 patients with DM1, and cardiac imaging was performed on 180 (44.

Genesis of phase 3 early afterdepolarizations and triggered activity in acquired long-QT syndrome.

Background: Both phase 2 and phase 3 early afterdepolarizations (EADs) occur in long-QT syndromes, but their respective roles in generating arrhythmias in intact cardiac tissue are incompletely understood.

Methods And Results: Intracellular Ca (Ca(i)) and membrane voltage (V(m)) were optically mapped in a quasi 2-dimensional model of cryoablated Langendorff-perfused rabbit ventricles (n=16). E-4031 (an I(Kr) blocker) combined with reduced extracellular K ([K(+)](o)) and Mg ([Mg(2+)](o)) prolonged action potential duration heterogeneously and induced phase 2 and phase 3 EADs.

Delayed afterdepolarization in intact canine sinoatrial node as a novel mechanism for atrial arrhythmia.

Introduction: Recent evidence indicates that spontaneous sarcoplasmic reticulum Ca release and Na-Ca exchanger current activation contribute to the sinoatrial node (SAN) automaticity. These findings suggest that SAN activity may share mechanisms that underlie both automaticity and triggered activity. The aim of this study is to test the hypothesis that spontaneous, nonvoltage gated, intracellular Ca (Ca(i)) elevation may induce delayed afterdepolarization (DAD) in intact SAN during isoproterenol infusion.

Ca2+ clock malfunction in a canine model of pacing-induced heart failure.

The mechanisms of sinoatrial node (SAN) dysfunction in heart failure (HF) remain unclear. We hypothesized that impaired rhythmic spontaneous sarcoplasmic reticulum Ca(2+) release (Ca(2+) clock) plays an important role in SAN dysfunction in HF. HF was induced in canine hearts by rapid ventricular pacing.

Calcium dynamics and the mechanisms of atrioventricular junctional rhythm.

Objectives: The purpose of this study was to test the hypothesis that rhythmic spontaneous sarcoplasmic reticulum calcium (Ca) release (the "Ca clock") plays an important role in atrioventricular junction (AVJ) automaticity.

Background: The AVJ is a primary backup pacemaker to the sinoatrial node. The mechanisms of acceleration of AVJ intrinsic rate during sympathetic stimulation are unclear.

Synergistic dual automaticity in sinoatrial node cell and tissue models.

Background: The mechanism of sinoatrial node (SAN) automaticity is traditionally attributed to membrane ion currents. Recent evidence indicates spontaneous sarcoplasmic reticulum (SR) Ca(2+) cycling also plays an important role.

Methods And Results: A computer simulation on SAN cell and 1D tissue model was performed.

Tachybradycardia in the isolated canine right atrium induced by chronic sympathetic stimulation and pacemaker current inhibition.

The mechanisms of sinoatrial node (SAN) dysfunction in patients with chronically elevated sympathetic tone and reduced pacemaker current (I(f); such as heart failure) are poorly understood. We simultaneously mapped membrane potential and intracellular Ca(2+) in the Langendorff-perfused canine right atrium (RA). Blockade of either I(f) (ZD-7288) or sarcoplasmic reticulum Ca(2+) release (ryanodine) alone decreased heart rate by 8% (n = 3) and 16% (n = 3), respectively.

Clinical significance of early recurrences of atrial tachycardia after atrial fibrillation ablation.

Background: atrial tachycardia (AT) commonly recurs within 3 months after radiofrequency catheter ablation for atrial fibrillation (AF). However, it remains unclear whether early recurrence of atrial tachycardia (ERAT) predicts late recurrence of AF or AT.

Methods: of 352 consecutive patients who underwent circumferential pulmonary vein isolation with or without linear ablation(s) for AF, 56 patients (15.