Slow conduction through an arc of block: A basis for arrhythmia formation postmyocardial infarction.

Introduction: The electrophysiologic basis for characteristic rate-dependent, constant-late-coupled (390 + 54 milliseconds) premature ventricular beats (PVBs) present 4-5 days following coronary artery occlusion were examined in 108 anesthetized dogs.

Methods And Results: Fractionated/double potentials were observed in injured zone bipolar and composite electrograms at prolonged sinus cycle lengths (1,296 ± 396 milliseconds). At shorter cycle lengths, conduction of the delayed potential decremented, separating from the initial electrogram by a progressively prolonged isoelectric interval.

Slow antegrade excitation and delayed retrograde activation through an "inexcitable zone": A basis for arrhythmia formation in infarcted myocardium ex vivo.

Introduction: The electrophysiologic mechanism for rate-dependent PVBs associated with double potentials (DPs) was investigated in infarcted canine hearts using bipolar and intracellular microelectrode recordings.

Methods And Results: Dogs exhibiting rate-related ventricular ectopic beats (coupling interval, 390 ± 54 milliseconds) during sinus rhythm or atrial pacing were studied 4-5 days (N = 63) or 25 days (N = 16) following anterior descending coronary artery ligation. Sites of DP and rate-dependent arrhythmia formation were identified in vivo using bipolar recordings for subsequent ex vivo studies.

Extra- and intracellular recordings from the avjunction: discerning the mechanisms for irregular ventricular responses during supraventricular arrhythmias.

Introduction: There has been a long-standing controversy regarding the mechanism(s) to explain the irregular ventricular response during atrial tachycardia (AT) or atrial fibrillation (AF) and where the site of block, if any, resides in the atrioventricular (AV) junction.

Methods: We studied 12 Langendorff preparations perfused with modified Tyrode's solution containing 5-10 mM diacetyl monoxime which suppressed contractility but allowed the use of intracellular action potential (AP) recordings. Octapolar catheters (2-mm rings, 2-mm spacing) were secured along the tricuspid annulus from the apex to the base of the triangle of Koch and along the anterior limbus of the fossa ovalis to record extracellular, slow pathway, fast pathway, His bundle (Hb) and AV nodal (AVN) extracellular potentials as well as intracellular action potentials.

Development of cardiomyopathy and atrial tachyarrhythmias associated with activating autoantibodies to beta-adrenergic and muscarinic receptors.

A 71-year-old male with well-controlled hypertension developed atrial tachyarrhythmias in 2002 and a restrictive cardiomyopathy in 2006 to 2007. Sera from 1992, 2001, and 2006 to 2008 demonstrated activating autoantibodies against beta-adrenergic (AAbetaAR) and M2 muscarinic receptors (AAM2R). These sera have been characterized for bioactivity using in vitro assays of cardiac contractility and automaticity using a canine cardiac Purkinje fiber assay as well as protein kinase assay activation in H9c2 cells.

Stable patterns of AH block arising from longitudinal dissociation and reentry within the superfused rabbit AV junction.

Introduction: Multiple forms of antegrade AH Wenckebach block (WB) observed in 14 of 221 superfused rabbit AV junctions.

Methods: Bipolar and microelectrode recordings were used to examine the mechanism of multiple forms of AH WB.

Results: Each of the 14 preparations demonstrated typical 3:2 and 2:1 AV block, but also demonstrated longitudinal dissociation within the slow pathway input (N = 11) or compact AV node (N = 3).

Opposing cardiac effects of autoantibody activation of β-adrenergic and M2 muscarinic receptors in cardiac-related diseases.

Background: Activating autoantibodies to β-adrenergic receptors (AAβ1/2AR) and M2 muscarinic receptors (AAM2R) have been reported in several cardiac diseases and may have pathophysiologic relevance. However, the interactions and relative effects of AAβ1AR, AAβ2AR and AAM2R on contractile function have not been characterized.

Methods: The inotropic effects of IgG from 18 selected patients with cardiomyopathy and/or atrial tachyarrhythmias positive by ELISA for antibodies to β1/2AR were studied using an isolated canine Purkinje fiber contractility assay.

Pathophysiologic basis of autonomic ganglionated plexus ablation in patients with atrial fibrillation.

The intrinsic cardiac autonomic nervous system (ganglionated plexuses [GP]) plays a significant role in the initiation and maintenance of atrial fibrillation (AF) in both experimental models and AF patients. Left atrial GP, located in epicardial fat pads and the ligament of Marshall, contain afferent neurons from the atrial myocardium and the central autonomic nervous system, efferent neurons (cholinergic and adrenergic neurons), and interconnecting neurons, which allow communication between GP. Stimulation of the GP produces both parasympathetic stimulation (markedly shortens action potential duration) and sympathetic stimulation (increases calcium transient) in the pulmonary vein (PV) myocardium and atrial myocardium.

An acute experimental model demonstrating 2 different forms of sustained atrial tachyarrhythmias.

Background: The objective of this study was to develop an acute experimental model showing both focal and macroreentrant sustained atrial fibrillation (AF).

Methods And Results: In 31 anesthetized dogs, bilateral thoracotomies allowed the attachment of electrode catheters at the right and left superior pulmonary veins, atrial free walls, and atrial appendages. Acetylcholine, 100 mmol/L, was applied topically to either appendage.

Activating autoantibodies to the beta-1 adrenergic and m2 muscarinic receptors facilitate atrial fibrillation in patients with Graves' hyperthyroidism.

Objectives: We studied activating autoantibodies to beta-1 adrenergic receptors (AAbeta1AR) and activating autoantibodies to M2 muscarinic receptors (AAM2R) in the genesis of atrial fibrillation (AF) in Graves' hyperthyroidism.

Background: Atrial fibrillation frequently complicates hyperthyroidism. Both AAbeta1AR and AAM2R have been described in some patients with dilated cardiomyopathy and AF.

The Autonomic Nervous System and Atrial Fibrillation:The Roles of Pulmonary Vein Isolation and Ganglionated Plexi Ablation.

After the sequential successes of catheter ablation for the treatment of pre-excitation syndromes (WPW), junctional reentry (AVNRT) atrial flutter (AFL) and ventricular arrhythmias, clinical electrophysiologists have focused on the myocardial basis of atrial fibrillation (AF). Thus, the strategy for ablation of drug and cardioversion refractory AF was to isolate the myocardial connections from the focal firing pulmonary veins (PVs) in addition to altering the atrial substrate maintaining AF. However, the overall success rates have not achieved those of the other types of ablation procedures.

Autonomic elements within the ligament of Marshall and inferior left ganglionated plexus mediate functions of the atrial neural network.

Objectives: We sought to systematically investigate the role of the ligament of Marshall (LOM) and inferior left ganglionated plexi (ILGP) in modulating electrophysiological functions.

Methods: The following structures were exposed in 36 dogs: (1) LOM, (2) superior left GP (SLGP) near the junction of left superior pulmonary vein (LSPV) and left atrium, (3) ILGP near the left inferior pulmonary vein-atrial junction, (4) anterior right GP (ARGP) near the sino-atrial node, and (5) inferior right GP (IRGP) at the junction of inferior vena cava and atria. High frequency stimulation (HFS; 0.

Targeting proteasomes for cardioprotection.

The ubiquitin-proteasome system (UPS) plays a central role in intracellular protein degradation and regulates many cellular processes, including cell proliferation, inflammation, adaptation to stress, cell death, and the removal of damaged or misfolded proteins. Numerous studies have demonstrated that altered UPS function is involved in the pathogenesis of a wide range of cardiac diseases including hypertrophy and failure, myocardial ischemia, atherosclerosis, and diabetic cardiovascular disease. Impairment of proteasome function is a common feature of cardiac disease; however several studies have also demonstrated increased proteasome activity in models similar but not identical with those having decreased function.

Inducibility of atrial and ventricular arrhythmias along the ligament of marshall: role of autonomic factors.

Background: The mechanism(s) underlying atrial fibrillation (AF) initiation along the ligament of Marshall (LOM) remains controversial.

Objectives: We sought to examine the role of the autonomic nervous system in arrhythmogenesis along the LOM.

Methods: In 31 anesthetized dogs, a left thoracotomy exposed the LOM.

Antifibrillatory actions of cisatracurium: an atrial specific M2 receptor antagonist.

Introduction: Muscarinic receptor antagonists are proposed to prevent atrial fibrillation (AF), but also facilitate AV conduction, limiting clinical usefulness.

Methods: Cisatracurium, a neuromuscular blocker, was administered to anesthetized dogs (0.05-0.

Antifibrillatory properties of mivacurium in a canine model of atrial fibrillation.

The electrophysiologic actions of the competitive neuromuscular blocker mivacurium (0.05-0.8 mg/kg IV; N = 10) and atropine sulfate [0.

An acute model for atrial fibrillation arising from a peripheral atrial site: evidence for primary and secondary triggers.

Background: We previously demonstrated that acetylcholine (Ach) injected into cardiac ganglionated plexi (GP) causes pulmonary vein (PV) ectopy initiating atrial fibrillation (AF).

Objective: To determine the effects of Ach applied at non-PV sites.

Methods: Overall, 54 dogs were anesthetized with Na-pentobarbital.

Proteasome inhibition 1 h following ischemia protects GRK2 and prevents malignant ventricular tachyarrhythmias and SCD in a model of myocardial infarction.

Arrhythmia-prone epicardial border zone (EBZ) tissues demonstrate decreased G protein-coupled receptor kinase-2 (GRK2) activity and increased sensitivity to isoproterenol 6-24 h after coronary artery ligation in the dog. We previously demonstrated that the ischemia-mediated decrease in GRK2 in cardiac ischemic tissue was largely blocked by proteasome blockade initiated 1 h before the onset of ischemia, and this was associated with significant cardioprotection against malignant ventricular tachyarrhythmias. For application to clinical circumstances, it is desirable to determine whether a clinical window exists following the onset of ischemia for such a protective effect.

Autonomic mechanism to explain complex fractionated atrial electrograms (CFAE).

Objective: To simulate complex fractionated atrial electrograms (CFAE) during sustained atrial fibrillation (AF) in experimental animals.

Background: The mechanism(s) underlying CFAE has not been fully elucidated.

Methods: Twenty-two dogs were subjected to a right and/or left thoracotomy.

Electrophysiologic actions of d,l-sotalol and GLG-V-13 in ischemically injured canine epicardium.

The electrophysiologic actions of the class III antiarrhythmic agents, GLG-V-13 and d,l-sotalol, were examined in superfused normal and ischemically injured epicardium. Both drugs produced concentration and reverse-use dependent prolongation of the action potential duration in normal myocardium without altering resting potential, action potential amplitude, or Vmax. Both drugs increased the slope of restitution curves in normal epicardium but prevented action potential alternans at short cycle lengths.

Spontaneous pulmonary vein firing in man: relationship to tachycardia-pause early afterdepolarizations and triggered arrhythmia in canine pulmonary veins in vitro.

Introduction: Rapid firing originating within pulmonary veins (PVs) initiates atrial fibrillation (AF). The following studies were performed to evaluate spontaneous PV firing in patients with AF to distinguish focal versus reentrant mechanisms.

Methods: Intracardiac recordings were obtained in 18 patients demonstrating paroxysmal AF.

Ganglionated plexi modulate extrinsic cardiac autonomic nerve input: effects on sinus rate, atrioventricular conduction, refractoriness, and inducibility of atrial fibrillation.

Objectives: This study sought to systematically investigate the interactions between the extrinsic and intrinsic cardiac autonomic nervous system (ANS) in modulating electrophysiological properties and atrial fibrillation (AF) initiation.

Background: Systematic ganglionated plexi (GP) ablation to evaluate the extrinsic and intrinsic cardiac ANS relationship has not been detailed.

Methods: The following GP were exposed in 28 dogs: anterior right GP (ARGP) near the sinoatrial node, inferior right ganglionated plexi (IRGP) at the junction of the inferior vena cava and atria, and superior left ganglionated plexi (SLGP) near the junction of left superior pulmonary vein and left pulmonary artery.

Early myocardial dysfunction in streptozotocin-induced diabetic mice: a study using in vivo magnetic resonance imaging (MRI).

Background: Diabetes is associated with a cardiomyopathy that is independent of coronary artery disease or hypertension. In the present study we used in vivo magnetic resonance imaging (MRI) and echocardiographic techniques to examine and characterize early changes in myocardial function in a mouse model of type 1 diabetes.

Methods: Diabetes was induced in 8-week old C57BL/6 mice with two intraperitoneal injections of streptozotocin.

Interactive atrial neural network: Determining the connections between ganglionated plexi.

Background: The electrophysiologic functions of the intrinsic cardiac autonomic nervous system (ANS) are not well understood.

Objectives: The purpose of this study was to investigate the functional interactions between ganglionated plexi within the intrinsic cardiac ANS.

Methods: The hearts of 21 dogs were exposed via right and/or left thoracotomy to expose the (1) anterior right ganglionated plexi near the caudal end of the sinoatrial node, (2) inferior right ganglionated plexi at the junction of inferior vena cava and atria, and (3) superior left ganglionated plexi near the junction of left superior pulmonary vein and left pulmonary artery.

The neural basis of atrial fibrillation.

Unlabelled: This review addresses recent basic and clinical studies which suggest that targeting autonomic nerves and ganglia on the heart can result in suppression of atrial fibrillation (AF) with less damage to myocardium than the presently employed procedure which involves extensive pulmonary vein (PV) isolation from the rest of the left atrium.

Clinical Studies: Clinical electrophysiologists in 1998 discovered that the majority of patients with paroxysmal form of AF, resistant to drugs and cardioversion, had focal, ectopic firing arising from the myocardial sleeves covering the PVs. They developed a strategy which called for inducing radiofrequency lesions which would supposedly isolate the PVs from the atria thereby curing this form of AF.