Nonpharmacologic rate control of postoperative atrial fibrillation in the canine sterile pericarditis model.

Introduction: Postoperative atrial fibrillation (POAF) is common following open heart surgery, and is associated with significant morbidity. Medications used for ventricular rate control of POAF may not be effective in controlling rapid ventricular rates during the postoperative period because of increased sympathetic tone. The purpose of this study was to develop nonpharmacologic rate control of POAF by atrioventricular node (AVN) fat pad stimulation using clinically available temporary pacing wires in the canine sterile pericarditis model.

Validation of a new species for studying postoperative atrial fibrillation: Swine sterile pericarditis model.

Background: The canine sterile pericarditis model associated with atrial inflammation is an experimental counterpart of postoperative atrial fibrillation (POAF). However, the use of canines for research is restricted by ethics committees in many countries, and social acceptance is declining.

Objective: To validate the feasibility of the swine sterile pericarditis model as an experimental counterpart to study POAF.

An Evaluation of Phase Analysis to Interpret Atrial Activation Patterns during Persistent Atrial Fibrillation for Targeted Ablation.

Background: Phase analysis has been used to identify and localize atrial fibrillation (AF) sources for targeted ablation. We previously demonstrated that repetitive wannabe reentry (incomplete reentry) often generated an apparent stable rotor using phase analysis. The misinterpretation caused by phase analysis using atrial electrograms (AEGs) may result from detecting inaccurate time points at phase inversion (π to -π) in the instantaneous phase waveform converted from AEG.

Reliable pace termination of postoperative atrial fibrillation in the canine sterile pericarditis model: Implications for atypical atrial flutter.

Background: We have identified a reentrant circuit in the pulmonary vein region, which drives the atria, producing fibrillatory conduction, as one mechanism of postoperative atrial fibrillation (POAF) in the canine sterile pericarditis model.

Objective: In this model, we tested the hypothesis that overdrive pacing from a site at or near such a reentrant circuit would interrupt it and thereby terminate POAF.

Methods: We studied 11 sterile pericarditis dogs on postoperative days 1-4.

New Insights Into Understanding Rotor Versus Focal Activation in Patients With Persistent Atrial Fibrillation.

Objectives: This study was to test the hypotheses that: 1) when using phase analysis, repetitive Wannabe re-entry produces a phase singularity point (i.e., a rotor); and 2) the location of the stable rotor is close to the focal source.

Reconsidering the multiple wavelet hypothesis of atrial fibrillation.

Background: Moe and Abildskov proposed the multiple wavelet hypothesis of atrial fibrillation (AF) on the basis of observations in the canine vagal nerve stimulation (VNS) AF model. Data from mapping studies in an in vitro canine AF model by Allessie et al (Allessie MA, Lammers WJEP, Bonke FIM, Hollen SJ. Experimental evaluation of Moe's multiple wavelet hypothesis of atrial fibrillation.

Effect of Lidocaine Injection of Ganglionated Plexi in a Canine Model and Patients With Persistent and Long-Standing Persistent Atrial Fibrillation.

Background This study assessed the effect of blockading neural transmission in the ganglionated plexi by injecting lidocaine into fat pads in the vagal nerve stimulation canine model and patients with persistent atrial fibrillation ( AF ). Methods and Results An efficacy test of lidocaine injection was performed in 7 canines. During vagal nerve stimulation, AF was sustained for >5 minutes.

Characterization of Foci and Breakthrough Sites During Persistent and Long-Standing Persistent Atrial Fibrillation in Patients: Studies Using High-Density (510-512 Electrodes) Biatrial Epicardial Mapping.

Background: We previously demonstrated that persistent and long-standing persistent atrial fibrillation is maintained by activation emanating from foci and breakthrough sites of different cycle lengths (CLs). The purpose of this study was to characterize the behavior of focal and nonrandom breakthrough activation identified during high-density mapping of atrial fibrillation in these patients.

Methods And Results: During open heart surgery, we recorded activation from both atria simultaneously using 510 to 512 epicardial electrodes along with ECG lead II in 12 patients with persistent and long-standing persistent atrial fibrillation.

Simultaneous Biatrial High-Density (510-512 Electrodes) Epicardial Mapping of Persistent and Long-Standing Persistent Atrial Fibrillation in Patients: New Insights Into the Mechanism of Its Maintenance.

Background: The mechanism(s) of persistent and long-standing persistent (LSP) atrial fibrillation (AF) is/are poorly understood. We performed high-density, simultaneous, biatrial, epicardial mapping of persistent and LSP AF in patients undergoing open heart surgery (1) to test the hypothesis that persistent and LSP AF are due to ≥ 1 drivers, either focal or reentrant, and (2) to characterize associated atrial activation.

Methods And Results: Twelve patients with persistent and LSP AF (1 month to 9 years duration) were studied at open heart surgery.

Insights into new-onset atrial fibrillation following open heart surgery and implications for type II atrial flutter.

Aims: Postoperative atrial fibrillation (POAF), new-onset AF after open heart surgery (OHS), is thought to be related to pericarditis. Based on AF studies in the canine sterile pericarditis model, we hypothesized that POAF in patients after OHS may be associated with a rapid, regular rhythm in the left atrium (LA), suggestive of an LA driver maintaining AF. The aim of this study was to test the hypothesis that in patients with POAF, atrial electrograms (AEGs) recorded from at least one of the two carefully selected LA sites would manifest a rapid, regular rhythm with AEGs of short cycle length (CL) and constant morphology, but a selected right atrial (RA) site would manifest AEGs with irregular CLs and variable morphology.

Termination of Atrial Flutter and Fibrillation by K201's Metabolite M-II: Studies in the Canine Sterile Pericarditis Model.

Introduction: K201, a 1,4-benzodiazepine derivative, acts on multiple cardiac ion channels and the ryanodine receptor. We tested whether administration of M-II, the main metabolite of K201, would terminate induced atrial flutter (AFL) or atrial fibrillation (AF) in the canine sterile pericarditis model.

Methods: In 6 dogs, electrophysiologic studies were performed at baseline and after drug administration, measuring atrial effective refractory period (AERP), and conduction time from 3 sites during pacing at cycle lengths (400, 300, and 200 milliseconds) on postoperative days 1-4.

Ranolazine terminates atrial flutter and fibrillation in a canine model.

Background: Ranolazine has been shown to have antiarrhythmic properties.

Objective: We tested the hypothesis that intravenous ranolazine would terminate induced atrial flutter (AFL) or atrial fibrillation (AF) in the canine sterile pericarditis model.

Methods: In 6 dogs with sterile pericarditis, we performed electrophysiological measurements of the atrial effective refractory period (AERP) and conduction time (CT) while pacing from the right atrial appendage, Bachmann bundle, and the posteroinferior left atrium at cycle lengths (CLs) of 400, 300, and 200 ms before and after the administration of ranolazine.

High density mapping of atrial fibrillation during vagal nerve stimulation in the canine heart: restudying the Moe hypothesis.

Introduction: Moe et al. hypothesized that multiple wavelets (random reentry) were the mechanism of atrial fibrillation (AF) based on studies in a vagal nerve stimulation (VNS) canine model and a computer model of AF, but atrial mapping during AF in this model has not been done. We restudied this model using high density, simultaneous site mapping to test the hypothesis that AF was due to multiple wavelets.

An algorithm to measure beat-to-beat cycle lengths for assessment of atrial electrogram rate and regularity during atrial fibrillation.

Introduction: Experimental models have demonstrated that atrial fibrillation (AF) may be due to one or more rapid drivers (source) producing AF. These drivers may be characterized by rapid and regular cycle lengths (CLs), producing fibrillatory conduction to the rest of the atria. The ability to reliably identify such drivers would be invaluable.

Oral vanoxerine prevents reinduction of atrial tachyarrhythmias: preliminary results.

Background: Vanoxerine is a promising, new, investigational antiarrhythmic drug. The purpose of this study was to test the hypothesis that oral dosing of vanoxerine would first terminate induced atrial flutter (AFL) and atrial fibrillation (AF), and then prevent their reinduction.

Methods: In 5 dogs with sterile pericarditis, on the fourth day after creating the pericarditis, we performed electrophysiologic (EP) studies at baseline, measuring atrial excitability, refractoriness (AERP), and conduction time (CT) when pacing from the right atrial appendage, Bachmann's bundle (BB), and the posteroinferior left atrium at cycle lengths (CLs) of 400, 300, and 200 ms.

Characterization of atrial activation (A-A) intervals during atrial fibrillation due to a single driver: do they reflect atrial effective refractory periods?

Background: The mean, median, and minimum local atrial activation (A-A) intervals have been used to determine the local atrial effective refractory period (AERP) during atrial fibrillation (AF), the underlying assumption being that AF is due to multiple reentrant wavelets.

Objective: We tested the hypothesis that when AF is due to a single, rapid, stable reentrant circuit (driver), the minimum and mean local A-A intervals will be similar at sites in the reentrant circuit, but will vary widely at sites with fibrillatory conduction, making these latter intervals unreliable indicators of AERP.

Methods: During sustained AF due to a left atrial (LA) driver in 6 sterile pericarditis dogs, electrograms were recorded from 186 bipolar electrodes from both atria.

Vanoxerine, a new drug for terminating atrial fibrillation and flutter.

Background: Vanoxerine produces potent block of cardiac hERG, sodium, and L-type calcium channels. Block is strongly frequency dependent, is unassociated with transmural dispersion of repolarization, and occurs at concentrations safe in humans. Therefore, we proposed that vanoxerine might be antiarrhythmic.

Frequency analysis of atrial electrograms identifies conduction pathways from the left to the right atrium during atrial fibrillation-studies in two canine models.

Unlabelled: Studies of atrial fibrillation (AF) have demonstrated that a stable rhythm of very short cycle length in the left atrium (LA) can cause fibrillatory conduction in the rest of the atria. We tested the hypothesis that fast Fourier transform (FFT) analysis of atrial electrograms (AEGs) during this AF will rapidly and reliably identify LA-to-right atrium (RA) conduction pathway(s) generated by the driver.

Methods And Results: During induced atrial tachyarrhythmias in the canine sterile pericarditis and rapid ventricular pacing-induced congestive heart failure models, 380-404 AEGs were recorded simultaneously from epicardial electrodes on both atria.

Fixed intercaval block in the setting of atrial fibrillation promotes the development of atrial flutter.

Background: In the canine sterile pericarditis model, typically only atrial fibrillation (AF) is inducible on postoperative day 2.

Objective: In this model, we tested the hypothesis that on postoperative day 2, placing a fixed line of block (LoB) between the vena cavae critically alters the atrial substrate, favoring the induction of sustained atrial flutter (AFL) instead of AF.

Methods: In 6 sterile pericarditis dogs, sustained AF was induced by rapid atrial pacing.

Termination of a tachyarrhythmia by flunarizine is not a specific marker for a triggered mechanism.

Background: Prior studies have indicated that tachyarrhythmia termination by flunarizine demonstrates a triggered mechanism. This concept was not confirmed in atrial tachyarrhythmias.

Objective: The purpose of this study was to test the hypothesis that flunarizine will not terminate reentrant atrial flutter (AFL).

Prednisone prevents inducible atrial flutter in the canine sterile pericarditis model.

Background: Atrial fibrillation (AF) and atrial flutter (AFL) are common following cardiac surgery and are associated with significant morbidity. We tested the hypothesis that suppression of the inflammatory response with steroids would significantly modify the inducibility of postoperative AF/AFL in the canine sterile pericarditis model.

Methods: Twenty-three dogs were studied daily from creation of pericarditis to the fourth postoperative day: 11 dogs were treated with oral prednisone (PRED) starting 2 days preoperatively until the end of the study; 12 dogs were controls (CON).

Effects of sterile pericarditis on connexins 40 and 43 in the atria: correlation with abnormal conduction and atrial arrhythmias.

The canine sterile pericarditis model is characterized by impaired conduction and atrial arrhythmia vulnerability. Electrical and structural remodeling processes caused by the inflammatory response likely promote these abnormalities. In the present study, we tested the hypothesis that altered distribution of atrial connexins is associated with markedly abnormal atrial conduction, thereby contributing to vulnerability to atrial flutter (AFL) and atrial fibrillation (AF) induction and maintenance.

Characterization of the critical cycle length of a left atrial driver which causes right atrial fibrillatory conduction.

A stable rhythm of very short cycle length (CL) in the left atrium (LA) can cause fibrillatory conduction, particularly in the right atrium (RA). Fast Fourier transform (FFT) analysis reliably identifies LA to RA conduction path(s) during atrial fibrillation (AF). We tested the hypotheses that FFT analysis of atrial electrograms (AEGs) during AF simulation will reliably identify the critical LA driver CL that causes RA fibrillatory conduction (i.

Use of fast fourier transform analysis of atrial electrograms for rapid characterization of atrial activation-implications for delineating possible mechanisms of atrial tachyarrhythmias.

Introduction: Different analysis techniques have been developed to help understand and characterize the mechanisms responsible for atrial arrhythmias. We tested the hypothesis that Fast Fourier Transform (FFT) analysis of recorded atrial electrograms (AEGs) will rapidly and accurately identify regular and irregular patterns of atrial activation, and, thereby, may provide evidence suggestive of underlying mechanisms of atrial tachyarrhythmias.

Methods And Results: During induced atrial tachyarrhythmias in both the canine sterile pericarditis model and canine rapid ventricular pacing-induced congestive heart failure model; 380-404 AEGs were recorded simultaneously from epicardial electrodes on both atria.

Mapping of atrial activation during sustained atrial fibrillation in dogs with rapid ventricular pacing induced heart failure: evidence for a role of driver regions.

Introduction: Dogs with rapid ventricular pacing (RVP)-induced congestive heart failure (CHF) have inducible atrial tachycardia, flutter, and fibrillation (AF). We tested the hypothesis that rapid atrial activation in multiple regions and at different rates is responsible for sustained AF in this CHF model.

Methods And Results: We studied 12 episodes of sustained (>10 minutes) AF induced in 12 dogs with CHF produced by 3-6 weeks of RVP at 230 beats/minute.