Atrial Refractory Period Research Articles

The Effect of Vernakalant (RSD1235), an Investigational Antiarrhythmic Agent, on Atrial Electrophysiology in Humans

To determine the acute effects of vernakalant (RSD1235) on electrophysiologic (EP) properties in humans. Vernakalant is an investigational mixed ion channel blocker that can terminate acute atrial fibrillation (AF) in humans at 2 to 5 mg/kg and may be more "atrial-selective" than available agents. Patients (N=19; 53% male; age, 48+/-11 years) underwent EP study before and after 25 minutes of intravenous vernakalant administration: 2 mg/kg over 10 min+0.5 mg/kg/hr for 35 min or 4 mg/kg over 10 min+1 mg/kg/hr for 35 min. EP measurements, including atrial refractory period (AERP) and ventricular refractory period (VERP), were obtained. The lower dose prolonged AERP at 600, but not at 400 or 300 msec paced cycle length. The higher dose significantly prolonged AERP from 203+/-31 msec to 228+/-24 msec at 600 msec, 182+/-30 msec to 207+/-27 msec at 400 msec, and 172 msec+/-24 to 193+/-21 msec at 300 msec. There was no significant prolongation of VERP at either dose or at any cycle length. There was a small but significant prolongation of AV nodal refractoriness; Wenckebach cycle length prolonged by 18+/-12 msec (from baseline 343+/-54 msec) at the higher dose (P<0.05). Sinus node recovery time also increased by 123+/-158 msec (from baseline 928+/-237 msec) at the higher dose (P<0.05). There was a slight prolongation of QRS duration at the higher dose, during ventricular pacing at CL=400 msec (15+/-15 msec, P=0.0547). QT and HV intervals were unchanged. At doses similar to those tested clinically, vernakalant dose-dependently prolonged atrial refractoriness, prolonged AV nodal conduction and refractoriness, and slightly prolonged QRS duration, but it had no effect on ventricular refractoriness.

Cardioversion for Atrial Fibrillation: Does Inflammation Matter?

m t A s s e p p t I p t n The long-term maintenance of sinus rhythm after cardioersion for atrial fibrillation (AF) has long been acknowledged s problematic. Even after initial successful restoration of sinus hythm, some 53% patients will return to AF over the followng months, whereas only approximately 25% remain in sinus hythm at 5 years.1,2 This is despite an aggressive rhythm ontrol strategy, using serial attempts at cardioversion and oncomitant antiarrhythmic drug prescription. More recently, he advent of catheter-based (and surgical-based) technologies as offered the potential of a cure for AF, with some promising esults,3 but even after these procedures, recurrence, often symptomatic, is common, further highlighting the difficulties ncountered in maintaining sinus rhythm.4,5 What contributes to the poor results of cardioversion and ong-term maintenance of sinus rhythm? Structural and lectrical remodeling within the atria may perpetuate AF— hat is, “AF begets AF”—admittedly in an experimental oat model.6 These remodeling changes include progressive eft atrial dilatation and increasing atrial fibrosis,7 the loss of ate adaptation, and the prolongation of atrial conductivity.8 alcium may also accumulate within atrial myocytes, hereby shortening the atrial refractory period, and hence, romoting the propagation of multiple wavelet reentry ciruits.7 The net result is that the biophysical properties of trial tissue are altered at microscopic and macroscopic evels in AF,9 thereby serving to perpetuate the arrhythmia. Does inflammation have a role in this, contributing to the erpetuation and maintenance of AF? Although the precise timulus for the initiation of these atrial changes remains oorly understood, an increasing body of evidence suggests hat inflammation may be central to this pathogenic proess.10 The histology of atrial biopsies taken from patients ith AF has demonstrated evidence of inflammatory infilrates and oxidative damage within the atrial tissue.11,12 Of ourse, these changes may clearly be a consequence of the arious underlying co-morbidities that commonly associate ith AF (e.g., ischemic heart disease, hypertension, diabees mellitus). However, this observation holds true even for hose with lone AF, thereby raising the possibility that nflammation may still play some role in the initiation of F, at least in this patient group.12 Systemic indexes of inflammation are also reported in F.10 For example, C-reactive protein (CRP) is a circulating cute-phase reactant and is considered the prototypic downtream marker of inflammation.13,14 CRP is synthesized by he liver in response primarily to interleukin-6 (IL-6) but also o interleukin-1. Many markers of inflammation exist, but

In Vivo Cardiac Electrophysiologic and Antiarrhythmic Effects of an Isoquinoline IKur Blocker, ISQ-1, in Rat, Dog, and Nonhuman Primate

The cardiac electrophysiologic effects of ISQ-1, an isoquinolinone I(Kur) blocker, were characterized in vivo. In rat, ISQ-1 elicited maximal 33% to 36% increases in atrial and ventricular refractoriness at a plasma concentration of 11.5 microM. In African green monkey, ISQ-1 increased atrial refractory period (maximal 17% at plasma concentration up to 20 microM) with no effect on ventricular refractory period or ECG QTc. Likewise in dog, ISQ-1 increased atrial refractory period (maximal 16% at plasma concentration up to 2 microM) with no effect on ventricular refractory period or QTc. In contrast, studies with ibutilide in nonhuman primate and dog demonstrated concomitant increases in atrial and ventricular refractoriness and QTc. Additionally, in a dog model of atrial flutter, ISQ-1 terminated ongoing flutter at doses (2.5 +/- 0.5 mg/kg IV) that selectively prolonged atrial refractoriness (13% increase), whereas flutter termination with ibutilide occurred at doses that increased both atrial and ventricular refractoriness as well as QTc. Of note, the cardiac electrophysiologic profiles displayed by ISQ-1 in these species were similar to those reported previously by our lab with a structurally distinct I(Kur) blocker. Taken together, these results further support the inhibition of I(Kur) as an approach to terminate atrial arrhythmia.

Cardioversion of persistent atrial fibrillation by a combination of atrial specific and non-specific class III drugs in the goat

In electrically remodeled atria the effect of blockers of the delayed rectifier K+ current I(Kr) on repolarization is reduced, whereas the efficacy of 'early' class III drugs (I(Kur)/I(to)/I(Kach) blockers) is enhanced. We evaluated the electrophysiological and antifibrillatory effects of AVE0118, dofetilide, and ibutilide (alone and in combination) on persistent atrial fibrillation (AF) in the goat. The effects of separate and combined administration of AVE0118, dofetilide, and ibutilide were determined before and after 48 h of AF. AVE0118 alone markedly prolonged the atrial refractory period (400 ms cycle length) (AERP400) before and after 48 h of AF. The prolongation of AERP(400) by dofetilide and ibutilide, respectively, was reduced by AF from 22+/-2 to 7+/-2 ms (p<0.01) and 25+/-5 to 5+/-2 ms (p=0.01). Pre-treatment with AVE0118 restored the prolongation of AERP400 by dofetilide or ibutilide (to 20+/-3 and 30+/-6 ms; p<0.01). This effect was atrial specific since the QT-interval was not changed. The antifibrillatory action was evaluated in 10 goats that were in persistent AF for 57+/-7 days. Dofetilide (20 microg/kg/h) or ibutilide (4 mg/h) alone restored sinus rhythm in only 20% of the animals. AVE0118 (1, 3 and 10 mg/kg/h) [DOSAGE ERROR CORRECTED] terminated AF in 11, 30, and 60%, respectively. Additional infusion of I(Kr) blockers caused an additional number of cardioversions, resulting in a final cardioversion rate of 56, 80, and 100%, respectively. AVE0118 alone prolonged the AF cycle length (AFCL) while the conduction velocity during AF (CV(AF)) remained unchanged (70+/-1 vs. 68+/-2 cm/s; p=0.3). Addition of dofetilide or ibutilide caused a synergistic increase in AFCL and a slight increase in CV(AF) to 74+/-1 cm/s (p<0.001). The length of the reentrant trajectories increased from 7.6+/-0.3 (control) to 11.6+/-0.5 cm after AVE0118 alone (p<0.001) and 14.8+/-0.8 cm after addition of dofetilide or ibutilide (p<0.001). In electrically remodeled atria, blockade of I(Kur)/I(to)/I(KAch) restored the class III action of I(Kr) blockers. Persistent AF could be effectively cardioverted by infusion of a combination of AVE0118 and dofetilide or ibutilide. This antifibrillatory action was associated with an almost twofold lengthening of the intra-atrial pathways for reentry.

Temporary epicardial pacing after cardiac surgery: a practical review

The first part of this two-part review discussed the indications for various types of epicardial pacing systems and an overview of the routine care of a pacemaker-dependent patient. Dual chamber temporary pulse generators now feature many of the refinements developed initially for use in permanent pacemakers. Few of these are utilised in the immediate postoperative period, often solely due to lack of familiarity with all but basic functions. The second part of the review deals with the selection of pacing modes. Troubleshooting real and apparent pacemaker malfunctions, including manual adjustment of parameters such as the AV interval, post atrial refractory period and upper rate limit, to avoid over- and undersensing, cross-talk and pacemaker-mediated tachycardia will also be addressed.

First-degree atrioventricular block

Marked first-degree AV block (PR> or =0.30 s) can produce a clinical condition similar to that of the pacemaker syndrome. Clinical evaluation often requires a treadmill stress test because patients are more likely to become symptomatic with mild or moderate exercise when the PR interval cannot adapt appropriately. Uncontrolled studies have shown that many such symptomatic patients with normal left ventricular (LV) function improve with conventional dual chamber pacing (Class IIa indication). In contrast, marked first-degree AV block with LV systolic dysfunction and heart failure is still a Class IIb indication, a recommendation that is now questionable because a conventional DDD(R) pacemaker would be committed to right ventricular pacing (and its attendant risks) virtually 100% of the time. It would seem prudent at this juncture to consider a biventricular DDD device in this situation. Patients with suboptimally programmed pacemakers may develop functional atrial undersensing because the P wave tends to migrate easily into the postventricular atrial refractory period (PVARP). Retrograde vetriculoatrial conduction block is uncommon in marked first-degree AV block so a relatively short PVARP can often be used at rest with little risk of endless loop tachycardia. The usefulness of a short PVARP may be negated by special PVARP functions in some pulse generators designed to time out a long PVARP at rest and a gradually shorter one with activity. First-degree AV block during cardiac resynchronization therapy (CRT) predisposes to loss of ventricular resynchronization during biventricular pacing because it favors the initiation of electrical "desynchronization" especially in association with a relatively fast atrial rate and a relatively slow programmed upper rate. Patients with first-degree AV block have a poorer outcome with CRT than patients with a normal PR interval, a response that may involve several mechanisms. (1) The long PR interval may be a marker of more advanced heart disease. (2) Patients with first-degree AV block may experience more episodes of undetected "electrical desynchronization". (3) "Concealed resynchronization" whereupon ventricular activation in patients with a normal PR interval may result from fusion of electrical wavefronts coming from the right bundle branch and the impulse from the LV electrode. The resultant hemodynamic response may be superior because the detrimental effects of right ventricular stimulation (required in the setting of a longer PR interval) are avoided.

Focus, reentry, or “focal” reentry?

the question whether tachyarrhythmias are caused by enhanced impulse formation (“focus”) or by reentrant excitation (“reentry”) has been the subject of debate for more than a century. In 1887 McWilliam ([12][1]) was the first to suggest that disturbances in impulse propagation could be

Pulmonary vein encircling ablation alters the atrial electrophysiologic response to autonomic stimulation

Pulmonary vein encircling ablation is often effective in the treatment of atrial fibrillation (AF). The success of the procedure does not depend upon creation of continuous lines of block. Thus mechanisms by which pulmonary vein encircling can cure AF remain unclear. Stimulation of cardiac autonomic ganglia alters atrial refractoriness and potentiates AF. We hypothesized that pulmonary vein encircling alters atrial autonomic function and that these alterations account in part for prevention of AF recurrences following ablation. Atrial effective refractory periods (ERP) and AF inducibility were quantified in ten dogs before and during central autonomic nerve stimulation. Pulmonary vein encircling ablation was then performed and electrophysiologic testing repeated. In two dogs subjected to sham procedures measurements were repeated without performance of ablation. Hearts were examined histologically. Autonomic nerve stimulation led to decreased atrial refractoriness and increased AF inducibility and duration. Each of these effects were attenuated following pulmonary vein encircling (e.g., mean ERP decreased before (-23.7 +/- 1.8, p < 0.001) but not after ablation (-2.3 +/- 1.9, p = 0.25); AF inducibility increased by 26% before vs. 5% after ablation). No attenuation was seen in the sham operated animals. Histologic analysis following pulmonary vein encircling demonstrated destruction of some but not all autonomic ganglia. Autonomic stimulation shortens atrial refractory periods and potentiates AF. Pulmonary vein encircling ablation partially destroys atrial autonomic inputs, attenuates the refractory period shortening effect of autonomic stimulation and decreases AF inducibility. Destruction of autonomic ganglia may contribute to the anti-fibrillatory effects of pulmonary vein encircling and warrants further investigation.

NEURALLY INDUCED ATRIAL ARRHYTHMIAS ARE MODIFIED BY ALPHA‐ADRENOCEPTOR BLOCKADE.

Objective: To determine whether neurally induced atrial arrhythmias can be modified by α-adrenergic receptor blockade. Methods: In 24 anaesthetized dogs, trains of 5 electrical stimuli were delivered during the atrial refractory period to mediastinal nerves associated with the superior vena cava. Regional atrial electrical events were characterized using multiple unipolar electrodes. Active neural sites which induce atrial arrhythmias were identified and then re-stimulated following administration of naftopidil (α1-adrenergic blocker: 0.2 mg/kg iv) and/or yohimbine (α2-adrenergic blocker: 1 mg/kg iv). Results: Stimulation of select mediastinal nerves sites consistently elicited atrial tachyarrhythmias. Combined α-adrenergic blockade eliminated atrial tachydysrythmia induction in every animal. Naftopidil or yohimbine alone mitigated atrial arrhythmia induction. Conclusions: Excessive activation of select intrinsic cardiac neural components induces atrial arrhythmia. This neurally based arrhythmic substrate can be suppressed by α-adrenoceptor blockade. Treatment targeting select neural elements with ICN has potential therapeutic benefits for atrial arrhythmias management. Supported by the CIHR, the Québec Heart & Stroke Foundation and the NIH.

The Rho/Rho-kinase Systems Are Involved in Rapid Pacing-induced Changes of Atrial Refractory Period in a Canine Model

Introduction: The Rho/Rho-kinase pathway has been related to various physiological responses of the cardiovascular system. Previous reports have suggested a significant effect of Rho signals on the electrophysiological characteristics of the heart. We hypothesized that the Rho/Rho-kinase system would contribute to the rapid pacing-related change of atrial effective refractory period (AERP).Methods and Results: In 17 dogs, AERP was measured at the right atrial appendage (RAA) and posterior left atrium (LA) before, during, and after 6-hours rapid atrial pacing at 500 bpm. Saline control (n = 5), verapamil (n = 5), or fasudil (n = 7) were infused throughout the protocol. The shortening of AERP after rapid pacing was abrogated by the administration of verapamil, as reported in previous studies. Furthermore, fasudil (Rho/Rho-kinase inhibitor) influenced the change of AERP in a manner similar to the infusion of verapamil throughout the experiments.Conclusions: Since the AERP was attenuated by fasudil, rapid pacing-related atrial electrophysiological changes might involve the Rho/Rho-kinase pathway.

Electrophysiology of the electrocardiographic changes of atrial fibrillation

The history of atrial fibrillation is described in terms of its electrocardiographic delineation, characteristics and clinical associations. The variant configurations are described and their relationship to rhythm duration and cardioversion success. The inter-relationship of fibrillation with flutter and their diagnostic differences are reviewed. The electrophysiologic basis of atrial remodeling is exemplified, together with its relationship to failure of rate adaptation of the atrial refractory period. Electric countershock causes an acute abbreviation of the atrial refractory period as does the induction of hyperthyroidism in the experimental animal. Current theories of the mechanism of fibrillation and the issue of originating pulmonary venous foci are reviewed. The lack of protection from ventricular fibrillation that exists with preexcitation via an accessory pathway is discussed in terms of the teleological role of orthograde downstream refractory periods.

148: RSD1235 Effectively Converts Acute Atrial Fibrillation to Sinus Rhythm Independent of Background Use of Oral Rate- or Rhythm-Control Medications

RSD1235 is a novel, frequency-dependent Na+ and early activating K+ channel blocker that selectively prolongs the atrial refractory period. The efficacy and safety of intravenous RSD1235 for conversion of atrial fibrillation (AF) to sinus rhythm (SR) were evaluated in 2 multicenter, randomized, placebo-controlled Atrial Arrhythmia Conversion Trials (ACT I and ACT III). Reported here is a pooled analysis of patients with acute AF from ACT I and ACT III, which assessed the efficacy and safety of RSD1235 in patients using concomitant rate- or rhythm-control medication.

Passive pericardial constraint protects against stretch-induced vulnerability to atrial fibrillation in rabbits

Atrial fibrillation is more common in conditions with elevated atrial pressure and can be induced experimentally with acute increases in atrial pressure. We examined the effect of increased atrial pressure with and without pericardial constraint to better separate the effects of increased pressure and atrial stretch. In Langendorff-perfused rabbit hearts with intact pericardium, after ligating the pulmonary and caval veins, intra-atrial pressures were increased in a stepwise manner by adjusting the pulmonary outflow cannula. Rapid burst pacing was applied to induce atrial fibrillation at increasing intra-atrial pressures from 0 to 24 cmH(2)O. The atrial refractory period was recorded at each pressure using a single extra stimulus. The protocol was repeated after the pericardium was removed. When the pericardium was intact, atrial stretch was limited by passive constraint, and sustained atrial fibrillation could not be induced despite atrial pressures in excess of 20 cmH(2)O. In contrast, when the pericardium was removed, atrial fibrillation could be reliably induced when atrial pressure exceeded 15 cmH(2)O. This suggests that the electrophysiological effects of acute atrial volume loading rely on atrial stretch rather than increased atrial pressure alone.

Spinal cord stimulation suppresses bradycardias and atrial tachyarrhythmias induced by mediastinal nerve stimulation in dogs

Spinal cord stimulation (SCS) applied to the dorsal aspect of the cranial thoracic cord imparts cardioprotection under conditions of neuronally dependent cardiac stress. This study investigated whether neuronally induced atrial arrhythmias can be modulated by SCS. In 16 anesthetized dogs with intact stellate ganglia and in five with bilateral stellectomy, trains of five electrical stimuli were delivered during the atrial refractory period to right- or left-sided mediastinal nerves for up to 20 s before and after SCS (20 min). Recordings were obtained from 191 biatrial epicardial sites. Before SCS (11 animals), mediastinal nerve stimulation initiated bradycardia alone (12 nerve sites), bradycardia followed by tachyarrhythmia/fibrillation (50 sites), as well as tachyarrhythmia/fibrillation without a preceding bradycardia (21 sites). After SCS, the number of responsive sites inducing bradycardia was reduced by 25% (62 to 47 sites), and the cycle length prolongation in residual bradycardias was reduced. The number of responsive sites inducing tachyarrhythmia was reduced by 60% (71 to 29 sites). Once elicited, residual tachyarrhythmias arose from similar epicardial foci, displaying similar dynamics (cycle length) as in control states. In the absence of SCS, bradycardias and tachyarrhythmias induced by repeat nerve stimulation were reproducible (five additional animals). After bilateral stellectomy, SCS no longer influenced neuronal induction of bradycardia and atrial tachyarrhythmias. These data indicate that SCS obtunds the induction of atrial arrhythmias resulting from excessive activation of intrinsic cardiac neurons and that such protective effects depend on the integrity of nerves coursing via the subclavian ansae and stellate ganglia.

Vermeidung von intermittierendem T-Wellen-Oversensing durch Programmierung

We report the case of a 35-year-old man who was suffering from severe heart failure due to cardiomyopathy. He underwent heart transplantation years ago and developed complex ventricular arrhythmias in the following months in combination with recurrent episodes of syncope due to hypertrophic non-obstructive cardiomyopathy in the transplanted heart, so a dual chamber ICD was implanted. Months later repetitive episodes of intermittent T-wave oversensing with consecutive activation of the ICD could be observed. Surgical revision of the electrode was performed and the patient was closely followed up. One year later, further episodes of T-wave oversensing led to multiple inappropriate IDC-shocks. A very short AV-conduction time was programmed to allow ventricular capture whenever possible, because T-wave oversense after ventricular capture would be annotated as single ventricular ectopy not resulting in antitachycardia pacing. As a consequence, the patient was free from inappropriate ICD-shocks, but showed several shorter episodes of T-wave oversensing. They were all initiated by atrial activity that was seen in the refractory period, thus leading to a loss of AV synchrony. Programming a very short post ventricular atrial refractory period (PVARP) in addition to a short AV-delay led to the complete disappearance of T-wave oversensing in this patient. During a 9-month follow-up, no further tachycardia episodes were detected by the device.

Hypertension begets hypertrophy begets atrial fibrillation? Insights from yet another sheep model

Atrial fibrillation (AF) affects approximately two million patients in the USA and an equal number in Europe and increases morbidity and mortality in affected patients and population worldwide. Although acute conversion of AF to sinus rhythm can be achieved in almost all patients, therapeutic options to maintain sinus rhythm (repeated cardioversions, anti-arrhythmic drugs, catheter ablation, or surgical procedures) are often ineffective. Understanding the different mechanisms that contribute to AF may guide us towards a more effective ‘rhythm control’ therapy. Arterial hypertension, found in 65–70% of AF patients1,2 but only in 25–50% of the population,3 is the most common co-morbidity found in AF registries in Germany and Europe. Although this suggests a causal link between hypertension and AF, the mechanisms by which hypertension predisposes to AF are not well understood. Electrical, structural, and ultrastructural changes usually concur in the atria before AF develops. Some of the electrical changes that precipitate AF, shortening of the atrial action potential and refractory period and/or local conduction disturbances, have been delineated in detail during the past decade. The underlying pathophysiological concept of electrical remodelling (AF-induced shortening of atrial refractoriness) stems from studies in … *Corresponding author: Medizinische Klinik und Poliklinik C, Kardiologie und Angiologie, Universitatsklinikum Munster, D-48129 Munster, Germany. Tel: +49 251 8345185; fax: +49 251 8347864. E-mail address : kirchhp{at}uni-muenster.de

Prediction of sinus rhythm maintenance following DC-cardioversion of persistent atrial fibrillation – the role of atrial cycle length

BackgroundAtrial electrical remodeling has been shown to influence the outcome the outcome following cardioversion of atrial fibrillation (AF) in experimental studies.The aim of the present study was to find out whether a non-invasively measured atrial fibrillatory cycle length, alone or in combination with other non-invasive parameters, could predict sinus rhythm maintenance after cardioversion of AF.MethodsDominant atrial cycle length (DACL), a previously validated non-invasive index of atrial refractoriness, was measured from lead V1 and a unipolar oesophageal lead prior to cardioversion in 37 patients with persistent AF undergoing their first cardioversion.Results32 patients were successfully cardioverted to sinus rhythm. The mean DACL in the 22 patients who suffered recurrence of AF within 6 weeks was 152 ± 15 ms (V1) and 147 ± 14 ms (oesophagus) compared to 155 ± 17 ms (V1) and 151 ± 18 ms (oesophagus) in those maintaining sinus rhythm (NS). Left atrial diameter was 48 ± 4 mm and 44 ± 7 mm respectively (NS). The optimal parameter predicting maintenance of sinus rhythm after 6 weeks appeared to be the ratio of the lowest dominant atrial cycle length (oesophageal lead or V1) to left atrial diameter. This ratio was significantly higher in patients remaining in sinus rhythm (3.4 ± 0.6 vs. 3.1 ± 0.4 ms/mm respectively, p = 0.04).ConclusionIn this study neither an index of atrial refractory period nor left atrial diameter alone were predictors of AF recurrence within the 6 weeks of follow-up. The ratio of the two (combining electrophysiological and anatomical measurements) only slightly improve the identification of patients at high risk of recurrence of persistent AF. Consequently, other ways to asses electrical remodeling and / or other variables besides electrical remodeling are involved in determining the outcome following cardioversion.

Chronic Atrial Dilation, Electrical Remodeling, and Atrial Fibrillation in the Goat

This study was designed to investigate the mutual effects of chronic atrial dilation and electrical remodeling on the characteristics of atrial fibrillation (AF). Both electrical remodeling and atrial dilation promote the inducibility and perpetuation of AF. In seven goats AF was induced during 48 h by burst pacing, both at baseline and after four weeks of slow idioventricular rhythm (total AV block). Atrial size and refractory period (AERP) were monitored together with the duration and cycle length of AF paroxysms (AFCL). After four weeks of total atrioventricular (AV) block, the conduction in both atria was mapped during AF. Six non-instrumented goats served as controls. At baseline, AF-induced electrical remodeling shortened AERP and AFCL to the same extent (from 185 +/- 9 ms to 149 +/- 14 ms [p < 0.05] and from 154 +/- 11 ms to 121 +/- 5 ms [p < 0.05], respectively). After four weeks of AV block the right atrial diameter had increased by 13.2 +/- 3.0% (p < 0.01). Surprisingly, in dilated atria electrical remodeling still shortened the AERP (from 165 +/- 9 ms to 132 +/- 15 ms [p < 0.05]) but failed to shorten the AFCL (140 +/- 19 ms vs. 139 +/- 11 ms [p = 0.98]). Mapping revealed a higher incidence of intra-atrial conduction delays during AF. Histologic analysis showed no atrial fibrosis but did reveal a positive correlation between the size of atrial myocytes and the incidence of intra-atrial conduction block (r = 0.60, p = 0.03). In a goat model of chronic atrial dilation, AF-induced electrical remodeling was unchanged. However, AFCL no longer shortened during electrical remodeling. Thus, in dilated atria a wider excitable gap exists during AF, probably caused by intra-atrial conduction defects and a higher contribution of anatomically defined re-entrant circuits.

Left Atrial Posterior Wall and Pulmonary Vein Refractory Periods Are Associated With Atrial Fibrillation Inducibility in a Swine Model

Ectopic activity originating inside the pulmonary veins has been associated with paroxysmal atrial fibrillation in some patients. However, the roles played by the pulmonary veins and the posterior wall of the left atrium in maintaining atrial fibrillation are not well understood. Our aim was to determine whether there is a correlation between the refractory period of either the lateral wall of the right atrium, the lateral wall of the left atrium, the posterior wall of the left atrium, or the pulmonary veins, and the inducibility of atrial fibrillation in an experimental swine model. We assessed atrial fibrillation inducibility using programmed atrial stimulation before and after intravenous administration of a high dose of methacholine in 20 pigs. Atrial fibrillation was induced in 17 out of the 20 pigs. Univariate analysis showed that there were negative correlations between all refractory periods and atrial fibrillation inducibility. A short refractory period was associated with greater inducibility. In the multivariate analysis, only the refractory periods of the posterior wall of the left atrium and the pulmonary veins were associated with inducibility. We also investigated the relationship between the local atrial fibrillation cycle length and refractory period; the only significant correlation was with the refractory period of the lateral wall of the right atrium (Pearson correlation coefficient 0.97). In an experimental swine model, the inducibility of atrial fibrillation was found to be associated with the refractory periods of both the pulmonary veins and the posterior wall of the left atrium.

The Rho/Rho-kinase Systems Are Involved in Rapid Pacing-induced Changes of Atrial Refractory Period in a Canine Model

The Rho/Rho-kinase Systems Are Involved in Rapid Pacing-induced Changes of Atrial Refractory Period in a Canine Model