Cellular electrophysiology of atrial fibrillation

Bosch, Ralph F.; Nattel, Stanley

doi:10.1016/s0008-6363(01)00529-6

Cited by 83 publications

(45 citation statements)

References 107 publications

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“…As expected, APD 80 in RAP atria was significantly reduced compared with control, corresponding to the electrical remodeling process that has been extensively characterized in earlier studies (reviewed in Ref. 8). By contrast, the LA and RA APD 80 was not different between control and MR, indicating that the increase in ERP observed in open-chest studies was not caused by electrical remodeling at the cellular level.…”

Section: Discussionsupporting

confidence: 77%

Direction-dependent conduction abnormalities in a canine model of atrial fibrillation due to chronic atrial dilatation

Verheule

Wilson

Banthia

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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Chronic rapid atrial pacing (RAP) leads to changes that perpetuate atrial fibrillation (AF). Chronic atrial dilatation due to mitral regurgitation (MR) also increases AF inducibility, but it is not clear whether the underlying mechanism is similar. Therefore, we have investigated atrial electrophysiology in a canine MR model (mitral valve avulsion, 1 mo) using high-resolution optical mapping and compared it with control dogs and with the canine RAP model (6 -8 wk of atrial pacing at 600 beats/min, atrioventricular block, and ventricular pacing at 100 beats/min). At followup, optical action potentials were recorded using a 16 ϫ 16 photodiode array from 2 ϫ 2-cm left atrial (LA) and right atrial (RA) areas in perfused preparations, with pacing electrodes around the field of view to study direction dependency of conduction. Action potential duration at 80% repolarization (APD 80) was not different between control and MR but was reduced in RAP atria. Conduction velocities during normal pacing were not different between groups. However, the MR LA showed increased conduction heterogeneity during pacing at short cycle lengths and during premature extrastimuli, which frequently caused pronounced regional conduction slowing. Conduction in the MR LA during extrastimulation also displayed a marked dependence on propagation direction. These phenomena were not observed in the MR RA and in control and RAP atria. Thus both models form distinctly different AF substrates; in RAP dogs, the decrease in APD80 may stabilize reentry. In MR dogs, regional LA conduction slowing and increased directional dependency, allowing unidirectional conduction block and preferential paths of conduction, may account for increased AF inducibility. atrial conduction; optical mapping ATRIAL FIBRILLATION (AF) is a frequently occurring arrhythmia, present in ϳ5% of people over 65 yr old (5). Among the risk factors predisposing to AF are congestive heart failure (CHF), hypertension, and mitral valve disease, including both stenosis and insufficiency (reviewed in Ref. 5). In general, atrial dilatation is associated with an increased occurrence of AF (17,28).Prevailing theory suggests that inducibility of sustained AF requires either a shortening of refractoriness, increased dispersion of refractoriness, or conduction slowing (1). Other factors that have been implicated in the stabilization of AF include increased conduction heterogeneity and anisotropy (23). The presence of one or more of these proarrhythmic factors would thus represent a "substrate for AF," contributing to increased AF stability. Various animal models of AF have been developed to study AF substrate. Parasympathetic stimulation (either with direct vagal nerve stimulation or circulating cholinergic agents) results in shortening of atrial refractoriness and sustained AF (10, 16). Prolonged rapid atrial pacing (RAP) leads to shortening of refractoriness and sustained AF (18,30). In a dog model of CHF due to rapid ventricular pacing, no changes in refractoriness were found, but increased con...

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Section: Discussionsupporting

confidence: 77%

Direction-dependent conduction abnormalities in a canine model of atrial fibrillation due to chronic atrial dilatation

Verheule

Wilson

Banthia

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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“…Previous studies demonstrated that negative plateau potentials exhibited a lower driving force for the conduction of early premature beats (18,19). Therefore, the results of the present study suggested that the change in the AP in aged atria may lead to a decreased conduction of premature beats.…”

Section: B a C Discussionsupporting

confidence: 61%

Alterations in the expression of atrial calpains in electrical and structural remodeling during aging and atrial fibrillation

Gan

Tang

et al. 2013

Molecular Medicine Reports

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Abstract. The aim of this study was to investigate the correlation between the change in the expression of atrial calpains and electrical, molecular and structural remodeling during aging and atrial fibrillation (AF). Adult and aged canines in sinus rhythm (SR) and with persistent AF (induced by rapid atrial pacing) were investigated. A whole-cell patch clamp was used to measure the L-type Ca 2+ current (I Ca-L ) in cells in the left atrium. The mRNA and protein expression of the L-type calcium channel alc subunit (LVDCC a1c ) and calpains were measured by quantitative (q)PCR and western blot analysis. Histopathological and ultrastructural changes were analyzed via light and electron microscopy. The quantity of apoptotic myocytes was determined by a terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL) assay. In SR groups, atrial cells of the aged canines exhibited a longer action potential (AP) duration to 90% repolarization (APD 90 ), lower AP plateau potential and peak I Ca-L current densities (P<0.05). In the adult and aged groups, AF led to a higher maximum diastolic potential, an increase in AP amplitude and decreases in APD 90 , AP plateau potential and peak I Ca-L densities (P<0.05). Compared with the control group, the mRNA and protein expression levels of LVDCC a1c were decreased in the aged groups; however, the mRNA and protein expression of calpain 1 was increased in the adult and the aged groups with AF (P<0.05). Samples of atrial tissue exhibited abnormal histopathological and ultrastructural changes, such as accelerated fibrosis and apoptosis with aging and in AF. Age-related alterations in atrial tissues were attributed to the increased expression of calpain 1. The general pathophysiological alterations in normal aged atria may therefore produce a substrate that is conducive to AF.

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“…[12][13][14] Ionic remodeling has important implications for the action of antifibrillatory drugs. It was recently demonstrated that the action of the I Kr blocker dl-sotalol was reduced in patients with long-lasting AF.…”

Section: Effects Of Electrical Remodeling On "Early" and "Late" Classmentioning

confidence: 99%

“Early” Class III Drugs for the Treatment of Atrial Fibrillation

et al. 2004

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Background-Currently available antiarrhythmic drugs are only moderately effective against atrial fibrillation (AF) and may cause ventricular proarrhythmia. AVE0118 is a blocker of atrium-specific early K ϩ currents (I Kur /I to ). Methods and Results-Effects of intravenous AVE0118 and dofetilide on atrial effective refractory period (AERP) and inducibility of AF were measured before and after 48-hours of AF-induced electrical remodeling in the goat. During persistent AF (53Ϯ19 days), the cardioversion efficacy and effects on atrial wavelength of AVE0118, dofetilide, and ibutilide were evaluated. QT durations were measured during atrial pacing and persistent AF. After 48 hours of AF, the effect of dofetilide on AERP was reduced, and induction of AF was not prevented. In contrast, the class III action of AVE0118 was enhanced, and AF inducibility decreased from 100% to 32% (PϽ0.001). At 1, 3, and 10 mg · kg Ϫ1 · h Ϫ1 , AVE0118 terminated persistent AF in 1 of 8, 3 of 8, and 5 of 8 goats, respectively. Dofetilide and ibutilide terminated AF in 1 of 5 and 2 of 7 goats. AVE0118 0.5, 1.5, and 5 mg/kg prolonged the AERP during AF and increased the fibrillation wavelength from 6.7Ϯ0.6 to 8.5Ϯ0.5, 9.7Ϯ0.5, and 11.2Ϯ0.9 cm (PϽ0.01). Whereas dofetilide and ibutilide prolonged QT duration, AVE0118 had no appreciable effect. Conclusions-AVE0118 markedly prolongs the AERP during AF without affecting QT duration. Cardioversion of AF was due to an Ϸ2-fold increase in fibrillation wavelength. Atrium-selective class III drugs like AVE0118 may be a promising new option for safe and effective cardioversion of AF.

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Cellular electrophysiology of atrial fibrillation

Cited by 83 publications

References 107 publications

Direction-dependent conduction abnormalities in a canine model of atrial fibrillation due to chronic atrial dilatation

Direction-dependent conduction abnormalities in a canine model of atrial fibrillation due to chronic atrial dilatation

Alterations in the expression of atrial calpains in electrical and structural remodeling during aging and atrial fibrillation

“Early” Class III Drugs for the Treatment of Atrial Fibrillation

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