Alterations in atrial electrophysiology associated with chronic atrial fibrillation in man

Kamalvand, Kayvan; Tan, Kay Sin; Lloyd, Guy; Gill, Jaswinder; Bucknall, Cliff; Sulke, Neil

doi:10.1053/euhj.1998.1404

Cited by 45 publications

(21 citation statements)

References 29 publications

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“…The reduction in rate adaptation shown by the models is in agreement with a number of experimental studies that show little rate adaptation in MAP recordings shortly after cardioversion of chronic AF (Franz et al, 1997;Kamalvand et al, 1999;Manios et al, 2000;Osaka et al, 2000) and in isolated myocytes (Bosch et al, 1999;Van Wagoner et al, 1999;Workman et al, 2001) and tissues (Boutjdir et al, 1986) obtained from right atrial appendage tissue of patients with chronic AF. In some cases, more significant rate adaptation can be observed at the shortest CLs (Kim et al, 2002;Dobrev and Ravens, 2003).…”

Section: Atrial Fibrillation-induced Changes In Rate Dependence and Msupporting

confidence: 88%

Dynamics of human atrial cell models: Restitution, memory, and intracellular calcium dynamics in single cells

Cherry

Hastings

Evans

2008

Progress in Biophysics and Molecular Biology

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Mathematical models of cardiac cells have become important tools for investigating the electrophysiological properties and behavior of the heart. As the number of published models increases, it becomes more difficult to choose a model appropriate for the conditions to be studied, especially when multiple models describing the species and region of the heart of interest are available. In this paper, we will review and compare two detailed ionic models of human atrial myocytes, the Nygren et al. model (NM) and the Courtemanche et al. model (CM). Although both models include the same transmembrane currents and are largely based on the same experimental data from human atrial cells, the two models exhibit vastly different properties, especially in their dynamical behavior, including restitution and memory effects. The CM produces pronounced rate adaptation of action potential duration (APD) with limited memory effects, while the NM exhibits strong rate dependence of resting membrane potential (RMP), limited APD restitution, and stronger memory, as well as delayed afterdepolarizations and auto-oscillatory behavior upon cessation of rapid pacing. Channel conductance modifications based on experimentally measured changes during atrial fibrillation modify rate adaptation and memory in both models, but do not change the primary rate-dependent properties of APD and RMP for the CM and NM, respectively. Two sets of proposed changes to the NM that yield a spike-and-dome action potential morphology qualitatively similar to the CM at slow pacing rates similarly do not change the underlying dynamics of the model. Moreover, interchanging the formulations of all transmembrane currents between the two models while leaving calcium handling and ionic concentrations intact indicates that the currents strongly influence memory and the rate adaptation of RMP, while intracellular calcium dynamics primarily determine APD rate adaptation. Our results suggest that differences in intracellular calcium handling between the two human atrial myocyte models are responsible for marked dynamical differences and may prevent reconciliation between the models by straightforward channel conductance modifications.

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Section: Atrial Fibrillation-induced Changes In Rate Dependence and Msupporting

confidence: 88%

Dynamics of human atrial cell models: Restitution, memory, and intracellular calcium dynamics in single cells

Cherry

Hastings

Evans

2008

Progress in Biophysics and Molecular Biology

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“…This model helps to understand the mechanisms underlying the tendency of paroxysmal AF to become persistent but does not relate closely to the most frequent clinical conditions associated with AF, in which the left atrium (LA) dilates and is fibrosed, exhibiting conduction slowing (14,21). The other commonly used model is rapid ventricular pacing (RVP) to induce heart failure (240 -280 beats/min for 3-8 wk), sometimes combined with RAP (RVP at 240 beats/min for 2 wk combined with additional RAP at 400 beats/min during the second week) (5).…”

mentioning

confidence: 99%

Experimental studies of atrial fibrillation: a comparison of two pacing models

Laurent¹,

Moe²,

Hu³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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is a well-established animal model of atrial fibrillation (AF). However, this model is limited by a high mortality rate and severe heart failure. The purpose of our study was to assess a new canine model of inducible AF. We performed acute, short-term, simultaneous atrioventricular pacing (SAVP) and RVP (in random order) in 14 dogs for 30 s. SAVP produced more echocardiographic pulmonary venous flow reversal, a greater increase in mean pulmonary capillary wedge pressure, and a significantly greater decrease in left atrial emptying function (Ϫ84.4 Ϯ 38.6% vs. Ϫ23.7 Ϯ 27.1%, P Ͻ 0.05) than RVP. Thirty dogs were randomized to three, longer-term, study groups: eight dogs in the control group (no pacing), eight dogs in the RVP group (2 wk at 240 beats/min followed by 3 wk at 220 beats/min), and fourteen dogs in the SAVP group (2 wk at 220 beats/min). SAVP induced less left ventricular dysfunction but more left atrial dysfunction than RVP. SAVP dogs had similar atrial effective refractory periods as RVP dogs but more heterogeneity in conduction and more AF inducibility (83% vs. 40%, P Ͻ 0.05) and maintenance (median 1,660 vs. 710 s, P Ͻ 0.05) than RVP dogs. SAVP induced more collagen turnover and was associated with a significantly greater increase in type III collagen in the atria compared with RVP dogs (6.9 Ϯ 1.5 vs. 4.8 Ϯ 1.6, respectively, P Ͻ 0.05 vs. 1.1 Ϯ 0.7 in unpaced control dogs). In conclusion, the SAVP model induced profound mechanical and substrate atrial remodeling and reproducible sustained AF. This new model is clinically relevant and may be useful for testing AF interventions. experimental atrial arrhythmia; extracellular matrix; remodeling ATRIAL FIBRILLATION (AF) is the most common sustained cardiac arrhythmia and frequently causes cardiovascular morbidity and mortality. Although AF can occur in patients with normal hearts (lone AF), the majority of patients with AF have coexisting structural heart disease, most commonly hypertension or heart failure (1). To better understand the relationship between the atrial substrate and AF vulnerability and to evaluate therapies for AF, multiple animal models of AF have been developed. They include sterile pericarditis, acute atrial ischemia, atrial volume overload, mitral regurgitation, pacemakerinduced atrial tachycardia, and ventricular pacing-induced heart failure (25).One of the most commonly used models employs rapid atrial pacing (RAP) at 400 beats/min with control of the ventricular response (atrioventricular node ablation) (24). This model helps to understand the mechanisms underlying the tendency of paroxysmal AF to become persistent but does not relate closely to the most frequent clinical conditions associated with AF, in which the left atrium (LA) dilates and is fibrosed, exhibiting conduction slowing (14, 21). The other commonly used model is rapid ventricular pacing (RVP) to induce heart failure (240 -280 beats/min for 3-8 wk), sometimes combined with RAP (RVP at 240 beats/min for 2 wk combined with additional RAP at 400 beats/min during the sec...

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“…Clinical studies of AF-induced electrical remodeling have produced more variable results than experimental studies in normal hearts, with ERP alterations and ERP rate maladaptation varying much more widely than in experimental studies. [1][2][3][4][5][6][7][8][9][10][11] Our results suggest that these discrepancies may be due to the effects of cardiac pathology on AT-induced remodeling. The extent and nature of cardiac disease associated with AF varies in different clinical populations, with this variation potentially being reflected in different results of AF-induced remodeling in different studies.…”

Section: Relationship To Previous Observations Regarding Atrial Tachymentioning

confidence: 99%

“…6 Clinical studies of AF support the relevance of experimental studies of AT-induced remodeling, but changes have been more variable and sometimes smaller than in animal models. [7][8][9][10][11] All previous experimental work on AT remodeling has been performed in normal animals. Clinical AF commonly occurs in the presence of atrial pathology, and AT could have different electrophysiological effects in pathological compared with normal atria.…”

mentioning

confidence: 99%

Consequences of Atrial Tachycardia-Induced Remodeling Depend on the Preexisting Atrial Substrate

Shinagawa

Leung

et al. 2002

Circulation

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Background-All animal studies of atrial tachycardia (AT) remodeling to date have been performed in normal hearts, but clinical atrial fibrillation (AF) often occurs in the setting of heart disease. This study evaluated the effects of a pathological AF substrate on AT-induced remodeling. Methods and Results-Fourteen control dogs, 12 AT-only dogs (400 bpm for 1 week), 14 congestive heart failure (CHF) dogs (CHF only, ventricular tachypacing, 220 to 240 bpm for 5 weeks), and 13 CHFϩAT dogs (ventricular tachypacing-induced CHF, 1 week of AT superimposed on the last week of ventricular tachypacing) were studied for evaluation of AT effects in normal hearts (AT-only versus control dogs) and CHF hearts (CHFϩAT versus CHF-only dogs). In normal hearts, AT strongly decreased the effective refractory period (ERP) and abolished ERP rate adaptation, whereas conduction velocity was unaltered. In CHF dogs, AT reduced ERP to a significantly lesser extent, did not alter ERP rate adaptation, and reduced conduction velocity. AT alone increased atrial vulnerability to extrastimuli and prolonged AF. In the presence of CHF, AT had no clear effect on atrial vulnerability but increased the prevalence of prolonged AF. Conclusions-The

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Alterations in atrial electrophysiology associated with chronic atrial fibrillation in man

Cited by 45 publications

References 29 publications

Dynamics of human atrial cell models: Restitution, memory, and intracellular calcium dynamics in single cells

Dynamics of human atrial cell models: Restitution, memory, and intracellular calcium dynamics in single cells

Experimental studies of atrial fibrillation: a comparison of two pacing models

Consequences of Atrial Tachycardia-Induced Remodeling Depend on the Preexisting Atrial Substrate

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