Verapamil Reduces Tachycardia-Induced Electrical Remodeling of the Atria

Tieleman, Robert G; Langen, C. D. J. de; Gelder, Isabelle C. Van; Kam, P.J. de; Grandjean, Jan G.; Bel, Kj; Wijffels, Maurits C.E.F.; Allessie, Maurits A.; Crijns, Harry J.G.M.

doi:10.1161/01.cir.95.7.1945

Cited by 307 publications

(174 citation statements)

References 68 publications

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“…3,10 The present study is the first to quantify in vivo subcellular Ca distribution during AF. After 3-minute pacing, mean total cytoplasmic Ca increased by 1.1 mmol/kg dry wt, which, given a total/free Ca ratio of Ϸ500:1, represents an increase of Ϸ550 nmol/L of free Ca.…”

Section: Subcellular Changes In Total Camentioning

confidence: 87%

“…Calcium overload has been suggested to be involved in electrical remodeling largely on the basis of indirect evidence using L-type Ca-channel antagonists. 2,10 Mitochondrial Ca accumulation has been implicated in the process of electrical remodeling because mitochondria can buffer large increases in intracellular Ca when cytoplasmic free Ca reaches pathologically high (micromolar) levels. 7 However, under physiological conditions, total mitochondrial Ca is low (Ͻ1 mmol/kg dry wt) and does not increase significantly during systole, 11 despite a Ca transient of approximately 500 to 600 nmol/L.…”

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confidence: 99%

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Intracellular Chloride Accumulation and Subcellular Elemental Distribution During Atrial Fibrillation

Akar

Everett

et al. 2003

Circulation

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Background-Ion channel remodeling occurs during atrial fibrillation (AF); however, the extent of alteration in the subcellular distribution of elements (Na, K, Cl, Ca, Mg, P) is unknown. Electron probe microanalysis was used to determine the total (freeϩbound) in vivo subcellular concentration of these elements during AF. Methods and Results-The left atrial appendage (LAA) was snap-frozen in situ after pacing (640 bpm) for 3 minutes (nϭ5 dogs), 30 minutes (nϭ3), or 48 hours (nϭ5). Dogs in sinus rhythm (nϭ3) served as controls. Whole-cell, cytosolic, and mitochondrial elemental concentrations were measured in cryosections. LAA effective refractory period (ERP) was measured before and after pacing. LAA ERP decreased significantly after 48 hours (116Ϯ3 to 88Ϯ10 ms, Pϭ0.02).Whole-cell Cl increased by 9.0 mmol/L and 17 mmol/L after 3 and 30 minutes of pacing, respectively (PϽ0.0001), without a concomitant increase in Na. However, at 48 hours, whole-cell Na was reduced by 51% (PϽ0.01). Cytosolic Ca increased by 1.1 mmol/kg dry wt after 3 minutes (PϽ0.005), but mitochondrial Ca remained low and unchanged. Cell size measured in transverse cryosections increased after 3 minutes of pacing (75Ϯ5 to 109Ϯ11 m 2 , Pϭ0.007) but returned to baseline by 30 minutes (66Ϯ5 m 2 ). Conclusions-IntracellularCl accumulation induced by rapid pacing is a novel finding and may play a role in AF pathogenesis by causing resting membrane depolarization and ERP reduction. There was no evidence of cellular or mitochondrial Ca overload despite the development of electrical remodeling and transient increase in cytoplasmic Ca.

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Section: Subcellular Changes In Total Camentioning

confidence: 87%

mentioning

confidence: 99%

Intracellular Chloride Accumulation and Subcellular Elemental Distribution During Atrial Fibrillation

Akar

Everett

et al. 2003

Circulation

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“…Tieleman et al demonstrated in a goat model that the shortening of the AERP caused by rapid atrial pacing was significantly attenuated by verapamil, but only during short-term pacing. 7 Several studies have similarly reported that verapamil might suppress the shortening of AERP in the relatively short term (<24 h). 1,11,12,15 Lee et al demonstrated that verapamil did not suppress the shortening of AERP in a relatively long-term model (1 and 6 weeks), although they did not evaluate the progression of the atrial electrical remodeling.…”

Section: Effect Of Antiarrhythmic Drugs On Atrial Electrical Remodelingmentioning

confidence: 98%

“…Atrial electrical remodeling has been evaluated in several animal models of rapid atrial pacing, 1,2,4,7,9,10,[20][21][22][23] which have documented the shortening of the AERP and prolongation in atrial conduction time, but few have reported the inhomogeneity in the process of atrial electrical remodeling. We previously reported that the shortening of the AERP was larger at the RAA and LA sites than at the other atrial sites when the rapid pacing was performed from the RAA site for 2 weeks.…”

Section: Inhomogeneity Of Electrical Remodelingmentioning

confidence: 99%

“…[1][2][3][4][5][6][7][8][9][10] Although suppressive effect of a calcium channel blocker on electrical remodeling was expected, its effect was relatively short term 1,7,11,12 and the outcome of long term electrical remodeling varied depending on the anatomical site in the atria. 13 It has also been reported that sodium channel blockers might suppress the shortening of the AERP, [14][15][16] possibly through the action of the Na -Ca exchanger, but its effect on long-term electrical remodeling is unknown.…”

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Effect of Pilsicainide on Atrial Electrophysiologic Properties in the Canine Rapid Atrial Stimulation Model. A Possible Suppressive Effect on Atrial Electrical Remodeling.

Kojima

Niwano

Moriguchi

et al. 2003

Circ J

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The heterogeneous process of atrial electrical remodeling (AER) in the canine rapid atrial stimulation model has been previously reported although it has been reported that a sodium channel blocker might suppress the shortening of the atrial effective refractory period (AERP), its effect on long-term electrical remodeling is unknown. In the present study, the effect of pilsicainide on AER was evaluated. The right atrial appendage (RAA) was paced at 400 beats/min for 2 weeks. In the RAA, Bachmann's bundle (BB), the right atrium near the inferior vena cava (IVC) and in the left atrium (LA), AERP, AERP dispersion (AERPd) and the inducibility of atrial fibrillation (AF) were evaluated at several time points of the pacing phase and the recovery phase (1 week). The same protocol was performed during the administration of pilsicainide (4.5 mg/kg per day) and the parameters were compared with the controls. In the control dogs, the AERP was significantly shortened by rapid pacing at all atrial sites studied and the AERP shortening ( AERP) was larger at the RAA and LA sites (p<0.03). However, pilsicainide decreased these AERPs at all 4 atrial sites. AERPd was increased during the pacing phase whereas it was decreased during the recovery phase in the control dogs. In contrast, this pacing-induced AERPd was attenuated by the administration of pilsicainide. The AF inducibility was highest at the LA site in both groups, and the inducibility was lower in the pilsicainide group than the control group at all atrial sites. During the rapid pacing phase, the ventricular heart rate was significantly lower in the pilsicainide group than the control because of intraatrial conduction block. In a canine rapid right atrial stimulation model, pilsicainide suppressed the shortening of the AERP at all atrial sites, possibly through the improvement of the hemodynamics as well as the action of the Na -Ca exchanger. (Circ J 2003; 67: 340 -346)

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Atrial Plasticity

Sanders¹,

Morton²,

and³

et al. 2005

Innovative Management of Atrial Fibrillation

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Verapamil Reduces Tachycardia-Induced Electrical Remodeling of the Atria

Abstract: Electrical remodeling of the atrium during rapid atrial pacing was significantly attenuated by verapamil. This suggests that electrical remodeling of the atrium is triggered by the high calcium influx during rapid atrial pacing rates.

Cited by 307 publications

References 68 publications

Intracellular Chloride Accumulation and Subcellular Elemental Distribution During Atrial Fibrillation

Intracellular Chloride Accumulation and Subcellular Elemental Distribution During Atrial Fibrillation

Effect of Pilsicainide on Atrial Electrophysiologic Properties in the Canine Rapid Atrial Stimulation Model. A Possible Suppressive Effect on Atrial Electrical Remodeling.

Atrial Plasticity

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