Effect of 60 Minutes of Rapid Atrial Pacing on Atrial Action Potential Duration in the In-Situ Canine Heart

Right atrial monophasic action potentials were recorded before and after 60 minutes of rapid atrial pacing (pacing cycle length (CL); 127 ± 10 ms) in 12 closed-chest dogs. The right atrial (RA) monophasic action potential (MAP) duration at 90% repolarization (RAMAPD) was measured at CLs of 400 ms and 250 ms. CL-dependent changes in RAMAPD (CL 400 ms – 250 ms) before and after rapid atrial pacing were 24 ± 1 ms and 16 ± 5 ms, respectively (p < 0.02). RAMAP was recorded at each atrial pacing CL starting at 240 ms decreasing by 10-ms increments. RAMAPD alternans was observed in 10 of 12 dogs at a CL of 163 ± 17 ms before and in 10 of 12 dogs at s CL of 198 ± 29 ms (p < 0.01) after rapid atrial pacing. Sustained atrial fibrillation (AF) (>5 minutes) was induced in 1 of 12 dogs at a pacing CL of 130 ms before rapid atrial pacing and in 4 of 12 dogs at a pacing CL of 135 ± 17 ms after rapid atrial pacing. Onset of AF was always preceded by the RAMAPD alternans. Sixty minutes of rapid atrial pacing leads to diminution of rate adaptation of atrial action potential duration (APD) and appearance of APD alternans of greater magnitude at longer CL, both of which may contribute to the initiation and perpetuation of AF during its early phase.     

Dispersion and delay of electrical restitution in the globally ischaemic heart

Altemans of action potential duration (APD) has been shown tobe a precursor of ventricular fibrillation in ischaemic myocardium.We postulated that magnitude of alternans of APD during ischaemiadepends not only on the severity of ischaemia but also on disturbedbeat-to-beat restitution of APD. Monophasic action potentials were recorded simultaneously fromright (RV) and left ventricular (LV) epicardial sites of isolatedrabbit hearts. The inter-beat time courses of APD recovery weredetermined both during normal flow and ischaemia by interposingsingle cycle length changes ranging from 200 to 800 ms (=electricalrestitution) simultaneously at the three recording sites. During normal perfusion, electrical restitution curves showeda steep initial recovery of APD, attaining steady-state valuesat extrastimulus cycle lengths of only 298±12 ms, witha high degree of uniformity between the three recording sites(inter-site variability <2%). Ischaemia produced a markedslowing of electrical restitution which, on average, reacheda plateau at extrastimulus cycle lengths of 415±45 ms,650 ± 72 ms and >800 ms at 2 min, 5 min and 9 minof ischaemia, respectively (each P<0·001 vs control).In addition, iscliaemia resulted in a large inter-site variability,with RV and LV restitution curves deviating from each otherby as much as 28·5% (P<0·0001 vs baseline). We conclude that global ischaemia not only leads to a delayedbut also non-uniform electrical restitution. The delay in electricalrestitution may be causally related to the development of alternansof APD, whereas the dispersion of electrical restitution mayproduce electrical instability and set the stage for ischaemia-relatedventricular arrhythmias.     

Sotalol reverses remodeled action potential in patients with chronic atrial fibrillation but does not prevent arrhythmia recurrence

INTRODUCTION: Recurrence of atrial fibrillation (AF) may be related to AF-induced electrical remodeling characterized by shortening of the atrial action potential duration (APD) and loss of its rate adaptation. We investigated the effects of pretreatment with oral d,l-sotalol on rate-dependent changes in atrial monophasic action potential (MAP) duration after cardioversion of chronic AF with reference to the efficacy in preventing the arrhythmia recurrence. METHODS AND RESULTS: MAPs were recorded from the right atrium at six pacing cycle lengths (CLs) from 300 to 750 ms in 19 chronic AF patients after electrical cardioversion; 9 had been pretreated with oral d,l-sotalol (196 +/- 42 mg/day) for 7 days and 10 were untreated. MAP duration at 90% repolarization (MAPD90) in 11 control patients increased progressively with increases in CLs from 209 +/- 19 ms at CL = 300 ms to 264 +/- 28 ms at CL = 750 ms. In AF patients without sotalol, the CL-MAPD relation was shifted downward and flattened at longer CLs; MAPD90 values were 206 +/- 11 ms and 227 +/- 16 ms at CLs of 300 and 750 ms, respectively. MAPD90 values at CLs > or =500 ms in AF were significantly shorter than controls. In AF patients with sotalol, the normal CL-MAPD relation was preserved; MAPD90 increased from 226 +/- 19 ms to 282 +/- 46 ms in the CL range. AF recurred within 2 weeks after cardioversion in 14 of 24 patients pretreated with d,l-sotalol (216 +/- 51 mg/day) despite of continuation of sotalol treatment. CONCLUSION: Sotalol reverses AF-induced decrease in MAPD adaptation to rate in the atria of chronic AF patients, but this effect does not lead to prevention of AF recurrence.     

Role of repolarization restitution in the development of coarse and fine atrial fibrillation in the isolated canine right atria

INTRODUCTION: Although the role of action potential duration restitution (APD-R) in the initiation and maintenance of ventricular fibrillation (VF) has been the subject of numerous investigations, its role in the generation of atrial fibrillation (AF) is less well studied. The cellular and ionic basis for coarse versus fine AF is not well delineated. METHODS AND RESULTS: We measured APD-R during acetylcholine-mediated AF as well as during pacing (standard and dynamic protocols) in crista teriminalis, pectinate muscle, superior vena cava, and appendage of isolated canine arterially perfused right atria (n = 15). Transmembrane action potential (TAP), pseudo-ECG, and isometric tension development were simultaneously recorded. Acetylcholine flattened APD-R measured by both standard and dynamic protocols, but promoted induction of AF. AF was initially coarse, converting to fine within 3-15 minutes of AF. Coarse, but not fine AF was associated with dramatic fluctuations in tension development, reflecting wide variations in intracellular calcium activity ([Ca(2+)](i)). During coarse AF, APD-R data displayed a cloud-like distribution pattern, with a wide range of maximum APD-R slope (from 1.21 to 0.35). A maximum APD-R slope >1 was observed only in crista terminalis (3/10). The APD-R relationship was relatively linear and flat during fine AF. Reduction of [Ca(2+)](i) was associated with fine AF whereas augmentation of [Ca(2+)](i) with coarse AF. CONCLUSIONS: Our data indicate that while APD-R may have a limited role in the maintenance of coarse AF, it is unlikely to contribute to the maintenance of fine AF and that [Ca(2+)](i) dynamics determine the degree to which AF is coarse or fine.     

The Electrical Restitution Curve Revisited:

The electrical restitution curve (ERC) traditionally describes the recovery of action potential duration (APD) as a function of the interbeat interval or, more correctly, the diastolic interval (DI). Often overlooked in modeling studies, the normal ventricular ERC is triphasic, starting with a steep initial recovery at the shortest DIs, a transient decline, and a final asymptotic rise to a plateau phase reached at long DIs. Recent studies have proposed that it would be advantageous to lower the slope of the ERC by drug intervention, as this might reduce the potential for electrical alternans and ventricular fibrillation. This review discusses the pros and cons of a flat versus steep slope of the ERC and draws attention to mechanisms that justify the (physiologically) steep slope, rather than a flat slope, as a better design against arrhythmias. Five potential mechanisms are discussed, which allows for a different interpretation of the effect of the slope on arrhythmogenicity. The most important appears to be the physiologic rate adaptive shortening of APD that, by reciprocal lengthening of the DI, allows the subsequent APD to move more quickly from the steep initial ERC phase onto the flat phase. A less steep initial ERC phase would protract the transition toward more fully recovered APD and, in fact, may perpetuate electrical alternans. The triphasic ERC time course in normal myocardium cannot be explained by or fitted to single exponentials or single ion channel recovery kinetics. A simple tri-ionic model is suggested that may help explain the shape of the ERC at various repolarization levels and place APD recovery into perspective with intracellular calcium recycling and recovery of contractile force. (J Cardiovasc Electrophysiol, Vol. 14, pp. S140-S147, October 2003, Suppl.)     

Effects of chronic amiodarone on the electrical restitution in the human ventricle with reference to its antiarrhythmic efficacy

Modulation of Electrical Restitution with Amiodarone. Introduction: Dynamic instability of ventricular refractoriness represented by electrical restitution operates synergistically with tissue heterogeneity to increase the propensity for functional reentry leading to ventricular tachycardia/fibrillation (VT/VF). Little is known about the effect of chronic amiodarone on the electrical restitution in the human ventricle. Methods and Results: Restitution kinetics of monophasic action potential duration (MAPD₉₀) in the right ventricular outflow tract (RVOT) and apex (RVA), and of inverse of conduction time from RVOT to RVA (CT^?1), were estimated by an S1–S2 protocol in 22 patients treated with amiodarone (180 ± 33 mg/day for 7 ± 9 months) and in 30 without treatment. In the untreated patients, the restitution kinetics of CT^?1 was steeper in the group with structural heart disease (SHD) (UNT_SHD+, n = 18) than without SHD (UNT_SHD‐, n = 12), whereas MAPD₉₀ restitution parameters were comparable. In the amiodarone‐treated patients (all with SHD), the shortest diastolic interval to produce a ventricular response (DI_min) was increased, the maximum slope of MAPD₉₀ was flattened, and the magnitude of CT^?1 restitution was reduced as compared with UNT_SHD+. Sustained VT/VF was induced in 7 of 18 UNT_SHD+ (38.9%) and in 4 of 22 amiodarone‐treated patients (18.2%, P = 0.07). Concomitant presence of increased CT^?1 restitution and dispersion of MAPD₉₀ restitution was required for the VT/VF induction. The suppression of VT/VF in the amiodarone‐treated patients was associated with a smaller magnitude of CT^?1 restitution in the presence of limited dispersion of MAPD₉₀ restitution. Conclusion: Chronic amiodarone flattens restitution kinetics of MAPD₉₀ and CT^?1 in the human ventricle, which could be antiarrhythmic in patients with limited tissue heterogeneity . (J Cardiovasc Electrophysiol, Vol. 22, pp. 669‐676, June 2011)     

Effect of action potential duration and conduction velocity restitution and their spatial dispersion on alternans and the stability of arrhythmias

INTRODUCTION: The slope of the action potential duration (APD) restitution curve has been used to explain wavebreaks during arrhythmia initiation and maintenance. This hypothesis remains incomplete to fully describe the experimental data. Other factors contributing to wavebreaks must be studied to further understand arrhythmia dynamics. METHODS AND RESULTS: Control APDs were measured from isolated rabbit hearts using a monophasic action potential probe. APD and conduction velocity (CV) restitution were quantified over the heart surface for two drugs, diacetyl monoxime (DAM) and cytochalasin D (CytoD), using a dual camera video imaging system. For all pacing intervals: (1) control APDs were shorter than for CytoD but longer than for DAM; and (2) CV was greater for CytoD compared with DAM. APD dispersion increased as pacing interval decreased for both drugs. For DAM, increased dispersion was due to a difference in APD restitution between the right and left ventricle. For CytoD, increased dispersion was due to discordant alternans, with no significant spatial variation in restitution. Fibrillation was sustained only in the control hearts; with DAM, stable reentry was sustained with shorter APD and cycle length compared with CytoD for which only nonsustained unstable reentry occurred. CONCLUSION: Alternans and arrhythmia dynamics are affected by the spatial dispersion of APD restitution as well as CV restitution, not simply the slope of APD restitution. Therefore, a direct link of the APD restitution slope to alternans and arrhythmia dynamics in rabbit heart does not exist. Designing antiarrhythmic drugs to alter only the restitution slope may not be appropriate.     

Atrial Electrical Remodeling by Rapid Pacing in the Isolated Rabbit Heart: Effects of Ca++ and K+ Channel Blockade

Introduction: Electrical remodeling describes atrial electrophysiologic changes that occur following atrial fibrillation. The mechanism(s) responsible for this phenomenon is not well understood. The purpose of this study was to examine the effects of rapid atrial pacing on atrial action potential duration, conduction time and refractoriness in the isolated rabbit heart. The effects of Ca⁺⁺ and K⁺ blockade in this model were also studied.Methods and Results: Monophasic action potential recordings were made from 12 epicardial atrial sites in 50 isolated perfused rabbit heart preparations. These recordings were analyzed for activation time (AT), 90% action potential duration (APD) and conduction times (CT) measured at a 250 msec cycle length. Atrial effective refractory periods (ERP) were determined at a 200 msec cycle length. All measurements were made at baseline and repeated after 2 hours of biatrial pacing at 250 msec (control group, n = 10) or 2 hours of rapid biatrial pacing (80 msec) in 4 groups: rapid pacing alone (rapid pacing group); rapid pacing in the presence of 0.1mM verapamil (verapamil group) for L-type Ca⁺⁺ channel blockade; rapid pacing with 1 mM 4-aminopyridine (4-AP group) for K⁺ channel blockade; and rapid pacing with 50 M nickel chloride (Ni⁺⁺ group) for T-type Ca⁺⁺ channel blockade (n = 10 each group). All baseline and post pacing measurements were taken in the presence of Ca⁺⁺ or K⁺ blockers for the respective groups.After rapid atrial pacing alone the average APD shortened by 8.2±10.4 msec compared to 3.6±12.5 msec shortening for control group (p = 0.002). The shortening of APD was uniform at all recording sites. For the rapid pacing group, CT was unchanged for right to left atrial conduction but shortened significantly for left to right atrial conduction (26.8±1.9 msec at baseline to 22.3±4.1 msec post pacing, p = 0.005). Conduction times were unchanged in the control group. The dispersion of repolarization was unchanged by rapid pacing alone. The decrease in APD from baseline to post rapid pacing was similar to the control group for those hearts treated with verapamil and 4-AP (1.5±12.3 and 4.7±10.4 msec, respectively, both p 0.18 vs control group). The decrease in APD was significantly greater for the Ni⁺⁺ group (11.8± 14.3 msec) than for either the control group or rapid pacing group (both p 0.023). The dispersion of repolarization was increased only in the 4-AP group post rapid pacing (41.7±6.2 msec at baseline to 53.5±9.6 msec post pacing, p = 0.01). ERPs were unchanged in any of the 5 groups except for a decrease in left atrial ERP in the Ni⁺⁺ group after rapid pacing (98±14 msec at baseline to 88±8 msec post rapid pacing, p = 0.005).Conclusions: In the isolated rabbit heart model: 1) atrial APD is shortened after rapid pacing; 2) the shortening of APD is attenuated by verapamil and 4-AP but exaggerated by Ni⁺⁺ 3) atrial conduction times are shortened in a direction specific manner after rapid pacing; and 4) shortening of ERP in this model is measured only in the presence of Ni⁺⁺. These findings suggest that both L-type Ca⁺⁺ and 4-AP sensitive channels may participate in atrial electrical remodeling.     

应用单相动作电位研究房颤模型心房电重构的发生机制

目的应用单相动作电位(MAP)技术检测心房颤动模型电生理参数改变的特点,探讨房颤电重构发生的分子机制。方法健康杂种犬17只,随机分为房颤组(n=11)和对照组(n=6)。房颤组安装固定频率起搏器,以350~430次/min的频率快速心房起搏,对照组行假手术。于起搏前和8周后测量右房有效不应期(AERP)和单相动作电位,测量单相动作电位振幅(MAPA)、单相动作电位时限(MAPD)、复极90%时动作电位时限(MAPD90)、复极50%时动作电位时限(MAPD50)、复极90%动作电位时限与复极50%动作电位时限之差(MAPD90-50)。原子发射光电直读光谱法测定心房肌组织Ca2+含量。RT-PCR法检测心房肌浆网Ca2+-ATP酶和L型钙通道mRNA转录水平。结果对照组MAP时相明显。房颤组MAP形态发生改变。与对照组相比,房颤组MAPA有下降趋势;MAPD,MAPD90,MAPD50,MAPD90-50分别缩短13.79%,19.65%,13.59%和31.25%。MAPD,MAPD90,MAPD90-50与右房心肌Ca2+呈显著负相关;MAPD90-50与L型钙通道显著正相关。上述指标与肌浆网钙ATP酶均无相关性。结论 MAP是研究房颤电重构的可靠手段,心房肌细胞膜L型钙通道和肌浆网Ca2+-ATP酶mRNA表达改变可能是电重构的分子机制之一     

Mechanism of repolarization alternans has restitution of action potential duration dependent and independent components

INTRODUCTION: Investigation of relationship between diastolic-interval (DI)-dependent restitution of action potential duration (APD) and alternans of APD has produced conflicting results. We used a novel pacing protocol to determine the role of restitution in alternans by minimizing changes in DI preceding each activation. METHODS: Transmembrane potentials were recorded from right ventricular endocardial tissue isolated from five dogs. We used three pacing sequences: (i) The tissue was paced at a constant DI for 100 beats. (ii) The DIs were changed randomly between two sequences of constant DI. (iii) Each constant DI trial was followed by constant cycle length trial where pacing cycle length was equal to average cycle length during previous constant DI trial. RESULTS: Alternans of APD occurred even when DIs preceding each activation were invariant. Slopes of restitution during constant DI pacing were both negative and positive and were much larger than unity. Alternans amplitude during constant cycle length pacing was larger than during constant DI, 32.2 +/- 12.3 versus 7.5 +/- 2.8 msec, P < 0.01. Random perturbation of DI decreased alternans amplitude during constant DI pacing from 14.7 +/- 4.8 to 10.5 +/- 3.4 msec, P < 0.01. CONCLUSION: Our results indicate that mechanism of repolarization alternans has restitution-dependent and restitution-independent components. However, our results also provide direct evidence that shows that DI-dependent restitution of APD is not a necessary mechanism for the alternans to exist. Ability to pace with explicit control of DI provides a novel approach to dissect mechanisms of alternans into restitution-dependent and restitution-independent effects.     

Electroanatomic mapping of right atrial activation in patients with and without paroxysmal atrial fibrillation

Inter-atrial conduction delay in patients with atrial fibrillation (AF) has been reported. However, the area of this conduction delay has not been well identified. The activation time and conduction velocity over the right atrial endocardium were evaluated during sinus rhythm using the CARTO mapping technique in 6 patients with paroxysmal AF (AF group) and 11 patients without history of AF (control group). No significant differences were observed between the 2 groups in the mean activation times and conduction velocities from the earliest activation site to the superior septum, His bundle area and coronary sinus ostium, or in the total activation times of the right atrium. There was no significant difference between the two groups in the local conduction velocity between 2 adjacent sites in the free wall, septum and bottom of the right atrium. This study suggests the previously reported conduction delay in the posteroseptal region in patients with paroxysmal AF might locate within the posterior inter-atrial septum.     

Effects of successful cardioversion of persistent atrial fibrillation on right ventricular refractoriness and repolarization.

AIM: Changes in ventricular refractoriness and repolarization after successful electrical cardioversion to sinus rhythm in persistent atrial fibrillation (AF) patients were studied. METHODS AND RESULTS: In 33 AF patients with controlled ventricular response, right ventricular ERP (VERP) at three basic cycle lengths (600, 500, 400 ms), as well as monophasic action potential duration (MAPd(90)) at a drive cycle length of 500 ms, were measured just before, 20 min and 24 h after cardioversion. VERP at 600 ms changed from 241+/-19 ms to 249+/-21 ms to 253+/-24 ms (P<0.001), VERP at 500 ms changed from 234+/-19 ms to 242+/-22 ms to 246+/-23 ms (P<0.001) and VERP at 400 ms changed from 224+/-20 ms to 232+/-23 ms to 236+/-24 ms (P<0.001). MAPd(90) changed from 247+/-16 ms preconversion to 252+/-17 ms 20 min postconversion to 253+/-19 ms after 24 h (P<0.05). Change in refractoriness at 500 ms was well correlated with change of mean RR interval before and 20 min after conversion (R=0.616, P<0.001). There was no correlation between RR variability and VERP before cardioversion. CONCLUSION: Restoration of sinus rhythm in persistent AF patients is followed by significant effects on ventricular refractoriness and repolarization related to cycle length change. No AF related ventricular electrophysiological alterations were found.     

The restitution portrait: a new method for investigating rate-dependent restitution

INTRODUCTION: Electrical restitution, relating action potential duration (APD) to diastolic interval (DI), was believed to determine the stability of heart rhythm. However, recent studies demonstrate that stability also depends on long-term APD changes caused by memory. This study presents a new method for investigation of rate- and memory-dependent aspects of restitution and for assessment of mapping models of APD. METHODS AND RESULTS: Bullfrog ventricular myocardium was paced with a "perturbed downsweep protocol." Starting from a basic cycle length (BCL) of 1,000 ms, the tissue was paced until steady state was achieved, followed by single beats of longer and shorter cycle lengths. BCL was decreased by 50 to 100 ms and the process repeated. All APDs were plotted as a function of the preceding DI, which allowed simultaneous observation of dynamic, S1-S2, and two constant-BCL restitution curves in a "restitution portrait." Responses were classified as 1:1 (stimulus:response), transient 2:2, or persistent 2:2 (alternans) and were related to the slopes of the restitution curves. None of these slopes approached unity for the persistent 2:2 response, demonstrating that the traditional restitution condition does not predict alternans. The restitution portrait was used to evaluate three mapping models of APD. The models with no memory and with one-beat memory did not produce restitution portraits similar to the experimental one. A model with two-beat memory produced a qualitatively similar portrait. CONCLUSION: The restitution portrait allows a more comprehensive assessment of cardiac dynamics than methods used to date. Further study of models with memory may result in a clinical criterion for electrical instability.     

肺静脉起搏时犬房间隔激动时序特征的研究

目的 :研究肺静脉起搏时犬房间隔激动的时序特征 ,进一步了解起源于肺静脉的异位搏动引发心房颤动的电生理机制。方法 :选用 5只犬 ,放置电生理标测导管于 Bachm ann氏束 （BB）右房间隔侧、卵园窝 （FO ）及冠状窦（CS）。同步记录 BB、FO及 CS近端 （CSp）处心内电图。作左上肺静脉 （L SPV）、右下肺静脉 （L IPV）、右上肺静脉（RSPV）及右下肺静脉 （RIPV）开口处起搏 ,观察房间隔激动的时序特征。结果 :L SPV起搏时 BB及 FO为最早激动点 ,刺激波至 CSp的传导时间与 FO及 BB处相比 ,虽未达到统计学差异 ,但呈延长的倾向 （4 0± 12 ms vs 2 9± 7ms及 2 9± 15 m s）。L IPV起搏时 CSp,FO及 BB处几乎同时激动 ,刺激波至该三处的激动时间无明显差别 （2 9± 12 ,2 8± 8及 33± 10 ms）。 RSPV起搏时 BB及 FO为最早激动点 ,刺激波至 FO及 BB的时间短于至 CSp的时间 （2 6± 6ms及 2 4± 11ms vs 40± 10 m s,均 P<0 .0 5 ）。 RIPV起搏时 BB,FO及 CSp均可为最早激动点 ,刺激波至该三处的激动时间无明显差异 （2 8± 15 ,2 6± 15及 2 9± 14ms） ,L IPV起搏较窦性心律时房间隔激动时间缩短 （9± 10 ms vs2 9± 9ms,P<0 .0 5 ） ,下肺静脉与上肺静脉起搏相比 ,房间隔激动时间虽未达统计学差异 ,但呈缩短的倾向 (11± 9ms及 2 1     

不同部位起搏对阵发性心房颤动患者心房激动时间的影响

目的　比较右心耳 (RAA)、冠状窦远端 (DCS)、右心房双部位 (右心耳加冠状窦口 ,DSA)和双房 (右心耳加冠状窦远端 ,Bi A)起搏对阵发性心房颤动 (PAf)患者心房激动时间的影响。方法 2 2例接受心脏电生理评价试验的PAf患者在窦性心律下行心房不同部位起搏 ,同步记录 12导心电图 ,测量最大 P波时限。结果　与窦性 P波时限相比 ,RAA起搏明显延长 P波时限 (P<0 .0 1) ,DCS、DSA及 Bi A起搏则明显缩短 P波时限 (P<0 .0 1,P<0 .0 1,P<0 .0 1)。结论　 DCS、DSA及 Bi A起搏明显缩短心房激动时间 ,减少心房电活动的离散度 ,有利于 PAf的防治。     

Model for the onset of fibrillation following coronary artery occlusion

INTRODUCTION: It is the hypothesis of this article that the onset of fibrillation following a coronary artery occlusion is a direct consequence of the spatial inhomogeneity of chemical processes that occur following the occlusion. In particular, the localized increase of extracellular potassium and decrease of ATP availability lead to an increase of resting potential in the affected cells. This difference in potential between affected cells and normal cells drives a current, the "current of injury," which may drive oscillations in the border zone, a "border zone arrhythmia." The border zone arrhythmia may drive a "breakup instability" (related to the action potential duration restitution instability) in the surrounding tissue, leading to self-sustained fibrillation. METHODS AND RESULTS: In this article, we present a mathematical model demonstrating this transition from normal to fibrillatory dynamics, describing the general conditions under which this transition occurs and showing in a simple ionic model the way in which spatial inhomogeneity alone can initiate self-sustained reentrant activity. CONCLUSION: Using general arguments and numerical simulations with generic models of excitable media, we have demonstrated that a spatial region with an elevated resting potential surrounded by a spatial region wherein action potentials are foreshortened can drive a breakup instability, leading to the rapid initiation of a fibrillatory state.     

Clinical evaluation of a policy of early repeated internal cardioversion for recurrence of atrial fibrillation

INTRODUCTION: The clinical value of cardioversion (CV) of persistent atrial fibrillation (AF) is limited by the high rate of early AF recurrence, which may be related to the persistence of atrial electrical remodeling. We examined the hypothesis that the likelihood of maintaining sinus rhythm after CV of persistent AF is significantly enhanced by a policy of early repeated CV. METHODS AND RESULTS: Fifty-nine patients with persistent AF underwent internal CV (CV 1). Those patients cardioverted were monitored with daily transtelephonic ECG. In the event of AF recurrence, these patients were admitted rapidly for repeat CV (CV 2) and, if further recurrence occurred, a third CV (CV 3) was performed. Daily ECG monitoring was continued until 1 month of sinus rhythm was maintained or a total of three CVs were performed. Of the 59 patients undergoing CV 1, 43 were discharged in sinus rhythm and 29 subsequently had AF recurrence during monitoring. Twenty-three of these underwent CV 2 and 11 of these underwent CV 3. Of those having repeated CVs, only 4 patients maintained sinus rhythm for 1 month (3 after CV 2 and 1 after CV 3). The remaining patients had repeated AF recurrence during the monitoring period. Mean time from AF recurrence to CV 2 was 20+/-13 hours and from AF recurrence to CV 3 was 13+/-7.2 hours. Atrial effective refractory periods increased from 189+/-16 msec at CV 1 to 215+/-18 msec at CV 3 (P < 0.05), indicating reversal of atrial electrical remodeling during this period. CONCLUSION: A policy of early repeated CVs for AF recurrence has very limited clinical value despite evidence of reversal of atrial electrical remodeling. The time between AF recurrence and repeat CV may need to be reduced further if such a policy is to succeed.     

Morphologic remodeling of pulmonary veins and left atrium after catheter ablation of atrial fibrillation: insight from long-term follow-up of three-dimensional magnetic resonance imaging

INTRODUCTION: Understanding the structural remodeling and reverse remodeling of the left atrium (LA) and pulmonary vein (PV) after radiofrequency ablation of atrial fibrillation (AF) may provide important insights into the mechanism and management of AF. This study used magnetic resonance angiographic (MRA) images to investigate changes in PV and LA morphologies before and more than 1 year after ablation. METHOD AND RESULTS: Forty-five patients (36 men and 9 women, mean age 60 +/- 13 years) who underwent MRA before and more than 12 months (mean 21 +/- 11) after ablation of paroxysmal AF were included in the study. The patients were divided into two groups: group I included 35 patients without AF recurrence, and group II included 10 patients with late (>1 month postablation) recurrence of AF. The sizes of the LA and nonablated PV were compared before and after ablation. In group I, significant reduction of ostial area of both superior PVs was noted (left superior PV: from 2.85 +/- 0.67 to 2.59 +/- 0.73 cm2; right superior PV: from 2.89 +/- 0.85 to 2.60 +/- 0.73 cm2, both P <0.001). Geometric alteration toward a round shape was noted in the ostia of superior PVs during follow-up (eccentricity of right superior PV and left superior PV decreased from 0.31 +/- 0.10 to 0.22 +/- 0.13 and from 0.27 +/- 0.11 to 0.19 +/- 0.13, respectively, both P <0.01). However, LA volume showed only borderline reduction (from 61.52 +/- 19.06 to 56.64 +/- 17.13 mL, P=0.05). In group II, significant dilation of the LA (from 61.14 +/- 17.54 to 78.73 +/- 25.27 mL, P=0.004) and right superior PV (from 3.41 +/- 1.12 to 4.08 +/- 1.31 cm2, P=0.016) was noted during follow-up. Ostial area and eccentricity of the left superior, left inferior, and right inferior PVs and LA were similar before and after ablation. CONCLUSION: Structural remodeling of the superior PVs and LA can be reversible after successful ablation without AF recurrence; however, late recurrence of AF is associated with progressive LA dilation.     

Pharmacologic cardioversion of chronic atrial fibrillation in the goat by class IA, IC, and III drugs: a comparison between hydroquinidine, cibenzoline, flecainide, and d-sotalol

INTRODUCTION: Recently, we reported that repetitive induction of atrial fibrillation (AF) in the goat causes electrical remodeling of the atria leading to the development of sustained AF. The aim of the present study was to compare Class IA, IC, and III drugs in their ability to cardiovert chronic AF in remodeled atria. METHODS AND RESULTS: In 16 goats with sustained AF, hydroquinidine (HQ), cibenzoline (Ci), flecainide (FI), and d-sotalol (dS) were infused. HQ, Ci, Fl, and dS restored sinus rhythm (SR) in 83%, 91%, 67%, and 92% of the cases, while adverse drug effects occurred in 17%, 36%, 56%, and 8%. Prior to restoration of SR, AF cycle length prolonged by 68%, 103%, 53%, and 20%, respectively. The QRS width increased by 14%, 64%, and 58% (HQ, Ci, and Fl), and remained unchanged by administration of dS. RR intervals were slightly prolonged by HQ, Ci, and Fl, and markedly prolonged by dS (48%). The QT interval was moderately prolonged by HQ, Ci, and Fl, and considerably by dS (34%). QTc was only slightly prolonged by each of the drugs. Directly after cardioversion of AF, the atrial refractory period was 87+/-29 (HQ), 119+/-32 (Ci), 66+/-10 (Fl), and 73+/-18 msec (dS) (control: 146+/-18 msec). Atrial conduction velocity was 85+/-6, 71+/-11, 86+/-12, and 110+/-11 cm/sec compared with a control value of 116+/-10 cm/sec. Because directly after cardioversion the atrial wavelength was still very short (5.7 to 8.4 cm), the vulnerability for AF was still very high, and a single premature beat reinduced AF in 71% (Ci) to 100% (HQ, Fl, and dS) of the cases. CONCLUSION: In a goat model of sustained AF, Class IA, IC, and III drugs restored sinus rhythm in 67% to 92% of the cases. However, after cardioversion, the atrial wavelength was still abnormally short, and AF was readily inducible in 71% to 100% of the cases.