心房有效不应期离散度与心房颤动

心房颤动是临床最常见的心律失常之一,有较高的致残率及致死率,关于心房颤动的机制有较多的学说,目前研究已经证实心房电重构能够促进心房颤动的发生与维持,心房电重构包括心房有效不应期的缩短,心房有效不应期离散度的增加及局部电传导的减慢,现就心房有效不应期离散度与心房颤动的关系及其影响机制做一综述。     

Reversal of electrical remodeling after cardioversion of persistent atrial fibrillation

INTRODUCTION: In animals, atrial fibrillation results in reversible atrial electrical remodeling manifested as shortening of the atrial effective refractory period, slowing of intra-atrial conduction, and prolongation of sinus node recovery time. There is limited information on changes in these parameters after cardioversion in patients with persistent atrial fibrillation. METHODS AND RESULTS: Thirty-eight patients who had been in atrial fibrillation for 1 to 12 months underwent electrophysiologic testing 10 minutes and 1 hour after cardioversion. At 1 week, 19 patients still in sinus rhythm returned for repeat testing. Reverse remodeling of the effective refractory period was not uniform across the three atrial sites tested. At the lateral right atrium, there was a highly significant increase in the effective refractory period between 10 minutes and 1 hour after cardioversion (drive cycle length 400 ms: 204 +/- 17 ms vs 211 +/- 20 ms, drive cycle length 550 ms: 213 +/- 18 ms vs 219 +/- 23 ms, P < 0.001). The effective refractory period at the coronary sinus and distal coronary sinus did not change in the first hour but had increased by 1 week. The corrected sinus node recovery time did not change in the first hour but was shorter at 1 week (606 +/- 311 ms vs 408 +/- 160 ms, P = 0.009). P wave duration also was shorter at 1 week (135 +/- 18 ms vs 129 +/- 13 ms, P = 0.04) consistent with increasing atrial conduction velocity. CONCLUSION: The atrial effective refractory period increases, sinus node function improves, and atrial conduction velocity goes up in the first week after cardioversion of long-standing atrial fibrillation in humans. Reverse electrical remodeling of the effective refractory period occurs at different rates in different regions of the atrium.     

Reversal of atrial electrical remodeling following cardioversion of long-standing atrial fibrillation in man.

BACKGROUND: In animal studies, atrial fibrillation has been shown to shorten the atrial refractory period and impair its rate adaptation. However, little is known about the effects of chronic atrial fibrillation on atrial electrophysiology and its recovery course in humans. METHODS AND RESULTS: Nineteen patients, mean age 64 +/- 14 years, with chronic atrial fibrillation of more than six months duration were included in this study. All of them were successfully converted to sinus rhythm with an external defibrillator. Atrial effective refractory periods at right atrial appendage and distal coronary sinus were determined with five pacing cycle lengths (300, 400, 500, 600 and 700 ms) at 30 min after cardioversion and once a day for four days. The atrial conduction properties, including P wave duration of surface ECG, and right and left atrial conduction times, were also measured at the same time interval. Twenty age-matched patients without a history of atrial tachyarrhythmia were evaluated as controls. In comparison with controls, chronic atrial fibrillation significantly shortened the atrial effective refractory period, impaired its rate adaptation response, especially at distal coronary sinus, and depressed the conduction properties of atria. The atrial conduction properties did not change during the four-day follow-up period; however, the atrial effective refractory period was gradually prolonged and its rate adaptation response improved after restoration of sinus rhythm. CONCLUSIONS: In humans, chronic atrial fibrillation significantly shortened the atrial effective refractory period, and impaired its rate adaptation response. Restoration and maintenance of sinus rhythm could reverse these electrophysiological changes.     

Recovery of electrophysiological parameters after conversion of atrial fibrillation.

We investigated the recovery of electrophysiological parameters from electrical remodeling after conversion of chronic lone atrial fibrillation in humans. Clinical studies have shown that the longer atrial fibrillation lasts, the more difficult it becomes to maintain the sinus rhythm after cardioversion. To explore the effects of the duration of atrial fibrillation on changes of electrophysiological parameters after conversion, we determined the atrial effective refractory period and P wave duration during right atrial pacing at 1 and 24 h after electrical cardioversion in 15 patients with chronic lone atrial fibrillation (median duration, 6 months). By 24 h after cardioversion, the effective refractory period at a pacing cycle length of 600 ms increased from 225+/-19 to 254+/-27 ms. However, the P wave duration did not decrease significantly 24 h after conversion. As the duration of atrial fibrillation became longer, the prolongation of effective refractory period was more delayed (P<0. 001, r=0.82), and the shortening of P wave duration was significantly smaller within 24 h after cardioversion (P<0. 001, r=0.67). After cardioversion of chronic lone atrial fibrillation, the recovery of shortened atrial refractoriness and prolonged intraatrial conduction time is dependent on the duration of preexisting atrial fibrillation.     

Wolff-Parkinson-White syndrome and atrial fibrillation: Relation between refractory period of accessory pathway and ventricular rate during atrial fibrillation

To assess the relation between the length of the effective refractory period of the accessory pathway and the ventricular rate during atrial fibrillation, we studied two groups of patients with the Wolff-Parkinson-White syndrome: Group I, 17 patients with electrocardiographlcally documented episodes of atrial fibrillation, and Group II, 9 patients without this arrhythmia. In 17 of these 26 patients the effective refractory period of the accessory pathway could be determined by the single test stimulus method during atrial pacing.

After measurement of the refractory period, atrial fibrillation was induced by rapid atrial pacing (400 to 500/min). The duration of the effective refractory period of the accessory pathway was found to correlate with the shortest R-R interval and the mean ventricular rate during documented or induced atrial fibrillation. In nine patients the effective refractory period of the accessory pathway could not be determined because the atrium became refractory while atrioventricular (A-V) conduction was still occurring over this pathway. In these patients the right atrium was regularly paced at rates of up to 280/min. All nine patients had 1:1 A-V conduction over the accessory pathway up to driving rates of 240/min. In five patients conduction still manifested a 1:1 ratio at pacing rates of 280/min. During atrial fibrillation all nine patients had a mean ventricular rate greater than 200/min.

Although factors other than the effective refractory period of the accessory pathway affect ventricular rate during atrial fibrillation in patients with the Wolff-Parkinson-White syndrome, the duration of this period is of value in identifying patients at risk of having life-threatening high ventricular rates when atrial fibrillation occurs.     

Effect of phenylephrine infusion on atrial electrophysiological properties.

OBJECTIVE: To determine the effect of changes in autonomic tone induced by phenylephrine infusion on atrial refractoriness and conduction. DESIGN: Left and right atrial electrophysiological properties were measured before and after a constant phenylephrine infusion designed to increase sinus cycle length by 25%. SUBJECTS: 20 patients, aged 53 (SD 6) years, undergoing electrophysiological study for investigation of idiopathic paroxysmal atrial fibrillation (seven patients) or for routine follow up after successful catheter ablation of supraventricular tachycardia (13 patients). MAIN OUTCOME MEASURES: Changes in left and right atrial effective refractory periods, atrial activation times, and frequency of induction of atrial fibrillation. RESULTS: Phenylephrine (mean dose 69 (SD 18) mg/min) increased mean blood pressure by 22 (12) mm Hg (range 7 to 44) and lengthened sinus cycle length by 223 (94) ms (20 to 430). Left atrial effective refractory period lengthened following phenylephrine infusion from 250 (25) to 264 (21) ms (P < 0.001) but there was no significant change in right atrial effective refractory period: 200 (20) v 206 (29), P = 0.11. There was a significant relation between the effect of phenylephrine on sinus cycle length and on right atrial refractoriness (r = 0.6, P = 0.005) with shortening of right atrial refractoriness in patients with the greatest prolongation in sinus cycle length. During phenylephrine infusion, the right atrial stimulus to left atrial activation time at the basic pacing cycle length of 600 ms was unchanged, at 130 (18) v 131 (17) ms, but activation delay with a premature extrastimulus increased: 212 (28) v 227 (38) ms, P = 0.002. Atrial fibrillation was induced by two of 58 refractory period measurements at baseline and by 12 of 61 measurements during phenylephrine infusion (P < 0.01). Phenylephrine increased the difference between left and right atrial refractory periods by 22.8 (19.4) ms in the five patients with induced atrial fibrillation after phenylephrine compared to 0.9 (16.2) ms in the 13 patients without induced atrial fibrillation after phenylephrine infusion (P = 0.02). CONCLUSIONS: Phenylephrine infusion increased left atrial refractoriness and intra-atrial conduction delay following a premature right atrial extrastimulus. Induction of atrial fibrillation during phenylephrine infusion was associated with non-uniform changes in atrial refractoriness. These data support the concept that changes in autonomic tone may precipitate atrial fibrillation in susceptible individuals.     

心电散点图在心律失常快速诊断中的应用

目的通过与诊断结果对比观察,探讨心电散点图在快速诊断心律失常方面的临床应用价值。方法应用动态心电图记录仪记录患者连续24h心电信号,利用计算机自动检测技术,进行心电分析,并同步绘制24h心电散点图。将诊断结果分为窦性心律、室上性早搏、室性早搏、心房颤动、差异性传导5组,分别将4组心律失常结果与心电散点图检测的诊断结果进行对照,计算出二者的符合率及各组的B线斜率,进行分析对比。结果室上性早搏组与室性早搏、心房颤动、差传组差异显著(p<0.001);室性早搏组与室上性早搏、心房颤动、差传组差异显著(p<0.001);心房颤动组与差传组差异不显著(p>0.05)。结论心电散点图在长程大样本心电数据中,快速诊断心律失常,尤其是室上性早搏、室性早搏、心房颤动等时具有较好的临床应用价值。     

迷走神经干预对犬心房电生理的影响

目的心房电重构可导致心房有效不应期缩短,通过测量心房有效不应期来研究迷走神经对心房电重构的影响。方法 10只成年犬给予酒石酸美托洛尔和阿托品阻断交感神经和迷走神经。分别测量心房电重构前后基础状态及迷走神经刺激下的心房有效不应期（ERP）和房颤易感窗口（VW）。结果①阿托品应用前后基础状态下的ERP无变化。阿托品应用前后迷走神经刺激下的ERP变化明显;②心房电重构后ERP：基础状态及迷走神经刺激下,无论右心房还是冠状静脉窦远端测得的ERP与重构前（阿托品应用后）ERP相比无明显差异（p值均〉0.05）;③VW的变化：阿托品应用前,迷走神经刺激下容易诱发房颤。阿托品应用后,心房电重构前后无论基础状态或迷走神经刺激均不能诱发房颤。结论迷走神经阻滞能减轻心房电重构所导致的心房不应期缩短,从而抑制迷走神经介导的房颤诱发。     

Comparison of the ventricular response during atrial fibrillation in patients with enhanced atrioventricular node conduction and Wolff-Parkinson-White syndrome

Although ventricular fibrillation is a well known sequel to atrial fibrillation in the Wolff-Parkinson-White syndrome, ventricular fibrillation is not generally associated with supraventricular tachycardia in the presence of enhanced atrioventricular (AV) node conduction without pre-excitation. It was hypothesized that the ventricular response during atrial fibrillation may be less in patients with enhanced AV node conduction than in their counterparts with Wolff-Parkinson-White syndrome matched for anterograde effective refractory period. Slower ventricular rates during atrial fibrillation would suggest an increased propensity for concealed conduction in the enhanced AV node conduction group than in the group with an accessory pathway. Three groups of patients aged 16 to 65 years underwent electrophysiologic testing for supraventricular tachycardia or after surgical correction of Wolff-Parkinson-White syndrome. Sixteen patients had enhanced AV node conduction, 16 had Wolff-Parkinson-White syndrome and 16 had normal AV node conduction. Patients with enhanced AV node conduction and Wolff-Parkinson-White syndrome were well matched for anterograde effective refractory period (245 +/- 22 versus 258 +/- 25 ms) and minimal cycle length, maintaining 1:1 anterograde conduction (261 +/- 21 versus 260 +/- 40). There was no difference in intervals during atrial fibrillation (average RR interval = 372 +/- 37 versus 346 +/- 66) or shortest RR interval (266 +/- 27 versus 243 +/- 51). Thus, patients with Wolff-Parkinson-White syndrome and those with enhanced AV node conduction matched for anterograde refractory period exhibit similar ventricular rates during atrial fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Determinants of the ventricular rate during atrial fibrillation

Determinants of the ventricular cycle length during atrial fibrillation were examined in 52 patients. Thirty-three patients had structural heart disease and none had an accessory atrioventricular (AV) connection. The AV node effective and functional refractory periods, the shortest atrial pacing cycle length associated with 1:1 conduction, the AV node conduction time and indexes of concealed conduction in the AV node were measured in the baseline state (36 patients) and after modification of sympathetic tone by infusion of isoproterenol or propranolol (8 patients each). Atrial fibrillation was then induced with rapid atrial pacing, and the mean, shortest and longest ventricular cycle lengths were measured. Variables that correlated most strongly with the mean RR interval during atrial fibrillation were the AV node effective refractory period (r = 0.93; p less than 0.001), AV node functional refractory period (r = 0.87; p less than 0.001) and shortest atrial pacing cycle length associated with 1:1 conduction (r = 0.91; p less than 0.001). The AH interval during sinus rhythm (r = 0.74; p less than 0.001) and during atrial pacing at the shortest cycle length with 1:1 conduction (r = 0.52; p less than 0.001) had weaker correlations. Measures of concealed conduction did not improve the prediction of the mean or longest ventricular cycle length during atrial fibrillation. In conclusion, the refractory periods and conductivity of the AV node are the best indicators of the potential of the node to transmit atrial impulses to the ventricles during atrial fibrillation. The degree of concealed conduction in the AV node is a less important determinant of the mean ventricular rate during atrial fibrillation.     

Atrial conduction: effects of extrastimuli with and without atrial dysrhythmias

The effects of cycle length and stimulation site on intraatrial conduction and refractoriness were evaluated in patients with and without atrial flutter (AFI) or fibrillation (AF) using the extrastimulus technique. Nineteen patients with spontaneous sustained AFI or AF were compared with 19 control patients. Programmed stimulation was performed at the right atrium and coronary sinus at drive cycle lengths of 600 and 450 ms. The atrial effective refractory period was similar in the patients with atrial dysrhythmias and the control group. The right atrial effective refractory period at a drive cycle length of 600 ms was significantly shorter in patients with AF (211 ms) than in patients with AFI (235 ms, p = 0.05). The conduction time of late (coupling intervals more than 50% of the drive cycle length) premature impulses was similar in the patients with atrial dysrhythmias and the control group. However, early extrastimuli (coupling intervals less than 50% of the drive cycle length) at a drive cycle length of 600 ms produced significantly more intraatrial conduction delay in the patients with atrial dysrhythmias than in the control patients. At a drive cycle length of 450 ms, similar delays in intraatrial conduction occurred in the patients with and without atrial dysrhythmias because of an increase in the maximal-observed intraatrial conduction delay in the control patients. This study shows that delay in conduction of early premature atrial stimuli at a drive cycle length of 600 ms is a marker of patients with spontaneous AFI and AF.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mechanisms of atrial remodeling and clinical relevance

PURPOSE OF REVIEW: Atrial fibrillation usually occurs in the context of an atrial substrate produced by alterations in atrial tissue properties referred to as remodeling. Remodeling can result from cardiac disease, cardiac arrhythmias, or biologic processes such as senescence. Recent advances in understanding remodeling have allowed for insights into mechanisms underlying atrial fibrillation that have been transferred from experimental models to humans. This paper reviews recent progress in understanding atrial remodeling, as well as the consequent clinical insights into atrial fibrillation pathophysiology and treatment. RECENT FINDINGS: Two principal forms of remodeling have been described in animal models of atrial fibrillation: ionic remodeling, which affects cellular electrical properties, and structural remodeling, which alters atrial tissue architecture. Atrial tachycardias (particularly rapid tachyarrhythmias such as atrial flutter and atrial fibrillation) cause ionic remodeling, which decreases the atrial refractory period and promotes atrial reentry. Congestive heart failure produces atrial interstitial fibrosis, which promotes arrhythmogenesis by interfering with atrial conduction properties. Recent animal studies have provided insights into the pathways involved in remodeling, and have indicated the pathophysiological role of remodeling in specific contexts. In addition, work in animal models has provided information about pharmacological interventions that can prevent the development of remodeling. Clinical studies have shown that novel approaches to remodeling prevention identified in animal work have potential therapeutic value in man. SUMMARY: Understanding atrial remodeling has the potential to improve our appreciation of the pathophysiology of clinical atrial fibrillation and to allow for the development of useful new therapeutic approaches.     

Frequency-dependent electrophysiological effects of flecainide, nifekalant and d,l-sotalol on the human atrium

To compare the effects of class Ic and III antiarrhythmic agents on the termination and prevention of atrial fibrillation, the present study investigated the use-dependent electrophysiological effects of flecainide, nifekalant and d,l-sotalol on the human atrium. Flecainide significantly prolonged effective refractory period (ERP), intra-atrial conduction time (IACT) and monophasic action potential duration (MAPD), and its effects on ERP and IACT were use-dependent. Nifekalalant significantly prolonged ERP and MAPD, and these effects were reverse use-dependent; however, there was no significant change in IACT. d,l-Sotalol significantly prolonged MAPD and the effect was reverse use-dependent. It significantly prolonged ERP, but the effect was not reverse use-dependent. d,l-Sotalol increased IACT in a use-dependent manner. Thus, for atrial fibrillation, class Ic antiarrhythmic agents might be more effective in termination and class III antiarrhythmic agents might be more effective in prevention.     

Atrial fibrillation: pathophysiology

BACKGROUND: Although several classical studies seemed to provide clear ideas on the pathophysiology of atrial fibrillation, current concepts have to be modified on the basis of more recent findings. REENTRANT CIRCUITS: Based on the findings of Garrey and of Moe & Abildskov, atrial fibrillation has long been considered as the prototype of an arrhythmia being caused by multiple, random reentrant circuits, the number of which would determine the stability of the reentrant process. Local refractory and conduction properties would determine the size of individual circuits, a hypothesis quite convincing with respect to refractoriness, but so far hard to prove with respect to conduction. The finding that rapid atrial rates shorten atrial refractory periods and reverse rate adaptation (atrial remodeling) has coined the phrase "atrial fibrillation begets atrial fibrillation", indicating that any atrial tachyarrhythmia modifies the substrate in a way that favors reentry. With intracellular calcium overload being the initial trigger, down-regulation of genes encoding for calcium channels seems to primarily account for atrial remodeling. Primarily neglected concepts on the pathophysiology of atrial fibrillation suggesting single, meandering circuits or focal activity have regained attention. Atrial fibrillation as a random phenomenon is questioned not only by the dominant role of the left atrium for the maintenance of the arrhythmia, but also by most recent data demonstrating a spatio-temporal periodicity in activation patterns. Finally, ablation studies have provided convincing evidence that there is a subset of patients with focal or at least focally induced atrial fibrillation.     

Atrial fibrillation in patients with an accessory pathway: importance of the conduction properties of the accessory pathway

To investigate how the electrophysiologic properties of the accessory pathway affect the occurrence of atrial fibrillation in the Wolff-Parkinson-White syndrome, programmed stimulation data of 57 patients with overt pre-excitation and 33 patients with a concealed accessory pathway with documented circus movement tachycardia were reviewed. Atrial fibrillation had occurred spontaneously in 31 (54%) of the 57 patients with the Wolff-Parkinson-White syndrome and in 1 (3%) of the 33 with a concealed accessory pathway (p less than 0.001). Sustained atrial fibrillation was induced in 23 of 31 patients with the Wolff-Parkinson-White syndrome and spontaneous atrial fibrillation (Group A), in 7 of 26 patients with the Wolff-Parkinson-White syndrome without spontaneous atrial fibrillation (Group B) and in 5 of 33 patients with a concealed accessory pathway (Group C). The anterograde effective refractory period of the accessory pathway was shorter in Group A than in Group B (252 versus 297 ms, p less than 0.001). There were no differences among groups in PA interval, right to left atrium conduction time, cycle length of tachycardia and atrial and retrograde accessory pathway effective refractory period. Atrial fibrillation is more frequent in patients with the Wolff-Parkinson-White syndrome than in those with a concealed accessory pathway. Patients with overt pre-excitation and atrial fibrillation have a shorter anterograde accessory pathway refractory period. It seems therefore that the anterograde rather than the retrograde conduction properties of the accessory pathway are the critical determinants of atrial fibrillation in the Wolff-Parkinson-White syndrome.     

Postrepolarization Refractoriness as a Potential Anti–Atrial Fibrillation Mechanism of Pilsicainide, a Pure Sodium Channel Blocker with Slow Recovery Kinetics

The antifibrillatory effect of pilsicainide, a sodium channel blocker with slow recovery kinetics, was investigated in a canine model of atrial fibrillation. Prolonging the atrial effective refractory period is an important mechanism for pharmacological termination of atrial fibrillation. However, the effectiveness of potassium channel blockers has been questioned because of their reverse-use–dependent property. In eight open-chest dogs, the duration of the atrial endocardial monophasic action potential and the atrial effective refractory period were determined using a Franz catheter. Conduction velocity was obtained from a 96-channel mapping electrode at multiple cycle lengths. Inducibility of sustained atrial fibrillation (>30 minutes) was confirmed by atrial burst pacing during bilateral vagal stimulation, and local fibrillation cycle lengths were measured. Five minutes after restarting fibrillation, pilsicainide (0.6 mg/kg + 0.04 mg/kg/min) was administered. After fibrillation was terminated, measurements were repeated. Pilsicainide successfully terminated atrial fibrillation in 7 of 8 dogs after the median time of 5.1 minutes. The conduction velocity decreased significantly. Although pilsicainide did not affect monophasic action potential duration, it caused use-dependent prolongation of the atrial effective refractory period (P < 0.05), creating postrepolarization refractoriness. Accordingly, pilsicainide prolonged the atrial fibrillation cycle length from 80.6 to 113.8 ms (P < 0.05) before termination of fibrillation. Sodium channel blockers with slow recovery kinetics can prolong the atrial effective refractory period without affecting monophasic action potential duration. Unlike potassium channel blockers, these sodium channel blockers maintain postrepolarization refract     

Effects of adenosine on wavelength of premature atrial complexes in patients without structural heart disease

In conclusion, although adenosine produced slight decreases in conduction times for premature impulses, there was a proportionally greater decrease in functional refractory period resulting in a decrease in wavelength. A shorter wavelength increases the probability that reentry will occur and may provide a basis for transient atrial fibrillation which is sometimes observed after adenosine administration.     

伊布利特逆转犬48小时房颤心房肌电重构作用研究

目的探讨国产富马酸伊布利特逆转犬48h房颤心房肌电重构的作用。方法健康成年杂种犬20只,随机分为快速起搏组（Pacing组,10只）和假手术组（Sham组,10只）。Pacing组通过右侧股静脉置入起搏电极,600次／min频率起搏高右房（HRA）制备房颤模型。48h后终止起搏,在心电和血液动力学监测下,给予国产富马酸伊布利特0．001m·kg^-1·min^-1静脉推注,房颤转复或累计剂量达0．04mg／kg停止给药。观察给药前后HRA的有效不应期（ERP,BCL=300ms）、传导速度（CV）、折返波长（WL）、频率自适应性、房颤诱发率等心房肌电生理指标的变化。结果Pacing组在起搏停止后,8只犬恢复窦律,2只犬持续房颤,给予伊布利特后1min内房颤终止。起博48h后,Pacing组ERP、CV、WL较Sham组减少,频率自适应性较Sham组降低,房颤诱发率明显增加;而给药后均恢复到起博前及Sham组水平。结论国产富马酸伊布利特能够逆转犬高右房快速起搏48h的心房肌电重构,有预防阵发性房颤发生的作用。其电药理学作用机制为：延长房颤时的心房不应期、心房肌电传导的速度及折返波长,提高心房肌频率的自适应性。     

肾素-血管紧张素系统阻断剂与心房颤动

心房颤动是临床最常见的心律失常之一,发病率呈增加趋势。心房电重构和结构重构是心房颤动维持和复发的主要机制,肾素-血管紧张素系统在心房重构中起重要作用。肾素-血管紧张素系统阻断剂（血管紧张素转化酶抑制剂和血管紧张素受体阻断剂）通过抑制心房不应期缩短和抗心房结构重构等作用抑制心房重构并减少心房颤动的发作。肾素-血管紧张素系统阻断剂影响心房结构和功能,为心房颤动的防治提供了一种新的选择。     

Electrophysiological mechanism of combination therapy with disopyramide and propranolol for paroxysmal atrial fibrillation

OBJECTIVES: Combined administration of propranolol and disopyramide treatment often leads to better results in patients with atrial fibrillation refractory to only disopyramide administration. The electrophysiological mechanism of this combination therapy was investigated. METHODS: Nineteen patients with paroxysmal atrial fibrillation without organic heart disease were studied. The indices for atrial vulnerability were compared in the control state, 10 min after injection of disopyramide (2 mg/kg) and 10 min after additional administration of propranolol (0.2 mg/kg). RESULTS: Administration of both drugs did not significantly change the percentage fragmented atrial activity and the interatrial conduction delay. Disopyramide increased the atrial effective refractory period and the wavelength index, defined as the ratio of the atrial effective refractory period to the interatrial conduction delay and represented the length of the reentry circuit. Additional injection of propranolol caused further increases in both values. CONCLUSIONS: Combination therapy with disopyramide and propranolol improves atrial vulnerability by increasing the wavelength.