心房肌复极的电整复性与阵发性心房颤动发生机制的实验研究

目的 研究在体犬左、右心房肌的电整复性即动作电位时程整复性(APDR),观察其与阵发性心房颤动(房颤)发生的潜在机制.方法 使用单相动作电位技术记录14只犬左、右心房复极达90%的动作电位时程(APD_(90)),并通过S_1S_2程序刺激,观察APDR变化,即每一个舒张间期与刺激后发生心房肌复极APD_(90)的关系,并观察房颤的诱发情况.结果 APD_(90)左心房为(157.4±43.5)ms明显小于右心房(170.9±37.9)ms,P<0.05.心房肌在S_1S_2递减程序刺激下,左心房与右心房具有不同斜率的APDR曲线,左心房的APDR曲线斜率1.3±0.4大于右心房0.9±0.3,P<0.05.进行心房快速起搏S_1S_2刺激时,14只犬中共诱发出18阵房颤,其中左心房刺激发作12阵,明显多于右心房6阵(P<0.05).结论 左、右心房间具有单相动作电位时程的异质性及APDR不均一的复极特性,是诱发折返、发生和维持房颤的基质之一.     

心房肌复极的电整复性与阵发性心房颤动发生机制的实验研究

Objective Electrical restitution was believed to be a determinant responsible for the stability of heart rhythm. Although numerous studies focused on the role of action potential duration restitution (APDR) in the initiation and maintenance of ventricular fibrillation (VF), the relationship between atrial APDR and atrial fibrillation (AF) has not been fully understood. This study aims to investigate the characteristics of APDR of left atrium (LA) and right atrium (RA) in canines and the relevance to induction of AF. Methods Monophasic action potential (MAP) was recorded from LA and RA in 14 canines using the MAP recording-pacing combination catheter. APDR, plotted as action potential duration (APD) on the preceding diastolic interval (DI), was assessed by use of programmed stimulation with a single extrastimulus (S_1S_2) at LA and RA. Episodes of AF were recorded and analyzed. Results APD_(90) was significantly shorter in the LA than that in the RA [( 157.4 ± 43.5 ) ms vs. ( 170. 9 ± 37. 9)ms, P < 0. 05]. The mean slope of the APDR curve by S_1S_2 in the LA was significantly greater than that in the RA ( 1.3 ±0. 4 vs. 0. 9 ± 0. 3, P < 0. 05 ). The incidence of induced AF was significantly higher in the LA than in the RA (11/18 vs. 7/18, P < 0. 05). Conclusions The APDR and MAP characteristics are not uniform between atriums, which may be one of the important mechanisms responsible for the initiation of AF. Heterogeneity of APDR between LA and RA might create critical gradients or a dispersion of repolarization and subatrate for re-entrant arrhythmias and vulnerability to AF.     

心房肌复极的电整复性与阵发性心房颤动发生机制的实验研究

Objective Electrical restitution was believed to be a determinant responsible for the stability of heart rhythm. Although numerous studies focused on the role of action potential duration restitution (APDR) in the initiation and maintenance of ventricular fibrillation (VF), the relationship between atrial APDR and atrial fibrillation (AF) has not been fully understood. This study aims to investigate the characteristics of APDR of left atrium (LA) and right atrium (RA) in canines and the relevance to induction of AF. Methods Monophasic action potential (MAP) was recorded from LA and RA in 14 canines using the MAP recording-pacing combination catheter. APDR, plotted as action potential duration (APD) on the preceding diastolic interval (DI), was assessed by use of programmed stimulation with a single extrastimulus (S_1S_2) at LA and RA. Episodes of AF were recorded and analyzed. Results APD_(90) was significantly shorter in the LA than that in the RA [( 157.4 ± 43.5 ) ms vs. ( 170. 9 ± 37. 9)ms, P < 0. 05]. The mean slope of the APDR curve by S_1S_2 in the LA was significantly greater than that in the RA ( 1.3 ±0. 4 vs. 0. 9 ± 0. 3, P < 0. 05 ). The incidence of induced AF was significantly higher in the LA than in the RA (11/18 vs. 7/18, P < 0. 05). Conclusions The APDR and MAP characteristics are not uniform between atriums, which may be one of the important mechanisms responsible for the initiation of AF. Heterogeneity of APDR between LA and RA might create critical gradients or a dispersion of repolarization and subatrate for re-entrant arrhythmias and vulnerability to AF.     

Dispersion of atrial repolarization in patients with paroxysmal atrial fibrillation.

To study the role of the dispersion of atrial repolarization (DAR) in the genesis of atrial fibrillation (AF), monophasic action potentials (MAP) were recorded simultaneously from a catheter at the high lateral right atrium (HLRA) and a catheter moving around the high, middle and low lateral right atrium (RA) the high, anterior and posterior septal RA and the RA appendage in 15 patients with paroxysmal AF and 15 patients with atrioventricular nodal re-entry tachycardia (AVNRT) or concealed Wolff-Parkinson-White syndrome (WPW) without history of AF. After recordings during sinus rhythm (SR), MAPs were recorded during programmed stimulation (PS) via the HLRA catheter at a drive cycle length (CL) of 500 ms. Thus, MAPs were recorded simultaneously from 2 sites at a time and sequentially from 4 to 12 sites during SR, drive pacing and PS. Taking the MAP at the HLRA as reference, the dispersion of repolarization time (dispersion of RT) and its two components, the dispersions of activation time (dispersion of AT) and MAP duration (dispersion of MAP duration) among the 4 to 12 sites were calculated and taken as parameters of DAR. RESULTS: During SR and PS, the maximal dispersion of RT was significantly greater in AF than in control patients, 113+/-49 ms vs 50+/-28 ms (P<0.001) and 114+/-56 vs 70+/-43 ms (P<0.05) respectively. The increased dispersion of RT in the AF group was caused by increases in both dispersion of MAP duration and dispersion of AT. CONCLUSION: During SR and PS, DAR increased in patients with paroxysmal AF due to increases in dispersion of MAP duration and dispersion of AT, which suggests the involvement of both repolarization and conduction disturbances in the development of paroxysmal AF.     

心房复极波增大诱发异位心房激动的临床分析

目的观察心房复极波增大诱发异位心房激动的临床和心电图特征。方法对7例心房复极波间歇性增大致PR段及ST段同步下移并诱发房性早搏及心房扑动的临床表现和常规心电图特征进行分析。结果出现这一心电现象的导联广泛,以V3、V4导联显著,房性早搏及心房扑动的配对问期短且固定,而配对间期较长的房性早搏则无PR段及ST段下移。患者存在心脑肺结构破坏及功能损害或低钾血症,病情好转时上述现象减轻或消失。结论在病理条件下心房复极波增大致心房复极离散度增大,提示心电活动不稳定,易于诱发折返性异位心房激动。     

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.     

Cycle length-dependent repolarization changes during atrial fibrillation in the Brugada syndrome

This is a case report of a patient with Brugada syndrome who developed paroxysmal atrial fibrillation. During the episode, beat-to-beat changes in ventricular repolarization were observed. These changes were a paradoxical ST-segment alteration after a short-coupled ventricular beat. These findings, not reported before, may be helpful for the diagnosis of this syndrome.     

Kinetics of atrial repolarization alternans in a free-behaving ovine model

Kinetics of Atrial Repolarization Alternans. Introduction: Repolarization alternans (Re‐ALT), a beat‐to‐beat alternation in action potential repolarization, promotes dispersion of repolarization, wavebreaks, and reentry. Recently, Re‐ALT has been shown to play an important role in the transition from rapid pacing to atrial fibrillation (AF) in humans. The detailed kinetics of atrial Re‐ALT, however, has not been reported so far. We developed a chronic free‐behaving ovine pacing model to study the kinetics of atrial Re‐ALT as a function of pacing rate. Methods: Thirteen sheep were chronically implanted with 2 pacemakers for the recording of broadband right atrial unipolar electrograms and delivery of rapid pacing protocols. Beat‐to‐beat differences in the atrial T‐wave apex amplitude as a measure of Re‐ALT and activation time were analyzed at incremental pacing rates until the effective refractory period (ERP) defined as stable 2:1 capture. Results: Atrial Re‐ALT appeared intermittently but without periodicity, and increased in amplitude as a function of pacing rate until ERP. Intermittent 2:1 atrial capture was observed at pacing cycle lengths 40 ms above ERP, and increased in duration as a function of pacing rate. Episodes of rapid pacing‐induced AF were rare, and were preceded by Re‐ALT or complex oscillations of atrial repolarization, but without intermittent capture. Conclusion: We show in vivo that atrial Re‐ALT developed and increased in magnitude with rate until stable 2:1 capture. In rare instances where capture failure did not occur, Re‐ALT and complex oscillations of repolarization surged and preceded AF initiation. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1003‐1012, September 2012)     

Gender-based differences in cardiac repolarization in mouse ventricle

The mouse heart has become a widely used model for genetic studies of heart diseases. Thus, understanding gender differences in mouse cardiac repolarization is crucial to the interpretation of such studies. The objective of this study was to evaluate whether there are gender differences in cardiac repolarization in mouse ventricle and to gain insights into the ionic and molecular mechanisms underlying these differences. Action potential durations (APDs) and K(+) currents in male and female ventricular myocytes were compared using a patch-clamp technique. APD(20), APD(50), and APD(90) were found to be significantly longer in females than males. Examination of the different K(+) currents revealed that a significantly lower current density exists in female ventricular myocytes compared with male myocytes for the ultrarapid delayed rectifier K(+) current, I(Kur) (at +30 mV, male, 33.2+/-2.9 pA/pF [n= 22]; female, 20.9+/-1.73 pA/pF [n= 19], P<0.001). Consistent with these findings were the results of the ribonuclease protection assay, Western blots, and confocal analysis that showed a significantly lower expression level of Kv1.5 (coding for I(Kur)) in female compared with male ventricle. The additional K(+) currents present in mouse ventricle exhibited no gender differences. In agreement with these electrophysiological data, no differences in the expression levels for the K(+) channels underlying these currents were detected between both sexes. This study demonstrates that adult mice exhibit gender differences in cardiac repolarization. The expression of Kv1.5 and of its corresponding K(+) current, I(Kur), is significantly lower in female mouse ventricle, and as a result, the APD is lengthened.     

心房复极波增大诱发房早与阵发房颤的关系

目的 探讨心房复极波增大诱发的房性早搏与阵发性心房颤动的关系.方法 对频发房早患者进行随访,行心电图和动态心电图检查,房早前有心房复极波增大的为观察组,反之为对照组.观察两组阵发房颤的发生率、持续时间、发作时的临床诊断和并发症.结果 与对照组比较,观察组阵发房颤的发病率较高、发作阵次较多、持续时间较长,分别为31.13...     

Alterations of atrial repolarization after tricyclic antidepressant drugs absorption

We describe a case of voluntary intoxication with tricyclic antidepressant drugs: initial electrocardiogram showed alterations of atrial repolarization (Ta segment) which were more pronounced than usual ST-T alterations. Evolution was uneventful (and repolarization normalized). Tricyclic antidepressant drugs absorption can lead to Ta segment alterations, which may be a useful clue in the differential diagnosis of drugs intoxication.     

Determination of the spatial and intensity properties of atrial repolarization potentials in the dog

Body surface electrical potentials generated by atrial repolarization (Ta wave) normally extend from the P wave into or through the QRS complex. Thus, the Ta wave is partially obscured by the QRS complex and, conversely, the QRS complex is composed of atrial recovery as well as ventricular depolarization forces. To better study the spatial patterns and magnitudes of the Ta wave, transient atrioventricular (AV) block was induced in 15 dogs by atrial pacing using surgically implanted left or right atrial electrodes. ECG potentials were registered from 84 torso electrodes, and cycles with normal and with blocked AV conduction were segregated. In blocked cycles, the duration of the Ta wave measured 248.0 +/- 25.3 msec with right and 256.0 +/- 38.4 msec with left atrial stimulation. In all cases, the Ta wave extended into the QRS and, in 75% of cases, it extended into the S-T segment. Peak Ta magnitudes, measuring 50.7 +/- 17.9 and 51.8 +/- 21.7 uV RMS with right and left atrial stimulation, respectively, occurred during the P-R segment in all cases. The effect of Ta wave superposition on the QRS complex was assessed by subtraction of patterns in cycles with blocked AV conduction from those with intact AV conduction. Differences between directly recorded QRS waveforms and those computed by subtraction of the Ta wave were small; correlation coefficients exceeded 0.96 and differences in instantaneous RMS potential were less than 6%. Thus, the atrial recovery waveform does extend into the QRS and into the S-T segment in most cases, but the effect of this superposition of Ta on QRS waveforms is quantitatively small.     

Novel electrophysiologic parameter of dispersion of atrial repolarization: comparison of different atrial pacing methods

INTRODUCTION: Heterogeneity of ventricular repolarization plays a major role in reentrant tachyarrhythmias in cardiac tissue. However, the role of atrial repolarization added activation time (AT) to refractoriness in atrial vulnerability has not been investigated in detail. METHODS AND RESULTS: The study population consisted of 34 patients: 18 with atrial fibrillation (AF) and 16 without AF (control group). The effective refractory periods (ERPs) in the right atrial appendage, low lateral right atrium, high right septum, and distal coronary sinus, and ATs from P wave onset to each electrogram during sinus rhythm and right atrial appendage, low lateral right atrial, high right septal, distal coronary sinus, and biatrial pacing were measured. Atrial recovery time, defined as the sum of AT and ERP, and its dispersions during sinus rhythm, right atrial appendage, low lateral right atrial, high right septal, distal coronary sinus, and biatrial pacing were calculated. Both ERP dispersion and atrial recovery time dispersion during sinus rhythm were significantly greater in the AF group than in the control group. Atrial recovery time dispersion during distal coronary sinus, high right septal, or biatrial pacing was significantly smaller than that during right atrial appendage or low lateral right atrial pacing in each group. In particular, atrial recovery time dispersion during distal coronary sinus pacing was the smallest of the five pacing methods in the AF group. P wave duration during biatrial or high right septal pacing was significantly shorter than during right atrial appendage, low lateral right atrial, or distal coronary sinus pacing in each group. CONCLUSION: Atrial recovery time dispersion is suitable as an electrophysiologic parameter of atrial vulnerability. Distal coronary sinus pacing may prevent AF by increasing homogeneity of atrial repolarization, whereas biatrial and high right septal pacing contribute not only homogeneity of atrial repolarization but also improvement of atrial depolarization.