迷走神经刺激对心力衰竭兔跨室壁复极离散的影响

目的探讨迷走神经刺激对心力衰竭(简称心衰)兔跨室壁复极离散度(TDR)的影响。方法用阿霉素制作兔心衰模型,采用单相动作电位(MAP)记录技术分别记录10只开胸心衰兔(心衰组)和10只开胸正常兔(对照组)迷走神经刺激前后左室游离壁心尖上方1cm处三层心肌的MAP,测量并分析MAP时程(MAPD),TDR。结果对照组刺激前后TDR没有显著性差异,心衰组刺激后TDR显著减少(P<0.05)。迷走神经刺激前,与对照组比较,心衰组TDR明显延长(12.80±2.57ms vs8.82±1.33ms,P<0.05),刺激后两者相比无显著性差异(7.89±3.80ms vs9.44±3.21ms,P>0.05)。结论迷走神经刺激可使心衰组的TDR降低。     

迷走神经刺激对心力衰竭兔跨室壁离散度影响的研究

目的研究迷走神经刺激对心力衰竭兔跨室壁离散度的影响。方法用阿霉素制作兔心力衰竭模型,采用单相动作电位（MAP）记录技术分别记录10只正常兔和9只心力衰竭兔左心室心肌内、中、外膜3层的MAP,分别于刺激前、后记录MAP,测量90％的动作电位时限（MAPD90）,分析跨室壁复极离散度（TDR）的变化。结果在迷走神经刺激前,心力衰竭组与正常组比较,MAPD90有所缩短,TDR则明显增大（P〈0．05）;在迷走神经刺激前后的自身比较中,心力衰竭组和正常组MAPD90都有所延长,正常组TDR差异无统计学意义（P〉0．05）,心力衰竭组TDR差异有统计学意义（P〈0．05）。结论迷走神经刺激可使心力衰竭组的TDR减小,从而减少恶性室性心律失常的发生率。     

急性心肌缺血犬心肌细胞瞬时外向钾电流和跨壁复极离散度变化致心律失常机制研究

目的:探讨急性心肌缺血对犬左室心肌楔形组织块瞬时外向钾电流(Ito)、跨壁复极离散度(TDR)变化及其与室性心律失常的关系。方法:建立冠状小动脉灌注犬左室心肌楔形组织块模型,应用浮置玻璃微电极和心电图同步记录技术,观察急性无灌流心肌缺血对内、中、外3层心肌细胞Ito、动作电位时程(APD)、TDR和心律失常的影响。结果:急性心肌缺血早期犬左室内、中、外3层心肌细胞的Ito增大,APD缩短,均以外膜心肌细胞最明显,TDR增加,诱发早期后除极、R-on-T期前收缩和室性心动过速。结论:急性心肌缺血时Ito增大,TDR增加,产生2相位折返,是多型性室性心动过速发生的重要机制。     

IKs blockade reduces dispersion of repolarization in heart failure

BACKGROUND: The slow and rapid (I(Kr)) components of I(K) are major determinants of ventricular repolarization. Unlike I(Kr), which is homogeneously expressed across the transmural wall, I(Ks) expression is reduced in midmyocardial cells and presumably contributes significantly to transmural dispersion of repolarization. Increased dispersion of repolarization during pharmacologic blockade of I(Kr) is proarrhythmic, primarily due to relatively selective prolongation of midmyocardial cell action potential duration (APD). The mechanisms underlying proarrhythmia in heart disease associated with impaired repolarization, such as heart failure, are unknown. We hypothesize that, in contrast to I(Kr) blockade, I(Ks) blockade will have little effect on midmyocardial cells and hence decrease dispersion of repolarization in heart failure. OBJECTIVES: The purpose of this study was to determine the effect of blockade of the slow component of the delayed rectifier current (I(Ks)) on arrhythmogenic dispersion of repolarization and proarrhythmia in heart failure. METHODS: Optical action potentials were simultaneously recorded from 256 sites spanning the transmural wall of the arterially perfused canine wedge preparation. Hearts from dogs with heart failure induced by rapid pacing (n = 6) were compared with normals (n = 6). RESULTS: Baseline dispersion of repolarization, as measured from the range of transmural APD during stimulation at a cycle length of 2,000 ms, was significantly higher in heart failure (75 +/- 24 ms) compared with controls (39 +/- 21 ms, P < .04). I(Ks) blockade with 30 microM chromanol decreased dispersion of repolarization by 40% (P < .02) in heart failure, reducing it to values found in normals. Decreased dispersion of repolarization was due to a larger, relatively selective, drug-induced APD prolongation of epicardial (23%) compared with midmyocardial cells (9%, P < .02). VT could not be induced in failing hearts under conditions of I(Ks) blockade, and no proarrhythmia was observed. CONCLUSION: I(Ks) blockade significantly reduced heart failure-induced dispersion of repolarization to values seen in nonfailing hearts. By prolonging repolarization without increasing dispersion of repolarization, I(Ks) blockade may have antiarrhythmic effects without creating proarrhythmia.     

Factors affecting epicardial dispersion of repolarization: a mapping study in the isolated porcine heart.

OBJECTIVE: Non-uniform drug-induced prolongation of repolarization predominating in the midmyocardial (M) cell layers has been shown to be responsible for perpetuation of reentry, giving rise to torsade de pointes. However, the absence of M cells in immature animals, especially the pig, suggests other possible underlying mechanisms. We sought to examine, in this species, the effects of predisposing factors to torsade de pointes on the dispersion of epicardial repolarization and their contribution to arrhythmogenesis. METHODS: Computerized mapping of repolarization and activation was conducted on the epicardial surface in 29 Langendorff-perfused hearts of eight-week-old pigs. Activation-recovery intervals were measured simultaneously from 128 unipolar electrograms. RESULTS: Baseline iso-interval maps were dipolar (41%) or multipolar (59%). Dispersion of repolarization was reverse frequency-dependent but was unaffected by lowering [K+]o. DL-Sotalol (0.1 mmol/l) reinforced local gradients and thus increased epicardial dispersion, whereas intramural recordings did not demonstrate any predominant effect in midmyocardial layers. Phenylephrine (1 mumol/l) notably augmented DL-sotalol effects. After [Mg++]o lowering, although dispersion was not significantly increased, DL-sotalol was associated with the spontaneous occurrence of polymorphic ventricular tachycardia in seven out of nine experiments. When maps of repolarization of escape beats were compared with activation maps of first arrhythmic beats, an arc of functional dissociation was observed in the vicinity of a steep gradient of repolarization in two out of nine tachycardias. CONCLUSION: Epicardial dispersion of repolarization is increased by slow rates, DL-sotalol and phenylephrine but is not the only requirement for initiation of polymorphic ventricular tachycardia. In combination with other factors, it helps continuation of the arrhythmia in this model.     

束支传导阻滞对充血性心力衰竭复极离散度的影响

目的：探讨充血性心力衰竭合并束支传导阻滞患者Q－T离散度测定的影响因素。方法：分析62例充血性心力衰竭患者合并束支付导阻滞（Ⅰ组）、94例不合并束支传导阻滞（Ⅱ组）及40例正常组（Ⅲ组）Q－T离散度,Q－T离散度以12导联体表心电图上最长与最短Q－T间期之差（绝对离散度）及其变异系数（相对离散度）计算。结果：Ⅰ组Q－T、Q－Tc间期及其绝对离散度比Ⅱ组显著延长,但相对离散度相近;J－T、J－Tc绝对和相对离散度均显著长于Ⅱ组和Ⅲ组。结论：束支传导阻滞可影响充血性心力衰竭患者复极离散度的测定,但其离散程度主要与潜在的基础心脏疾病相关。     

Increased dispersion of ventricular repolarization and ventricular tachyarrhythmias in the globally ischaemic rabbit heart

Contemporary concepts of ischaemic ventricular tachyarrhythmias(VTA) are based on increased electrophysiological heterogeneityof the myocardium. We developed a multi-site monophasic actionpotential recording system for an isolated rabbit heart to studythe effects of global ischaemia on the electrophysiologicalproperties at different ventricular sites simultaneously. Thehearts were paced from the right ventricle (RV) andconductiontime (CT), action potential duration (APD) and total repolarizationtime (TRT= [CT + APD]) were measured during normal perfusionand ischaemia. The dispersion of these parameters was calculatedas the maximal difference between simultaneous recordings. Inducibilityof VTA by programmed extrastimulation (ES) was investigatedunder normal and ischaemic conditions. During global ischaemia, CT increased progressivey showing afaster and greater increase at the left ventricle (LV) thanat the RV. After 10 min the prolongation of CT reached a plateauat the LV while it continued to rise in the RV. The dispersionof CT increased from 14 ± 2.7 ms during normal perfusionto a maximum of 79.8 ± 17.2 ms after 14 min of ischaemnia(P<00001). APD was uniform at the three sites (190.9±02,185.0 and 179.3±9.8 ms, ns) during normal perfusion butchanged non-uniformly during ischaemia. There was a transientlengthening of APD until 1 and 3 min of ischaemia at the LVsites followed by a rapid shortening of APD. At the RV site,APD continued to increase until 5 min of ischaemia and thenshortened gradually. Consequently, dispersion of APD showeda rapid initial rise from 177.8 ± 2.7 ms to 77.8 ±10 ms (P<0.0001) followed by a slower final increase. TRTwas uniform during normal perfusion (210.4 ± 10.3, 213.1±7.8,212.1±10.3 ms, ns) but became non-uniform during globalischaemia. The dispersion of TRT increased from 15.4±4.2ms to 92.6 ± 23.2 ms (P<0.0001) during 14 min of globalischaemia. Both CT and APD contributed independently to TRTand could either augment or partially compensate for the ischaemicalterations of the other parameter. ES induced VTA only during ischaemia (3.7±1.1 VTA perheart, P<0.0001) at coupling intervals between 220 and 380ms. The dispersion of TRT of the last regular beat precedingVTA was 67.7±17.4 ms (P<0.001). ES which triggeredVTA showed a more than two-fold increase of CT dispersion comparedto the last steady state beat (122.7±29.4%, P = 0.0001). The present results show that global ischaemia results in considerableelectrophysiologic heterogeneity in the intact heart. Thesechanges may be regarded as a suitable basis of VTA, inducedby ES.     

Increased dispersion of ventricular repolarization and ventricular tachyarrhythmias in the globally ischaemic rabbit heart

Contemporary concepts of ischaemic ventricular tachyarrhythmias(VTA) are based on increased electrophysiological heterogeneityof the myocardium. We developed a multi-site monophasic actionpotential recording system for an isolated rabbit heart to studythe effects of global ischaemia on the electrophysiologicalproperties at different ventricular sites simultaneously. Thehearts were paced from the right ventricle (RV) andconductiontime (CT), action potential duration (APD) and total repolarizationtime (TRT= [CT + APD]) were measured during normal perfusionand ischaemia. The dispersion of these parameters was calculatedas the maximal difference between simultaneous recordings. Inducibilityof VTA by programmed extrastimulation (ES) was investigatedunder normal and ischaemic conditions. During global ischaemia, CT increased progressivey showing afaster and greater increase at the left ventricle (LV) thanat the RV. After 10 min the prolongation of CT reached a plateauat the LV while it continued to rise in the RV. The dispersionof CT increased from 14 ± 2.7 ms during normal perfusionto a maximum of 79.8 ± 17.2 ms after 14 min of ischaemnia(P<00001). APD was uniform at the three sites (190.9±02,185.0 and 179.3±9.8 ms, ns) during normal perfusion butchanged non-uniformly during ischaemia. There was a transientlengthening of APD until 1 and 3 min of ischaemia at the LVsites followed by a rapid shortening of APD. At the RV site,APD continued to increase until 5 min of ischaemia and thenshortened gradually. Consequently, dispersion of APD showeda rapid initial rise from 177.8 ± 2.7 ms to 77.8 ±10 ms (P<0.0001) followed by a slower final increase. TRTwas uniform during normal perfusion (210.4 ± 10.3, 213.1±7.8,212.1±10.3 ms, ns) but became non-uniform during globalischaemia. The dispersion of TRT increased from 15.4±4.2ms to 92.6 ± 23.2 ms (P<0.0001) during 14 min of globalischaemia. Both CT and APD contributed independently to TRTand could either augment or partially compensate for the ischaemicalterations of the other parameter. ES induced VTA only during ischaemia (3.7±1.1 VTA perheart, P<0.0001) at coupling intervals between 220 and 380ms. The dispersion of TRT of the last regular beat precedingVTA was 67.7±17.4 ms (P<0.001). ES which triggeredVTA showed a more than two-fold increase of CT dispersion comparedto the last steady state beat (122.7±29.4%, P = 0.0001). The present results show that global ischaemia results in considerableelectrophysiologic heterogeneity in the intact heart. Thesechanges may be regarded as a suitable basis of VTA, inducedby ES.     

Amiodarone reduces transmural heterogeneity of repolarization in the human heart

Objectives. The present work was designed to test the effects of amiodarone therapy on action potential characteristics of the three cell types observed in human left ventricular preparations.Background. The electrophysiologic basis for amiodarone’s exceptional antiarrhythmic efficacy and low proarrhythmic profile remains unclear.Methods. We used standard microelectrode techniques to investigate the effects of chronic amiodarone therapy on transmembrane activity of the three predominant cellular subtypes (epicardial, midmyocardial [M] and endocardial cells) spanning the human left ventricle in hearts explanted from normal, heart failure and amiodarone-treated heart failure patients.Results. Tissues isolated from the ventricles of heart failure patients receiving chronic amiodarone therapy displayed M cell action potential duration (404 ± 12 ms) significantly briefer (p < 0.05) than that recorded in tissues isolated from normal hearts (439 ± 22 ms) or from heart failure patients not treated with amiodarone (449 ± 18 ms). Endocardial cells from amiodarone-treated heart failure patients displayed longer (p < 0.05) action potential duration (363 ± 10 ms) than endocardial cells isolated from normal hearts (330 ± 6 ms). As a consequence, the heterogeneity of ventricular repolarization in tissues from patients treated with amiodarone was considerably smaller than in the two other groups, especially at long pacing cycle lengths.Conclusions. These findings may explain, at least in part, the reduction of ventricular repolarization dispersion and the lower incidence of torsade de pointes observed with chronic amiodarone therapy as compared with other class III agents.     

Estimates of repolarization and its dispersion from electrocardiographic measurements: direct epicardial assessment in the canine heart

This study investigates a technique to estimate dispersion based on the root mean square (RMS) signal of multiple electrocardiographic leads. Activation and recovery times were measured from 64 sites on the epicardium of canine hearts using acute in situ or Langendorff perfused isolated heart preparations. Repolarization and its dispersion were altered by varying cycle length, myocardial temperature, or ventricular pacing site. Mean and dispersion of activation and recovery times, and activation-recovery interval (ARI) were calculated for each beat. The waveform was then calculated from all leads. Estimates of mean and dispersion of activation and recovery times and mean ARI were derived using only inflection points from the RMS waveform. QT intervals were also measured and QT dispersion was determined. Estimates determined from the RMS waveform provided accurate estimates of repolarization and were, in particular, a better measure of repolarization dispersion than QT dispersion.     

兔心力衰竭时跨室壁复极离散度和缝隙连接蛋白43变化的研究

目的:探讨阿霉素诱导的兔心力衰竭(heart failure,HF)时跨室壁离散度和缝隙连接蛋白43的变化。方法:将18只日本大耳白兔随机分为对照组(n=10)及模型组(n=8)。采用阿霉素诱导建立兔HF模型。采用单相动作电位(monophasic action potential,MAP)记录技术,分别记录HF组和对照组左室心肌内、中、外膜的MAP,分别测量获得20列三层心室肌的90%动作电位时程(monophasic action potential duration,MAPD90),计算并分析跨室壁复极离散度(transmural dispersity of repolarization,TDR)的变化,TDR为每列中MAPD90 max与MAPD90 min的差值。应用免疫荧光染色法检测缝隙连接蛋白43(gap junction connexin43,CX43)在心肌细胞间分布的变化。结果:与对照组比较HF组的MAPD90缩短,TDR则明显增大(P<0.05)。免疫荧光染色法检测显示,HF组CX43分布与对照组有所差别。结论:HF组心脏TDR增加,CX43分布发生改变,其可能与HF时恶性心律失常的发生有关。     

Differential modulation of electrocardiographic indices of ventricular repolarization dispersion depending on the site of pacing during premature stimulation

INTRODUCTION: Dispersion of ventricular repolarization has been shown to increase with premature stimulation. Moreover, a straight correlation between the amount of dispersion of repolarization and the vulnerability to ventricular fibrillation was reported. On the other hand, differences between right ventricular (RV) and left ventricular (LV) fibrillation threshold have been reported. However, no data exist regarding the influence of the site of stimulation on modulation of dispersion of repolarization. METHODS AND RESULTS: In the present study, several ECG indices of dispersion of repolarization, as a function of the coupling interval and the site of stimulation, were evaluated in a modified Langendorff-perfused rabbit heart (n = 12), with a 5 x 8 array of a simulated body surface unipolar lead system. As the coupling interval was shortened, a biphasic modulation of dispersion of repolarization was found when stimuli were elicited at the LV. In contrast, when the heart was paced from the RV, the dispersion increased monotonically as coupling interval was shortened. CONCLUSION: A differential behavior of the modulation of dispersion of repolarization was found as a function of the site of stimulation.     

Temporal and spatial dispersion of repolarization during premature impulse propagation in human intact ventricular muscle: comparison between single vs double premature stimulation.

AIMS: This study was performed to determine whether or not the kinetics of action potential duration restitution during double premature stimuli (S3) differ from that during single premature stimuli (S2) in the human intact right ventricle. METHODS AND RESULTS: A monophasic action potential (MAP) was simultaneously recorded from the right ventricular apex (RVA) and outflow tract (RVOT) during programmed ventricular pacing in 11 patients with symptomatic bradyarrhythmias (five males, six females, mean age 58 years). In the five most recent patients, the RV pressure and its dp/dt were also obtained during the protocol. A substantial difference in the restitution of the MAP duration (MAPD) between S2 and S3 was observed at short diastolic intervals (< l00 ms), that is, the restitution curve of S2 showed an early biphasic pattern (upward hump), while such a phenomenon was not seen during the restitution of S3. All the quantitative parameters of MAPD restitution representing its kinetics were significantly greater in S3 than S2. Maximum attainable dispersion of repolarization between the two MAPs was significantly greater during S3 than S2 (76 +/- 17 vs 59 +/- 17 ms, P<0.05) and was mainly caused by the difference in the MAPD difference, thus by the difference in the restitution kinetics of S2 and S3. The dp/dt of the RV pressure was significantly greater during S3 than S2 for all diastolic intervals tested. CONCLUSION: It was concluded that similar to previously reported canine experimental studies, the APD restitution of S3 is substantially different from that of S2 in the human intact ventricle (endocardium).