急性血栓性心肌缺血室性心律失常的实验研究(I.方法学)

目的　用三维标测方法观察急性冠状动脉血栓性心肌缺血室性心律失常的机制。方法　向左冠状动脉回旋支（ＬＣＸ）近端释放阳极电流刺激血栓形成。结果　９ 例发生非持续性室速（ＮＳｕＶＴ）,其激动的起源和维持在心室的不同部位。６例发生持续性室速（ＳｕＶＴ）,其诱发是由于局灶性机制。Ｓｕ－ＶＴ的维持在３／６ 例是由于局灶性机制,另３ 例ＳｕＶＴ的维持,是由于心肌内的一个大折返径路,即以前壁缺血区心内膜下经间隔作为快径,而左室后壁心外膜并经心肌内返回心内膜下作为慢径。４／６ 例Ｓｕ－ＶＴ在１０～４１ｓ内蜕变成心室颤动（室颤,ＶＦ）。１ 例ＳｕＶＴ自行终止,但于１４ ｍ ｉｎ 后出现４ 个连续的室性激动诱发ＶＦ。ＶＦ诱发是由于多发的折返波形成。平均总的心肌激动时间（ＡＴ）在缺血前是（４０±４）ｍ ｓ,缺血后增加达２７～１０２ ｍ ｓ。ＳｕＶＴ发作前ＡＴ值（１０１±２８）ｍ ｓ比１ ｍ ｉｎ 前的ＡＴ值（７９±１５）ｍ ｓ明显延长（Ｐ＜ ０．０１）。ＶＦ前１０ 个持续性室速激动的平均ＡＴ值为（１６９±２９）ｍ ｓ,比ＳｕＶＴ没有发展为ＶＦ的犬的ＡＴ值明显延长。结论　ＬＣＸ的血栓栓塞可导致９０％ 的犬出现ＮＳｕＶＴ,６０％ 的ＳｕＶＴ及５０％ 的ＶＦ。     

实验性心肌梗塞后室性心动过速的低温标测与冷凝消融

对１２条犬进行了冷凝后病理学、血液动力学及动态心电图观察，另１０条犬建立心肌梗塞（简称心梗）和室性心动过速（ＶＴ）模型，并进行低温标测和冷凝消融。结果显示：①心内膜冷凝损伤灶的长、短径和深度大于心外膜冷凝（３６．６０±１１．０６ｍｍｖｓ２２．８０±３．７０ｍｍ、２９．３０±１０．９７ｍｍｖｓ１９．６０±３．１２ｍｍ、８．１４±２．４１ｍｍｖｓ５．１６±２．０３ｍｍ，Ｐ均＜０．０５），冷凝损伤灶与其周围正常心肌分界清楚。②１０条心梗犬采用电刺激或乌头碱诱发出２０次持续性ＶＴ，低温标测和冷凝消融均成功。③心外膜冷凝６条犬行动态心电图监测，均于术后３日内出现室性心律失常，７日后动态心电图检查基本恢复正常。依据上述较高的成功率、短暂致心律失常作用及无心功能障碍等可以认为低温标测和冷凝消融是治疗难治性室性心动过速的一种安全可行的方法。     

射频消融特发性室性心动过速的标测方法初探（附五例分析）

５例特发性室性心动过速（ＶＴ）经射频电流导管消融（ＲＦＣＡ）而获治愈。本文从成功的ＲＦＣＡ结果着重探讨特发性ＶＴ兴奋灶的标测方法。心内膜激动时间标测，以局部电图较体表导联ＱＲＳ波时间提前≥１０ｍｓ处定为心室最早激动点（ＥＶＡ），５例平均心室最早激动至ＱＲＳ波起始时间为１８±１１．７ｍｓ，在ＥＶＡ处放电消融仅１例成功。采用起搏标测法定位以略低于自发ＶＴ的频率沿ＥＶＡ上下左右逐点标测，寻找起搏电图至少１１个导联的ＱＲＳ波形态、振幅、极性与自发ＶＴ相同的标测点放电消融，４例均获成功。消融成功的局部电图较ＱＲＳ波平均提前２６±１２．８ｍｓ。结果提示联合应用心内膜激动时间标测和起搏标测并侧重于后者，可能是提高ＲＦＣＡ特发性ＶＴ成功率的一种有效方法。     

再灌注性心律失常的电生理实验研究

本文在20只犬实验性缺血—再灌注时。应用心电活动三维标测系统。对心肌多层次(双极针电极)进行电生理检查。结果表明,27%的非持续性室性心动过速(下简称室速)起源于缺血区的心内膜下,并与室速前—窦性心搏在缺血区发生延迟激动有关,支持壁内折返机制;73%的非持续性室速起源于再灌注的正常交界处的心内膜下,支持非折返机制,导致心室颤动(下简称室颤)的室速也起源于再灌注的正常交界处的心内膜下,支持非折返机制。上述结果支持再灌注性心律失常的多种机制学说。     

切割前房结通路对家兔房室结电生理特性的影响

为进一步了解房室结整体电生理特性以及消融治疗房室结折返性心动过速的机制，选择性切割无房室结双径现象离体家兔心的前房结通路（Ｋｃｈ三角前区）观察其对房室结电生理参数的影响。与切割前相比，切割后ＡＨ间期、房室结功能不应期、房室结前传文氏周长、室房逆传文氏周长及ＶＡ间期延长（分别为４５．６４±８．６８ｍｓｖｓ３８．２３±６．１３ｍｓ，１６６．３４±１５．３３ｍｓｖｓ１４４．４８±１０．８６ｍｓ，１６３．３７±１７．２２ｍｓｖｓ１３８．３６±１２．４３ｍｓ，２０２．６０±４１．５０ｍｓｖｓ１６８．５０±２０．３０ｍｓ，６８．６０±１．６０ｍｓｖｓ５４．５０±７．１０ｍｓ，Ｐ均＜０．０５）。提示毁损房室交界区特定部位可以影响房室结整体电生理特性。     

用实验性心力衰竭制作持续性心房颤动模型

为探讨实验性心力衰竭（简称心衰）形成持续性心房颤动（简称房颤）的可行性，用２００～２５０ｐｐｍ的频率以ＶＯＯ方式起搏犬心室３～７周形成实验性心衰，在犬清醒状态下观察心衰前、后刺激诱发的房性快速心律失常。快速起搏右室３～７周，８条犬均发生充血性心衰，３周时体重由心衰前的２８±６ｋｇ降至２４±４ｋｇ（Ｐ＜０．０５）；左室射血分数由０．６４±０．０６降至０．２３±０．０９（Ｐ＜０．０１），右房直径由２５±３ｍｍ增至３６±６ｍｍ（Ｐ＜０．０１），心房不应期由１１６±５ｍｓ增至１３７±１２ｍｓ（Ｐ＝０．０１），不应期离散度无显著性改变（１６±１２ｍｓｖｓ２０±９ｍｓ，Ｐ＝０．２０），心房平均传导时间亦无显著性变化（６１±１９ｍｓｖｓ６６±２４ｍｓ，Ｐ＝０．２０）。１条犬于起搏后第６周夜间突然死亡。心衰前，８条犬均未诱发心房扑动，４条犬诱发短暂房颤；心衰后，８条犬均可反复诱发心房扑动和持续性房颤（持续时间超过１５ｍｉｎ，平均周长９５±５ｍｓ），最长者持续２４ｈ以上。结果表明起搏心室导致犬心衰可形成非瓣膜病性慢性房颤的实验模型。     

房室慢旁道的电生理表现及射频消融治疗

报道射频导管消融（ＲＦＣＡ）治疗慢旁道参与的房室折返性心动过速患者１１例。电生理检查和静脉注射ＡＴＰ（７例）试验发现：①增频刺激右室心尖部时，ＶＡ文氏点为１８３．２±２２．６（１６０～２３０）ｂｐｍ，达１１室房传导的最高刺激频率时最早心房激动部位的室房传导时间较基础频率刺激时最早心房激动部位的室房传导时间（ＢＶＡＥ）延长６８．８±２９．８（４６～１０９）ｍｓ，Ｐ＜０．０１。心室程控刺激时旁道阻滞前最早心房激动部位的室房传导时间较ＢＶＡＥ延长１０７．６±４１．８ｍｓ，Ｐ＜０．０１，表明慢旁道传导表现为传导速度慢以及出现频率依赖性递减传导和文氏阻滞。②连续心室刺激时静脉注射ＡＴＰ７例中有５例于注射后２０．６±２．０（１８～２３）ｓ出现完全性室房阻滞，另２例室房传导时间逐渐延长。提示ＡＴＰ可使慢旁道的室房传导发生阻滞或传导时间延长。③心动过速时逆传激动顺序异常，与Ｈ波同步刺激心室均能夺获心房。④ＲＦＣＡ可成功阻断慢旁道，有效靶点的室房传导时间为１３３．６±２１．１（１２８～１６０）ｍｓ，Ａ波超前最早参照点为２６．４±８．４（２０～４０）ｍｓ，有效靶点逆传房波前有旁道电位。结论：上述结果提示慢旁道的电生理特点和     

与室性心动过速有关的心电学改变

目的　观察在动态心电图中，室性心动过速（室速）发生前，心电学指标的改变。方法　７ 例在动态心电图中有持续性室速或频发非持续性室速的患者被列入观察。结果　与无室速时的ＱＴｃ差值（７．３±１．９ｍ ｓ）相比，室速前１０ 分钟的ＱＴｃ差值（３０．６±２４．２ｍ ｓ）较大（Ｐ＝ ０．０４９）。结论　心室复极的不稳定参与了室速的形成。     

缺血性心脏病患者心率变异性研究

应用Ｈｏｌｔｅｒ，测定４０～４９，５０～５９，６０～６９以及７０岁以上４个年龄段的缺血性心脏病患者的心率变异性（ＨＲＶ）并与相应年龄的对照组进行比较，指标为时域法的２４ｈ平均正常Ｒ－Ｒ间期标准差（ＳＤＮＮ）。结果：缺血组与对照组各年龄段比较有显著性差异，分别为：１４１．５２±２８．９２ｍｓＶＳ９３．７２±２７．５４ｍｓ；１３２．４２±２７．６３ｍｓＶＳ９３．１９±３３．１８ｍｓ；１２１．８４±２７．８７ｍｓＶＳ７４．５０±２４．０１ｍｓ；１１０．３１±２３．９６ｍｓＶＳ６３．９３±２３．７３ｍｓ，Ｐ均＜０．０１；对照组及缺血组的ＨＲＶ均随年龄增长呈下降趋势（组内比较，Ｐ均＜０．０１），呈完全负相关（ｒ（对照组）＝－０．９５，ｒ（缺血组）＝－０．９８）。随访发现缺血组中ＨＲＶ≤５０ｍｓ患者发生心源性猝死（ＳＣＤ）９例和室性心动过速１例；＞５０ｍｓ者发生ＳＣＤ２例。     

室性早搏的定位研究

本文将乌头碱注入犬(22只)心肌内诱发室速,在乌头碱注射点及周围诸点描记心外膜电图。初步证明室速的心外膜电图在乌头碱注射点呈QS波,在外周诸点呈rS(或Rs)波。说明室速发生部位的心外膜电图以QS波为特征。因为连续室早可构成室速,因此上述规律也适用于室性早搏。而且发现结扎犬冠脉前降支诱发室性早搏,其心外膜电图的QS波发生在心肌缺血区。临床21例频发室性早搏病人的胸前导联电图分析表明,15例室早在右侧胸壁上呈QS波;另6例室早在左侧胸壁上呈QS波,皆有器质性病变。     

Intramural activation of the human ventricle: findings in normal and abnormal myocardial segments in patients with coronary artery disease

To define the intramural electrical activation of normal and abnormal myocardial segments in patients with coronary artery disease, mapping was performed using a plunge electrode with 10 electrodes 1 mm apart. Five transmural bipolar electrograms (40 to 500 Hz) were recorded from 79 sites in 13 patients at the time of open-heart surgery. The results were correlated with ventriculography. In 64 sites with normal contraction, activation spread from endocardium to epicardium in 20.5 +/- 2 msec, and no electrograms were abnormal. Activation time did not differ between the different anatomic segments. In the eight hypokinetic sites, activation spread from endocardium to epicardium in 22.2 +/- 2 msec, and no electrograms were abnormal. In the seven sites with akinesis or dyskinesis, abnormal electrograms were noted and were concentrated towards the endocardium. In four patients, the 40% to 80% of electrograms closest to the endocardium were abnormal, while in three patients all transmural electrograms were abnormal. The variable depth of electrically abnormal tissue should be considered in operations and ablative procedures for ventricular arrhythmias.     

Activation sequence of ventricular tachycardia: endocardial and epicardial mapping studies in the human ventricle

Thirty-five patients with ischemic heart disease and ventricular arrhythmias underwent intraoperative activation mapping at the time of coronary artery bypass surgery. During ventricular tachycardia, the sequence of activation in the intact ventricle was recorded simultaneously from 110 endocardial or 110 epicardial sites, or both. A balloon array of electrodes, inserted across the mitral valve, was used to obtain endocardial recordings in the left ventricle, and this appeared to facilitate the induction of ventricular tachycardia. Of 61 episodes of tachycardia, 16 (15 patients) were recorded with the epicardial sock and 45 (20 patients) with the additional use of the endocardial balloon. The sequence of activation during tachycardia was observed to conform to one of four configurations: monoregional spread was the most common activation sequence recorded on both the endocardium and epicardium, while biregional activation and figure eight sequences were recorded exclusively on the epicardium and endocardium, respectively. The fourth sequence was a circular spread of activation observed on both surfaces. Continuous activation throughout the tachycardia cycle length was an infrequent finding. Simultaneous recordings of endocardial and epicardial activation were obtained in 45% of episodes. The sequence of activation recorded on one surface was matched by a similar sequence on the remaining surface in less than half of these. The onset of endocardial activation preceded that of the epicardium in greater than 90% of tachycardia episodes, and the duration of left ventricular endocardial excitation often exceeded that recorded epicardially over both ventricles. The epicardium, however, did appear to be an important determinant of surface electrocardiographic configuration.     

Layered activation of epicardial scar in arrhythmogenic right ventricular dysplasia: possible substrate for confined epicardial circuits

Background- Ventricular tachycardia ablation in arrhythmogenic right ventricular dysplasia (ARVD) is more successful when including epicardial ablation. Scarring may cause independent, layered epicardial activation and promote epicardially confined ventricular tachycardia circuits. We aimed to characterize transmural right ventricular activation in ARVD patients and to compare this with reference patients without structural heart disease. Methods and Results- Eighteen ARVD patients underwent detailed endocardial and epicardial sinus rhythm electroanatomic mapping. Bipolar activation was annotated at the sharpest intrinsic deflection including late potentials and compared with 6 patients with normal hearts. Total scar area was larger on the epicardium (97±78 cm(2)) than the endocardium (57±44 cm(2); P=0.04), with significantly more isolated potentials. Total epicardial activation time was longer than endocardial (172±54 versus 99±27 ms; P<0.01), and both were longer than in reference patients. Earliest endocardial site was the right ventricular anteroseptum in 17 of 18 ARVD patients versus 5 of 6 controls (P=0.446), and latest endocardial site was in the outflow tract in 13 of 18 ARVD patients versus 4 of 6 controls and tricuspid annulus in 5 of 18 ARVD patients versus 2 of 6 controls (P=1.00). In reference patients, epicardial activation directly opposite endocardial sites occurred in 5.2±1.9 ms, suggesting direct transmural activation. In contrast, ARVD patients had major activation delay to the epicardium with laminar central scar activation from the scar border, not by direct transmural spread from the endocardium. Conclusions- Transmural right ventricular activation is modified by ARVD scarring with a delayed epicardial activation sequence suggestive of independent rather than direct transmural activation. This may predispose ventricular tachycardia circuits contained entirely within the epicardium in ARVD and explains observations on the need for direct epicardial ablation to eliminate ventricular tachycardia.     

Epicardial electrogram of the right ventricular outflow tract in patients with the Brugada syndrome: using the epicardial lead

OBJECTIVES: We tried to record an epicardial electrogram directly, and we examined local electrograms before and after administration of a class IC anti-arrhythmic drug in patients with the Brugada syndrome. BACKGROUND: Electrical heterogeneity of the epicardium in the right ventricular outflow tract (RVOT) has been thought to be related to the Brugada syndrome. However, an epicardial abnormality has not been demonstrated in patients with the Brugada syndrome. METHODS: In five patients with a Brugada-type electrocardiogram (ECG), local unipolar electrograms were recorded at the epicardium and endocardium of the RVOT. To record the epicardial electrogram directly, we introduced an electrical guidewire into the conus branch (CB) of the right coronary artery. The duration of the local electrogram after termination of the QRS complex (DP) was measured before and after class IC anti-arrhythmic drug administration. The signal-averaged electrocardiogram (SAECG) was also obtained in all patients. RESULTS: A definite DP was observed at the epicardium, but not at the endocardium. After administration of a class IC anti-arrhythmic drug, the DP at the epicardium was prolonged from 38 +/- 10 ms to 67 +/- 24 ms. The late potential corresponding to the DP at the epicardium was observed in all patients on the SAECG. CONCLUSIONS: An epicardial electrogram can be recorded from the CB. Recording from the CB enables identification of an epicardial abnormality in patients with the Brugada syndrome. These abnormal electrograms may be related to a myocardial abnormality in the epicardium of patients with the Brugada syndrome.     

氯沙坦对犬在体急性缺血心肌跨室壁复极不均一性的影响

目的:探讨氯沙坦对犬在体心肌急性缺血时跨室壁复极离散度(TDR)及心律失常发生率的影响。方法:16只健康家犬,均分为2组:①单纯缺血组:阻断左前降支主干30 min,同步记录犬在体心外膜、中层及心内膜心肌单相动作电位(MAP)及体表心电图,分析其相关参数的变化。②氯沙坦组:氯沙坦5mg·kg-1·d-1经胃管灌入,持续2周后开胸,余同单纯缺血组。结果:单纯急性缺血状态下3层心肌MAP时程(MAPD)均明显缩短,且心外膜、心内膜的MAPD缩短程度较中层心肌的MAPD缩短程度更为明显,心外膜、心内膜的MAPD与中层心肌的MAPD相比差异有显著性意义(P<0.05)。3层心肌间TDR增大。急性缺血30 min内,4只出现了室性心动过速或(和)心室颤动而死亡,恶性心律失常发生率达50％。氯沙坦组在急性缺血时,3层心肌MAPD缩短程度趋于一致,TDR较单纯缺血组减小,差异有显著性意义(P<0.05),无一例出现室性心动过速或(和)心室颤动,与单纯缺血组恶性心律失常发生率相比差异有显著性意义(P<0.01)。结论:氯沙坦可减小急性缺血心肌的TDR,且可能因此而降低急性缺血时恶性心律失常的发生率。     

Substrate in the interventricular septum for left ventricular and right ventricular outflow tract tachycardia: ablation from the right side of the septum

Simultaneous epicardial and endocardial mapping demonstrated that in a substantial number of ventricular tachycardias (VTs) endocardial, intramural, and epicardial structures are involved in the substrate of the reentrant circuits. Both right and left ventricular breakthrough has also been described during VT originating in the interventricular septum. We report the case of a patient with a nonischemic left ventricular aneurysm presenting with a left ventricular outflow tract (LVOT) tachycardia and a right ventricular outflow tract (RVOT) tachycardia. Mapping from the anterior interventricular vein and the endocardium of the RVOT revealed mid-diastolic potentials at the epicardium of the LVOT and the endocardium of RVOT, where the criteria of central isthmus sites could be demonstrated. Ablation targeting an isolated late potential during sinus rhythm in RVOT eliminated both the LVOT tachycardia and the RVOT tachycardia. In this patient with a nonischemic left ventricular aneurysm, the substrate of a LVOT tachycardia and RVOT tachycardia is described, and successful catheter ablation of the right and left ventricular tachycardia from the septal wall of RVOT is reported.     

The relationship between ventricular arrhythmias and ischemia-induced conduction delay in closed-chest animals within 24 hours of myocardial infarction

To investigate the myocardial conduction characteristics of premature impulses during the first 24 hours following coronary ligation and its relationship to late infarction ventricular arrhythmias, transmural electrodes were positioned in the normal and ischemic myocardium in nine dogs. Cardiac conduction in ischemic myocardium was delayed 15 minutes post coronary occlusion both in the epicardium and endocardium, both in the anterograde (base to apex) and retrograde (apex to base) direction, and was maintained at the same level throughout the experiment. Conduction across the border of ischemic myocardium from ischemic to the normal segment was also delayed, especially in the endocardium. Spontaneous ventricular arrhythmias recorded on Holter tapes showed significant increase in the number of premature ventricular complexes and ventricular tachyarrhythmias 9 hours after infarction. Thus our findings suggest that spontaneous arrhythmias occurring in the late phase of acute myocardial infarction (AMI) are independent of the ischemia-induced conduction delay and an alternate mechanism such as abnormal automaticity may be responsible for late ventricular arrhythmias.     

Anterior left ventricular aneurysm: factors associated with the development of sustained ventricular tachycardia

Fifty patients with anteroapical left ventricular aneurysm secondary to prior myocardial infarction underwent aneurysmectomy, at which time endocardial sinus rhythm mapping was performed. Forty patients had a history of recurrent sustained monomorphic ventricular tachycardia, and 10 had an aneurysm but no history of spontaneous sustained tachycardia. A comparison of the clinical, angiographic and sinus rhythm endocardial electrographic characteristics of these two groups revealed that the patients without spontaneous ventricular tachycardia had more severe coronary artery disease (2.6 +/- 0.5 versus 1.9 +/- 0.8 coronary arteries having greater than 70% stenosis; p less than 0.03), underwent surgery earlier after infarction (3 +/- 2 versus 46 +/- 53 months; p less than 0.03) and had less extensive wall motion abnormalities on contrast ventriculography (0 of 8 versus 13 of 35 patients assessed had an abnormally contracting ventriculographic segment length greater than 60%; p less than 0.04). During intraoperative programmed electrical stimulation, all 40 patients with and 4 of 10 without a history of spontaneous ventricular tachycardia had inducible tachycardia. The patients with inducible tachycardia had a larger area of endocardium from which abnormal electrograms (duration greater than 70 ms or amplitude less than 0.7 mV) were recorded (62 +/- 17 versus 45 +/- 20% of electrograms; p less than 0.03) as well as fractionated (duration greater than 90 ms, amplitude less than 0.3 mV) electrograms (20 +/- 14 versus 9 +/- 7% of electrograms; p less than 0.04) than did patients without inducible tachycardia, but there were no angiographic differences between groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ablação epicárdica percutânea em arritmias ventriculares

IntroductionReentrant circuits of ventricular tachycardia may involve not only the endocardium but also the epicardium. Epicardial ablation can be useful in these situations.ObjectiveThe aim of this study was to assess efficacy, safety and complications in a series of consecutive patients who underwent ablation of ventricular tachycardia with epicardial mapping.MethodsThe study included all patients undergoing ventricular tachycardia ablation with epicardial mapping from 2004 to 2012. Of a total of 95 ablations, an epicardial approach was attempted in nine patients, eight male, mean age 58±12 years. Endocardial mapping was performed in all patients previously or simultaneously. The etiology of the arrhythmia was non‐ischemic in eight patients and ischemic in one. We compared the number of events in the six months prior to the epicardial procedure and six months after.ResultsPercutaneous epicardial access was achieved in eight patients. In one case it was not possible due to the presence of adhesions. In none of the patients was the procedure repeated and there were no major complications during hospitalization. In a mean follow‐up of 3.5±1.2 years, one patient suffered stroke; there were no other medium‐to‐long‐term complications and the number of ventricular tachycardia episodes was reduced in all patients after ablation.ConclusionsEpicardial radiofrequency ablation of ventricular tachycardia was effective in reducing morbidity in eight patients, with a low risk of complications in the short and medium‐to‐long term.     

Nonuniform epicardial activation and repolarization properties of in vivo canine pulmonary conus

The relation between nonuniform epicardial activation and ventricular repolarization properties was studied in 14 pentobarbital anesthetized dogs and with a computer model. In 11 dogs, isochrone maps of epicardial activation sequence were constructed from electrograms recorded from the pulmonary conus with 64 electrodes on an 8 X 8 grid with 2-mm electrode separation. The heart was paced from multiple sites on the periphery of the array. Uniformity of epicardial activation was estimated from activation times at test sites and their eight neighboring sites. Acceleration shortened and deceleration prolonged refractory periods. The locations of acceleration and deceleration sites of activation differed during drives from various sites, and differences in uniformity of activation during pairs of drives were correlated to differences in refractory periods (r = 0.76, range 0.59-0.93). In three additional experiments, transmural activation sequence maps were constructed from electrograms recorded from needle-mounted electrodes placed upstream and downstream to epicardial activation delays. Activation proceeded from epicardium to endocardium upstream to the delays and from endocardium to epicardium downstream to the delays. A computer simulation of two-dimensional action potential propagation based on the Beeler-Reuter myocardial membrane model provided insights to the mechanism for the results of the animal experiments. The two-dimensional sheet modeled the transmural anisotropic histology of the canine pulmonary conus and corresponded to previous reports and histology of specimens from five experiments. Simulated activation patterns were similar to those found in the experimental animals. In addition, action potentials were electronically prolonged at sites of deceleration and shortened at sites of acceleration, results comparable to the animal experiments. Our findings demonstrate that the location of areas of nonuniform epicardial activation is dependent on drive site and that nonuniform activation electronically modulates repolarization properties. Therefore it seems likely that the site of origin of ectopic ventricular complexes, especially in ischemic myocardium where activation is nonuniform, could be an important determinant of whether ectopic activity initiates sustained tachyarrhythmias.