Reentry site during fibrillation induction in relation to defibrillation efficacy for different shock waveforms

INTRODUCTION: Unsuccessful defibrillation shocks may reinitiate fibrillation by causing postshock reentry. METHODS AND RESULTS: To better understand why some waveforms are more efficacious for defibrillation, reentry was induced in six dogs with 1-, 2-, 4-, 8-, and 16-msec monophasic and 1/1- (both phases 1 msec) 2/2-, 4/4-, and 8/8-msec biphasic shocks. Reentry was initiated by 141+/-15 V shocks delivered from a defibrillator with a 150-microF capacitance during the vulnerable period of paced rhythm (183+/-12 msec after the last pacing stimulus). The shock potential gradient field was orthogonal to the dispersion of refractoriness. Activation was mapped with 121 electrodes covering 4 x 4 cm of the right ventricular epicardium, and potential gradient and degree of recovery of excitability were estimated at the sites of reentry. Defibrillation thresholds (DFTs) were estimated by an up-down protocol for the same nine waveforms in eight dogs internally and in nine other dogs externally. DFT voltages for the different waveforms were positively correlated with the magnitude of shock potential gradient and negatively correlated with the recovery interval at the site at which reentry was induced by the waveform during paced rhythm for both internal (DFT = 1719 + 64.5VV - 11.1RI; R2 = 0.93) and external defibrillation (DFT = 3445 + 150VV - 22RI; R2 = 0.93). CONCLUSION: The defibrillation waveforms with the lowest DFTs were those that induced reentry at sites of low shock potential gradient, indicating efficacious stimulation of myocardium. Additionally, the site of reentry induced by waveforms with the lowest DFTs was in myocardium that was more highly recovered just before the shock, perhaps because this high degree of recovery seldom occurs during defibrillation due to the rapid activation rate during fibrillation.     

Alteration of Ventricular Fibrillation by Propranolol and Isoproterenol Detected by Epicardial Mapping with 506 Electrodes

Adrenergic Effects on VF. Introduction: We hypothesized that drugs which alter ventricular refractoriness or excitability produce quantifiable changes in ventricular fibrillation. Methods and Results: We used a 528-channel mapping system to quantify the effects of the beta-antagonist, propranolol, and the beta-agonist, isoproterenol, on activation patterns in ventricular fibrillation. A plaque of 506 (22 × 23) electrodes spaced 1.12 mm apart and covering about 5% of the ventricular epicardium was sewn to the anterior right ventricle in 18 pigs (30 kg). Propranolol (0.25 to 0.4 mg/kg) increased the refractory period at a right ventricular epicardial site while isoproterenol (3 to 5 μg/min) shortened it. Ventricular fibrillation was induced by programmed stimulation, and unipolar electrograms were recorded from the 506 plaque electrodes for 2 seconds beginning 1, 15, and 30 seconds after the onset of fibrillation. Active epicardial recording sites were identified from the first derivative of the unipolar potentials (dV/dt) detected at each electrode. Then, neighboring active sites were grouped into activation fronts by computer analysis. In six pigs the effect of repeated inductions of ventricular fibrillation was assessed by comparing ventricular fibrillation after saline with a preceding control episode of fibrillation. Each activation front excited 40%± 46% of the mapped region before blocking. No changes were observed with saline and multiple inductions of fibrillation. In another six pigs, ventricular fibrillation after propranolol was compared with a preceding control episode of fibrillation. Ventricular fibrillation alter propranolol exhibited a decreased activation rate per epicardial recording site and fewer activation fronts per second. There was no change in the amount of tissue excited by each activation front or the number of reentry cycles per activation front compared with control. In addition, there was no change in the maximum negative dV/dt detected per activation at an epicardial site. In six pigs ventricular fibrillation during isoproterenol was compared with control episodes of ventricular fibrillation before and 45 minutes after washout of the drug. The control episodes of fibrillation were not different from each other. Compared with control, ventricular fibrillation during isoproterenol exhibited an increased activation rate per epicardial site, an increased amount of tissue excited by each activation front, and an increased maximum negative dV/dt for each activation. There was no change in the number of activation fronts per second or the number of reentry cycles per activation front compared with control. Conclusions: Quantitative analysis revealed that propranolol and isoproterenol do not have symmetrically opposite effects on ventricular fibrillation. Propranolol decreased the number of activation fronts while isoproterenol increased the amount of tissue excited by each activation front. Thus, drugs that alter ventricular refractoriness or excitability alter ventricular fibrillation.     

Effect of site of pacing on dispersion of refractoriness

The variation in dispersion of ventricular refractoriness with different sites of pacing was measured in 11 patients not taking antiarrhythmic drugs. Dispersion of refractoriness between 3 right ventricular sites was determined at constant paced cycle lengths (S1S1). Refractoriness to ventricular extrastimulation (S2) using atrial pacing vs "clinical" pacing (drive or S1 at the right ventricular apex) vs the conventional measurement of dispersion (S1 at the site of S2) was compared. Effective and functional refractory periods (ERP and FRP) were measured from electrograms at the site of application of S2. Dispersion of ERP was always wider using clinical pacing (65.4 +/- 26 ms [+/- standard deviation]) than atrial pacing or traditional drive (20.4 +/- 14 and 19.1 +/- 10 ms, p less than 0.0001). Similarly, dispersion of FRP was greater with clinical pacing (45.0 +/- 35 vs 21.8 +/- 14 and 17.3 +/- 13, p less than 0.011). In 2 patients with left bundle branch block these differences were most striking. Clinical pacing foreshortened FRP relative to ERP (FRP shorter than ERP by an average 12.5 ms at nonapical sites) but this did not induce tachycardias, perhaps because FRP was still longer than the shortest V1V2 achieved conventionally (FRP was longer at nonapical sites than at the apex using clinical pacing, p less than 0.05). With atrial pacing there is less dispersion of refractoriness than with clinical ventricular pacing, although this difference is not appreciated when dispersion is measured in the conventional manner.     

Cellular mechanism of reentry induced by a strong electrical stimulus: implications for fibrillation and defibrillation

The objective of this review article is to describe the graded response hypothesis of reentry induced by a strong single electrical stimulus in the normal canine ventricular myocardium. It is shown that the graded responses (subthreshold depolarization during phase 3 of the action potential) induced at a site distant (S2) from the regular S1--S1 pacing site, propagate slowly over short distances (approximately 5 mm) and initiate a regenerative action potentials in recovered cells near the S1 site. Activation wave then blocks near the S2 site (unidirectional block) but reenters when the S2 site recovers it excitability. Super strong S2 currents do not induce reentry (upper limit of vulnerability). Since similar activation sequence and properties are shown to exist in intact canine hearts during induction of ventricular fibrillation with a similar S2 stimulus, the graded response hypothesis may have relevance to vulnerability to fibrillation. Furthermore, since the upper limit of vulnerability is closely related to defibrillation threshold, the graded response hypothesis might also be relevant to defibrillation mechanism. Other proposed mechanisms of fibrillation and defibrillation (critical point hypothesis, the progressive depolarization hypothesis and the hypothesis of phase singularity of defibrillation failure) are also discussed in this review paper and compared to the graded response hypothesis.     

Proarrhythmic effects of ventricular electrical catheter ablation in dogs

Electrical catheter ablation of arrhythmogenic sites is a new therapy for ventricular tachycardia that is still being investigated. Recent studies have shown, however, that the procedure itself can provoke serious ventricular arrhythmias. The incidence, course and mechanism of these arrhythmias were studied in 10 beagles treated with a single R wave-synchronized cathodal shock delivered to the endocardial ventricular wall (5 dogs left ventricular, 5 dogs right ventricular). Shocks were delivered at 30 (four dogs), 80 (two dogs) or 250 J (four dogs). Each dog underwent programmed electrical stimulation at or near the ablation site before, within 1 hour after and 1 week after the shock. Holter electrocardiographic monitoring (24 hours) was performed during day 1 and 7 after the shock in all the dogs, and extended Holter monitoring was done during the first 5 days in four dogs. All dogs survived for 1 week. Within 10 minutes after the shock, a sustained ventricular tachycardia was recorded in nine dogs; deterioration into ventricular fibrillation occurred in two dogs. In nine dogs, 60 to 169 monomorphic ventricular tachycardia episodes (mean 101) occurred on day 1 and 0 to 11 (mean 3) occurred on day 7; Holter monitoring failed for technical reasons in one dog. Extended Holter monitoring showed a marked decline in the incidence of tachycardia during the first 3 days. Early activation during ventricular tachycardia was always derived at or near the ablation site, and the QRS configuration during pre- and postablation pacing at this site was identical to the tachycardia configuration. Ventricular tachycardia was never inducible with programmed stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reentrant ventricular rhythms in the late myocardial infarction period: prevention of reentry by dual stimulation during basic rhythm

Stimulation at two ventricular sites during basic rhythm as a means of preventing the induction of ventricular arrhythmias in the postinfarction heart was investigated. Isochronal maps of ventricular epicardial activation from dogs were analyzed 4 days after ligation of the left anterior descending coronary artery. Activation patterns were obtained by use of a computerized data acquisition system recording from 62 sites. Effective refractoriness and conduction time during basic paced rhythm (S1) for each site were summed to construct isochronal maps of recovery time. The patterns of recovery time on the heart were eccentrically layered, with a narrow zone of differentially prolonged recovery time along one border of the infarct. The formation of an arc of functional conduction block after premature stimulation (S2) was correlated with regions of differentially prolonged recovery time (59 +/- 30 msec, mean +/- SD) between recording sites spaced 5 to 10 mm apart. The recovery time difference between sites that did not block (17 +/- 14 msec) was significantly shorter. The spatial distribution of recovery time on the heart could be modified by application of stimuli at two sites during the basic rhythm. Reentry was prevented by appropriate placement of the secondary site in the ischemic zone and the temporal sequencing of the paired stimuli. Stimulation at the secondary site "peeled back" refractoriness in the ischemic zone. Prevention of reentry was a result of either: (1) a shift in the arc of conduction block toward the ischemic zone, (2) a reduction in the extent of the continuous arc, (3) early activation of regions distal to the arc, or (4) a combination of the above. In two dogs, the arc of block was abolished entirely after dual stimulation. This report illustrates the criteria for effective prevention of reentry, applied to a well-described verifiable model of reentrant activation.     

Factors related to the induction of ventricular fibrillation in the normal canine heart by programmed electrical stimulation

Programmed electrical stimulation was performed in eight normal dogs using a stimulator and endocardial electrode catheters identical to those used in human studies. The right and left ventricular apex were paced at a drive cycle length of 400 ms and, in some cases, 500 ms, with a pacing sequence of single (S1S2), double (S1S2S3) and triple (S1S2S3S4) premature impulses introduced after eight paced complexes. Pacing sequences were performed using combinations of pulse width (1, 2 and 4 ms) and current strengths of 2, 5 and 10 times diastolic threshold, and in three dogs, 15 times diastolic threshold. Twenty-two episodes of ventricular fibrillation were initiated in five dogs in 170 pacing sequences using current strengths up to 10 times diastolic threshold, and six episodes of ventricular fibrillation in the two of three remaining dogs tested at 15 times diastolic threshold. Ventricular fibrillation was reproducible on seven of nine occasions. Ventricular fibrillation was never induced by S1S2 at up to 15 times diastolic threshold; it was induced by S1S2S3 in 3 (1.8%) of 170 sequences, but only at 10 times diastolic threshold. It was induced by S1S2S3S4 in 19 (11.4%) of 167 sequences using 2 to 10 times diastolic threshold, although 20 of 28 episodes only occurred with S1S2S3S4 at 10 or more times diastolic threshold.(ABSTRACT TRUNCATED AT 250 WORDS)     

左心室心外膜不同部位起搏对心室不应期离散度的影响

目的:通过模拟心脏再同步治疗中左室电极在左心室心外膜不同部位起搏情况,观察不同部位起搏对心室不应期离散度的影响。方法:采用6只犬开胸,在其左心室前侧壁心外膜缝上1块含有144(12×12)个单极电极(电极间距2 mm)的电极板。选取位于电极板对角处的2个起搏部位(左上角靠近心底部,右下角靠近心尖部),采用连续起搏方法,记录起搏周期为300 ms时整个电极板上每个单极电极上的激动恢复间期,通过其标准差及变异系数评估不应期离散度。结果:近心底部与近心尖部起搏时起搏阈值及心室激动恢复间期无显著差异[起搏阈值(0.34±0.22)mA比(0.26±0.05)mA;激动恢复间期(144.3±12.4)ms比(147.7±14.8)ms,均P>0.05]。但是,近心底部位起博的不应期离散度较近心尖部起搏的不应期离散度显著减小[标准差(4.3±0.8)ms比(5.8±0.7)ms,P<0.01;变异系数(0.030±0.006)比(0.039±0.005),P<0.01]。结论:在心脏再同步治疗左室电极植入过程中,选择恰当的左室电极植入部位有利于降低不应期离散度。     

心室不应期离散度及激动周期变异与心室颤动诱发的关系

目的 研究不应期离散度及激动周期变异与心室颤动(VF)诱发的关系.方法 采用6只开胸犬,在其左心室前壁心外膜缝上一块含有12×12个单极电极(电极间距2mm)的电极板.采用连续起搏方法,分别记录300 ms、200 ms及诱发VF或失去1:1心室夺获前不应期及激动周期.通过不应期标准差及其变异系数测定不应期离散度,激动...     

Spatiotemporal heterogeneity in the induction of ventricular fibrillation by rapid pacing: importance of cardiac restitution properties.

The mechanism by which rapid pacing induces ventricular fibrillation (VF) is unclear. We performed computerized epicardial mapping studies in 10 dogs, using 19-beat pacing trains. The pacing interval (PI) of the first train was 300 ms and then was progressively shortened until VF was induced. For each PI, we constructed restitution curves for the effective refractory period (ERP). When the PI was long, the activation cycle length (CL) was constant throughout the mapped region. However, as the PI shortened, there was an increase in the spatiotemporal complexity of the CL variations and an increase in the slope of the ERP restitution curve. In 5 dogs, we documented the initiation of VF by wavebreak at the site of long-short CL variations. Computer simulation studies using the Luo-Rudy I ventricular action potential model in simulated 2-dimensional tissue reproduced the experimental results when normal ERP and conduction velocity (CV) restitution properties were intact. By altering CV and ERP restitutions in this model, we found that CV restitution creates spatial CL variations, whereas ERP restitution underlies temporal, beat-to-beat variations in refractoriness during rapid pacing. Together, the interaction of CV and ERP restitutions produces spatiotemporal oscillations in cardiac activation that increase in amplitude as the PI decreases, ultimately causing wavebreak at the site of intrinsic heterogeneity. This initial wavebreak then leads to the formation of spiral waves and VF. These findings support a key role for both CV and ERP restitutions in the initiation of VF by rapid pacing.     

Excitation of ischemic myocardium: altered properties of conduction,refractoriness, and excitability

Reentrant ventricular arrhythmias arise in variable epicardium overlying the “transmural” infarction zone in the dog 3 to 9 days after left anterior descending coronary artery ligation. Effects of pacing (90 to 360 beats/minute) from the epicardium in the normal zone and ischemic zone were studied in 18 dogs using standard ECG leads and epicardial recordings. Pacing in the normal zone at any stimulus strength showed no changes in QRS morphology at these heart rates. During pacing at ischemic zone sites, QRS morphology changed with heart rate in association with conduction delays in the ischemic zone. This effect could be reversed by increasing the stimulus strength. Refractoriness in the ischemic zone was tested by programmed pacing. Abnormally short (≤ 130 msec.) and long (≥ 330 msec.) refractoriness coexisted within the ischemic zone. This marked dispersion of refractoriness was related to the occurrence of reentrant ventricular arrhythmia. In 10 dogs a 3 × 4 cm. section of ventricular epicardium was removed which included normal and ischemic zones. Action potentials were recorded during superfusion with Tyrode's solution at 37°C. Rate-dependent reentrant ventricular arrhythmias were initiated in 90% of the tissue studied. At a constant stimulus strength, action potentials recorded close to the stimulation site showed progressively shorter (< 100 msec.), diminutive responses as the heart rate was increased. Intermittent failure of excitation was noted at higher rates. Rate-sensitive changes in conduction, refractoriness, and excitation are determinants of reentrant ventricular arrhythmia originating in the ischemic zone epicardium.     

Comparison of activation during ventricular fibrillation and following unsuccessful defibrillation shocks in open-chest dogs

The purpose of this study was to map in detail the spread of activation away from sites of early postshock excitation following unsuccessful defibrillation to determine whether these activation fronts are the unaltered continuation of activation fronts present just before the shock. We recorded simultaneously from 120 bipolar electrodes on 40 plunge needles in a 20 x 35 x 5-mm volume of tissue of the right ventricular outflow tract immediately before and after shocks of 190-350 V were given via electrodes on the right atrium and left ventricular apex to six open-chest dogs with electrically induced ventricular fibrillation. For 20 shocks approximately 100 V below the defibrillation threshold, the site of earliest recorded activation following the shock was near the center of the mapped region. At the earliest recorded activation sites, there was an isoelectric window in the immediate postshock period lasting 42 +/- 15 msec after which activation fronts either spread away from a site in all directions in a focal pattern (12 episodes) or else spread away in only one direction (eight episodes). Comparison of activation patterns immediately before and after the shock revealed that in 18 of the 20 episodes, the location and pathway of activation fronts after the shock were markedly different from those before the shock. The preshock intervals at the sites of earliest activation following the shock, that is, the interval between the last activation at the site and the time of the shock, were not randomly distributed but were similar, averaging 64 +/- 11 msec, and were negatively correlated with the isoelectric postshock window (r = -0.70, p = 0.0001). These findings indicate that the presence and the site of origin of activation fronts after the shock are influenced by at least two factors: the shock itself and the electrophysiological state of the myocardium at the time of the shock. Thus, epicardial shocks approximately 100 V below the defibrillation threshold markedly alter the activation sequences of fibrillation but are unsuccessful because the activation fronts following the shock reinitiate fibrillation.     

射频消融房室交界区慢、快经区域对犬和人心房颤动时心室率的影响

本文观察经导管射频消融房室交界区慢、快径区域对大和人心房颤动时心室率的影响.方法 杂种犬4条,体重11±1.2kg.房室结折返性心动过速患者7例,年龄29～65岁.阵发性房颤患者4例,年龄62～70岁,其中2例为短P-R间期综合征.均先采用“下位法”消融慢径区域后,若房室结有效不应期或房颤时平均R-R间期无明显变化,则加行“快径”区域消融.房颤诱发采用猝发脉冲电刺激(人)或静滴氯化乙酰胆碱后猝发脉冲电刺激(犬).结果 7例房室结折返性心动过速患者中5例经下位法射频消融阻断慢径,房室结前传有效不应期及诱发房颤时平均R-R间期明显延长(222±33ms vs 285±42ms和539±44ms vs 656±53ms P<0.01),无并发症.4条大及4例阵发性房颤患者经心内电生理检查证实均无房室结双径路表现,选择性消融“慢径区域”后,房室结有效不应期和房颤时平均R—R间期无明显变化,加行“快径区域”消融后,房室结有效不应期和房颤时平均R—R间期明显延长(犬145±16ms vs 185±22ms和305±13ms vs 403±17ms P<0.01,人220ms vs 490ms和367ms vs 690msP<0.01),1例房颤患者术后3天出现Ⅲ°AVB,2周后恢复为Ⅰ°AVB.本文还在动物实验中观察到消融快径区域时,房侧靶点(A/V>1)较室侧靶点(A/V<1)更易于造成Ⅲ°AVB.结论 选择性射频消融慢径区域对减?     

Ventricular tachyarrhythmia initiation in a canine model of recent myocardial infarction. Comparison of unipolar cathodal, anodal and bipolar stimulation

Ventricular tachyarrhythmia initiation was compared using unipolar cathodal, anodal and bipolar programmed stimulation at 21 sites in 5 normal adult mongrel dogs and 67 noninfarct sites in 16 dogs 3-5 days after experimental myocardial infarction. For this purpose, the minimum number of extrastimuli required for tachyarrhythmia initiation was determined in each pacing mode using twice cathodal threshold current for the drive beats and all extrastimuli except the last. The current and pacing mode were varied for the last extrastimulus (S2, S3 or S4). In the 5 normal dogs, ventricular fibrillation was reproducibly inducible from only 1/21 sites, and only in the cathodal mode. In 15/16 (94%) of the myocardial infarction dogs, a sustained ventricular tachycardia or ventricular fibrillation could be reproducibly initiated with either one (4 dogs), two (5 dogs) or three extrastimuli (6 dogs). Diastolic excitability thresholds were 0.08 +/- 0.03, 0.30 +/- 0.17, and 0.09 +/- 0.04 mA (median +/- SD) for unipolar cathodal, anodal and bipolar pacing, respectively (p less than 0.001 for anodal vs. cathodal and bipolar). The median absolute current required for ventricular tachyarrhythmia initiation was also highest with anodal pacing (0.72 +/- 0.77 mA), versus both the cathodal and anodal modes (0.18 +/- 0.28 and 0.20 +/- 0.28 mA, respectively, each p less than 0.001) but was comparable in all three modes relative to the threshold current (2.0, 2.4 and 2.6 mA for cathodal, anodal and bipolar pacing, respectively) required for initiation. Overall, ventricular tachyarrhythmia initiation was concordant in all three modes at 58/67 (87%) sites and discordant at only 9/67 (13%) sites (p less than 0.001). Moreover, there was no difference in either the pattern of arrhythmia initiated in each of the pacing modes with respect to ventricular tachycardia versus ventricular fibrillation, or in the median current required to initiate ventricular tachycardia (0.30 +/- 0.36 mA) versus ventricular fibrillation (0.31 +/- 0.44 mA; p greater than 0.1). Thus, ventricular tachyarrhythmia initiation was comparable in all three pacing modes with respect to overall success rate, number of ventricular extrastimuli required and the pattern of ventricular tachyarrhythmia initiated. Bipolar pacing with similar size anodal and cathodal electrodes appear to be appropriate for electrophysiologic ventricular tachyarrhythmia studies and are not likely to induce spurious arrhythmias resulting from stimulation at the anodal pole.     

Long-term cardiac memory in canine heart is associated with the evolution of a transmural repolarization gradient

OBJECTIVE: The contribution of regional electrophysiologic heterogeneity to the T-wave changes of long-term cardiac memory (CM) is not known. We mapped activation and repolarization in dogs after induction of CM and in sham animals. METHODS AND RESULTS: CM was induced by three weeks of AV-sequential pacing at the anterior free wall of the left ventricle (LV), midway between apex and base in 5 dogs. In 4 sham controls a pacemaker was implanted but ventricular pacing was not performed. At 3 weeks, unipolar electrograms were recorded (98 epicardial, 120 intramural and endocardial electrodes) during atrial stimulation (cycle length 450 ms). Activation times (AT) and repolarization times (RT) were measured and activation recovery intervals (ARIs) calculated. CM was associated with 1) deeper T waves on ECG, with no change in QT interval; 2) longer activation time at the site of stimulation in CM (29.7+/-1.0, X+/-SEM) than sham (23.9+/-1.3 ms p<0.01); 3) an LV transmural gradient in repolarization time such that repolarization at the epicardium terminated 12.4+/-2.4 ms later than at the endocardium p<0.01), in contrast to no gradient in shams (2.7+/-4.2 ms); in memory dogs, the repolarization time gradient was greatest at sites around the pacing electrode varying from 13.1+/-2.3 ms to 25.5+/-3.8 ms; 4) more negative left ventricular potentials at the peak of the body surface T wave (-4.9+/-0.8 vs -2.2+/-0.4 mV; p<0.05) but no altered right ventricular epicardial T-wave potentials. ARIs did not differ between groups. Right ventricular activation was delayed but was not associated with altered repolarization because of compensatory shortening of the right ventricular ARIs. CONCLUSION: CM-induced T-wave changes are caused by evolution of transmural repolarization gradients manifested during atrial stimulation that are maximal near the site of ventricular pacing.     

Programmed electrical stimulation at potential ventricular reentry circuit sites. Comparison of observations in humans with predictions from computer simulations

The purpose of this study was to define specific types of resetting responses to programmed electrical stimulation during human ventricular tachycardia and to use computer simulations of reentry circuits to assess the possible mechanisms and pacing site location relative to the reentry circuit for each type of response. The effects of scanning single stimuli at 35 left ventricular endocardial sites during sustained monomorphic ventricular tachycardia in 12 patients were studied. In considering alterations in QRS configuration and the delay between the stimulus and the advanced QRS, we identified three types of resetting responses to scanning stimuli consistent with stimulation at sites in or near the reentry circuit at 12 abnormal endocardial sites in eight patients. Type 1: all capturing stimuli were followed after a delay by early QRS complexes that had the same configuration as the tachycardia complexes. Type 2: late stimuli reset tachycardia as in type 1 but early stimuli reset the tachycardia after altering the QRS configuration. Type 3: late stimuli reset tachycardia as in type 1, but early stimuli advanced tachycardia with a short stimulus to QRS delay without altering the QRS configuration. In the simulations, premature depolarization of sites in the circuit produced orthodromic and antidromic wavefronts. The orthodromic wavefront propagated through the circuit and exited the circuit at the same site as did the previous tachycardia wavefronts and advanced the tachycardia without altering the configuration of the advanced QRS. The antidromic wavefront of relatively late stimuli was confined within or near the circuit by collision with the orthodromic wavefront of the preceding tachycardia beat and failed to alter ventricular activation distant from the circuit. Therefore, the QRS configuration after the stimulus was unchanged. A type 1 response occurred when all capturing stimuli produced this effect. However, with increasing stimulus prematurity, the antidromic wavefront propagated farther before colliding with an orthodromic wavefront, and under some conditions, it exited the circuit from a site other than the original circuit "exit," and altered the ventricular activation sequence distant from the circuit and, therefore, the QRS configuration, producing a type 2 pattern. The type 3 pattern occurred when the antidromic wavefront of early premature beats captured the original circuit exit. The effect of a stimulus was dependent on the stimulus prematurity, the relative conduction times from the stimulation site to the potential sites of "exit" from the circuit, and the timing of the excitable gap at the stimulation site.(ABSTRACT TRUNCATED AT 400 WORDS)     

Reentrant ventricular arrhythmias in the late myocardial infarction period in the dog. 13. Correlation of activation and refractory maps

Isochronal maps of ventricular activation were analyzed in dogs 3-5 days after ligation of the left anterior descending coronary artery utilizing a 64-channel multiplexer. Isochronal maps of the effective refractory period were determined from 62 epicardial sites and correlated with the activation maps. The ischemia occurring in the surviving epicardial layer prolonged refractoriness in a spatially nonuniform manner. The resulting pattern of refractoriness on the epicardial surface resembled concentric rings of isorefractoriness which increased in duration from the normal zone to the center of the ischemic zone. The formation of an arc of functional unidirectional conduction block occurred along the gradient of refractoriness and the exact location of the arc depended on the S1-S2 interval. When a short S1-S2 failed to induce reentry, fewer adjacent sites with sufficiently disparate refractoriness formed a smaller arc of block. A subsequent S3 encountered further nonuniformly shortened refractoriness (normal areas had shortened refractoriness greater than ischemic areas) and the arc of block was lengthened. This required a longer time for the wavefront to circulate around the arc. When it then reached the distal side of the arc, refractoriness had expired proximal to the arc and reentry occurred. Similarly, nonuniform shortening of refractoriness explained why one reentrant beat may or may not produce successive reentrant beats. Therefore, the spatial pattern of refractoriness forms the substrate for the arc of unidirectional conduction block that is fundamental to the development of ventricular reentry in this experimental model.     

Focal origin of atrial tachycardia in dogs with rapid ventricular pacing-induced heart failure

Mapping and Ablation of Atrial Tachycardia in Heart Failure. INTRODUCTION: Dogs with rapid ventricular pacing-induced congestive heart failure (CHF) have inducible atrial tachycardia (AT), with a mechanism consistent with delayed afterdepolarization-mediated triggered activity. We assessed the hypothesis that AT has a focal origin. METHODS AND RESULTS: Twenty-one CHF dogs undergoing 3 to 4 weeks of ventricular pacing at 235 beats/min were studied. Biatrial epicardial mapping of 20 sustained AT episodes (cycle length [CL], 175 +/- 53 msec) in 5 dogs revealed an area of earliest activation in the right atrial (RA) free wall (13 episodes), RA appendage (4 episodes), or between the pulmonary veins (3 episodes). Total epicardial activation time during AT (73 +/- 19 msec) was similar to that during sinus rhythm (72 +/- 13 msec) and on average was <50% of the AT CL. Higher-density mapping of the RA free wall during 30 sustained AT episodes (163 +/- 55 msec) in 9 dogs identified a site of earliest activation along the sulcus terminalis most frequently as a stable, focal activation pattern from a single site. Endocardial mapping of 49 sustained AT episodes (156 +/- 27 msec) in 10 dogs revealed multiple sites of AT origin arising along the crista terminalis and pulmonary veins. Right and left ATs were terminated with discrete radiofrequency ablation, but other ATs remained inducible. A rapid, left AT generating an ECG pattern of atrial fibrillation was ablated inside the pulmonary vein. CONCLUSION: AT induced in this CHF model after 3 to 4 weeks of rapid ventricular pacing has an activation pattern consistent with a focal origin. Sites of earliest activation are distributed predominately along the crista terminalis and within or near the pulmonary veins.     

Reentrant ventricular arrhythmias in the late myocardial infarction period: mechanism by which a short-long-short cardiac sequence facilitates the induction of reentry

The electrophysiological mechanism by which a short-long-short stimulated cardiac sequence facilitates the induction of ventricular tachyarrhythmia was investigated in dogs 4 days after ligation of the left anterior descending coronary artery. In these dogs, reentry develops in the surviving electrophysiologically abnormal epicardial layer that overlies the infarct zone when premature stimulation results in a critically long arc of functional conduction block. The activation wavefront circulates around both ends of the arc, coalesces, and conducts slowly distal to the arc before reactivating sites proximal to the arc to initiate a figure-eight reentrant circuit. Epicardial isochronal activation maps and effective refractory periods (ERPs) were determined during three different stimulation protocols: A, a basic train of eight beats at a cycle length of 300 msec followed by a single premature stimulus (S2); B, a basic train of eight beats at a cycle length of 300 msec with abrupt lengthening of the last cycle of the train before S2 to 600 msec; C, a basic train of eight beats at a cycle length of 600 msec followed by S2. Protocol B was found to result in a differential lengthening of ERP at adjacent sites within the border of the epicardial ischemic zone, whereas protocols A and C induced, respectively, comparable shortening and lengthening of ERPs at the same sites. The differential lengthening of ERPs at adjacent sites resulted in an increased dispersion of refractoriness so that a premature stimulus induced functional conduction block between those sites. The development of a longer arc of conduction block and, hence, a longer reentrant pathway as well as slower conduction of the circulating wavefront during protocol B allowed more time for refractoriness to expire proximal to the arc and for the circulating wavefront to reexcite those sites to initiate reentry. The lengthening of ERP, associated with a single long cycle (protocol B), ranged from 44% to 79% of the total increase in ERP after a series of eight long cycles (protocol C). Epicardial sites with longer ERPs located close to the center of the ischemic zone showed more lengthening of refractoriness during protocol B compared with more normal sites near the border of the ischemic zone. This strongly suggests that the increased dispersion of refractoriness during protocol B is caused by the shorter memory of ischemic myocardium to the cumulative effects of preceding cycle lengths.     

The Spatial Dispersion of Atrial Refractoriness and Atrial Fibrillation Vulnerability

The local dispersion of conduction and refractoriness has been considered essential for induction of atrial arrhythmias. This study sought to determine whether a difference of refractoriness and vulnerability for induction of atrial fibrillation between trabeculated and smooth as well as high and low right atrium may contribute to initiation of atrial fibrillation in dogs.In 14 healthy mongrel dogs weighing 22.4 ± 1 kg, closed-chest endocardial programmed stimulation was performed from four distinct right atrial sites. Atrial refractory periods and vulnerability for induction of atrial fibrillation or premature atrial complexes were determined during a basic cycle length of 400 and 300 ms and an increasing pacing current strength.For a pacing cycle length of 300ms, atrial refractory periods were longer on the smooth, as compared to the trabeculated right atrium (102 ± 25 vs. 97 ± 17ms, p < 0.05), whereas for a pacing cycle length of 400ms, there was no significant difference. The duration of the vulnerability zone for induction of atrial fibrillation was longer on the smooth right atrium, for a cycle length of both 400 ms (40 ± 30 vs. 31 ± 22 ms; p < 0.05) and 300 ms (33 ± 25 vs. 23 ± 21 ms; p < 0.01). When comparing high and low right atrium, refractory periods were longer on the the low right atrium, for a cycle length of both 400 ms (111 ± 23 vs. 94 ± 24ms; p < 0.01) and 300 ms (104 ± 20 vs. 96 ± 23ms; p < 0.01). For a pacing cycle length of 300 ms, the duration of the atrial fibrillation vulnerability zone was longer for the high, as compared to the low right atrium (34 ± 22 vs. 22 ± 22, p < 0.01). Seven dogs with easily inducible episodes of atrial fibrillation demonstrated significantly shorter refractory periods as compared to 7 non-vulnerable dogs, regardless of pacing site and current strength.In conclusion, significant differences in refractoriness and vulnerability for induction of atrial fibrillation can be observed in the area of the crista terminalis in healthy dogs. Thus, local anatomic factors may play a role in the initiation of atrial fibrillation.