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Notes: Introduction: The relative importance of nonuniform dispersion of refractoriness, steep restitution slopes, and anatomic heterogeneities in causing conduction block during ventricular fibrillation (VF) remains unknown. Methods and Results: In six open-chest pigs, ventricular refractoriness and restitution curves were estimated from activation recovery intervals (ARIs) calculated from 504 (21 × 24) unipolar electrode recordings 2 mm apart in a plaque sutured to the left ventricular (LV) free wall. A steady-state restitution protocol was performed twice at each of two pacing sites: the LV base and near the left anterior descending artery. VF was electrically induced four times and the incidence of conduction block at each electrode during the first 20 seconds was determined by an automated algorithm. The gradient of the ARI was calculated at each electrode to estimate the spatial dispersion of refractoriness. An exponential curve was fit to the restitution plots of ARIs versus the corresponding diastolic intervals (DIs) for all pacing cycle lengths at each electrode. The locations of epicardial blood vessels were noted after the study. Spatial patterns of conduction block were significantly correlated between the four VF episodes in the same animal (r = 0.66 ± 0.07, P 〈 0.05). At the shortest pacing cycle length, the spatial distribution of ARIs, ARI gradients, and restitution slopes was not random but formed clusters of similar values. However, none of these variables was significantly correlated with the incidence of conduction block, even though ARI gradients 〉2 msec/mm were present between many clusters and ∼90% of restitution slopes were 〉1. Instead, conduction block frequently appeared to cluster along epicardial vessels. Conclusion: Neither the dispersion of refractoriness nor action potential duration restitution determined during rapid pacing by itself is the major determinant of the location of conduction block during early VF in normal pigs. It may be that these factors interact synergistically with each other as well as with other factors, including anatomic heterogeneities such as those caused by blood vessels, which may be particularly important for the formation of conduction block and maintenance of VF.

Notes: Activation During Ventricular Fibrillation. Introduction: This study quantified how the organization of epicardial activation changes during the first 40 seconds of ventricular fibrillation (VF).Activation During Ventricular Fibrillation. Introduction: This study quantified how the organization of epicardial activation changes during the first 40 seconds of ventricular fibrillation (VF). Methods and Results: Unipolar potentials were mapped from a 504 (24 × 21) electrode array (2-mm interelectrode spacing) on the anterior right ventricle (RV) and left ventricle (LV) epicardium. The array covered approximately 20% of the epicardial surface. In each of seven pigs, six episodes of VF were induced by premature stimulation. One-half second epochs of VF were analyzed, starting 0, 10, 20, 30, and 40 seconds post induction and using novel pattern analysis algorithms. Eight parameters were quantified: (1) the number of wavefronts; (2) the epicardial area activated by wavefronts; (3) the fraction of wavefronts arising from epicardial breakthrough or from a focus; (4) the fraction of wavefronts terminated by conduction block; (5) the multiplicity index (number of distinct activation pathways in the rhythm); (6) the repeatability index (number of times activation pathways are traversed); (7) the activation rate; and (8) the wavefront propagation velocity. The results showed that VF patterns were less organized at 10 than at 0 seconds, with more, smaller wavefronts traversing a larger variety of pathways for fewer repetitions. VF activation patterns then gradually reorganized up to 40 seconds, but by a different mechanism: the spatial size of subpatterns grew, but the dynamics otherwise appeared unchanged. During both transitions, both activation rate and propagation velocity slowed monotonically. Conclusion: Thus, changes in organization during VF can occur by multiple mechanisms.

Notes: Spontaneous Arrhythmias in Acute Ischemia. Introduction: Ventricular tachycardia (VT) and ventricular fibrillation (VF) induced by thrombotic coronary occlusion were mapped in three dimensions in ten dogs. Methods and Results: Thrombotic occlusion was induced using a wire to deliver current to the proximal left circumflex artery (LCX). In nine doss, nonsustained VT (NSVT) anise from numerous focal sites. Sustained VT was initiated in six dogs (VT group) by a focus near or in the ischemic region. VT was maintained by a focus in the ischemic border in three dogs and by macroreentry that involved both the ischemic and nonischemic regions in the other three dogs. In five dogs, VT degenerated into VF due to intramural reentry in different locations. Mean total activation time (AT), the time for activation to traverse the ventricles, for a sinus heat when LCX current was first applied was 40 ± 4 msec. In the four dogs in which VT occurred 3 to 7 minutes after total occlusion, sinus AT increased to 98 to 146 msec just before VT. Sinus VT in the four dogs without VT was always 〈 98 msec. Mean AT of the first ten cycles of VT was significantly longer in those VTs that degenerated into VF (169 ± 29 msec) than in those that did not (81 ± 12 msec). Conclusion: Thrombotic LCX occlusion induced NSVT in 9%, VT in 60%, and VF in 50% of dogs, Focal mechanisms caused most NSVTs and VT initiation. VT was maintained by a focus near or in the ischemic region or by macroreentry involving both the ischemic and nonischemic regions. AT identified animals in which VT occurred soon after LCX occlusion and in which VT progressed to VF.

Notes: Introduction: Ablation of muscular fascicles around the ostium of pulmonary veins (PVs) resulting in electrical isolation of the veins may prove to be an effective treatment for atrial fibrillation (AF). Correctly discriminating atrial and PV potentials is necessary to effectively isolate PVs from the left atrium in patients with paroxysmal AF. Methods and Results: A training set of 151 electrode recordings obtained from 10 patients with AF was used to develop an algorithm to discriminate atrial and PV potentials. Bipolar electrograms were collected from a multielectrode basket catheter placed sequentially into each PV. Amplitude, slope, and normalized slopes of both bipolar and quadripolar electrograms (difference between adjacent bipoles) were entered into a binary logistic regression model. A receiver operating characteristic curve was used to define a threshold able to effectively discriminate atrial and PV potentials. The normalized slopes of both domains, bipolar and quadripolar, produced a logistic function that discriminated atrial and PV potentials against a threshold (0.38) with 97.8% sensitivity and 94.9% specificity. The algorithm then was evaluated on a test set of 214 electrode recordings from four patients who also had paroxysmal AF. These patient electrograms also were evaluated by two independent electrophysiologists. The algorithm and electrophysiologists matched identification of activation origin in 84% of electrograms.Conclusion: Atrial and PV potentials acquired from a multielectrode basket catheter can be discriminated using the normalized slopes of bipolar and quadripolar electrograms. These additional parameters need to be included by physicians determining the preferential ablation site within PVs. (J Cardiovasc Electrophysiol, Vol. 14, pp. 698-704, July 2003)

Notes: Background: Earliest postshock activation following failed defibrillation shocks slightly lower than the defibrillation threshold (DFT) in large animals appears to arise from a focus. We tested the hypothesis that these foci are caused by early or delayed afterdepolarizations (EADs or DADs) by performing epicardial electrical mapping and giving the EAD inhibitor pinacidil or the DAD inhibitor flunarizine to see if the foci were extinguished or altered in timing or location. Methods and Results: A sock containing 504 electrodes was placed over the entire ventricular epicardium of 12 open-chested pigs. After the DFT was determined and additional shocks given, pinacidil was administered to 6 pigs and flunarizine to 6 pigs. Then, the DFT was again determined and additional shocks were given. Pinacidil significantly shortened the effective refractory period (ERP) (162 ± 16 vs 130 ± 28 msec) and action potential duration (APD90) (179 ± 6 vs 149 ± 19 msec) and significantly increased the peak frequency of the power spectrum of a left ventricle (LV) electrode during ventricular fibrillation (VF) (9.3 ± 0.6 vs 10.5 ± 1.0 Hz), while flunarizine did not significantly alter the ERP (162 ± 8 vs 167 ± 18 msec) or APD90 (187 ± 12 vs 191 ± 20) but significantly reduced the peak frequency (9.2 ± 0.5 vs 7.5 ± 1.0 Hz). These findings suggest the drugs had their expected electrophysiological effects. However, the DFT was not significantly changed by either drug. Following the same strength shock 10% below the predrug DFT, earliest postshock activation arose in a focal epicardial pattern from the anterior-apical LV both before and after the drugs. The time from the shock until the appearance of this activation was not significantly different before and after either drug. Conclusion: The lack of change in DFT as well as the lack of change in the incidence, location, and timing of the postshock focus with sub-DFT strength shocks before and after pinacidil and flunarizine provide evidence that these foci are not caused by triggered activity.

Notes: Reduction of Shock Strength with Balanced Sequential Shocks. Introduction: The aim of this study was to determine the atrial defibrillation threshold (ADFT) of a first shock across the standard right atrium (RA) to distal coronary sinus (dCS) configuration followed by a second shock along the atrial septum with a standard sequential waveform (the second shock leading edge equaled the first shock trailing edge) and a balanced sequential waveform (the leading edges of both shocks were equal). Methods and Results: In nine sheep atrial fibrillation was induced with acetyl-β-methylcholine and burst pacing. A catheter was placed with electrodes in the dCS, proximal coronary sinus (pCS), and RA. A J-shaped catheter was positioned with an electrode at Bachmann's bundle (BB) while another catheter was positioned with an electrode in the superior vena cava (SVC). The ADFTs of six single- and dual-pathway configurations were determined with single, standard sequential, or balanced sequential shocks. The ADFT of the RA→dCS configuration (0.86 ± 0.27 J, 159 ± 29 V, 2.42 ± 0.36 A) was significantly reduced when followed by an SVC→pCS (0.58 ± 0.17 J, 112 ± 20 V, 1.64 ± 0.39 A) or a BB→pCS shock (0.64 ± 0.16 J, 119 ± 18 V, 1.81 ± 0.38 A) with standard sequential shocks. With balanced sequential shocks, the peak voltage and current ADFTs were further significantly reduced (85 ± 11 V and 1.24 ± 0.21 A for second shock SVC→pCS, and 93 ± 13 V and 1.38 ± 0.27 A for second shock BB→pCS). Conclusion: The ADFT of the standard RA→dCS shock is significantly reduced when followed by a second shock along the atrial septum delivered between electrodes in the pCS and either SVC or BB and ADFT is further reduced with balanced sequential shocks.

Notes: Reentry Site and Defibrillation Waveform Efficacy. 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- μ F 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 × 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 + 64.5 ∇ V − 11.1RI; R2= 0.93) and external defibrillation (DFT = 3445 + 150 ∇ V − 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.

Notes: Continuous Telemetry in a Dog Model of Sudden Death. Introduction: We sought to develop a continuously telemetered animal model of sudden cardiac death (SCD) to study the role of existing infarcts and acute ischemia in fatal arrhythmias. Methods and Results: A telemetry system capable of recording eight channels of electrophysiologic data continuously and chronically has been developed. To demonstrate the use of this technology in an animal model of sudden death. 12 anesthetized dogs were instrumented with eight electrodes located in endocardium of the right side of the heart, epicardium of the left ventricle (LV), or in the subcutaneous tissues. The left anterior descending (LAD) coronary artery was occluded for 90 minutes and reperfused to produce LV infarction. A copper wire was placed in the left circumflex (LCX) coronary artery to cause intimal injury in a second arterial bed. The telemetry unit recorded deaths in seven animals between 19 to 64 hours after surgery. Five animals that did not experience SCD by the fifth postoperative day served as controls. There were three modes of SCD: complex ventricular ectopy that degenerated into ventricular fibrillation VF (n = 4); normal sinus rhythm that suddenly degenerated into VF (n = 1); and bradycardia (RK intervals 〉 1.000 msec) that lasted 〉3 minutes and preceded VF (n = 2). ST segment changes were significantly greater in the LCX-bed electrograms for tachyarrhythmic compared to bradyarrhythmic deaths (mean ± SD; 4.0 ± 3.4 mV and 0.2 ± 0.8 mV, respectively). Fast Fourier transform showed the peak frequency of VF 10 seconds after onset was significantly higher in the five dogs with initial tachyarrhythmic compared with the VF that followed profound bradycardia (6.5 ± 3.1 Hz and 3.7 ± 0.6 Hz. respectively). Computer-assisted planimetry of postmortem heart slices revealed that infarcts in the two dogs with bradycardie events were larger (19.7%± 2.2% of the LV and septal mass) than in the five dogs with tachyarrhythmias (7.7%± 2.4%) or in the five control dogs (11.9%± 8.1%). Conclusion: It is possible to record via telemetry the events leading to SCD in an animal model. Continuous telemetry monitoring demoastrated that both tachyarrhythmias and bradyarrhythmias ultimately resulted in VF in an animal model of SCD. Animals with tachyarrhythmic deaths had greater ischemia in the LCX bed, smaller preexisting infarcts, and higher VF peak frequency than animals with bradyarrhythmic deaths.

Notes: VF Patterns in the Right and Left Ventricles. Introduction: The mechanisms that maintain ventricular fibrillation (VF) are not completely understood. It has been proposed that increased ventricular wall thickness destabilizes VF wavefronts and therefore is an important determinant of VF activation patterns. We hypothesized that if this is the case, then VF patterns on the thin-walled right ventricle (RV) should he simpler than those on the thick-walled left ventricle (LV). Methods and Results: In seven open chest pigs, we mapped VF simultaneously from two epicardial recording arrays, one on the RV and one on the LV. Each array contained 504 unipolar electrodes (in a 21 × 24 grid) spaced by 2 mm. We used specialized pattern analysis methods to compute quantitative descriptors of RV and LV activation patterns. Our data show that VF is more organized in the RV than the LV, containing fewer, larger wavefronts that follow fewer distinct pathways and are less likely to fragment or collide with other wavefronts. The incidence, size, and cycle length of reentrant circuits were similar in the two ventricles, but RV reentry persisted for more cycles. These results are not predicted by the differences in electrophysiologic properties between LV and RV that have been reported in mammalian hearts. Conclusion: The geometry of the ventricular wall, particularly wall thickness, is an important determinant of VF activation patterns.

Notes: Block and Frequency Distribution During VF. Introduction: A proposed mechanism of the maintenance of ventricular fibrillation (VF) determined by studying small hearts or segments of large hearts is that a single stable rotor exists at the site of maximal activation rate, which gives rise to activation fronts that propagate into slower activating regions where they frequently block. We wished to determine if two predictions of this hypothesized mechanism are true during VF in large hearts: (1) there is a single maximum in the distribution of activation rates with the activation rate decreasing with distance away from this maximum; and (2) the incidence of block is greater outside than inside the fastest activating region. Methods and Results: Six 25-second episodes of VF from each of six pigs were recorded from 504 electrodes over the entire ventricular epicardium. The electrodes were divided into four zones: left ventricular base and apex (LVB and LVA) and right ventricular base and apex (RVB and RVA). A fast Fourier transform was performed on each electrogram, and the mean activation rate was estimated from the dominant (peak) frequency (DF) and block was estimated to be present during those time intervals when double peaks (DPs) were present in the power spectrum. The zones had statistically significant distributions of DF (LVB〉 LVA〉 RVA〉 RVB) and DP incidence (RVA〉 RVB〉 LVA〉 LVB). Conclusion: During VF, the LV base has the highest estimated activation rate and the lowest estimated block incidence, and the RV has the slowest rate but the highest block incidence. This is consistent with the concept of VF being maintained by activation fronts originating from the LV base.