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Notes: Chirality and Repolarization. Introduction: Two hypotheses have been proposed to explain the mechanisms of vulnerability and related failure of defibrillation therapy: the cross-field-induced critical point hypothesis and the virtual electrode-induced phase singularity hypothesis. These two hypotheses predict the opposite effect of preshock repolarization on the chirality (direction of rotation) of shock-induced reentry. The former suggests its reversal upon reversal of repolarization, whereas the latter suggests its preservation. The aim of this study was to determine, by reversing the repolarization sequence, which of the mechanisms is responsible for internal shock-induced arrhythmia in the Langendorff-perfused rabbit heart. Methods and Results: We used high-resolution optical mapping to assess the chirality of postshock reentry in 11 hearts. Hearts were paced at a coupling interval of 300 msec at various sites around the field of view (13.5 × 13.5 to 16.5 × 16.5 mm). Cathodal monophasic implantable cardioverter defibrillator shocks (-100 V, 8 msec) were applied during the T wave from a 10-mm coil electrode placed into the right ventricular cavity. We used 3.5 ± 0.8 different pacing sites per heart. Change in direction of repolarization did not result in change of chirality. Chirality was constant in all 11 hearts despite the complete reversal of activation and repolarization patterns. However, the position of resulting vortices depended on transmembrane polarization gradient δVm and amplitude of negative polarization Vm (deexcitation). Stronger gradients and deexcitation produced earlier epicardial break excitation (P = 0.04 and P 〈 0.0001, respectively). Conclusion: Virtual electrode-induced phase singularity mechanism underlies internal shock-induced arrhythmia in this model.

Notes: Deexcitation During Fibrillation Induction and Defibrillation. Previous models of fibrillation induction and defibrillation stressed the contribution of depolarization during the response of the heart to a shock. This article reviews recent evidence suggesting that comprehending the role of negative polarization (hyperpolarization) also is crucial for understanding the response to a shock. Negative polarization can “deexcite” cardiac cells, creating regions of excitable tissue through which wavefronts can propagate. These wavefronts can result in new reentrant circuits, inducing fibrillation or causing defibrillation to fail. In addition, deexcitation can lead to rapid propagation through newly excitable regions, resulting in the elimination of excitable gaps soon after the shock and causing defibrillation to succeed.

Notes: Scroll Waves in the Heart. Introduction: Rotating vortices have been observed in excitable media of different nature. Vortices may sustain life or kill in different species, by underlining morphogenesis in Dictiostelium discoideum during starvation, or arrhythmias during sudden cardiac death in mammals. Investigation of vortices in the heart has been limited by two-dimensional experimental techniques. In contrast, three-dimensional (3D) Belousov-Zhabotinsky excitable medium and mathematical models have been shown to sustain scroll-shaped waves. The heart is a 3D structure; therefore, scroll waves may underlie cardiac arrhythmias. Methods and Results: We used potentiometric dye and optical mapping techniques to study vortices during ventricular arrhythmias. The core of all observed vortices were linearly shaped and ≥ 9 mm (48 episodes, six hearts). As shown by Allessie et al. in the rabbit atrium, ventricular signals recorded within 1 to 2 mm from the line of block were dual humped, suggesting there is electrotonic interaction across the line of block. We hypothesized that the line of block represents epicardial intersection of ribbon-shaped filaments, which in some cases may be oriented under an angle or parallel to the epicardium. In 14 episodes we observed dualhumped optical recordings at one side of the line of block at a distance up to 12 mm. The two humps may represent the signatures of two activation wave fronts propagating above and below the filament, which in this area is close to the epicardial surface. The activation sequence of the two waves is consistent with the idea of a scroll wave with ribbon-like filament. Conclusion: Our data provide new insights into the shape and dynamics of the filament of the 3D scroll wave, which underlies the mechanism of ventricular tachycardia in the rabbit heart. The filament of the scroll wave may be ribbon shaped, with a significant width ≥ 9 mm and a thickness of 1 to 2 mm. No evidence of fully excitable cells in the core of vortex was observed.

Notes: Biventricular Shocking Leads:Introduction: A single lead active can configuration has been widely used in patients with life-threatening ventricular arrhythmias. Occasionally, however, such a defibrillation lead configuration may not achieve adequate defibrillation threshold (DFT). The purpose of this study was to determine whether addition of a left ventricular (LV) lead can improve defibrillation efficacy. Methods and Results: Three transvenous defibrillation leads (8.3-French with a 5-cm long unipolar coil) were placed in the right ventricle (RV), LV, and superior vena cava (SVC), along with an active can (92 cm2) in the left subpectoral area. The DFT stored energy of seven combinations of these defibrillation leads were compared in a pig ventricular fibrillation model using a biphasic defibrillation waveform (125 μF, 6.5/3.5 msec). A biventricular leads active can configuration in which the RV and LV leads were of the same polarity reduced the DFT stored energy by approximately 35% when compared to a single RV lead active can configuration (9.6 ± 3.0 J vs 15.0 ± 7.2 J, respectively, P = 0.02). Moreover, adding a SVC lead further reduced the DFT energy (8.4 ± 3.3 J). Conclusion: A biventricular leads active can configuration can significantly improve defibrillation efficacy as compared to a single lead active can configuration. In such a defibrillation lead configuration, the polarity of RV and LV leads should be the same.

Notes: GARRIGUE, S., et al.: Optical Mapping Technique Applied to Biventricular Pacing: Potential Mechanisms of Ventricular Arrhythmias Occurrence. Although it has been suggested that multisite ventricular pacing alleviates heart failure by restoring ventricular electrical synchronization, the respective roles of voltage output, interventricular delay, and pacing sites in the development of ventricular arrhythmias occurrence have not been studied during biventricular pacing or LV pacing. Voltage-sensitive dye was used in eight ischemic Langerdorff-perfused guinea pig hearts to measure ventricular activation times and examine conduction patterns during multisite pacing from three RV and four LV sites. The hearts were stained with di-4-ANEPPS and mapped with a 16 × 16 photodiode array at a resolution of 625 μm per diode. Isochronal maps of RV and LV activation were plotted. Ischemia was produced by gradually halving the perfusion output over 5 minutes. Pacing the RV apex and the base of the LV anterior wall was associated with the most homogeneous and rapid activation pattern ( 28 ± 9 vs 41 ± 12 ms with the other configurations, P 〈 0.01), and no inducible arrhythmia. In six hearts, ventricular tachycardia could be induced when pacing from the right and left free walls with 20 ms of interventricular delay, at six times the pacing threshold output. In four hearts, simultaneous RV and LV pacing at high voltage output induced ventricular fibrillation with complex three-dimensional propagation patterns, independently of the pacing sites. During biventricular pacing with ischemia, pacing at high voltage output with a long interventricular delay is likely to induce ventricular arrhythmias, particularly when left and right pacing results in a conduction pattern orthogonal to the ventricular myocardial fibers orientation. PACE 2003; 26[Pt. II]:197–205)

Notes: Defibrillation Shock-Induced Virtual Electrodes. Introduction: Epicardial point stimulation produces nonuniform changes in the trans membrane voltage of surrounding cells with simultaneous occurrence of areas of transient positive and negative polarization. This is the phenomenon of virtual electrode. We sought to characterize the responses of epicardial ventricular tissue to the application of monophasic electric shocks from an internal transvenous implantable cardioverter defibrillator (ICD) lead. Methods and Results: Langendorff-perfused rabbit hearts (n = 12) were stained with di-4-ANEPPS. A 9-mm-long distal electrode was placed in the right ventricle. A 6-cm proximal electrode was positioned horizontally 3 cm posteriorly and 1 cm superiorly with respect to the heart. Monophasic anodal and cathodal pulses were produced by discharging a 150-μF capacitor. Shocks were applied either during the plateau phase of an action potential (AP) or during ventricular fibrillation. Leading-edge voltage of the pulse was 50 to 150 V, and the pulse duration was 10 msec. Transmembrane voltage was optically recorded during application of the shock, simultaneously from 256 sites on a 11 × 11 mm area of the anterior right ventricular epicardium directly transmural to the distal electrode. The shock effect was evaluated by determining the difference between the AP affected by the shock and the normal AP. During cathodal stimulation an area of depolarization near the electrode was observed, surrounded by areas of hyperpolarization. The amplitude of polarization gradually decreased in areas far from the electrode. Inverting shock polarity reversed this effect. Conclusion: ICD monophasic defibrillation shocks create large dynamically interacting areas of both negative and positive polarization.

Notes: BDM Effects on AVN Conduction. Introduction: 2,3-Butanedione monoxime (BDM) has been found to reversibly block cardiac contraction, without blocking electrical conduction. This study characterizes the dose-dependent effects of BDM on the conduction through the atrioventricular node (AVN) of rabbit heart. Methods and Results: Thirteen isolated atrial-AVN preparations were used in control, during and after exposure to 5, 10, and 20 mM BDM. Anterograde and retrograde pacing protocols were used to obtain the Wenckebach cycle length, effective and functional refractory periods of the AVN, index of AVN conduction delay (the area under the AVN conduction curve), as well as index of intra-atrial conduction delay between the AVN inputs. Compared to control, 5 and 10 mM BDM produced either shortening or no effect on all of the above parameters except a slight (6% and 14%, respectively) increase in the intra-atrial delay. At 20 mM, BDM produced a further increase in the intra-atrial delay (up to 50%) as well as in the retrograde AVN conduction delay (up to 16%), while the characteristics of the anterograde conduction were still improved. The effects of perfusion with BDM on these parameters were reversible after washout. Conclusions: Aside from its known effect as an electromechanical uncoupler, BDM reversibly altered some of the electrical responses of the AVN. Most of these alterations, however, did not impede but rather improved AVN conduction. Since a dose of 10 mM is sufficient to fully eliminate undesirable motion, BDM should be considered a safe and valuable tool in AVN studies in vitro requiring a mechanically quiescent preparation.

Notes: Spatial Autocorrelation of APDs During Arrhythmogenic Insults. Introduction: Regional dispersions of repolarization (DOR) are arrhythmogenic perturbations that are closely associated with reentry. However, the characteristics of DOR have not been well defined or adequately analyzed because previous algorithms did not take into account spatial heterogeneities of action potential durations (APDs). Earlier simulations proposed that pathologic conditions enhance DOR by decreasing electrical coupling between cells, thereby unmasking differences in cellular repolarization between neighboring cells. Optical mapping indicated that gradients of APD and DOR are associated with fiber structure and are largely independent of activation. We developed an approach to quantitatively characterize APD gradients and DOR to determine how they are influenced by tissue anisotropy and cell coupling during diverse arrhythmogenic insults such as hypoxia and hypothermia. Methods and Results: Voltage-sensitive dyes were used to map APs from 124 sites on the epicardium of Langendorff-perfused guinea pig hearts during (1) cycles of hypoxia and reoxygenation and (2) after 30 minutes of hypothermia (32° to 25°C). We introduce an approach to quantitate DOR by analyzing two-dimensional spatial autocorrelation of APDs along directions perpendicular and parallel to the longitudinal axis of epicardial fibers. A spatial correlation length l was derived as a statistical measure of DOR. It corresponds to the distance over which APDs had comparable values, where l is inversely related to DOR. Hypoxia (30 min) caused a negligible decrease in longitudinal θL (from 0.530 ± 0.138 to 0.478 ± 0.052 m/sec) and transverse θT (from 0.225 ± 0.034 to 0.204 ± 0.021 m/sec) conduction velocities and did not alter θL/θT or activation patterns. In paced hearts (cycle length [CL] = 300 msec), hypoxia decreased APDs (123 ± 18.2 to 46 ± 0.6 msec; P 〈 0.001) within 10 to 15 minutes and enhanced DOR, as indicated by reductions of l from 1.8 ± 0.9 to 1.1 ± 0.5 mm (P 〈 0.005). Hypothermia caused marked reductions of θL, (0.53 ± 0.138 to 0.298 ± 0.104 m/sec) and θT (0.225 ± 0.034 to 0.138 ± 0.027 m/sec), increased APDs (128 ± 4.4 to 148 ± 14.5 msec), and reduced l from 2.0 ± 0.3 to 1.3 ± 0.6 mm (P 〈 0.05). l decreased with increased time of hypoxia and recovered upon reoxygenation. Hypoxia and hypothermia reduced l measured along the longitudinal (l1) and transverse (lT) axes of cardiac fibers while the ratio lL/lT remained constant.