Mechanism underlying initiation of paroxysmal atrial flutter/atrial fibrillation by ectopic foci: a simulation study.

BACKGROUND: The mechanisms underlying paroxysmal atrial flutter/atrial fibrillation initiation by ectopic foci from various locations are unclear. METHODS AND RESULTS: We used parallel computational techniques to study an anatomically accurate 3-dimensional atrial structure incorporating a detailed ionic-current model of an atrial myocyte. At the single-cell level, upregulation of the L-type Ca2+ current I(Ca,L) steepened restitution curves of action potential duration and conduction velocity compared with the control. Spontaneous firings of ectopic foci, coupled with sinus activity, produced dynamic spatial dispersions of repolarization, including discordant alternans, which caused conduction block and reentry only for the elevated I(Ca,L) case. For each foci location, a vulnerable window for atrial flutter/atrial fibrillation induction was identified as a function of the coupling interval and focus cycle length. For ectopic foci in the pulmonary veins and left atrium, the site of conduction block and reentry gradually shifted, as a function of coupling interval, from the right atrium to the interatrial area and finally to the left atrium. The size of the vulnerable window was largest for pulmonary vein foci, becoming markedly smaller for right atrial foci, especially those near the sinoatrial node. CONCLUSIONS: These findings suggest that a mechanism of dynamically induced repolarization dispersion, especially discordant alternans, underlies the induction of atrial flutter/atrial fibrillation by atrial ectopic foci. The sites and likelihood of reentry induction varied according to ectopic focus location and timing, with the largest vulnerable window corresponding to the pulmonary vein region.

Structural barrier increases QT-peak dispersion in swine left ventricle in vivo.

QT dispersion (QTD) is thought to represent the regional nonuniformity of ventricular repolarization and can serve as a prognostic marker for vulnerability to ventricular arrhythmias and risk for sudden cardiac death (SCD). In this study, we used an in vivo swine model to investigate the change of QT-peak dispersion before and after the introduction of a left-ventricular (LV) free-wall structural barrier (SB). Baseline and post-ablation pacing were delivered to: (i) the epicardial LV base, (ii) the epicardial LV apex, and (iii) the right ventricular (RV) endocardium. Four unipolar electrograms were measured from LV free wall epicardial sites referenced to an intrathorax electrode. An SB (approximately 4 x 1 x 1 cm (length, width, depth)) was created by cryoablation in the middle of the two electrode pairs. QTD was computed as the difference between QT-peak intervals for each beat from two electrodes across the SB region from one another. A significant increase of QTD occurred (p<0.05) after the introduction of the SB in all six animals. These results may reflect the accentuation of anatomical repolarization heterogeneity due to SB disruption of electrotonic coupling. Given the link between dispersion of repolarization and initiation of reentry, these findings are consistent with the increased arrhythmia risk of structural heart disease.

Antispiral waves in reaction-diffusion systems.

We report spontaneous antispiral wave formation in typical reaction-diffusion systems. Our findings qualitatively reproduce a series of phenomena recently observed in a Belousov-Zhabotinsky-type chemical reaction. We found that antispiral waves can occur only near the Hopf bifurcation, when the system is characterized by small amplitude oscillatory (as opposed to excitable) dynamics. For reaction-diffusion systems in the vicinity of the Hopf bifurcation, the specific conditions required for antispiral formation are established here through theoretical analyses and numerical simulations. Thus, this work provides a comprehensive description of the mechanisms underlying antispiral waves in reaction-diffusion systems.

Model for stochastic-resonance-type behavior in sensory perception.

Recently it was found that noise could help improve human detection of sensory stimuli via stochastic-resonance-type behavior. Specifically, the ability of an individual to detect a weak tactile stimulus could be enhanced by adding a certain amount of noise. Here we propose, from the perspective of classical signal detection theory, a simple and general model to elucidate the mechanism underlying this phenomenon. We demonstrate that noise-mediated enhancements and decrements in human sensation can be well reproduced by our model. The predicted upper bound of the performance improvement by adding noise is also consistent with the experimental data. We suggest additional experiments to further test the model.