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Spatially discordant voltage alternans cause wavebreaks in ventricular fibrillation.

ABSTRACT: Ventricular fibrillation (VF) is characterized by complex ECG patterns emanating from multiple, short-lived, reentrant electrical waves. The incessant breakup and creation of new daughter waves (wavebreaks) perpetuate VF. Dispersion of refractoriness (static or dynamic) has been implicated as a mechanism underlying wavebreaks.The purpose of this study was to investigate the mechanisms underlying wavefront instability in VF by localizing wave fractionation sites (the appearance of multiple waves) and their relationship to local spatial dispersion of voltage (V(m)) oscillations.Wave fractionations were identified by tracking V(m) oscillations optically at unprecedented spatial (100 x 100 pixels) and temporal (2,000 frames per second) resolution using a CMOS camera viewing the surface (1 x 1 cm(2)) of perfused guinea pig hearts (n = 6). VF was induced by burst stimulation, and wavefront dynamics were highlighted using region-based image analysis to automatically detect wavebreaks. Direct detection of wavebreak locations by image analysis was more reliable than the phase reconstruction method because baseline noise obstructed the correct identification of phase singularities by detecting false-positives.Wave fractionations (34 +/- 4 splits/s.cm(2)) fell into three categories: decremental conduction (49% +/- 7%), wave collisions (32% +/- 8%), and wavebreaks (17 +/- 2%). Wavebreaks occurred at a frequency of 5.8 +/- 1 splits/s.cm(2) and did not preferentially occur at anatomic obstacles (i.e., coronary vessels) but coincided with discordant alternans where V(m) amplitudes and durations shifted from high to low to from low to high on opposite sides of wavebreak sites.Spatial discordant alternans cause wavebreaks most likely because they are sites of abrupt dispersion of refractoriness.

SUBMITTER: Choi BR

PROVIDER: S-EPMC2137164 | biostudies-literature | 2007 Aug

REPOSITORIES: biostudies-literature

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Spatially discordant voltage alternans cause wavebreaks in ventricular fibrillation.

Choi Bum-Rak BR Jang Woncheol W Salama Guy G

Heart rhythm 20070612 8

<h4>Background</h4>Ventricular fibrillation (VF) is characterized by complex ECG patterns emanating from multiple, short-lived, reentrant electrical waves. The incessant breakup and creation of new daughter waves (wavebreaks) perpetuate VF. Dispersion of refractoriness (static or dynamic) has been implicated as a mechanism underlying wavebreaks.<h4>Objective</h4>The purpose of this study was to investigate the mechanisms underlying wavefront instability in VF by localizing wave fractionation sit ...[more]

PMID: 17675081

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Project description:Background Ventricular tachyarrhythmias are often preceded by short sequences of premature ventricular complexes. In a previous study, a restitution-based computational model predicted which sequences of stimulated premature complexes were most likely to induce ventricular fibrillation in canines in vivo. However, the underlying mechanism, based on discordant-alternans dynamics, could not be verified in that study. The current study seeks to elucidate the mechanism by determining whether the spatiotemporal evolution of action potentials and initiation of ventricular fibrillation in in vitro experiments are consistent with model predictions. Methods and Results Optical mapping voltage signals from canine right-ventricular tissue (n=9) were obtained simultaneously from the entire epicardium and endocardium during and after premature stimulus sequences. Model predictions of action potential propagation along a 1-dimensional cable were developed using action potential duration versus diastolic interval data. The model predicted sign-change patterns in action potential duration and diastolic interval spatial gradients with posterior probabilities of 91.1%, and 82.1%, respectively. The model predicted conduction block with 64% sensitivity and 100% specificity. A generalized estimating equation logistic-regression approach showed that model-prediction effects were significant for both conduction block ( P<1×10-15, coefficient 44.36) and sustained ventricular fibrillation ( P=0.0046, coefficient, 1.63) events. Conclusions The observed sign-change patterns favored discordant alternans, and the model successfully identified sequences of premature stimuli that induced conduction block. This suggests that the relatively simple discordant-alternans-based process that led to block in the model may often be responsible for ventricular fibrillation onset when preceded by premature beats. These observations may aid in developing improved methods for anticipating block and ventricular fibrillation.

Project description:Rationale: Discordant alternans, a phenomenon in which the action potential duration (APDs) and/or intracellular calcium transient durations (CaDs) in different spatial regions of cardiac tissue are out of phase, present a dynamical instability for complex spatial dispersion that can be associated with long-QT syndrome (LQTS) and the initiation of reentrant arrhythmias. Because the use of numerical simulations to investigate arrhythmic effects, such as acquired LQTS by drugs is beginning to be studied by the FDA, it is crucial to validate mathematical models that may be used during this process. Objective: In this study, we characterized with high spatio-temporal resolution the development of discordant alternans patterns in transmembrane voltage (Vm) and intracellular calcium concentration ([Cai]+2) as a function of pacing period in rabbit hearts. Then we compared the dynamics to that of the latest state-of-the-art model for ventricular action potentials and calcium transients to better understand the underlying mechanisms of discordant alternans and compared the experimental data to the mathematical models representing Vm and [Cai]+2 dynamics. Methods and Results: We performed simultaneous dual optical mapping imaging of Vm and [Cai]+2 in Langendorff-perfused rabbit hearts with higher spatial resolutions compared with previous studies. The rabbit hearts developed discordant alternans through decreased pacing period protocols and we quantified the presence of multiple nodal points along the direction of wave propagation, both in APD and CaD, and compared these findings with results from theoretical models. In experiments, the nodal lines of CaD alternans have a steeper slope than those of APD alternans, but not as steep as predicted by numerical simulations in rabbit models. We further quantified several additional discrepancies between models and experiments. Conclusions: Alternans in CaD have nodal lines that are about an order of magnitude steeper compared to those of APD alternans. Current action potential models lack the necessary coupling between voltage and calcium compared to experiments and fail to reproduce some key dynamics such as, voltage amplitude alternans, smooth development of calcium alternans in time, conduction velocity and the steepness of the nodal lines of APD and CaD.

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Spatially discordant voltage alternans cause wavebreaks in ventricular fibrillation.

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Spatially discordant voltage alternans cause wavebreaks in ventricular fibrillation.

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