High-Frequency Periodic Sources Underlie Ventricular Fibrillation in the Isolated Rabbit Heart

Abstract

Abstract-The mechanism(s) underlying ventricular fibrillation (VF) remain unclear. We hypothesized that at least some forms of VF are not random and that high-frequency periodic sources of activity manifest themselves as spatiotemporal periodicities, which drive VF. Twenty-four VF episodes from 8 Langendorff-perfused rabbit hearts were studied using high-resolution video imaging in conjunction with ECG recordings and spectral analysis. Sequential wavefronts that activated the ventricles in a spatially and temporally periodic fashion were identified. In addition, we analyzed the lifespan and dynamics of wavelets in VF, using a new method of phase mapping that enables identification of phase singularity points (PSs), which flank individual wavelets. Spatiotemporal periodicity was found in 21 of 24 episodes. Complete reentry on the epicardial surface was observed in 3 of 24 episodes. The cycle length of discrete regions of spatiotemporal periodicity correlated highly with the dominant frequency of the optical pseudo-ECG (R 2 ϭ0.75) and with the global bipolar electrogram (R 2 ϭ0.79). The lifespan of PSs was short (14.7Ϯ14.4 ms); 98% of PSs existed for Ͻ1 rotation. The mean number of waves entering (6.50Ϯ0.69) exceeded the mean number of waves that exited our mapping field (4.25Ϯ0.56; PϽ0.05). These results strongly suggest that ongoing stable sources are responsible for the majority of the frequency content of VF and therefore play a role in its maintenance. In this model, multiple wavelets resulting from wavebreaks do not appear to be responsible for the sustenance of this arrhythmia, but are rather the consequence of breakup of high-frequency activation from a dominant reentrant source.

A Tale of Two Fibrillations

“…5,6 On the other hand, type II VF is characterized by large and repeatable patterns of epicardial activations with occasional wavebreaks. These patterns of VF are consistent with those reported by Gray et al 31 and Chen et al, 32 who found significant spatiotemporal organization during fibrillation, suggesting that an ongoing focal and relatively stable source is the engine of VF. Taken together, we propose that VF associated with steep APD restitution but flat CV restitution (normal excitability) has different patterns of activation than VF associated with flat APD restitution with broad CV restitution (low excitability).…”

Spatial Distribution of Phase Singularities in Ventricular Fibrillation

“…The focal source hypothesis 4,5,27 postulates that fibrillation is maintained by a stable, rapid reentrant circuit (the "mother rotor") from which activation wavelets emanate but fail to conduct 1:1 to the surrounding tissues because of preexisting heterogeneities. Fibrillatory conduction originates wavebreak and leads to multiple wavelets, which are considered an epiphenomenon rather than the origin of fibrillation.…”

“…These wavelets can present as rotors but most commonly appear nonreentrant. 1,2 New wavelets can either arise from fragmentation of preexisting wavelets 3 or emanate from a stable rotor 4,5 according to the 2 leading hypotheses. Phase singularities (PSs) 6,7 represent sites in which the activation state cannot be determined, surrounded by a continuum of activation states ranging from fully activated to fully recovered.…”

Mother Rotors and the Mechanisms of D600-Induced Type 2 Ventricular Fibrillation

“…The interaction between a sustained mother rotor and underlying heterogeneity could result in conduction blocks and a complex spatial distribution of excitation frequencies, leading to VF. 2,18 …”

“…1 In contrast, type 2 (slow) VF is associated with a flat APD restitution, reduced excitability, and local spatiotemporal periodicity, 1 compatible with VF due to a focal source. 2 However, the nature of this focal source during type 2 VF remains unclear. We [3][4][5] previously demonstrated that the papillary muscle (PM) can serve as a site for anchoring reentry.…”