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Heart Rhythm. 2008 Apr;5(4):575-84. doi: 10.1016/j.hrthm.2008.01.011. Epub 2008 Jan 17.

Excito-oscillatory dynamics as a mechanism of ventricular fibrillation.

Author information

1
Department of Biomedical Engineering at the University of Alabama at Birmingham, Birmingham, Alabama 35294-0019, USA. gray@uab.edu

Abstract

BACKGROUND:

The instabilities associated with reentrant spiral waves are of paramount importance to the initiation and maintenance of tachyarrhythmias, especially ventricular fibrillation (VF). In addition to tissue heterogeneities, there are only a few basic purported mechanisms of spiral wave breakup, most notably restitution.

OBJECTIVE:

We test the hypothesis that oscillatory membrane properties act to destabilize spiral waves.

METHODS:

We recorded transmembrane potential (V(m)) from isolated rabbit myocytes using a constant current stimulation protocol. We developed a mathematical model that included both the stable excitable equilibrium point at resting V(m) (-80 mV) and the unstable oscillatory equilibrium point at elevated V(m) (-10 mV). Spiral wave dynamics were studied in 2-dimensional grids using variants of the model.

RESULTS:

All models showed restitution and reproduced the experimental values of transmembrane resistance at rest and during the action potential plateau. Stable spiral waves were observed when the model showed only 1 equilibrium point. However, spatio-temporal complexity was observed if the model showed both excitable and oscillatory equilibrium points (i.e., excito-oscillatory models). The initial wave breaks resulted from oscillatory waves expanding in all directions; after a few beats, the patterns were characterized by a combination of unstable spiral waves and target patterns consistent with the patterns observed on the heart surface during VF. In our model, this VF-like activity only occurred when the single cell period of V(m) oscillations was within a specific range.

CONCLUSION:

The VF-like patterns observed in our excito-oscillatory models could not be explained by the existing proposed instability mechanisms. Our results introduce the important suggestion that membrane dynamics responsible for V(m) oscillations at elevated V(m) levels can destabilize spiral waves and thus may be a novel therapeutic target for preventing VF.

PMID:
18362026
PMCID:
PMC2362505
DOI:
10.1016/j.hrthm.2008.01.011
[Indexed for MEDLINE]
Free PMC Article

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