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Toward an Understanding of the Molecular Mechanisms of Ventricular Fibrillation

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Abstract

A major goal of basic research in cardiac electrophysiology is to understand the mechanisms responsible for ventricular fibrillation (VF). Here we review recent experimental and numerical results, from the ion channel to the organ level, which might lead to a better understanding of the cellular and molecular mechanisms of VF. The discussion centers on data derived from a model of stable VF in the Langendorff-perfused guinea pig heart that demonstrate distinct patterns of organization in the left (LV) and right (RV) ventricles. Analysis of optical mapping data reveals that VF excitation frequencies are distributed throughout the ventricles in clearly demarcated domains. The highest frequency domains are usually found on the anterior wall of the LV, demonstrating that a high frequency reentrant source (a rotor) that remains stationary in the LV is the mechanism that sustains VF in this model. Computer simulations predict that the inward rectifying potassium current (I K1) is an essential determinant of rotor stability and rotation frequency, and patch-clamp results strongly suggest that the outward component of the background current (presumably I K1) of cells in the LV is significantly larger in the LV than in the RV. These data have opened a new and potentially exciting avenue of research on the possible role played by inward rectifier channels in the mechanism of VF and may lead us toward an understanding of its molecular basis and hopefully lead to new preventative approaches.

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  1. Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY, USA

    José Jalife, Justus M.B. Anumonwo & Omer Berenfeld

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  1. José Jalife
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Jalife, J., Anumonwo, J.M. & Berenfeld, O. Toward an Understanding of the Molecular Mechanisms of Ventricular Fibrillation. J Interv Card Electrophysiol 9, 119–129 (2003). https://doi.org/10.1023/A:1026215919730

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