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• Articles by J.M. Starobin
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  Ionic Determinants of Functional Reentry in a 2-D Model of Human Atrial Cells During Simulated Chronic Atrial Fibrillation Biophysical Journal, Volume 88, Issue 6, 1 June 2005, Pages 3806-3821 Sandeep V. Pandit, Omer Berenfeld, Justus M.B. Anumonwo, Roman M. Zaritski, James Kneller, Stanley Nattel and José Jalife Abstract Recent studies suggest that atrial fibrillation (AF) is maintained by fibrillatory conduction emanating from a small number of high-frequency reentrant sources (rotors). Our goal was to study the ionic correlates of a rotor during simulated chronic AF conditions. We utilized a two-dimensional (2-D), homogeneous, isotropic sheet (5×5cm) of human atrial cells to create a chronic AF substrate, which was able to sustain a stable rotor (dominant frequency ∼5.7Hz, rosette-like tip meander ∼2.6cm). Doubling the magnitude of the inward rectifier K current () increased rotor frequency (∼8.4Hz), and reduced tip meander (∼1.7cm). This rotor stabilization was due to a shortening of the action potential duration and an enhanced cardiac excitability. The latter was caused by a hyperpolarization of the diastolic membrane potential, which increased the availability of the Na current (). The rotor was terminated by reducing the maximum conductance (by 90%) of the atrial-specific ultrarapid delayed rectifier K current (), or the transient outward K current (), but not the fast or slow delayed rectifier K currents (/). Importantly, blockade of / prolonged the atrial action potential at the plateau, but not at the terminal phase of repolarization, which led to random tip meander and wavebreak, resulting in rotor termination. Altering the rectification profile of also slowed down or abolished reentrant activity. In combination, these simulation results provide novel insights into the ionic bases of a sustained rotor in a 2-D chronic AF substrate. Abstract | Full Text | PDF (714 kb)

• Panoramic Optical Mapping Reveals Continuous Epicardial Reen...

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• Vulnerable Window for Conduction Block in a One-Dimensional ...

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Abstract

High-frequency arrhythmias leading to fibrillation are often associated with the presence of inhomogeneities (obstacles) in cardiac tissue and reduced excitability of cardiac cells. Studies of antiarrhythmic drugs in patients surviving myocardial infarction revealed an increased rate of sudden cardiac death compared with untreated patients. These drugs block the cardiac sodium channel, thereby reducing excitability, which may alter wavefront-obstacle interactions. In diseased atrial tissue, excitability is reduced by diminished sodium channel availability secondary to depolarized rest potentials and cellular decoupling secondary to intercellular fibrosis. Excitability can also be reduced by incomplete recovery between successive excitations. In all of these cases, wavefront-obstacle interactions in a poorly excitable medium may reflect an arrhythmogenic process that permits formation of reentrant wavelets leading to flutter, fibrillation, and sudden cardiac death. To probe the relationship between excitability and arrhythmogenesis, we explored conditions for new wavelet formation after collision of a plane wave with an obstacle in an otherwise homogeneous excitable medium. Formulating our approach in terms of the balance between charge available in the wavefront and the excitation charge requirements of adjacent medium, we found analytically the critical medium parameters that defined conditions for wavefront-obstacle separation. Under these conditions, when a parent wavefront collided with a primitive obstacle, the resultant fragments separated from the obstacle boundaries, subsequently curled, and spawned new "daughter" wavelets. We identified spatial arrangements of obstacles such that wavefront-obstacle collisions leading to spawning of new wavelets could produce high-frequency wavelet trains similar to fibrillation-like arrhythmias.