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(Circulation. 2005;112:2386-2396.)
© 2005 American Heart Association, Inc.

Arrhythmia/Electrophysiology

Remodeling in Cells From Different Regions of the Reentrant Circuit During Ventricular Tachycardia

Shigeo Baba, MD^*; Wen Dun, PhD^*; Candido Cabo, PhD; Penelope A. Boyden, PhD

From the Department of Pharmacology, Center for Molecular Therapeutics, Columbia University (S.B., W.D., C.C., P.A.B.), and the Department of Computer Systems, NYC College of Technology, City University of New York (C.C.), New York, NY.

Correspondence to Dr Penelope A. Boyden, Department of Pharmacology, Columbia College of Physicians and Surgeons, 630 W 168th St, New York, NY 10032.

Received January 7, 2005; revision received July 22, 2005; accepted July 25, 2005.

Background— Anisotropic reentrant excitation occurs in the remodeled substrate of the epicardial border zone (EBZ) of the 5-day infarcted canine heart. Reentry is stabilized because of the formation of functional lines of block. We hypothesized that regional differences of ionic currents in cells of the EBZ form these lines of block. Therefore, we first mapped reentrant circuits of sustained tachycardias, then dispersed cells (infarct zone cells, IZs) from the central common pathway of the circuit (IZc) as well as from the other side of the line of block (outer pathway, IZo) for study.

Methods and Results— We mapped reentrant circuits in the EBZ of infarcted hearts during sustained ventricular tachycardias (>30 seconds, n=17 episodes, cycle lengths=218±7.9 ms). I_Na density was reduced in both IZc and IZo, and the kinetic properties of IZc I_Na were markedly altered versus IZo. Structural remodeling of the sodium channel protein Na_v1.5 occurred in IZs, with cell surface localization differing from normal cells. Both IZc and IZo have similar but reduced I_CaL, whereas IZc showed changes in Ca²⁺ current kinetics with an acceleration of current decay. Computer simulations of the 2D EBZ showed that incorporating only differences between I_Na in IZc and IZo prevented stability of the reentrant circuit. Incorporating only differences between I_CaL in the IZc and IZo cells also prevented stability of the circuit. However, incorporating both I_Na and I_CaL current differences stabilized the simulated reentrant circuit, and lines of block formed between the 2 distinct regions.

Conclusions— Despite differences in I_Na and I_CaL properties in cells of the center and outer pathways of a reentrant circuit, the resulting changes in effective refractory periods tend to stabilize reentry in this remodeled substrate.

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