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Integrative Physiology |
From the Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center (M.V., C.O., S.-F.L., H.S.K., P.-S.C.), and Departments of Medicine (Cardiology) and Physiology and Physiological Science, UCLA School of Medicine (J.Y., J.K., S.T.L., Z.Q., A.G., J.N.W.), Los Angeles, Calif.
Correspondence to James N. Weiss, MD, Division of Cardiology, 3645 MRL Bldg, UCLA School of Medicine, Los Angeles, CA 90095-1760. E-mail jweiss{at}mednet.ucla.edu
It has been suggested from frequency analysis that cardiac fibrillation is driven by stable intramural reentry, with wavebreak occurring due to failure of 1:1 propagation. We tested this hypothesis with a combined experimental and theoretical approach. Optical mapping was performed on epicardial, endocardial, and transmural cut surfaces of fibrillating swine ventricles. Wavelets were characterized, the frequency content of optical signals analyzed, and space-time plots (STPs) constructed to detect Wenckebach-like conduction. The findings were compared with simulations in 2D and 3D cardiac tissue using the Luo-Rudy action potential model. The incidence of reentry in the cut transmural surface (11.8% in right ventricle, 14.3% in left ventricle) was similar to that on the endocardial surface (13.1%, P=NS) but greater than on the epicardial surface (7.7%, P<0.01). Frequency spectra of optically recorded membrane voltage were organized into spatial domains with the same dominant frequency, but these domains were nonstationary. In STPs, pseudo-2:1 conduction block was caused by double potentials arising when reentry occurred on the recording site rather than true Wenckebach conduction. The latter was observed in 11 of 166 STPs but did not occur at borders of high-to-low frequency domains. In simulations, similar findings were obtained when action potential duration (APD) restitution slope was steep. Stationary dominant frequency domains with Wenckebach conduction patterns were observed only in the presence of shallow APD restitution slope and marked nonuniform tissue heterogeneity. In conclusion, stable intramural reentry as the engine of fibrillation was not observed. Our findings support the idea that dynamic wavebreak plays a fundamental role in the generation and maintenance of ventricular fibrillation.
Key Words: fibrillation Fourier transform restitution reentry
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