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(Circulation. 1999;99:2819-2826.)
© 1999 American Heart Association, Inc.
Current Perspectives |
Chaos and the Transition to Ventricular Fibrillation
A New Approach to Antiarrhythmic Drug Evaluation
From the Departments of Medicine (Cardiology), Physiology, and Physiological Science and the UCLA Cardiovascular Research Laboratory, UCLA School of Medicine and Cedars-Sinai Medical Center, 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
Abstract—Sudden cardiac death resulting from ventricular fibrillation can be separated into 2 components: initiation of tachycardia and degeneration of tachycardia to fibrillation. Clinical drug studies such as CAST and SWORD demonstrated that focusing exclusively on the first component is inadequate as a therapeutic modality. The hope for developing effective pharmacological therapy rests on a comprehensive understanding of the second component, the transition from tachycardia to fibrillation. We summarize evidence that the transition from tachycardia to fibrillation is a transition to spatiotemporal chaos, with similarities to the quasiperiodic transition to chaos seen in fluid turbulence. In this scenario, chaos results from the interaction of multiple causally independent oscillatory motions. Simulations in 2-dimensional cardiac tissue suggest that the destabilizing oscillatory motions during spiral-wave reentry arise from restitution properties of action potential duration and conduction velocity. The process of spiral-wave breakup in simulated cardiac tissue predicts remarkably well the sequence by which tachycardia degenerates to fibrillation in real cardiac tissue. Modifying action potential duration and conduction velocity restitution characteristics can prevent spiral-wave breakup in simulated cardiac tissue, suggesting that drugs with similar effects in real cardiac tissue may have antifibrillatory efficacy (the Restitution Hypothesis). If valid for the real heart, the Restitution Hypothesis will support a new paradigm for antiarrhythmic drug classification, incorporating an antifibrillatory profile based on effects on cardiac restitution and the traditional antitachycardia profile (classes 1 through 4).
Key Words: arrhythmia • death, sudden • drugs • dynamics • fibrillation
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