Spatiotemporal complexity of ventricular fibrillation revealed by tissue mass reduction in isolated swine right ventricle. Further evidence for the quasiperiodic route to chaos hypothesis.

Kim, Young Hoon; Garfinkel, Alan; Ikeda, Takanori; Wu, Tsu Juey; Athill, Charles A.; Weiss, James N.; Karagueuzian, Hrayr S.; Chen, Peng Sheng

doi:10.1172/jci119791

Cited by 116 publications

(133 citation statements)

References 28 publications

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“…However, other work has questioned the chaotic fibrillation hypothesis (45,46). The current prevailing theory (47), supported by a range of mathematical (48)(49)(50)(51)(52)(53)(54)(55)(56), in vitro (57)(58)(59), and in vivo (57,(60)(61)(62)(63)(64)(65)(66)(67)(68)(69)(70) studies, is that fibrillation is a complex nonlinear combination of stochastic and deterministic components, such as scroll waves of electrical activity meandering within the ventricular wall. Given this body of evidence, it is apparent that fibrillation is characterized by high-dimensional nonstationary spatiotemporal dynamics that are too complex for current nonlinear-dynamical control techniques.…”

Section: Discussionmentioning

confidence: 99%

Nonlinear-dynamical arrhythmia control in humans

Christini

Steín²,

Markowitz³

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

114

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Nonlinear-dynamical control techniques, also known as chaos control, have been used with great success to control a wide range of physical systems. Such techniques have been used to control the behavior of in vitro excitable biological tissue, suggesting their potential for clinical utility. However, the feasibility of using such techniques to control physiological processes has not been demonstrated in humans. Here we show that nonlinear-dynamical control can modulate human cardiac electrophysiological dynamics by rapidly stabilizing an unstable target rhythm. Specifically, in 52͞54 control attempts in five patients, we successfully terminated pacing-induced period-2 atrioventricular-nodal conduction alternans by stabilizing the underlying unstable steady-state conduction. This proof-of-concept demonstration shows that nonlinear-dynamical control techniques are clinically feasible and provides a foundation for developing such techniques for more complex forms of clinical arrhythmia.I ncreasingly, it is recognized that many cardiac arrhythmias can be characterized on the basis of the physical principles of nonlinear dynamics (1, 2). A nonlinear-dynamical system is one that changes with time and cannot be broken down into a linear sum of its individual components. For certain nonlinear systems, known as chaotic systems, behavior is aperiodic and long-term prediction is impossible, even though the dynamics are entirely deterministic (i.e., the dynamics of the system are completely determined from known inputs and the previous state of the system, with no influence from random inputs). Importantly, such determinism actually can be exploited to control the dynamics of a chaotic system. To this end, a variety of nonlineardynamical control techniques, also known as chaos control, ‡ have been developed (3, 4) and applied successfully to a wide range of physical systems (5)(6)(7)(8)(9)(10)(11)(12)(13)(14). Such techniques are modelindependent, i.e., they require no a priori knowledge of the underlying equations of a system and are therefore appropriate for systems that are essentially ''black boxes.''The success of nonlinear-dynamical control techniques in stabilizing physical systems, together with the facts that many physiological systems are nonlinear (e.g., the cardiac conduction system, because of its numerous complex nonlinear component interactions) and lack the detailed analytical system models required for model-based control techniques, have fostered widespread interest in applying these model-independent techniques to biological dynamical systems (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). In a pioneering application, Garfinkel et al. (15) stabilized drug-induced irregular cardiac rhythms by means of dynamically timed electrical stimulation in an in vitro rabbit ventricular-tissue preparation. That work was an important demonstration that the physical principles of nonlinear-dynamical control could be extended into the realm of cardiac dynamics. Although extension of that work to the control of fibrill...

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Section: Discussionmentioning

confidence: 99%

Nonlinear-dynamical arrhythmia control in humans

Christini

Steín²,

Markowitz³

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

114

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“…As described in detail (14), the right coronary arteries of farm pigs were cannulated and perfused with oxygenated Tyrode's solution at 36°C, and the well-perfused right ventricular free wall was surgically isolated. The tissue was placed with the endocardial side down in a tissue bath containing a built-in electrode array with 478 bipolar recording electrodes (1.6-mm interelectrode distance).…”

Section: Methodsmentioning

confidence: 99%

Preventing ventricular fibrillation by flattening cardiac restitution

Garfinkel

Kim

Voroshilovsky

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

496

418

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Ventricular fibrillation is the leading cause of sudden cardiac death. In fibrillation, fragmented electrical waves meander erratically through the heart muscle, creating disordered and ineffective contraction. Theoretical and computer studies, as well as recent experimental evidence, have suggested that fibrillation is created and sustained by the property of restitution of the cardiac action potential duration (that is, its dependence on the previous diastolic interval). The restitution hypothesis states that steeply sloped restitution curves create unstable wave propagation that results in wave break, the event that is necessary for fibrillation. Here we present experimental evidence supporting this idea. In particular, we identify the action of the drug bretylium as a prototype for the future development of effective restitution-based antifibrillatory agents. We show that bretylium acts in accord with the restitution hypothesis: by flattening restitution curves, it prevents wave break and thus prevents fibrillation. It even converts existing fibrillation, either to a periodic state (ventricular tachycardia, which is much more easily controlled) or to quiescent healthy tissue.

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“…9,10 For right ventricular (RV) studies, the RV wall was excised, perfused with Tyrode's solution, and placed in a tissue bath. Optical mapping during VF was performed on the endocardial surface (nϭ12) as well as the epicardial surface (nϭ9).…”

Section: Isolated Swine Ventricle Preparationsmentioning

confidence: 99%