A Tale of Two Fibrillations

Chen, Peng Sheng; Wu, Tsu Juey; Ting, Chih Tai; Karagueuzian, Hrayr S.; Garfinkel, Alan; Lin, Shien Fong; Weiss, James N.

doi:10.1161/01.cir.0000094404.26004.07

Cited by 101 publications

(88 citation statements)

References 54 publications

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“…These 2 mechanisms are not totally incompatible, but may make complementary contributions in various heart diseases. 28 Based on the results of the present study, NIF is expected to be effective in preventing VF, if the VF is attributable to rapidly circulating mother rotors, as it destabilizes rotation activity. Failure of ventricular defibrillation by DC shocks at an energy below a certain level is mainly attributable to induction of new mother rotor-type excitations, giving rise to re-initiation of fibrillation.…”

Section: Discussionmentioning

confidence: 73%

Combined Effects of Nifekalant and Lidocaine on the Spiral-Type Re-Entry in a Perfused 2-Dimensional Layer of Rabbit Ventricular Myocardium

Amino

Yamazaki

Nakagawa

et al. 2005

Circ J

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piral-type excitation is the principal mechanism of functional re-entry for the genesis of life-threatening ventricular tachycardia and ventricular fibrillation (VT/VF). 1,2 Nifekalant (NIF) hydrochloride is a new class III antiarrhythmic drug developed in Japan that causes dose-dependent prolongation of action potential duration (APD) in both atrial and ventricular muscle, mainly by reducing the rapid component of the delayed rectifier potassium current (IKr). [3][4][5][6][7] The 2000 American Heart Association Guidelines for cardiopulmonary resuscitation (CPR) recommends intravenous amiodarone to prevent recurrent VT/VF, 8,9 but amiodarone has not yet been approved for CPR in Japan and intravenous NIF is used, often in combination with lidocaine (LID), as an alternative. 10 Nifekakant and LID are also used sequentially to treat recurrent VT/VF resistant to DC shocks; 11-13 however, little information is available on the electropharmacological basis for the combined use of these drugs. The present study was designed to investigate the effects of NIF and NIF + LID on the spiral-type excitation in a perfused 2-dimensional (D) layer of rabbit ventricle by using our custom-made high-resolution optical mapping system. Methods Experimental ModelJapanese White rabbits of both sexes weighing 1.7-2.0 kg (n=13) were anesthetized with thiamylal sodium (10-15 mg/kg), and after opening the thorax, the heart was rapidly removed. Complete atrioventricular block was produced by ligating the His bundle with fine silk thread. The aorta was then cannulated, and the heart was connected to a Langendorff perfusion apparatus. The coronary arteries were perfused with modified Krebs Ringer solution at a constant flow (35-45 ml/min). The solution was equilibrated with 95% O2 and 5% CO2 to maintain its pH at 7.4, and its temperature was maintained at 35°C.Because of its 3-D structure with variable filament configuration, vortex-type excitations appear only transiently and incidentally in the intact heart, 14 thereby hampering detailed analysis of spiral dynamics by optical mapping. To avoid this problem, we created a 2-D preparation by the method described by Schalij et al. 15 In brief, the Langendorff-perfused rabbit heart was immersed in a tissue bath containing perfusion fluid at 35°C, and a cryoprobe made of copper was inserted into the left ventricular cavity, and the probe was then filled with liquid nitrogen (-192°C) for 5 min. This freezing procedure destroyed the endocardial and intramural layers of the free wall of the left ventricle and the total interventricular septum, leaving only Background Spiral re-entry plays the principal role in the genesis of ventricular tachycardia and ventricular fibrillation (VT/VF). The specific IKr blocker, nifekakant (NIF) has, often in combination with lidocaine (LID), recently been used in Japan to prevent recurrent VT/VF, but the combined effects of these drugs on spiral reentry had never been investigated. Methods and ResultsA ventricular epicardial sheet was obtained from 13 Langendorff-pe...

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Section: Discussionmentioning

confidence: 73%

Combined Effects of Nifekalant and Lidocaine on the Spiral-Type Re-Entry in a Perfused 2-Dimensional Layer of Rabbit Ventricular Myocardium

Amino

Yamazaki

Nakagawa

et al. 2005

Circ J

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“…14 The initial VF in most situations is compatible with type 1 VF. Continued fibrillation induces acute global ischemia, which flattens APD restitution and decreases excitability, converting type 1 VF to type 2 VF.…”

Section: Discussionmentioning

confidence: 94%

“…These findings support the hypothesis that type 1 VF and type 2 VF have different underlying mechanisms. 1,14 …”

Section: Discussionmentioning

confidence: 99%

Mother Rotors and the Mechanisms of D600-Induced Type 2 Ventricular Fibrillation

Lin

Baher

et al. 2004

Circulation

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Background-Two types of ventricular fibrillation (VF) have been demonstrated in isolated rabbit hearts during D600 infusion. Type 1 VF is characterized by the presence of multiple, wandering wavelets, whereas type 2 VF shows local spatiotemporal periodicity. We hypothesized that a single mother rotor underlies type 2 VF. Methods and Results-One (protocol I) or 2 (protocol II) cameras were used to map the epicardial ventricular activations in Langendorff-perfused rabbit hearts. Multiple episodes of type 2 VF were induced in 22 hearts by high-concentration (Ն2.5 mg/L) D600 (protocol I). During type 2 VF, a single spiral wave (nϭ19) and/or an epicardial breakthrough pattern (nϭ11) was present in 14 hearts. These spiral waves either slowly drifted or intermittently anchored on the papillary muscle (PM) of the left ventricle. Dominant-frequency (DF) analyses showed that the highest local DF was near the PM (12.5Ϯ1.1 Hz). There was an excellent correlation between the highest local DF of these spiral waves and breakthroughs (11.8Ϯ1.7 Hz) and the DF of simultaneously obtained global pseudo-ECG (11.2Ϯ1.8 Hz, rϭ0.97, PϽ0.0001) during type 2 VF. We also successfully reproduced the major features of type 2 VF by using the Luo-Rudy action-potential model in a simulated, 3-dimensional tissue slab, under conditions of reduced excitability and flat action-potential duration restitution. Conclusions-Either a stationary or a slowly drifting mother rotor can result in type 2 VF. Colocalization of the stationary mother rotors with the PM suggests the importance of underlying anatomic structures in mother rotor formation.

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“…Another important type of restitution is of conduction velocity: if the DI is too short, Na + channels have not fully recovered from inactivation, and so propagation of the following depolarization wave is slowed. Both forms of restitution are important in the genesis of VF (12).…”

Section: Introductionmentioning

confidence: 99%

A simulation study of the effects of cardiac anatomy in ventricular fibrillation

Xie¹,

Qu²,

Yang³

et al. 2004

J. Clin. Invest.

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Nonstandard abbreviations used: action potential duration (APD); diastolic interval (DI); left ventricle (LV); Luo-Rudy phase 1 (LR1); right ventricle (RV); two-dimensional (2D); ventricular fibrillation (VF). Conflict of interest:The authors have declared that no conflict of interest exists. IntroductionIn the normal heart, the wave of electrical activation that triggers synchronized contraction moves in a roughly planar fashion through the ventricular myocardium. In ventricular fibrillation (VF), the most common cause of death from cardiovascular disease, this electrical wave breaks up into multiple wavelets that meander chaotically through the myocardium (1-7), precluding the coordinated contraction that is necessary to maintain blood pressure. This "electrical turbulence" is initiated and maintained by the process of wavebreak, in which new waves are continually generated to replace those that are extinguished because of encounters with each other or with refractory tissue. Traditionally, many cardiac researchers believed that wavebreak was due to external obstacles and focused on the role of anatomical and/or electrophysiological heterogeneities and obstacles, such as built-in gradients of electrophysiological properties, or the presence of infarction, ischemia, and/or fibrosis as the primary causes of wavebreak. However, dynamicists discovered that purely dynamical instabilities, arising from cellular properties such as ion channel dynamics, can also cause wavebreak even in perfectly homogeneous tissue.What drives fibrillation: fixed heterogeneities, dynamical instabilities, or a synergistic interaction between the two? The answer is controversial, because both factors are inevitably present in real cardiac tissue. Indeed, even in normal cardiac tissue without significant fibrosis, infarction, or ischemia, VF can be induced by a sufficiently large electrical stimulus, and it is still unclear what factors cause wavebreak. For example, one important aspect of the gross anatomy of the heart is the shape of the ventricular cavities, the interventricular septum, and the overall geometry of the lower heart (8). Another critical aspect of cardiac gross anatomy is the anisotropy of electrical conduction, which is created by the twisted distribution of cardiac fibers through the myocardial wall (9). This "fiber twist" can play a role in creating wavebreak, as has been shown in models of 3D rectangular slabs of tissue (10, 11). In addition to these fixed factors, one of the key dynamical factors that cause wavebreak is electrical restitution. After an action potential, the cardiac cell must recover ionic balance and replenish calcium stores in the sarcoplasmic reticulum. Ion channels (Na + , K + , or Ca ++ ), having been inactivated or deactivated, must recover to their resting state. These restorative processes take place during the electrical diastolic interval (DI), the interval between repolarization and the next action potential upstroke. Physiologically, it is important for the action potential duration (APD)...

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A Tale of Two Fibrillations

Cited by 101 publications

References 54 publications

Combined Effects of Nifekalant and Lidocaine on the Spiral-Type Re-Entry in a Perfused 2-Dimensional Layer of Rabbit Ventricular Myocardium

Combined Effects of Nifekalant and Lidocaine on the Spiral-Type Re-Entry in a Perfused 2-Dimensional Layer of Rabbit Ventricular Myocardium

Mother Rotors and the Mechanisms of D600-Induced Type 2 Ventricular Fibrillation

A simulation study of the effects of cardiac anatomy in ventricular fibrillation

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