Document Detail

Electrophysiological mechanisms of ventricular fibrillation induction.
Jump to Full Text
MedLine Citation:
PMID:  16943942     Owner:  NLM     Status:  PubMed-not-MEDLINE    
Abstract/OtherAbstract:
Ventricular fibrillation (VF) is known as a main responsible cause of sudden cardiac death which claims thousands of lives each year. Although the mechanism of VF induction has been investigated for over a century, its definite mechanism is still unclear. In the past few decades, the development of new advance technologies has helped investigators to understand how the strong stimulus or the shock induces VF. New hypotheses have been proposed to explain the mechanism of VF induction. This article reviews most commonly proposed hypotheses that are believed to be the mechanism of VF induction.
Authors:
Nipon Chattipakorn; Kirkwit Shinlapawittayatorn; Siriporn Chattipakorn
Publication Detail:
Type:  Journal Article     Date:  2005-01-01
Journal Detail:
Title:  Indian pacing and electrophysiology journal     Volume:  5     ISSN:  0972-6292     ISO Abbreviation:  Indian Pacing Electrophysiol J     Publication Date:  2005  
Date Detail:
Created Date:  2006-08-31     Completed Date:  2006-12-20     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  101157207     Medline TA:  Indian Pacing Electrophysiol J     Country:  India    
Other Details:
Languages:  eng     Pagination:  43-50     Citation Subset:  -    
Affiliation:
Cardiac Electrophysiology Unit, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Full Text
Journal Information
Journal ID (nlm-ta): Indian Pacing Electrophysiol J
Journal ID (publisher-id): Indian Pacing Electrophysiol J
ISSN: 0972-6292
Publisher: Indian Pacing and Electrophysiology Group
Article Information
Download PDF
Copyright: ? 2005 Chattipakorn et al.
open-access: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
collection publication date: Season: Jan?Mar Year: 2005
Electronic publication date: Day: 1 Month: 1 Year: 2005
Volume: 5 Issue: 1
First Page: 43 Last Page: 50
ID: 1502068
Publisher Id: ipej050043-00
PubMed Id: 16943942

Electrophysiological Mechanisms of Ventricular Fibrillation Induction
Nipon Chattipakorn, MD, PhD
Kirkwit Shinlapawittayatorn, MD
Siriporn Chattipakorn, PhD
Cardiac Electrophysiology Unit, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
Correspondence: Address for correspondence: Nipon Chattipakorn, MD, PhD, Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200 Thailand. E-mail: nchattip@mail.med.cmu.ac.th
This work is supported in part by Thailand Research Funds RSA4680010 (N.C.) and MRG4680144 (S.C.) and the Faculty of Medicine Endowment Fund for medical research

Introduction

Ventricular fibrillation (VF) was first described by Erichsen in 1842 [1]. It is known as a fatal cardiac arrhythmia that can cause sudden death. This life-threatening VF has drawn the strong attention of a number of investigators for over a century. The study of VF induction can be traced back to the original Ludwig and Hoffa study in 1850 in which they used a strong faradic current to induce VF. However, it was not until 1940 that Wigger and Wegria established the fundamental work which demonstrated that VF could be induced when a strong premature stimulus was applied during a certain period of the cardiac cycle [2]. This period is known as the ?vulnerable period?, a period which corresponded to a portion of the T-wave of the surface electrocardiogram. The finding of VF induction by a strong stimulus delivered during the vulnerable period has allowed many investigators to advance the understanding of its mechanism. Although many theories have been proposed as the fundamental mechanism of VF induction, none is universally accepted. Current debates are discussed base on whether (1) reentrant [3-5] or (2) focal pattern [6-8] that is responsible for VF induction after the shock. In this review, four commonly proposed hypotheses are presented.


The non-uniform dispersion of refractoriness hypothesis

It is known that membrane potential differences always exist in the intact heart during systole and diastole. This is a result of the unequal levels of the resting membrane potentials as well as the depolarization potentials in myocardial cells and pacemaker cells [9-11]. This heterogeneity is known as the ?dispersion of refractoriness? of the tissues [9,12] and already appears throughout the cardiac cycle of a normal heartbeat. It is well accepted that to induce VF, the strength of a premature stimulus must be sufficiently strong (i.e. a threshold level) and be delivered during the vulnerable period [2,13]. This shock strength is known as the VF threshold (VFT) [14,16]. It is believed that VF is induced when the amount of heterogeneity or dispersion of refractoriness reaches a level that allows unidirectional block to occur, leading to reentry and fibrillation [9,17]. This concept was supported by the discovery that VF is most likely to occur when the dispersion of refractoriness increases [4,5] [18,19]. By preconditioning the heart in a various setting to set up a non-uniform dispersion of refractoriness such as by slowing heart rate, stimulating cardiac sympathetic nerve, or by causing ischemic myocardium, many VF induction studies have demonstrated that the VFT was decreased when the degree of dispersion of refractoriness increased [4,14] [20]. Because of the heterogeneity of refractoriness of cardiac cells in various regions on the heart, activations are generated by the stimulus in excitable areas which are blocked unidirectionally when they encountered areas of greater refractoriness, leading to reentry and eventually VF. Therefore, in this hypothesis, VF occurs by reentry caused by non-uniform dispersion of refractoriness.

It has been shown that responses of cardiac tissues to the shock can be in one of three categories, depending on the state of the myocardium at the time of the shock [21-23]. First, the action potential duration will be extended if the shock is delivered to effective or relatively refractory tissue [12,24,25]. This is commonly known as the ?graded response?. Second, the action potential will not be affected by the shock if it falls into the absolute refractory tissue. And third, a new action potential will be created if the shock falls into the completely recovered tissue. The degree of dispersion of refractoriness caused by a strong stimulus is mainly due to different responses of cardiac cells in different areas, resulting in the heterogeneity of refractory period extension in different cardiac cells throughout the heart [18,26,27].

The vulnerable period is known to have a high degree of dispersion of excitability during the cardiac cycle [9]. Hence, when a premature stimulus is applied to the heart during the vulnerable period, the response of the myocardium to the shock creates an even greater dispersion of refractoriness because the cardiac myocardium is irregularly excitable during that period, facilitating reentry and resulting in the initiation of VF [4,19,28,29]. Since a certain amount of heterogeneity exists in the normally functioning heart, the differences between this amount of preexisting heterogeneity and the heterogeneity induced by the electrical stimulus required for VF induction (i.e. at VFT) is sometimes considered the margin of safety [9].

Other groups of investigators, however, suggested that focal activation could initiate fibrillation due to the non-uniform dispersion of refractoriness hypothesis [6-8]. In vitro studies have shown that abrupt differences in repolarization of adjacent cardiac cells were found at the site where the repetitive firing occurred (i.e. focal re-excitation), [8] and these sudden repolarization differences have been considered to be a mechanism for VF induction [8,30,31]. The role of premature stimulus delivered during the vulnerable period in the in vivo studies, however, is still controversial. Both the increase in automaticity of the pacemaker fibers and reentry due to the unidirectional block have been demonstrated to be responsible for VF induction [32-34].


The critical point hypothesis

It is known that the potential gradient created by the shock is very strong at sites close to the shocking electrode and is weaker at more distant sites [35]. This gradient distribution, therefore, creates a non-uniform gradient field. The critical point hypothesis is based on this fact and the fact that there are three possible responses of cardiac tissue when a premature stimulus is delivered to cells of different excitability: no response, graded response (i.e. refractoriness extension), and new activation. This hypothesis states that the mechanism for VF induction is due to unidirectional block and unidirectional propagation of activation caused by those three different responses of cardiac tissues, leading to reentrant activation and, finally, VF [21]. The difference between the critical point hypothesis and the non-uniform dispersion of refractoriness hypothesis is that the critical point hypothesis suggests the reentrant pattern as the sole mechanism for VF induction, whereas the latter could have either reentrant or focal excitation as the mechanism for VF induction [21].

The critical point hypothesis was first proposed mathematically by Winfree [36] considering the heart as an excitable media, and was later demonstrated experimentally by Frazier et al [21] in 1989. In this experimental study, a strong premature stimulus (S2) was delivered to myocardium after a train of basic pacing stimuli (S1). At an appropriate timing of the S2 delivery, they found the 3 types of myocardial responses to the S2 in 3 distinct regions (Figure 1). First, the new activation created by the S2 shock arose at the recovered tissues, close to the S1 electrode, and was ready to propagate toward the excitable region (area 1, Figure 1). (2) At the region far from the S1 electrode but close to the S2 electrode, the tissues were in their relative refractory period at the time the premature stimulus was delivered. The S2 shock was strong enough to create a graded response, prolonging the refractoriness of the tissues in that area (area 2, Figure 1). As a result, the new activation could not propagate through it. (3) At the region farthest away from the S1 electrode (area 3, Figure 1), the S2 shock had no effect on the tissues in this whole area because the tissues close to the S2 electrode were still in their refractory period and not excitable and the S2 shock was too weak to create any response in the tissues far from it. However, the myocardium in this region had sufficiently recovered in time to be excited by the activation front which propagates from the directly excited region. This activation front could then reenter the area 2 and return to the area 1 again, since these cardiac tissues were already excitable.

The activation front would circle around the point where the three different cellular-response regions met (dark circle in Figure 1). This reentrant activation front could continue if the pattern of refractoriness of myocardium were maintained, or could be interrupted if the excitable pattern was changed. It is important to note that in the critical point hypothesis, the angle between the S1 and S2 stimulus must be greater than zero to create the critical point for reentry [21]. This reentrant activation front could continue if the pattern of refractoriness of myocardium were maintained, or could be interrupted if the excitable pattern was changed. The formation of a critical point was thought to generate fibrillation in both VF induction by a premature stimulus and failed defibrillation [37-40]. However, reentry is not always the pattern observed during VF induction or failed defibrillation. Therefore, critical point formation may not be the sole mechanism of VF induction.


The upper limit of vulnerability hypothesis

It is known that when a premature stimulus is given during the vulnerable period, there is a minimal strength needed to generate the inhomogeneity of excitability of cardiac tissues required to induce VF. This strength is known as the VFT [14]. When the strength of a premature stimulus is increased up to a level that VF is no longer induced at any time during the vulnerable period, this lowest strength that cannot induce VF is known as the upper limit of vulnerability (ULV) [41] [42] The critical point hypothesis could be used to explain the existence of this ULV. Since the formation of a critical point requires the cross point between the critical potential gradient and optimal excitable tissues, if this cross point is removed from the heart, the critical point will not be formed [43]. It has been shown that as shock strength increases, distance of the critical potential away from the shocking electrode also increases [35]. When the shock reaches the ULV strength, the critical value is off the heart. Thus, no critical point is formed, and no VF is induced even when the shock strength is further increased [43] [44].


The virtual electrode polarization hypothesis

This is the recent hypothesis proposed by Efimov to explain the induction of fibrillation [45]. The concept of this hypothesis is similar to that of the critical point hypothesis, except that this hypothesis is not base on the potential gradient created by the shock delivered to the myocardium. The findings that the shock can cause (1) depolarization or hyperpolarization of cardiac cells close to the shocking electrode, and (2) opposite polarization of cardiac cells in the region adjacent to (1) are the fundamental concept of this hypothesis. When the optimal transmembrane potential gradient is generated in the region near the shocking electrode, reentry can be observed as activation propagates from depolarized tissues into hyperpolarized regions (see figure 7 in reference 45). This hypothesis is proposed to explain how fibrillating activation was observed after failed defibrillation (see figure 11 in reference 45).

Although reentry has been proposed in most hypotheses as the mechanism responsible for VF induction, recent VF induction studies in pigs have demonstrated different findings. Chattipakorn et al have shown that following near ULV shocks, the first few post-shock activations arose on the epicardium in a focal manner before degenerating into VF [46,47]. No reentry was observed in these studies. It has also been shown that ablation performed in the region where the early post-shock activation occurred could significantly decrease the ULV shocks [48]. It is possible that focal activation observed in these studies is epicardial breakthrough resulting from transmural or endocardial reentry. Further studies are under investigation to validate this hypothesis. Other mechanisms including the vortex theory and the mother rotor theory also have been proposed to be responsible for initiation and maintenance of VF [49-51]. The definite mechanism, however, have yet to be revealed.


Conclusion

Similar to defibrillation mechanism, the mechanism of VF induction is complicate. Although its mechanism has been investigated for so many decades, how VF is induced is still debated. Further studies of VF induction and defibrillation are essential since they will provide important information on the fundamental mechanism that can be used to improve the treatment and prevention of sudden cardiac death, which is mainly caused by VF in the future.


This work is supported in part by Thailand Research Funds RSA4680010 (N.C.) and MRG4680144 (S.C.) and the Faculty of Medicine Endowment Fund for medical research.


References
Erichsen JE. On the influence of the coronary circulation on the action of the heartLond Mag Gazette 1842;2:561–565.
Wiggers CJ,W?gria R. Ventricular fibrillation due to single, localized induction and condenser shocks applied during the vulnerable phase of ventricular systoleAm J Physiol 1940;128:500–505.
Mines GR. On circulating excitations in heart muscles and their possible relation to tachycardia and fibrillationTrans Roy Soc Can 1914;4:43–52.
Han J,Moe GK. Nonuniform recovery of excitability in ventricular muscleCirc Res 1964;14:44–60. [pmid: 14104163]
Kuo CS,Reddy CP,Munakata K,et al. Zipes DP,Jalife JArrhythmias dependent predominantly on dispersion of repolarizationCardiac Electrophysiology and Arrhythmias 1985Orlando: Grune and Stratton; :277–285.
Marques MG,Motta JC,Norgueira RA,et al. The mechanism of atrial flutterCardiologia 1962;40:269–280. [pmid: 14470150]
Sano T,Sawanobori T. Mechanism initiating ventricular fibrillation demonstrated in cultured ventricular muscle tissueCirc Res 1970;26:201–210. [pmid: 5412535]
Sano T,Sawanobori T. Abnormal automaticity in canine Purkinje fibers focally subjected to low external concentrations of calciumCirc Res 1972;31:158–164. [pmid: 4626123]
Surawicz B,Steffens T. Cardiac vulnerabilityCardiology Clinics 1973;5:160–181.
Moe GK,Abildskov JA,Han J. Surawicz B,Pellegrino EDFactors responsible for the initiation and maintenance of ventricular fibrillationSudden Cardiac Death. 1964New York: Grune and Stratton;
Han J,Millet D,Chizonitti B,et al. Temporal dispersion of recovery of excitability in atrium and ventricle as a function of heart rateAm Heart J 1966;71:481–487. [pmid: 4951481]
Koller BS,Karasik PE,Solomon AJ,et al. Relation between repolarization and refractoriness during programmed electrical stimulation in the human right ventricle: Implications for ventricular tachycardia inductionCirculation 1995;91:2378–2384. [pmid: 7729024]
Han J. Dreifus LS,Likoff WVentricular vulnerability to fibrillationCardiac Arrhythmias 1973New York: Grune and Stratton; :87–95.
Han J,de Jalon PG,Moe GK,et al. Fibrillation threshold of premature ventricular responsesCirc Res 1966;18:18–25. [pmid: 5901486]
Anderson JL,Rodier HE,Green LS. Comparative effects of beta-adrenergic blocking drugs on experimental ventricular fibrillation thresholdAm J Cardiol 1983;51:1196–1202. [pmid: 6132549]
Bransford PP,Varghese PJ,Tovar OH,et al. Epinephrine reduces ventricular fibrillation threshold and stabilizes fibrillation by reducing cellular refractory period during fibrillationPacing and Clin Electrophys 1993;16:866.
Moe GK,Rheinboldt WC,Abildskov JA. A computer model of atrial fibrillationAm Heart J 1964;67:200–220. [pmid: 14118488]
Fabritz CL,Kirchhof PF,Behrens S,et al. Myocardial vunerability to T wave shocks: relation to shock strength, shock coupling interval, and dispersion of ventricular repolarizationJ Cardiovasc Electrophysiol 1996;7:231–242. [pmid: 8867297]
Behrens S,Li C,Fabritz CL,et al. Shock-induced dispersion of ventricular repolarization: Implications for the induction of ventricular fibrillation and the upper limit of vulnerabilityJ Cardiovasc Electrophysiol 1997;8:998–1008. [pmid: 9300297]
Han J,Garcia de Jalon P,Moe GK,et al. Adrenergic effects on ventricular vulnerabilityCirc Res 1964;14:516–524. [pmid: 14169970]
Frazier DW,Wolf PD,Wharton JM,et al. Stimulus-induced critical point: Mechanism for electrical initiation of reentry in normal canine myocardiumJ Clin Invest 1989;83:1039–1052. [pmid: 2921316]
Knisley SB,Smith WM,Ideker RE,et al. Effect of field stimulation on cellular repolarization in rabbit myocardium: Implications for reentry inductionCirc Res 1992;70:707–715. [pmid: 1551197]
Dillon SM,Wit AL. Action potential prolongation by shock as a possible mechanism for electrical defibrillationCirculation 1989;80:II-96.
Dillon SM. Optical recordings in the rabbit heart show that defibrillation strength shocks prolong the duration of depolarization and the refractory periodCirc Res 1991;69:842–856. [pmid: 1873877]
Lee RJ,Liem LB,Cohen TJ,et al. Relation between repolarization and refractoriness in the human ventricle: Cycle length dependence and effect of procainamideJ Am Coll Cardiol 1992;19:614–618. [pmid: 1538018]
Kirchhof PF,Fabritz CL,Zabel M,et al. The vulnerable period for low and high energy T-wave shocks: Role of dispersion of repolarization and effect of d-sotalolCardiovasc Res 1996;31:953–962. [pmid: 8759252]
Tovar OH,Jones JL. Biphasic defibrillation waveforms reduce shock-induced response duration dispersion between low and high shock intensitiesCirc Res 1995;77:430–438. [pmid: 7614727]
Behrens S,Franz MR. Dunbar SB,Ellenbogen KA,Epstein AESubstrate-trigger interactions: Role of ventricular repolarizationSudden Cardiac Death: Past, Present, and Future 1997Armonk, NY: Futura Publishing Co., Inc; :53–73.
Kuo CS,Munakata K,Reddy CP,et al. Characteristics and possible mechanism of ventricular arrhythmia dependent on the dispersion of action potential durationsCirculation 1983;67:1356–1367. [pmid: 6851031]
Hoffman BF,Cranefield PF. The physiological basis of cardiac arrhythmiasAm J Med 1964;37:670. [pmid: 14242077]
Daggett WM,Wallace AG. Dreifus LS,Likoff WVagal and sympathetic influences on ectopic impulse formationMechanisms and Therapy of Cardiac Arrhythmias. 1966New York: Grune and Stratton;
Li HG,Jones DL,Yee R,et al. Defibrillation shocks produce different effects on Purkinje fibers and ventricular muscle: implications for successful defibrillation, refibrillation and postshock arrhythmiaJ Am Coll Cardiol 1993;22:607–614. [pmid: 8335836]
Shibata N,Chen P-S,Dixon EG,et al. Influence of shock strength and timing on induction of ventricular arrhythmias in dogsAm J Physiol 1988;255:H891–H901. [pmid: 3177678]
Chen P-S,Wolf PD,Dixon EG,et al. Mechanism of ventricular vulnerability to single premature stimuli in open-chest dogsCirc Res 1988;62:1191–1209. [pmid: 2454762]
Wharton JM,Wolf PD,Smith WM,et al. Cardiac potential and potential gradient fields generated by single, combined, and sequential shocks during ventricular defibrillationCirculation 1992;85:1510–1523. [pmid: 1555291]
Winfree AT. When time breaks down: The three-dimensional dynamics of electrochemical waves and cardiac arrhythmias. 1987Princeton, NJ: Princeton University Press;
Walcott GP,Walcott KT,Ideker RE. Mechanisms of defibrillationJ Electrocardiol 1995;28:1–6. [pmid: 8656095]
Chen P-S,Wolf PD,Melnick SD,et al. Comparison of activation during ventricular fibrillation and following unsuccessful defibrillation shocks in open chest dogsCirc Res 1990;66:1544–1560. [pmid: 2344664]
Zhou X,Daubert JP,Wolf PD,et al. Epicardial mapping of ventricular defibrillation with monophasic and biphasic shocks in dogsCirc Res 1993;72:145–160. [pmid: 8417837]
Usui M,Callihan RL,Walker RG,et al. Epicardial sock mapping following monophasic and biphasic shocks of equal voltage with an endocardial lead systemJ Cardiovasc Electrophysiol 1996;7:322–334. [pmid: 8777480]
Chen P-S,Shibata N,Dixon EG. Comparison of the defibrillation threshold and the upper limit of ventricular vulnerabilityCirculation 1986;73:1022–1028. [pmid: 3698224]
Chen P-S,Feld GK,Kriett JM,et al. The relationship between the upper limit of vulnerability and the defibrillation threshold in humansPacing and Clin Electrophys 1992;15:530.
Ideker RE,Tang ASL,Frazier DW,et al. El-Sherif N,Samet PVentricular defibrillation: Basic conceptsCardiac Pacing and Electrophysiology 1991Orlando: W. B. Saunders; :713–726.
Ideker RE,Chen PS,Zhou X-H. Basic mechanisms of defibrillationJ Electrocardiol 1991;23(suppl):36–38. [pmid: 2090759]
Efimov IR,Gray RA,Roth BJ. Virtual electrodes and deexcitation: new insights into fibrillation induction and defibrillationJ Cardiovasc Electrophysiol 2000;11:339–353. [pmid: 10749359]
Chattipakorn N,Fotuhi PC,Sreenan KM,et al. Pacing after shocks stronger than the upper limit of vulnerability: Impact on fibrillation inductionCirculation 2000;101:1337–1343. [pmid: 10725296]
Chattipakorn N,Rogers JM,Ideker RE. Influence of postshock epicardial activation patterns on initiation of ventricular fibrillation by upper limit of vulnerability shocksCirculation 2000;101:1329–1336. [pmid: 10725295]
Chattipakorn N,Fotuhi PC,Zheng X,et al. Left ventricular apex ablation decreases the upper limit of vulnerabilityCirculation 2000;101:2458–2460. [pmid: 10831517]
Davidenko JM,Kent PF,Chialvo DR,et al. Sustained vortex-like waves in normal isolated ventricular muscleProc Natl Acad Sci USA 1990;87:8785–8789. [pmid: 2247448]
Cabo C,Pertsov AM,Davidenko JM,et al. Vortex shedding as a precursor of turbulent electrical activity in cardiac muscleBiophys J 1996;70:1105–1111. [pmid: 8785270]
Jalife J,Berenfeld O,Mansour M. Mother rotors and fibrillatory conduction: a mechanism of atrial fibrillationCardiovasc Res 2002;54:204–216. [pmid: 12062327]

Article Categories:
  • Reviews

Keywords: ventricular fibrillation, induction, mechanism.

Previous Document:  Electrical storms in Brugada syndrome: review of pharmacologic and ablative therapeutic options.
Next Document:  Multiple arrhythmogenic substrate for tachycardia in a patient with frequent palpitations.