Donate Help Contact The AHA Sign In Home
American Heart Association
Circulation Research
Search: search_blue_button Advanced Search
Circulation Research. 1999;84:1318-1331

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cao, J.-M.
Right arrow Articles by Chen, P.-S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cao, J.-M.
Right arrow Articles by Chen, P.-S.
Related Collections
Right arrow Other myocardial biology
Right arrow Animal models of human disease
Right arrow Arrythmias-basic studies
(Circulation Research. 1999;84:1318-1331.)
© 1999 American Heart Association, Inc.


Original Contributions

Spatiotemporal Heterogeneity in the Induction of Ventricular Fibrillation by Rapid Pacing

Importance of Cardiac Restitution Properties

Ji-Min Cao1, Zhilin Qu1, Young-Hoon Kim, Tsu-Juey Wu, Alan Garfinkel, James N. Weiss, Hrayr S. Karagueuzian, Peng-Sheng Chen

From the Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center (J.-M.C., Y.-H.K., T.-J.W., H.S.K., P.-S.C.), and the Departments of Medicine (Cardiology), Physiology, and Physiological Science (Z.Q., A.G., J.N.W.), UCLA School of Medicine, Los Angeles, Calif.

Correspondence to Peng-Sheng Chen, MD, Rm 5342, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90048-1865. E-mail chenp{at}ucla.edu

Abstract—The mechanism by which rapid pacing induces ventricular fibrillation (VF) is unclear. We performed computerized epicardial mapping studies in 10 dogs, using 19-beat pacing trains. The pacing interval (PI) of the first train was 300 ms and then was progressively shortened until VF was induced. For each PI, we constructed restitution curves for the effective refractory period (ERP). When the PI was long, the activation cycle length (CL) was constant throughout the mapped region. However, as the PI shortened, there was an increase in the spatiotemporal complexity of the CL variations and an increase in the slope of the ERP restitution curve. In 5 dogs, we documented the initiation of VF by wavebreak at the site of long-short CL variations. Computer simulation studies using the Luo-Rudy I ventricular action potential model in simulated 2-dimensional tissue reproduced the experimental results when normal ERP and conduction velocity (CV) restitution properties were intact. By altering CV and ERP restitutions in this model, we found that CV restitution creates spatial CL variations, whereas ERP restitution underlies temporal, beat-to-beat variations in refractoriness during rapid pacing. Together, the interaction of CV and ERP restitutions produces spatiotemporal oscillations in cardiac activation that increase in amplitude as the PI decreases, ultimately causing wavebreak at the site of intrinsic heterogeneity. This initial wavebreak then leads to the formation of spiral waves and VF. These findings support a key role for both CV and ERP restitutions in the initiation of VF by rapid pacing.


Key Words: chaos • restitution curve • wavebreak • anatomical obstacles • bifurcation




This article has been cited by other articles:


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
L.-H. Xie and J. N. Weiss
Arrhythmogenic consequences of intracellular calcium waves
Am J Physiol Heart Circ Physiol, September 1, 2009; 297(3): H997 - H1002.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
Y. Xie, A. Garfinkel, J. N. Weiss, and Z. Qu
Cardiac alternans induced by fibroblast-myocyte coupling: mechanistic insights from computational models
Am J Physiol Heart Circ Physiol, August 1, 2009; 297(2): H775 - H784.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
A. R.M. Gelzer, M. L. Koller, N. F. Otani, J. J. Fox, M. W. Enyeart, G. J. Hooker, M. L. Riccio, C. R. Bartoli, and R. F. Gilmour Jr
Dynamic Mechanism for Initiation of Ventricular Fibrillation In Vivo
Circulation, September 9, 2008; 118(11): 1123 - 1129.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
S. Mironov, J. Jalife, and E. G. Tolkacheva
Role of Conduction Velocity Restitution and Short-Term Memory in the Development of Action Potential Duration Alternans in Isolated Rabbit Hearts
Circulation, July 1, 2008; 118(1): 17 - 25.
[Abstract] [Full Text] [PDF]


Home page
EuropaceHome page
L. D. Wilson and D. S. Rosenbaum
Mechanisms of arrythmogenic cardiac alternans
Europace, November 1, 2007; 9(suppl_6): vi77 - vi82.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
Z. Qu and J. N. Weiss
The chicken or the egg? Voltage and calcium dynamics in the heart
Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2054 - H2055.
[Full Text] [PDF]


Home page
J. Physiol.Home page
K. E. Brack, V. H. Patel, J. H. Coote, and G. A. Ng
Nitric oxide mediates the vagal protective effect on ventricular fibrillation via effects on action potential duration restitution in the rabbit heart
J. Physiol., September 1, 2007; 583(2): 695 - 704.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
M.-J. Yang, D. X. Tran, J. N. Weiss, A. Garfinkel, and Z. Qu
The pinwheel experiment revisited: effects of cellular electrophysiological properties on vulnerability to cardiac reentry
Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1781 - H1790.
[Abstract] [Full Text] [PDF]


Home page
Cardiovasc ResHome page
G. A. Ng, K. E. Brack, V. H. Patel, and J. H. Coote
Autonomic modulation of electrical restitution, alternans and ventricular fibrillation initiation in the isolated heart
Cardiovasc Res, March 1, 2007; 73(4): 750 - 760.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
K. H. W. J. ten Tusscher and A. V. Panfilov
Alternans and spiral breakup in a human ventricular tissue model
Am J Physiol Heart Circ Physiol, September 1, 2006; 291(3): H1088 - H1100.
[Abstract] [Full Text] [PDF]


Home page
Circ. Res.Home page
M. Allouis, F. Le Bouffant, R. Wilders, D. Peroz, J.-J. Schott, J. Noireaud, H. Le Marec, J. Merot, D. Escande, and I. Baro
14-3-3 Is a Regulator of the Cardiac Voltage-Gated Sodium Channel Nav1.5
Circ. Res., June 23, 2006; 98(12): 1538 - 1546.
[Abstract] [Full Text] [PDF]


Home page
Circ. Res.Home page
J. N. Weiss, A. Karma, Y. Shiferaw, P.-S. Chen, A. Garfinkel, and Z. Qu
From Pulsus to Pulseless: The Saga of Cardiac Alternans
Circ. Res., May 26, 2006; 98(10): 1244 - 1253.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
M. M. Scheinman and E. Keung
The Year in Clinical Electrophysiology
J. Am. Coll. Cardiol., March 21, 2006; 47(6): 1207 - 1213.
[Full Text] [PDF]


Home page
Circ. Res.Home page
W. Bian and L. Tung
Structure-Related Initiation of Reentry by Rapid Pacing in Monolayers of Cardiac Cells
Circ. Res., March 3, 2006; 98(4): e29 - e38.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
J. A. Fallavollita, B. J. Riegel, G. Suzuki, U. Valeti, and J. M. Canty Jr.
Mechanism of sudden cardiac death in pigs with viable chronically dysfunctional myocardium and ischemic cardiomyopathy
Am J Physiol Heart Circ Physiol, December 1, 2005; 289(6): H2688 - H2696.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
A. M. Yue, M. R. Franz, P. R. Roberts, and J. M. Morgan
Global Endocardial Electrical Restitution in Human Right and Left Ventricles Determined by Noncontact Mapping
J. Am. Coll. Cardiol., September 20, 2005; 46(6): 1067 - 1075.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
J. N. Weiss, Z. Qu, P.-S. Chen, S.-F. Lin, H. S. Karagueuzian, H. Hayashi, A. Garfinkel, and A. Karma
The Dynamics of Cardiac Fibrillation
Circulation, August 23, 2005; 112(8): 1232 - 1240.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
S. P. Thomas, A. Thiagalingam, E. Wallace, P. Kovoor, and D. L. Ross
Organization of Myocardial Activation During Ventricular Fibrillation After Myocardial Infarction: Evidence for Sustained High-Frequency Sources
Circulation, July 12, 2005; 112(2): 157 - 163.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
Z. Qu
Dynamical effects of diffusive cell coupling on cardiac excitation and propagation: a simulation study
Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2803 - H2812.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
J. Huang, X. Zhou, W. M. Smith, and R. E. Ideker
Restitution Properties During Ventricular Fibrillation in the In Situ Swine Heart
Circulation, November 16, 2004; 110(20): 3161 - 3167.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
T.-J. Wu, S.-F. Lin, A. Baher, Z. Qu, A. Garfinkel, J. N. Weiss, C.-T. Ting, and P.-S. Chen
Mother Rotors and the Mechanisms of D600-Induced Type 2 Ventricular Fibrillation
Circulation, October 12, 2004; 110(15): 2110 - 2118.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
A. Sambelashvili and I. R. Efimov
Dynamics of virtual electrode-induced scroll-wave reentry in a 3D bidomain model
Am J Physiol Heart Circ Physiol, October 1, 2004; 287(4): H1570 - H1581.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
L. C. Baker, R. Wolk, B.-R. Choi, S. Watkins, P. Plan, A. Shah, and G. Salama
Effects of mechanical uncouplers, diacetyl monoxime, and cytochalasin-D on the electrophysiology of perfused mouse hearts
Am J Physiol Heart Circ Physiol, October 1, 2004; 287(4): H1771 - H1779.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
S. C. Hao, D. J. Christini, K. M. Stein, P. N. Jordan, S. Iwai, O. Bramwell, S. M. Markowitz, S. Mittal, and B. B. Lerman
Effect of {beta}-adrenergic blockade on dynamic electrical restitution in vivo
Am J Physiol Heart Circ Physiol, July 1, 2004; 287(1): H390 - H394.
[Abstract] [Full Text] [PDF]


Home page
Physiol. Rev.Home page
A. G. KLEBER and Y. RUDY
Basic Mechanisms of Cardiac Impulse Propagation and Associated Arrhythmias
Physiol Rev, April 1, 2004; 84(2): 431 - 488.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
K. H. W. J. ten Tusscher, D. Noble, P. J. Noble, and A. V. Panfilov
A model for human ventricular tissue
Am J Physiol Heart Circ Physiol, April 1, 2004; 286(4): H1573 - H1589.
[Abstract] [Full Text] [PDF]


Home page
Circ. Res.Home page
R. Wu and A. Patwardhan
Restitution of Action Potential Duration During Sequential Changes in Diastolic Intervals Shows Multimodal Behavior
Circ. Res., March 19, 2004; 94(5): 634 - 641.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
H.-N. Pak, Y.-S. Oh, Y.-B. Liu, T.-J. Wu, H. S. Karagueuzian, S.-F. Lin, and P.-S. Chen
Catheter Ablation of Ventricular Fibrillation in Rabbit Ventricles Treated With {beta}-Blockers
Circulation, December 23, 2003; 108(25): 3149 - 3156.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
P.-S. Chen, T.-J. Wu, C.-T. Ting, H. S. Karagueuzian, A. Garfinkel, S.-F. Lin, and J. N. Weiss
A Tale of Two Fibrillations
Circulation, November 11, 2003; 108(19): 2298 - 2303.
[Full Text] [PDF]


Home page
CirculationHome page
R. Derksen, H. V.M. van Rijen, R. Wilders, S. Tasseron, R. N.W. Hauer, W. L.C. Rutten, and J. M.T. de Bakker
Tissue Discontinuities Affect Conduction Velocity Restitution: A Mechanism by Which Structural Barriers May Promote Wave Break
Circulation, August 19, 2003; 108(7): 882 - 888.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
J. J. Sims, K. L. Schoff, J. M. Loeb, and N. A. Wiegert
Regional gap junction inhibition increases defibrillation thresholds
Am J Physiol Heart Circ Physiol, June 5, 2003; 285(1): H10 - H16.
[Abstract] [Full Text] [PDF]


Home page
Circ. Res.Home page
A. V. Zaitsev, P. K. Guha, F. Sarmast, A. Kolli, O. Berenfeld, A. M. Pertsov, J. R. de Groot, R. Coronel, and J. Jalife
Wavebreak Formation During Ventricular Fibrillation in the Isolated, Regionally Ischemic Pig Heart
Circ. Res., March 21, 2003; 92(5): 546 - 553.
[Abstract] [Full Text] [PDF]


Home page
Cardiovasc ResHome page
M. L Walker and D. S Rosenbaum
Repolarization alternans: implications for the mechanism and prevention of sudden cardiac death
Cardiovasc Res, March 1, 2003; 57(3): 599 - 614.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
T. Ohara, Z. Qu, M.-H. Lee, K. Ohara, C. Omichi, W. J. Mandel, P.-S. Chen, and H. S. Karagueuzian
Increased vulnerability to inducible atrial fibrillation caused by partial cellular uncoupling with heptanol
Am J Physiol Heart Circ Physiol, September 1, 2002; 283(3): H1116 - H1122.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
C. Omichi, S. Zhou, M.-H. Lee, A. Naik, C.-M. Chang, A. Garfinkel, J. N. Weiss, S.-F. Lin, H. S. Karagueuzian, and P.-S. Chen
Effects of amiodarone on wave front dynamics during ventricular fibrillation in isolated swine right ventricle
Am J Physiol Heart Circ Physiol, March 1, 2002; 282(3): H1063 - H1070.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
M.-H. Lee, Z. Qu, G. A. Fishbein, S. T. Lamp, E. H. Chang, T. Ohara, O. Voroshilovsky, J. R. Kil, A. R. Hamzei, N. C. Wang, et al.
Patterns of wave break during ventricular fibrillation in isolated swine right ventricle
Am J Physiol Heart Circ Physiol, July 1, 2001; 281(1): H253 - H265.
[Abstract] [Full Text] [PDF]


Home page
Cardiovasc ResHome page
H. S Karagueuzian and P.-S. Chen
Cellular mechanism of reentry induced by a strong electrical stimulus: Implications for fibrillation and defibrillation
Cardiovasc Res, May 1, 2001; 50(2): 251 - 262.
[Abstract] [Full Text] [PDF]


Home page
Circ. Res.Home page
B.-R. Choi, T. Liu, and G. Salama
The Distribution of Refractory Periods Influences the Dynamics of Ventricular Fibrillation
Circ. Res., March 16, 2001; 88 (5): e49 - e58.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
T. Ohara, K. Ohara, J.-M. Cao, M.-H. Lee, M. C. Fishbein, W. J. Mandel, P.-S. Chen, and H. S. Karagueuzian
Increased Wave Break During Ventricular Fibrillation in the Epicardial Border Zone of Hearts With Healed Myocardial Infarction
Circulation, March 13, 2001; 103(10): 1465 - 1472.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
Z. Qu, A. Garfinkel, P.-S. Chen, and J. N. Weiss
Mechanisms of Discordant Alternans and Induction of Reentry in Simulated Cardiac Tissue
Circulation, October 3, 2000; 102(14): 1664 - 1670.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
O. Voroshilovsky, Z. Qu, M.-H. Lee, T. Ohara, G. A. Fishbein, H.-L. A. Huang, C. D. Swerdlow, S.-F. Lin, A. Garfinkel, J. N. Weiss, et al.
Mechanisms of Ventricular Fibrillation Induction by 60-Hz Alternating Current in Isolated Swine Right Ventricle
Circulation, September 26, 2000; 102(13): 1569 - 1574.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
A. Patwardhan, S. Moghe, K. Wang, and F. Leonelli
Frequency modulation within electrocardiograms during ventricular fibrillation
Am J Physiol Heart Circ Physiol, August 1, 2000; 279(2): H825 - H835.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
M. Yashima, T. Ohara, J.-M. Cao, Y.-H. Kim, M. C. Fishbein, W. J. Mandel, P.-S. Chen, and H. S. Karagueuzian
Nicotine increases ventricular vulnerability to fibrillation in hearts with healed myocardial infarction
Am J Physiol Heart Circ Physiol, June 1, 2000; 278(6): H2124 - H2133.
[Abstract] [Full Text] [PDF]


Home page
Circ. Res.Home page
J.-M. Cao, L. S. Chen, B. H. KenKnight, T. Ohara, M.-H. Lee, J. Tsai, W. W. Lai, H. S. Karagueuzian, P. L. Wolf, M. C. Fishbein, et al.
Nerve Sprouting and Sudden Cardiac Death
Circ. Res., April 14, 2000; 86(7): 816 - 821.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
F. J. Chorro, J. Canoves, J. Guerrero, L. Mainar, J. Sanchis, L. Such, and V. Lopez-Merino
Alteration of Ventricular Fibrillation by Flecainide, Verapamil, and Sotalol : An Experimental Study
Circulation, April 4, 2000; 101(13): 1606 - 1615.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
M. Swissa, T. Ohara, M.-H. Lee, S. Kaul, P. K. Shah, H. Hayashi, P.-S. Chen, and H. S. Karagueuzian
Sildenafil-nitric oxide donor combination promotes ventricular tachyarrhythmias in the swine right ventricle
Am J Physiol Heart Circ Physiol, May 1, 2002; 282(5): H1787 - H1792.
[Abstract] [Full Text] [PDF]