Effects of anisotropy on the development of cardiac arrhythmias associated with focal activity

Abstract. The anisotropy that normally exists in the myocardium may be either enhanced in peri-infarction zones by loss of lateral cell connections or reduced by redistribution of gap junctions. To test how the degree of anisotropy affects the development of ectopic focal activity, we carried out computer simulations in which a model of an ectopic focus is incorporated as the central element of a two-dimensional sheet of ventricular cells. At low values of intercellular coupling conductance (Gc), the focus region is spontaneously active, but the limited intercellular current flow inhibits propagation. At high Gc, automaticity is suppressed by the loading effects of the surrounding cells. At intermediate Gc, the ectopic activity may propagate into the sheet. In the case of isotropic coupling, the minimum size of the focus region for propagation to occur (in terms of number of collaborating cells within the focus) is as small as approximately ten cells, and this number decreases with increasing anisotropy. Thus, the presence of anisotropy facilitates the development of ectopic focal activity. We conclude that the remodeling that occurs in peri-infarction zones may create a substrate that either facilitates (enhanced anisotropy) or inhibits (reduced anisotropy) the development of cardiac arrhythmias associated with ectopic focal activity.

[1]  P. Ursell,et al.  Electrophysiologic and anatomic basis for fractionated electrograms recorded from healed myocardial infarcts. , 1985, Circulation.

[2]  D. Noble,et al.  Effects of gap junction conductance on dynamics of sinoatrial node cells: two-cell and large-scale network models , 1994, IEEE Transactions on Biomedical Engineering.

[3]  A. Wilde,et al.  Changes in conduction velocity during acute ischemia in ventricular myocardium of the isolated porcine heart. , 1986, Circulation.

[4]  A. Panfilov,et al.  Nonstationary vortexlike reentrant activity as a mechanism of polymorphic ventricular tachycardia in the isolated rabbit heart. , 1995, Circulation.

[5]  R C Barr,et al.  Electrophysiological effects of remodeling cardiac gap junctions and cell size: experimental and model studies of normal cardiac growth. , 2000, Circulation research.

[6]  R. W. Joyner,et al.  Alterations in endocardial activation of the canine papillary muscle early and late after myocardial infarction. , 1987, Circulation.

[7]  R. Hauer,et al.  Abnormal Automaticity as Mechanism of Atrial Tachycardia in the Human Heart—Electrophysiologic and Histologic Correlation: , 1994, Journal of cardiovascular electrophysiology.

[8]  R Wilders,et al.  Pacemaker activity of the rabbit sinoatrial node. A comparison of mathematical models. , 1991, Biophysical journal.

[9]  Y Rudy,et al.  Two components of the delayed rectifier K+ current in ventricular myocytes of the guinea pig type. Theoretical formulation and their role in repolarization. , 1995, Circulation research.

[10]  C. Luo,et al.  A dynamic model of the cardiac ventricular action potential. I. Simulations of ionic currents and concentration changes. , 1994, Circulation research.

[11]  C. Green,et al.  Altered patterns of gap junction distribution in ischemic heart disease. An immunohistochemical study of human myocardium using laser scanning confocal microscopy. , 1991, The American journal of pathology.

[12]  M. Pressler.  Cable analysis in quiescent and active sheep Purkinje fibres. , 1984, The Journal of physiology.

[13]  Y Rudy,et al.  Ionic mechanisms of propagation in cardiac tissue. Roles of the sodium and L-type calcium currents during reduced excitability and decreased gap junction coupling. , 1997, Circulation research.

[14]  D. Noble,et al.  The relation of Rushton's ‘liminal length’ for excitation to the resting and active conductances of excitable cells , 1972, The Journal of physiology.

[15]  J E Saffitz,et al.  Remodeling of ventricular conduction pathways in healed canine infarct border zones. , 1991, The Journal of clinical investigation.

[16]  F. V. Van Capelle,et al.  Propagation through electrically coupled cells. How a small SA node drives a large atrium. , 1986, Biophysical journal.

[17]  V. Fast,et al.  Cardiac tissue geometry as a determinant of unidirectional conduction block: assessment of microscopic excitation spread by optical mapping in patterned cell cultures and in a computer model. , 1995, Cardiovascular research.

[18]  R Wilders,et al.  A spontaneously active focus drives a model atrial sheet more easily than a model ventricular sheet. , 2000, American journal of physiology. Heart and circulatory physiology.

[19]  J. Saffitz,et al.  Quantitative Analysis of Intercellular Connections by Immunohistochemistry of the Cardiac Gap Junction Protein Connexin43 , 1989, Circulation research.

[20]  V. Fast,et al.  Role of wavefront curvature in propagation of cardiac impulse. , 1997, Cardiovascular research.

[21]  M. Allessie,et al.  Influences of anisotropic tissue structure on reentrant circuits in the epicardial border zone of subacute canine infarcts. , 1988, Circulation research.

[22]  R C Barr,et al.  Extracellular Potentials Related to Intracellular Action Potentials during Impulse Conduction in Anisotropic Canine Cardiac Muscle , 1979, Circulation research.

[23]  R Wilders,et al.  Electrical interactions between a real ventricular cell and an anisotropic two-dimensional sheet of model cells. , 2000, American journal of physiology. Heart and circulatory physiology.

[24]  J.M. Ferrero,et al.  Influence of electrical coupling on early after depolarizations in ventricular myocytes , 1999, IEEE Transactions on Biomedical Engineering.

[25]  R Wilders,et al.  Experimental model for an ectopic focus coupled to ventricular cells. , 1996, Circulation.

[26]  M. Allessie,et al.  Anisotropic conduction and reentry in perfused epicardium of rabbit left ventricle. , 1992, The American journal of physiology.

[27]  R L Winslow,et al.  Generation and propagation of ectopic beats induced by spatially localized Na–K pump inhibition in atrial network models , 1993, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[28]  H. Jongsma,et al.  Model clamp and its application to synchronization of rabbit sinoatrial node cells. , 1996, The American journal of physiology.

[29]  L. Clerc.  Directional differences of impulse spread in trabecular muscle from mammalian heart. , 1976, The Journal of physiology.

[30]  R. V. van Dam,et al.  Endocardial and epicardial activation pathways of the canine right atrium. , 1971, The American journal of physiology.

[31]  R Wilders,et al.  Action potential conduction between a ventricular cell model and an isolated ventricular cell. , 1996, Biophysical journal.

[32]  J. J. Denier van der Gon,et al.  Current thresholds and liminal size in excitation of heart muscle. , 1978, Cardiovascular research.

[33]  H A Fozzard,et al.  Strength—duration curves in cardiac Purkinje fibres: effects of liminal length and charge distribution , 1972, The Journal of physiology.

[34]  V. Fast,et al.  Anisotropic conduction in monolayers of neonatal rat heart cells cultured on collagen substrate. , 1994, Circulation research.

[35]  R. Kumar,et al.  Modulation of propagation from an ectopic focus by electrical load and by extracellular potassium , 1997 .

[36]  Ronald W. Joyner,et al.  Simulation of Action Potential Propagation in an Inhomogeneous Sheet of Coupled Excitable Cells , 1975, Circulation research.

[37]  V. Fast,et al.  Block of impulse propagation at an abrupt tissue expansion: evaluation of the critical strand diameter in 2- and 3-dimensional computer models. , 1995, Cardiovascular research.

[38]  J E Saffitz,et al.  Distribution and Three‐Dimensional Structure of Intercellular Junctions in Canine Myocardium , 1989, Circulation research.

[39]  P. Ursell,et al.  Structural and Electrophysiological Changes in the Epicardial Border Zone of Canine Myocardial Infarcts during Infarct Healing , 1985, Circulation research.

[40]  R Wilders,et al.  Gap junctions in cardiovascular disease. , 2000, Circulation research.

[41]  M. Spach,et al.  The stochastic nature of cardiac propagation at a microscopic level. Electrical description of myocardial architecture and its application to conduction. , 1995, Circulation research.