Slow conduction in cardiac tissue, II: effects of branching tissue geometry.

In cardiac tissue, functional or structural current-to-load mismatches can induce local slow conduction or conduction block, which are important determinants of reentrant arrhythmias. This study tested whether spatially repetitive mismatches result in a steady-state slowing of conduction. Patterned growth of neonatal rat heart cells in culture was used to design unbranched cell strands or strands releasing branches from either a single point or multiple points at periodic intervals. Electrical activation was followed optically using voltage-sensitive dyes under control conditions and in elevated [K+]o (5.8 and 14.8 mmol/L, respectively; in the latter case, propagation was carried by the L-type Ca2+ current). Preparations with multiple branch points exhibited discontinuous and slow conduction that became slower with increasing branch length and/or decreasing inter-branch distance. Compared with unbranched strands, conduction was maximally slowed by 63% under control conditions (from 44.9+/-3.4 to 16.7+/-1.0 cm/s) and by 93% in elevated [K+]o (from 15.7+/-2.3 to 1.1+/-0.2 cm/s). Local activation delays induced at a single branch point were significantly larger than the delays per branch point in multiple branching structures. Also, selective inactivation of inward currents in the branches induced conduction blocks. These 2 observations pointed to a dual role of the branches in propagation: whereas they acted as current sinks for the approaching activation thus slowing conduction ("pull" effect), they supplied, once excited, depolarizing current supporting downstream activation ("push" effect). This "pull and push" action resulted in a slowing of conduction in which the safety was largely preserved by the "push" effect. Thus, branching microarchitectures might contribute to slow conduction in tissue with discontinuous geometry, such as infarct scars and the atrioventricular node.

[1]  J. Francis Heidlage,et al.  Influence of the Passive Anisotropic Properties on Directional Differences in Propagation Following Modification of the Sodium Conductance in Human Atrial Muscle: A Model of Reentry Based on Anisotropic Discontinuous Propagation , 1988, Circulation research.

[2]  S. Rohr,et al.  Optical recording system based on a fiber optic image conduit: assessment of microscopic activation patterns in cardiac tissue. , 1998, Biophysical journal.

[3]  T. N. James,et al.  Function of the atrioventricular node considered on the basis of observed histology and fine structure. , 1985, Journal of the American College of Cardiology.

[4]  V. Fast,et al.  Paradoxical Improvement of Impulse Conduction in Cardiac Tissue by Partial Cellular Uncoupling , 1997, Science.

[5]  N. Sperelakis,et al.  Gap junction uncoupling and discontinuous propagation in the heart. A comparison of experimental data with computer simulations. , 1988, Biophysical journal.

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

[7]  Robert H. Anderson,et al.  A Combined Morphological and Electrophysiological Study of the Atrioventricular Node of the Rabbit Heart , 1974, Circulation research.

[8]  M S Spach,et al.  The Functional Role of Structural Complexities in the Propagation of Depolarization in the Atrium of the Dog: Cardiac Conduction Disturbances Due to Discontinuities of Effective Axial Resistivity , 1982, Circulation research.

[9]  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.

[10]  R. W. Joyner,et al.  Effects of the Discrete Pattern of Electrical Coupling on Propagation through an Electrical Syncytium , 1982, Circulation research.

[11]  H. Lux,et al.  Distribution of calcium currents in sprouting PC12 cells , 1989, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[12]  A. Noma,et al.  Slow current systems in the A-V node of the rabbit heart , 1980, Nature.

[13]  A. L. Wit,et al.  Conduction of the Cardiac Impulse , 1972, The Journal of general physiology.

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

[15]  Capelle,et al.  Slow conduction in the infarcted human heart. 'Zigzag' course of activation. , 1993, Circulation.

[16]  H. Jongsma,et al.  Modulating L-type calcium current affects discontinuous cardiac action potential conduction. , 1996, Biophysical journal.

[17]  J Jalife,et al.  Wave-front curvature as a cause of slow conduction and block in isolated cardiac muscle. , 1994, Circulation research.

[18]  M. Spach,et al.  Relating Extracellular Potentials and Their Derivatives to Anisotropic Propagation at a Microscopic Level in Human Cardiac Muscle: Evidence for Electrical Uncoupling of Side‐to‐Side Fiber Connections with Increasing Age , 1986, Circulation research.

[19]  A. Kleber,et al.  Propagation of Electrical Activity in Ischemic and Infarcted Myocardium as the Basis of Ventricular Arrhythmias , 1992 .

[20]  R C Barr,et al.  Reflection after delayed excitation in a computer model of a single fiber. , 1992, Circulation research.

[21]  M J Janse,et al.  Morphology and electrophysiology of the mammalian atrioventricular node. , 1988, Physiological reviews.

[22]  A. Resmini.  The conduction of the cardiac impulse : P. F. Cranefeld, Futura Publ. Co., Mount Kisko, N.Y. (1975), 404 pp., $ 27.50. , 1977 .

[23]  A. Kleber,et al.  Slow conduction in cardiac tissue, I: effects of a reduction of excitability versus a reduction of electrical coupling on microconduction. , 1998, Circulation research.

[24]  A. Kleber,et al.  Patterned growth of neonatal rat heart cells in culture. Morphological and electrophysiological characterization. , 1991, Circulation research.

[25]  D. Thompson,et al.  The Conduction System of the Heart , 1982, Springer Netherlands.

[26]  D. Durrer,et al.  Spread of Excitation in the Atrioventricular Node of Isolated Rabbit Hearts Studied by Multiple Microelectrode Recording , 1972, Circulation research.

[27]  S. Rohr,et al.  Involvement of the calcium inward current in cardiac impulse propagation: induction of unidirectional conduction block by nifedipine and reversal by Bay K 8644. , 1997, Biophysical journal.

[28]  W H Lamers,et al.  Immunohistochemical delineation of the conduction system. II: The atrioventricular node and Purkinje fibers. , 1993, Circulation research.

[29]  W. J. Mueller,et al.  Propagation of Impulses across the Purkinje Fiber‐Muscle Junctions in the Dog Heart , 1970, Circulation research.

[30]  W Rall,et al.  Changes of action potential shape and velocity for changing core conductor geometry. , 1974, Biophysical journal.

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

[32]  Robert H. Anderson,et al.  Electrophysiology and Structure of the Atrioventricular Node of the Isolated Rabbit Heart , 1978 .

[33]  C. Sandri,et al.  The structural correlate of saltatory conduction along the mauthner axon in the tench (Tinea tinea L.): Identification of nodal equivalents at the axon collaterals , 1982, The Journal of comparative neurology.

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

[35]  A. Becker,et al.  Posterior extensions of the human compact atrioventricular node: a neglected anatomic feature of potential clinical significance. , 1998, Circulation.

[36]  B M Salzberg,et al.  Multiple site optical recording of transmembrane voltage (MSORTV) in patterned growth heart cell cultures: assessing electrical behavior, with microsecond resolution, on a cellular and subcellular scale. , 1994, Biophysical journal.