Mechanistic Insights Into Very Slow Conduction in Branching Cardiac Tissue: A Model Study

It is known that branching strands of cardiac tissue can form a substrate for very slow conduction. The branches slow conduction by acting as current loads drawing depolarizing current from the main strand (“pull” effect). It has been suggested that, upon depolarization of the branches, they become current sources reinjecting current back into the strand, thus enhancing propagation safety (“push” effect). It was the aim of this study to verify this hypothesis and to assess the contribution of the push effect to propagation velocity and safety. Conduction was investigated in strands of Luo-Rudy dynamic model cells that branch from either a single branch point or from multiple successive branch points. In single-branching strands, blocking the push effect by not allowing current to flow retrogradely from the branches into the strand did not significantly increase the branching-induced local propagation delay. However, in multiple branching strands, blocking the push effect resulted in a significant slowing of overall conduction velocity or even in conduction failure. Furthermore, for certain slow velocities, the safety factor for propagation was higher when slow conduction was caused by branching tissue geometry than by reduced excitability without branching. Therefore, these results confirm the proposed “pull and push” mechanism of slow, but nevertheless robust, conduction in branching structures. Slow conduction based on this mechanism could occur in the atrioventricular node, where multiple branching is structurally present. It could also support reentrant excitation in diseased myocardium where the substrate is structurally complex.

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

[2]  A. L. Wit,et al.  Slow conduction, reentry, and the mechanism of ventricular arrhythmias in myocardial infarction. , 1971, Bulletin of the New York Academy of Medicine.

[3]  J. Lowenstein,et al.  Slow conduction, reentry, and the mechanism of ventricular arrhythmias in myocardial infarction. , 1971 .

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

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

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

[7]  S. Weidmann Heart: electrophysiology. , 1974, Annual review of physiology.

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

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

[10]  T. N. James,et al.  Structure and function of specific regions in the canine atrioventricular node. , 1982, The American journal of physiology.

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

[12]  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.

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

[14]  M. Spach,et al.  Properties of Discontinuous Anisotropic Propagation at a Microscopic Level a , 1990, Annals of the New York Academy of Sciences.

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

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

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

[18]  B M Salzberg,et al.  Characterization of impulse propagation at the microscopic level across geometrically defined expansions of excitable tissue: multiple site optical recording of transmembrane voltage (MSORTV) in patterned growth heart cell cultures , 1994, The Journal of general physiology.

[19]  M S Spach,et al.  Initiating Reentry: , 1994, Journal of cardiovascular electrophysiology.

[20]  J. Crank,et al.  A practical method for numerical evaluation of solutions of partial differential equations of the heat-conduction type , 1947, Mathematical Proceedings of the Cambridge Philosophical Society.

[21]  H. Tan,et al.  Electrophysiologic and extracellular ionic changes during acute ischemia in failing and normal rabbit myocardium. , 1996, Journal of molecular and cellular cardiology.

[22]  Y Rudy,et al.  Electrophysiologic effects of acute myocardial ischemia. A mechanistic investigation of action potential conduction and conduction failure. , 1997, Circulation research.

[23]  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.

[24]  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.

[25]  A. Kleber,et al.  Slow conduction in cardiac tissue, II: effects of branching tissue geometry. , 1998, Circulation research.

[26]  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.

[27]  Y Rudy,et al.  Action potential propagation in inhomogeneous cardiac tissue: safety factor considerations and ionic mechanism. , 2000, American journal of physiology. Heart and circulatory physiology.

[28]  F. L. Meijler,et al.  AV Node Function during Atrial Fibrillation , 2000 .

[29]  Y Rudy,et al.  Action potential and contractility changes in [Na(+)](i) overloaded cardiac myocytes: a simulation study. , 2000, Biophysical journal.

[30]  A. Becker,et al.  Proximal atrioventricular bundle, atrioventricular node, and distal atrioventricular bundle are distinct anatomic structures with unique histological characteristics and innervation. , 2001, Circulation.