Microstructure, Cell-to-Cell Coupling, and Ion Currents as Determinants of Electrical Propagation and Arrhythmogenesis.

Abstract

Rapid electric impulse spread from the SA node to the atria, the AV node, and the ventricles is prerequisite for coordinated cardiac contraction. In cardiac arrhythmias, disturbed impulse spread can lead to ventricular or atrial tachycardia, fibrillation, and sudden cardiac death. A change in electric impulse propagation had already been proposed to underlie reentrant arrhythmias at the beginning of the 20th century.1 Slowing of propagation and the formation of unidirectional propagation block represent the 2 most important changes leading to circulating and reentrant propagation. Unidirectional propagation block is the prerequisite for the wavefront to reenter nonrefractory tissue of the original propagation path. Knowledge of the mechanisms governing abnormal impulse propagation and formation of propagation block at the level of cellular networks is important for our understanding of arrhythmogenesis and the principles underlying electric and drug therapy. This article reviews experimental and modeling studies performed to understand the basic mechanisms of cardiac impulse propagation, with specific emphasis laid on the relation between propagation and cardiac microstructure. Normally, layers and strands of electrically coupled myocytes separated by connective tissue create a mostly anisotropic compartmentation in atrial and ventricular myocardium. However, compartmentalization can assume pathological forms when fibrosis is enhanced with increasing age and during reparative fibrosis in pathological settings (myocardial infarction, volume/pressure overload, some forms of hereditary diseases). Although structural heterogeneities favor the formation of reentrant circuits, spiral waves occur in tissues with homogeneous electric and structural properties on the basis of time-dependent local changes in refractoriness, which set up the scenario for unidirectional block formation.2 The selected references cited in this short review cannot cover the large body of published literature. Moreover, this article will cover neither the topic of spiral waves nor early and delayed afterdepolarizations (disturbed Ca2+ cycling), which play a major role in the initiation …