Crosstalk between theoretical and experimental studies for the understanding of cardiac electrical impulse propagation

Abstract

The repetitive electrical impulse generated by the sinoatrial node spreads rapidly through the atrial tissue and the atrioventricular node to the ventricles. Endocardial spread in the Purkinje system and subsequent endocardial-toepicardial spread in the working myocardium assure the rapid and coordinated excitation and subsequent mechanical contraction of the ventricles. The process of electrical impulse propagation involves downstream excitation of resting excitable myocardium by local circuit current generated by excited upstream tissue. It is determined (i) by the upstroke of the cardiac action potential, as the electrical driving force; (ii) tissue architecture; (iii) the electrical resistance of the extracellular space; and (iv) parameters that affect resistance to intraand intercellular current flow, such as cell-to-cell coupling by gap junctions, cell size, and cell surface-to-volume ratio. The complexity of this process is not only represented by the large number of variables but also by the fact that the variables interact in a highly complex manner. The advancement of computer technology during the past decades has critically enhanced our ability to investigate this complexity using increasingly sophisticated algorithms and shown that understanding the mechanisms of impulse propagation requires theoretical modeling. In the field of cardiac impulse propagation, the high degree of agreement between theoretical and experimental studies has strengthened our understanding of cardiac impulse propagation significantly. Although theoretical studies are probably the only tool that can (i) make us understand the complexities of interaction between the multitude of variables affecting impulse propagation and (ii)