Laminar Arrangement of Ventricular Myocytes Influences Electrical Behavior of the Heart

Abstract

Abstract-The response of the heart to electrical shock, electrical propagation in sinus rhythm, and the spatiotemporal dynamics of ventricular fibrillation all depend critically on the electrical anisotropy of cardiac tissue. A long-held view of cardiac electrical anisotropy is that electrical conductivity is greatest along the myocyte axis allowing most rapid propagation of electrical activation in this direction, and that conductivity is isotropic transverse to the myocyte axis supporting a slower uniform spread of activation in this plane. In this context, knowledge of conductivity in two directions, parallel and transverse to the myofiber axis, is sufficient to characterize the electrical action of the heart. Here we present new experimental data that challenge this view. We have used a novel combination of intramural electrical mapping, and experiment-specific computer modeling, to demonstrate that left ventricular myocardium has unique bulk conductivities associated with three microstructurally-defined axes. We show that voltage fields induced by intramural current injection are influenced by not only myofiber direction, but also the transmural arrangement of muscle layers or myolaminae. Computer models of these experiments, in which measured 3D tissue structure was reconstructed in-silico, best matched recorded voltages with conductivities in the myofiber direction, and parallel and normal to myolaminae, set in the ratio 4:2:1, respectively. These findings redefine cardiac tissue as an electrically orthotropic substrate and enhance our understanding of how external shocks may act to successfully reset the fibrillating heart into a uniform electrical state. More generally, the mechanisms governing the destabilization of coordinated electrical propagation into ventricular arrhythmia need to be evaluated in the light of this discovery. (Circ Res. 2007;101:e103-e112.)

Multiscale cardiac modelling reveals the origins of notched T waves in long QT syndrome type 2

“…Bulk conductivity tensors were implemented resulting in conductivities of 7 mS cm À 1 along myofibres, 3.5 mS cm À 1 transverse to myofibres but in the plane of myolaminae, and 1.6 mS cm À 1 normal to myolaminae 15 . An explicit time integration scheme, with time steps of 0.005 and 0.1 ms, was used in solution of cellular ordinary differential equations and the partial differential equation, respectively.…”

“…Furthermore, the electrical function of the heart is more than just the integrated activity of all the ion channels. The spread of electrical current from one region of the heart to another is influenced by myocyte connections, myofibre orientation and arrangement of muscle layers 15 and the overall geometry of the heart 16 . Not surprisingly then, it has been claimed that interrogation of such multivariable nonlinear dynamic systems necessarily involves the use of computer models 17 .…”

Modeling Defibrillation

“…The extracellular matrix consists of networks of collagen fibers which determine the passive mechanical properties of the myocardium. Electrically, it is assumed that the preferred directions are co-aligned between the two spaces, but that the conductivity ratios between the principal axes are unequal between the two domains (Clerc, 1976;Hooks et al, 2007;Roberts & Scher, 1982;Roth, 1997). All parameters influencing the electrical properties of the tissue, such as density and conductance of gap junctions, cellular geometry, orientation and cell packing density, and the composition of the interstitial space, are heterogeneous and may vary at all size scales, from the cellular level up to the organ.…”

“…However, the associated computational costs are prohibitive with current computing hardware, since a single heart consists of roughly 5 billion cells. Although a few high resolution modeling studies have been conducted where small tissue preparations were discretized at a sub-cellular resolution (Hooks et al, 2007;Roberts et al, 2008;Spach & Heidlage, 1995), in general the spatial discretization steps were chosen based on the spatial extent of electrical wave fronts and not on the size scales of the tissue's micro-structures. For this sake cardiac tissue is treated as a continuum for which appropriate material parameters have to be determined which translate the discrete cellular matrix into an electrically analog macroscopic representation.…”

Reconstruction and Quantification of Diffusion Tensor Imaging-Derived Cardiac Fibre and Sheet Structure in Ventricular Regions used in Studies of Excitation Propagation

“…Propagation of electrical activity [32,43] is orthotropically anisotropic, being fastest in the direction of the long axis of the fibre due to the presence of gap junctions that are principally located at the ends of the myocytes [17,52,66] and slowest across the sheet plane due to the small number of muscle branches connecting otherwise electrically-insulated muscle sheets [34,46]. Contraction of myocytes occurs in the long axis direction and, together with transmural shear along sheet planes [16], results in transmural thickening and apex-base shortening.…”