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.)

Rationale: Slow nonuniform electric propagation in the border zone (BZ) of a healed myocardial infarct (MI) cangive rise to reentrant arrhythmia. The extent to which this is influenced by structural rather than cellular electric remodeling is unclear.Objective: To determine whether structural remodeling alone in the infarct BZ could provide a substrate for re-entry by (i) characterizing the 3-dimensional (3D) structure of the myocardium surrounding a healed MI at high spatial resolution and (ii) modeling electric activation on this structure. Methods and Results: Anterior left ventricular (LV) infarcts were induced in 2 rats by coronary artery ligation.Three-dimensional BZ volume (4.1 mm 3 and 5.6 mm 3 ) were imaged at 14 days using confocal microscopy. Viable myocytes were identified, and their connectivity and orientation were quantified. Preserved cell networks were observed in the subendocardium and subepicardium of the infarct. Myocyte tracts traversed the BZ, and there was heavy infiltration of collagen into the adjacent myocardium. Myocyte connectivity decreased by Ϸ65% over 250 m across the BZ. This structure was incorporated into 3D network models on which activation was simulated using Luo-Rudy membrane dynamics assuming normal cellular electric properties. Repetitive stimulation was imposed at selected BZ sites. Stimulus site-specific unidirectional propagation occurred in the BZ with rate-dependent slowing and conduction block, and reentry was demonstrated in one substrate. Activation times were prolonged because of tract path length and local slowing. Conclusions:

Background-The anisotropy of cardiac tissue is a key determinant of 3D electric propagation and the stability of activation wave fronts in the heart. The electric properties of ventricular myocardium are widely assumed to be axially anisotropic, with activation propagating most rapidly in the myofiber direction and at uniform velocity transverse to this. We present new experimental evidence that contradicts this view. Methods and Results-For the first time, high-density intramural electric mapping (325 electrodes at Ϸ4ϫ4ϫ1-mm spacing) from pig left ventricular tissue was used to reconstruct 3D paced activation surfaces projected directly onto 3D tissue structure imaged throughout the same left ventricular volume. These data from 5 hearts demonstrate that ventricular tissue is electrically orthotropic with 3 distinct propagation directions that coincide with local microstructural axes defined by the laminar arrangement of ventricular myocytes. The maximum conduction velocity of 0.67Ϯ0.019 ms Ϫ1 was aligned with the myofiber axis. However, transverse to this, the maximum conduction velocity was 0.30Ϯ0.010 ms Ϫ1, parallel to the myocyte layers and 0.17Ϯ0.004 ms Ϫ1 normal to them. These orthotropic conduction velocities give rise to preferential activation pathways across the left ventricular free wall that are not captured by structurally detailed computer models, which incorporate axially anisotropic electric properties. Conclusions-Our findings suggest that current views on uniform side-to-side electric coupling in the heart need to be revised. In particular, nonuniform laminar myocardial architecture and associated electric orthotropy should be included in future models of initiation and maintenance of ventricular arrhythmia. (Circ Arrhythmia Electrophysiol. 2009;2:433-440.)Key Words: anisotropy Ⅲ mapping Ⅲ structure Ⅲ computer modeling Ⅲ intramural pacing A ccurate information about the electric properties of cardiac tissue is central to understanding the biophysical basis of normal and aberrant heart rhythm. Electric anisotropy influences the spread of activation in the heart, plays a critical role both in the initiation and maintenance of reentrant arrhythmia, and is an important determinant of the effectiveness of cardioversion. Knowledge of the nature and extent of electric anisotropy is required for computer models of heart activation that provide a means of probing intramural electric behavior that cannot be accessed from clinical and experimental measurements made on the surfaces of the heart. Clinical Perspective on p 440Normal ventricular myocardium is generally thought to function as a syncytium in which side-to-side electric coupling between adjacent myocytes is uniform. 1,2 The electric properties of ventricular myocardium are assumed to be axially anisotropic with respect to the local myofiber axis, 1,2 with activation propagating most rapidly in the myofiber direction and at uniform velocity in planes transverse to this.This view is not consistent with the laminar model of ventricular myocardium t...

High-resolution (HR) mapping has been used to study gastric slow-wave activation; however, the specific characteristics of antral electrophysiology remain poorly defined. This study applied HR mapping and computational modeling to define functional human antral physiology. HR mapping was performed in 10 subjects using flexible electrode arrays (128-192 electrodes; 16-24 cm) arranged from the pylorus to mid-corpus. Anatomical registration was by photographs and anatomical landmarks. Slow-wave parameters were computed, and resultant data were incorporated into a computational fluid dynamics (CFD) model of gastric flow to calculate impact on gastric mixing. In all subjects, extracellular mapping demonstrated normal aboral slow-wave propagation and a region of increased amplitude and velocity in the prepyloric antrum. On average, the high-velocity region commenced 28 mm proximal to the pylorus, and activation ceased 6 mm from the pylorus. Within this region, velocity increased 0.2 mm/s per mm of tissue, from the mean 3.3 ± 0.1 mm/s to 7.5 ± 0.6 mm/s (P < 0.001), and extracellular amplitude increased from 1.5 ± 0.1 mV to 2.5 ± 0.1 mV (P < 0.001). CFD modeling using representative parameters quantified a marked increase in antral recirculation, resulting in an enhanced gastric mixing, due to the accelerating terminal antral contraction. The extent of gastric mixing increased almost linearly with the maximal velocity of the contraction. In conclusion, the human terminal antral contraction is controlled by a short region of rapid high-amplitude slow-wave activity. Distal antral wave acceleration plays a major role in antral flow and mixing, increasing particle strain and trituration.