Syncytial heterogeneity as a mechanism underlying cardiac far-field stimulation during defibrillation-level shocks

Introduction: The mechanisms by which a defibrillation shock directly stimulates regions of cardiac tissue distal to the stimulus electrodes ("far-field" stimulation) are still not well understood, Existing hypotheses have proposed that intercellular discontinuities and/or fiber curvatures induce the requisite membrane polarizations, This article hypothesizes a third potential mechanism: one based on the existence and influences of syncytial (anatomic) heterogeneities inherent throughout the bulk myocardium itself. Methods and Results: We simulated the effects of such heterogeneities in a model of a two-dimensional region of passive cardiac tissue subjected to uniform 1 V/cm longitudinal or transverse field stimuli. Heterogeneities were manifested via random spatial variations of intracellular volume fractions (f(i)) over multiple length scales, with mean f(i) of 80% and standard deviation of f(i) (sigma(fi)) ranging from 0% to 10%. During field stimulation, many interspersed and variously shaped and sized islands of hyperpolarization and depolarization developed across the tissue, with their locations and extents correlated to the spatial gradients of the underlying heterogeneities. Increases in sigma(fi) correspondingly increased the shock-induced magnitudes of resulting membrane polarizations. The ratio of maximal polarizations for equivalent longitudinal and transverse shocks approximated 2:1 across all sigma(fi) tested. At sigma(fi) = 5%, these maximal induced polarizations were 17.4 +/- 2.4 mV and 8.18 +/- 1.5 mV, respectively. Assuming an excitation threshold of 25 mV, these data suggest corresponding diastolic thresholds of 1.47 +/- 0.20 V/cm and 3.14 +/- 0.50 V/cm, respectively. Conclusion: This study predicts that syncytial heterogeneities inherent within cardiac tissue could represent a significant-and heretofore unappreciated-mechanism underlying field-induced polarizations throughout the bulk myocardium.