TY - JOUR
T1 - Structural Heterogeneity Modulates Effective Refractory Period
T2 - A Mechanism of Focal Arrhythmia Initiation
AU - Bishop, Martin J
AU - Connolly, Adam
AU - Plank, Gernot
PY - 2014/10/7
Y1 - 2014/10/7
N2 - Reductions in electrotonic loading around regions of structural and electrophysiological heterogeneity may facilitate capture of focal triggered activity, initiating reentrant arrhythmias. How electrotonic loading, refractoriness and capture of focal ectopics depend upon the intricate nature of physiological structural anatomy, as well as pathological tissue remodelling, however, is not well understood. In this study, we performed computational bidomain simulations with anatomically-detailed models representing the rabbit left ventricle. We used these models to quantify the relationship between local structural anatomy and spatial heterogeneity in action potential (AP) characteristics, electrotonic currents and effective refractory periods (ERPs) under pacing and restitution protocols. Regions surrounding vessel cavities, in addition to tissue surfaces, had significantly lower peak downstream electrotonic currents than well coupled myocardium ([Formula: see text] vs [Formula: see text] [Formula: see text]A/cm2), with faster maximum AP upstroke velocities ([Formula: see text] vs [Formula: see text] mV/ms), although noticeably very similar APDs ([Formula: see text] vs [Formula: see text] ms) and AP restitution properties. Despite similarities in APDs, ERPs in regions of low electrotonic load in the vicinity of surfaces, intramural vessel cavities and endocardial structures were up to [Formula: see text] ms shorter compared to neighbouring well-coupled tissue, leading to regions of sharp ERP gradients. Consequently, focal extra-stimuli timed within this window of ERP heterogeneity between neighbouring regions readily induced uni-directional block, inducing reentry. Most effective induction sites were within channels of low ERPs between large vessels and epicardium. Significant differences in ERP driven by reductions in electrotonic loading due to fine-scale physiological structural heterogeneity provides an important mechanism of capture of focal activity and reentry induction. Application to pathological ventricles, particularly myocardial infarction, will have important implications in anti-arrhythmia therapy.
AB - Reductions in electrotonic loading around regions of structural and electrophysiological heterogeneity may facilitate capture of focal triggered activity, initiating reentrant arrhythmias. How electrotonic loading, refractoriness and capture of focal ectopics depend upon the intricate nature of physiological structural anatomy, as well as pathological tissue remodelling, however, is not well understood. In this study, we performed computational bidomain simulations with anatomically-detailed models representing the rabbit left ventricle. We used these models to quantify the relationship between local structural anatomy and spatial heterogeneity in action potential (AP) characteristics, electrotonic currents and effective refractory periods (ERPs) under pacing and restitution protocols. Regions surrounding vessel cavities, in addition to tissue surfaces, had significantly lower peak downstream electrotonic currents than well coupled myocardium ([Formula: see text] vs [Formula: see text] [Formula: see text]A/cm2), with faster maximum AP upstroke velocities ([Formula: see text] vs [Formula: see text] mV/ms), although noticeably very similar APDs ([Formula: see text] vs [Formula: see text] ms) and AP restitution properties. Despite similarities in APDs, ERPs in regions of low electrotonic load in the vicinity of surfaces, intramural vessel cavities and endocardial structures were up to [Formula: see text] ms shorter compared to neighbouring well-coupled tissue, leading to regions of sharp ERP gradients. Consequently, focal extra-stimuli timed within this window of ERP heterogeneity between neighbouring regions readily induced uni-directional block, inducing reentry. Most effective induction sites were within channels of low ERPs between large vessels and epicardium. Significant differences in ERP driven by reductions in electrotonic loading due to fine-scale physiological structural heterogeneity provides an important mechanism of capture of focal activity and reentry induction. Application to pathological ventricles, particularly myocardial infarction, will have important implications in anti-arrhythmia therapy.
U2 - 10.1371/journal.pone.0109754
DO - 10.1371/journal.pone.0109754
M3 - Article
C2 - 25291380
SN - 1932-6203
VL - 9
JO - PLoS ONE
JF - PLoS ONE
IS - 10
M1 - e109754
ER -