Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Bishop, MJ; Connolly, A; Plank, G.
Structural heterogeneity modulates effective refractory period: a mechanism of focal arrhythmia initiation.
PLoS One. 2014; 9(10):e109754-e109754
Doi: 10.1371/journal.pone.0109754
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Plank Gernot
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- 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 (72.6 vs 220.4 μA/cm2), with faster maximum AP upstroke velocities (257.3 vs 147.3 mV/ms), although noticeably very similar APDs (167.7 vs 168.4 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 40 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Action Potentials -
- Algorithms -
- Animals -
- Arrhythmias, Cardiac - pathology
- Cardiac Pacing, Artificial -
- Computer Simulation -
- Heart Conduction System - pathology
- Heart Ventricles - pathology
- Humans -
- Models, Anatomic -
- Myocardium - pathology
- Pericardium - pathology
- Rabbits -