Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Campos, FO; Shiferaw, Y; Prassl, AJ; Boyle, PM; Vigmond, EJ; Plank, G.
Stochastic spontaneous calcium release events trigger premature ventricular complexes by overcoming electrotonic load.
Cardiovasc Res. 2015; 107(1):175-183
Doi: 10.1093/cvr/cvv149
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- Führende Autor*innen der Med Uni Graz
- Campos Fernando Otaviano
- Plank Gernot
- Co-Autor*innen der Med Uni Graz
- Prassl Anton
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- Abstract:
- Premature ventricular complexes (PVCs) due to spontaneous calcium (Ca) release (SCR) events at the cell level can precipitate ventricular arrhythmias. However, the mechanistic link between SCRs and PVC formation remains incompletely understood. The aim of this study was to investigate the conditions under which delayed afterdepolarizations resulting from stochastic subcellular SCR events can overcome electrotonic source-sink mismatch, leading to PVC initiation. A stochastic subcellular-scale mathematical model of SCR was incorporated in a realistic model of the rabbit ventricles and Purkinje system (PS). Elevated levels of diastolic sarcoplasmic reticulum Ca(2+) (CaSR) were imposed until triggered activity was observed, allowing us to compile statistics on probability, timing, and location of PVCs. At CaSR≥ 1500 µmol/L PVCs originated in the PS. When SCR was incapacitated in the PS, PVCs also emerged in the ventricles, but at a higher CaSR (≥1550 µmol/L) and with longer waiting times. For each model configuration tested, the probability of PVC occurrence increased from 0 to 100% within a well-defined critical CaSR range; this transition was much more abrupt in organ-scale models (∼50 µmol/L CaSR range) than in the tissue strand (∼100 µmol/L) or single-cell (∼450 µmol/L) models. Among PVCs originating in the PS, ∼68% were located near Purkinje-ventricular junctions (<1 mm). SCR events overcome source-sink mismatch to trigger PVCs at a critical CaSR threshold. Above this threshold, PVCs emerge due to increased probability and reduced variability in timing of SCR events, leading to significant diastolic depolarization. Sites of lower electronic load, such as the PS, are preferential locations for triggering. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.
- Find related publications in this database (using NLM MeSH Indexing)
- Action Potentials -
- Animals -
- Arrhythmias, Cardiac - etiology
- Bundle of His - physiology
- Calcium - metabolism
- Computer Simulation -
- Heart Failure - physiopathology
- Heart Ventricles -
- Rabbits -
- Find related publications in this database (Keywords)
- Delayed afterdepolarization
- Triggered activity
- Computer-based model
- Purkinje system
- Arrhythmia