Delayed afterdepolarizations generate both triggers and a vulnerable substrate promoting reentry in cardiac tissue

Michael B. Liu, Enno de Lange, Alan Garfinkel, James N. Weiss, Zhilin Qu*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    31 Citations (Web of Science)

    Abstract

    BACKGROUND Delayed afterdepolarizations (DADs) have been well characterized as arrhythmia triggers, but their role in generating a tissue substrate vulnerable to reentry is not well understood.

    OBJECTIVE The purpose of this study was to test the hypothesis that random DADs can self-organize to generate both an arrhythmia trigger and a vulnerable substrate simultaneously in cardiac tissue as a result of gap junction coupling.

    METHODS Computer simulations in 1-dimensional cable and 2-dimensional tissue models were performed. The cellular DAD amplitude was varied by changing the strength of sarcoplasmic reticulum calcium release. Random DAD latency and amplitude in different cells were simulated using gaussian distributions.

    RESULTS Depending on the strength of spontaneous sarcoplasmic reticulum calcium release and other conditions, random DADs in cardiac tissue resulted in the following behaviors: (1) triggered activity (TA); (2) a vulnerable tissue substrate causing unidirectional conduction block and reentry by inactivating sodium channels; (3) both triggers and a vulnerable substrate simultaneously by generating TA in regions next to regions with subthreshold DADs susceptible to unidirectional conduction block and reentry. The probability of the latter 2 behaviors was enhanced by reduced sodium channel availability, reduced gap junction coupling, increased tissue heterogeneity, and less synchronous DAD latency.

    CONCLUSION DADs can self-organize in tissue to generate arrhythmia triggers, a vulnerable tissue substrate, and both simultaneously. Reduced sodium channel availability and gap junction coupling potentiate this mechanism of arrhythmias, which are relevant to a variety of heart disease conditions.

    Original languageEnglish
    Article number019
    Pages (from-to)2115-2124
    Number of pages10
    JournalHeart Rhythm
    Volume12
    Issue number10
    DOIs
    Publication statusPublished - Oct 2015

    Keywords

    • Delayed afterdepolarization
    • Conduction block
    • Reentry
    • Arrhythmia
    • Computer simulation
    • POLYMORPHIC VENTRICULAR-TACHYCARDIA
    • SPONTANEOUS CALCIUM-RELEASE
    • EPICARDIAL BORDER ZONE
    • INFARCTED HEART
    • PURKINJE-FIBERS
    • NA+ CURRENTS
    • U WAVE
    • MYOCYTES
    • ARRHYTHMIAS
    • MECHANISM

    Cite this