Severe Bradycardia Increases the Incidence and Severity of Torsade de Pointes Arrhythmias by Augmenting Preexistent Spatial Dispersion of Repolarization in the CAVB Dog Model

Frontiers in Physiology

Ruben Coronel¹  Veronique M. F. Meijborg¹  Jacques M. T. de Bakker¹  Marc A. Vos²  Marcel A. G. van der Heyden²  Valerie Y. H. van Weperen²  Jet D. M. Beekman²  Rosanne Varkevisser²  Albert Dunnink²  Alexandre Bossu² 

[1] Department of Clinical and Experimental Cardiology, Amsterdam UMC Locatie AMC, Amsterdam, Netherlands;Department of Medical Physiology, Universitair Medisch Centrum Utrecht, Utrecht, Netherlands;

关键词: CAVB dog model;    sudden cardiac death;    temporal dispersion of repolarization;    spatial dispersion of repolarization;    arrhythmogenesis;    severe bradycardia;   

DOI  :  10.3389/fphys.2021.642083

来源: DOAJ

【 摘 要 】

IntroductionTorsade de pointes arrhythmias (TdP) in the chronic atrioventricular block (CAVB) dog model result from proarrhythmic factors, which trigger TdP and/or reinforce the arrhythmic substrate. This study investigated electrophysiological and arrhythmogenic consequences of severe bradycardia for TdP.MethodsDofetilide (25 μg/kg per 5 min) was administered to eight anesthetized, idioventricular rhythm (IVR) remodeled CAVB dogs in two serial experiments: once under 60 beats per minute (bpm), right ventricular apex paced (RVA60) conditions, once under more bradycardic IVR conditions. Recordings included surface electrocardiogram and short-term variability (STV) of repolarization from endocardial unipolar electrograms. TdP inducibility (three or more episodes within 10 min after start of dofetilide) and arrhythmic activity scores (AS) were established. Mapping experiments in 10 additional dogs determined the effect of lowering rate on STV and spatial dispersion of repolarization (SDR) in baseline.ResultsIVR-tested animals had longer baseline RR-interval (1,403 ± 271 ms) and repolarization intervals than RVA60 animals. Dofetilide increased STV similarly under both rhythm strategies. Nevertheless, TdP inducibility and AS were higher under IVR conditions (6/8 and 37 ± 27 vs. 1/8 and 8 ± 12 in RVA60, respectively, both p < 0.05). Mapping: Pacing from high (128 ± 10 bpm) to middle (88 ± 10 bpm) to experimental rate (61 ± 3 bpm) increased all electrophysiological parameters, including interventricular dispersion, due to steeper left ventricular restitution curves, and intraventricular SDR: maximal cubic dispersion from 60 ± 14 (high) to 69 ± 17 (middle) to 84 ± 22 ms (p < 0.05 vs. high and middle rate).ConclusionIn CAVB dogs, severe bradycardia increases the probability and severity of arrhythmic events by heterogeneously causing electrophysiological instability, which is mainly reflected in an increased spatial, and to a lesser extent temporal, dispersion of repolarization.

【 授权许可】

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