van Weperen Valerie Y H, Dunnink Albert, Bossu Alexandre, Beekman Jet D M, Meijborg Veronique M F, de Bakker Jacques M T, Coronel Ruben, Varkevisser Rosanne, van der Heyden Marcel A G, Vos Marc A
Department of Medical Physiology, Universitair Medisch Centrum Utrecht, Utrecht, Netherlands.
Department of Clinical and Experimental Cardiology, Amsterdam UMC Locatie AMC, Amsterdam, Netherlands.
Front Physiol. 2021 Apr 26;12:642083. doi: 10.3389/fphys.2021.642083. eCollection 2021.
Torsade 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.
Dofetilide (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.
IVR-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 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 ( < 0.05 vs. high and middle rate).
In 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.
慢性房室传导阻滞（CAVB）犬模型中的尖端扭转型室性心律失常（TdP）由促心律失常因素引起，这些因素触发TdP和/或强化心律失常基质。本研究调查了严重心动过缓对TdP的电生理和致心律失常后果。
在两个连续实验中，对八只麻醉的、心室自主节律（IVR）重塑的CAVB犬给予多非利特（每5分钟25μg/kg）：一次在每分钟60次心跳（bpm）、右心室心尖起搏（RVA60）条件下，一次在更缓慢的IVR条件下。记录包括体表心电图和心内膜单极电图复极化的短期变异性（STV）。确定TdP诱发性（多非利特开始后10分钟内出现三次或更多次发作）和心律失常活动评分（AS）。另外十只犬的标测实验确定了降低心率对基线时STV和复极化空间离散度（SDR）的影响。
经IVR测试的动物的基线RR间期（1403±271毫秒）和复极化间期比RVA60动物更长。在两种节律策略下，多非利特对STV的增加作用相似。然而，在IVR条件下TdP诱发性和AS更高（分别为6/8和37±27，而RVA60时为1/8和8±12，两者均P<0.05）。标测：从高频率（128±10bpm）起搏到中等频率（
