Thomsen Morten B, Volders Paul G A, Beekman Jet D M, Matz Jørgen, Vos Marc A
Department of Medical Physiology, Heart Lung Center Utrecht, University Medical Center Utrecht, Utrecht, The Netherlands.
J Am Coll Cardiol. 2006 Sep 19;48(6):1268-76. doi: 10.1016/j.jacc.2006.05.048. Epub 2006 Aug 28.
We investigated whether increasing or decreasing beat-to-beat variability of repolarization (BVR) would change drug-induced proarrhythmic outcome accordingly.
Increased variability of repolarization has been suggested as a prelude to proarrhythmic circumstances in experimental and clinical situations.
The non-cardiovascular, I(Kr)-blocking drug sertindole was administered to anesthetized dogs with chronic atrioventricular block. Three interventions were used to prevent or suppress sertindole-induced torsades de pointes (TdP).
Supratherapeutic doses of sertindole (1.0 mg/kg intravenously) induced TdP in 10 of 13 dogs whereas 0.2 mg/kg induced no TdP, despite increases in QT intervals by both doses. The BVR, quantified as short-term variability (STV) from Poincaré plots, was the only parameter that predicted TdP outcome (1.0 mg/kg sertindole: 2.3 +/- 0.7 ms to 5.1 +/- 2.1 ms, p < 0.05; 0.2 mg/kg sertindole: 2.3 +/- 0.8 ms to 3.2 +/- 1.1 ms, p= NS).
Proarrhythmic intervention is related to an increase in BVR, whereas antiarrhythmic treatment is associated with a decrease in BVR. The BVR is superior to QT interval prolongation in the prediction and prevention of drug-induced TdP in this experimental model.
我们研究了复极化逐搏变异性（BVR）的增加或减少是否会相应地改变药物诱导的致心律失常结果。
在实验和临床情况下，复极化变异性增加被认为是致心律失常情况的前奏。
将非心血管类、阻断I(Kr)的药物舍吲哚给予患有慢性房室传导阻滞的麻醉犬。采用三种干预措施来预防或抑制舍吲哚诱导的尖端扭转型室性心动过速（TdP）。
超治疗剂量的舍吲哚（静脉注射1.0mg/kg）在13只犬中有10只诱发了TdP，而0.2mg/kg未诱发TdP，尽管两种剂量均使QT间期延长。通过庞加莱图量化为短期变异性（STV）的BVR是唯一预测TdP结果的参数（1.0mg/kg舍吲哚：从2.3±0.7ms增至5.1±2.1ms，p<0.05；0.2mg/kg舍吲哚：从2.3±0.8ms增至3.2±1.1ms，p=无显著性差异）。
1）静脉注射氯化钾将舍吲哚诱导的TdP发生率从7只犬中的6只降至7只犬中的1只（p<0.05），并防止了舍吲哚相关的STV增加：3.0±1.1ms对4.5±1.3ms（p<0.05）；2） 左西孟旦（I(K,ATP)激活剂）减少了舍吲哚诱导的TdP，并使STV从4.9±2.1ms降至2.6±0.9ms（p<0.05）；3） 稳态心室起搏（60次/分钟）消除了舍吲哚诱导的TdP，并使STV从4.9±1.5降至3.2±1.0（p<0.05）。恢复至非起搏的室性自主心律时TdP再次出现。三种干预措施均未减少舍吲哚诱导的QT间期延长。
致心律失常干预与BVR增加有关，而抗心律失常治疗与BVR降低有关。在该实验模型中，BVR在预测和预防药物诱导的TdP方面优于QT间期延长。
