Discordant Alternans as a Mechanism for Initiation of Ventricular Fibrillation In Vitro.
Discordant Alternans as a Mechanism for Initiation of Ventricular Fibrillation In Vitro.
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DOI：
10.1161/jaha.117.007898
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发表时间：
2018-09-04
影响因子：
5.4
通讯作者：
Otani NF
中科院分区：
文献类型：
--
作者：
Muñoz LM;Gelzer ARM;Fenton FH;Qian W;Lin W;Gilmour RF Jr;Otani NF
室性心动过速通常由短序列的过早心室复合体引起。在之前的一项研究中，基于恢复的计算模型预测了刺激的过早复合物的哪些序列最有可能在体内诱导犬心室颤动。然而，基于不协调交替动力学的潜在机制无法在该研究中得到验证。目前的研究旨在通过确定体外实验中动作电位的时空演变和心室颤动的开始是否与模型预测一致来阐明其机制。在过早刺激序列期间和之后，同时从整个心外膜和心内膜获得犬右心室组织（n=9）的光学映射电压信号。利用动作电位持续时间和舒张期间的数据，建立了动作电位沿1维电缆传播的模型预测。该模型预测动作电位持续时间和舒张期空间梯度的信号变化模式的后验概率分别为91.1%和82.1%。该模型预测传导阻滞的灵敏度为64%，特异性为100%。广义估计方程logistic回归方法显示，传导阻滞（P<1×10 - 15，系数44.36）和持续性心室颤动（P=0.0046，系数1.63）事件的模型预测效果均显著。观察到的信号变化模式倾向于不一致的交替，该模型成功地识别了诱导传导阻滞的过早刺激序列。这表明，导致模型中传导阻滞的相对简单的基于不协调-交替的过程可能经常导致早搏前心室颤动的发生。这些观察结果可能有助于开发预测传导阻滞和心室颤动的改进方法。
Ventricular tachyarrhythmias are often preceded by short sequences of premature ventricular complexes. In a previous study, a restitution‐based computational model predicted which sequences of stimulated premature complexes were most likely to induce ventricular fibrillation in canines in vivo. However, the underlying mechanism, based on discordant‐alternans dynamics, could not be verified in that study. The current study seeks to elucidate the mechanism by determining whether the spatiotemporal evolution of action potentials and initiation of ventricular fibrillation in in vitro experiments are consistent with model predictions. Optical mapping voltage signals from canine right‐ventricular tissue (n=9) were obtained simultaneously from the entire epicardium and endocardium during and after premature stimulus sequences. Model predictions of action potential propagation along a 1‐dimensional cable were developed using action potential duration versus diastolic interval data. The model predicted sign‐change patterns in action potential duration and diastolic interval spatial gradients with posterior probabilities of 91.1%, and 82.1%, respectively. The model predicted conduction block with 64% sensitivity and 100% specificity. A generalized estimating equation logistic‐regression approach showed that model‐prediction effects were significant for both conduction block (P<1×10−15, coefficient 44.36) and sustained ventricular fibrillation (P=0.0046, coefficient, 1.63) events. The observed sign‐change patterns favored discordant alternans, and the model successfully identified sequences of premature stimuli that induced conduction block. This suggests that the relatively simple discordant‐alternans‐based process that led to block in the model may often be responsible for ventricular fibrillation onset when preceded by premature beats. These observations may aid in developing improved methods for anticipating block and ventricular fibrillation.