Mechanism linking T-wave alternans to the genesis of cardiac fibrillation
Mechanism linking T-wave alternans to the genesis of cardiac fibrillation
复制标题
DOI：
10.1161/01.cir.99.10.1385
复制
发表时间：
1999-03-16
期刊：
影响因子：
37.8
通讯作者：
Rosenbaum, DS
中科院分区：
文献类型：
--
作者：
Pastore, JM;Girouard, SD;Rosenbaum, DS
背景-尽管T波电交替与室性心律失常的易感性密切相关，但T波电交替的细胞过程及其作用，如果有的话，方法和结果：在8只Langendorff灌流豚鼠心脏上，在固定时间内诱发体表心电图上的T波电交替。频率起搏，同时用电压敏感染料记录128个心外膜部位的动作电位。在临界阈值心率（HR）（209+/-46 bpm）以上观察到动作电位复极相交替，该心率显著低于（57+/-36 bpm）动作电位去极化交替的HR阈值。复极化交替的幅度（范围，2.7至47.0 mV）和HR阈值（范围，171至272 bpm）在心外膜表面的细胞之间变化很大。体表心电图上的T波电交替主要由细胞复极时程中的搏动交替来解释。在临界HR以上，膜复极化与相邻细胞之间的相反相位交替（即，不一致的交替），产生大的复极化空间梯度。在存在不一致的电交替，一个小的加速起搏周期长度产生的事件的特征序列：（1）单向块的脉冲传播对陡峭的梯度复极，（2）折返传播，和（3）心室fibrillation. Conclusions复极电交替在单细胞水平占T波电交替的表面EGG。不一致交替产生足够幅度的复极空间梯度，导致单向阻滞和折返性心室颤动。这些数据建立了心电图T波电交替与心源性猝死发病机制的联系。
Background-Although T-wave alternans has been closely associated with vulnerability to ventricular arrhythmias, the cellular processes underlying T-wave alternans and their role, if any, in the mechanism of reentry remain unclear.Methods and Results-T-wave alternans on the surface ECG was elicited in 8 Langendorff-perfused guinea pig hearts during fixed-rate pacing while action potentials were recorded simultaneously from 128 epicardial sites with voltage-sensitive dyes. Alternans of the repolarization phase of the action potential was observed above a critical threshold heart rate (HR) (209+/-46 bpm) that was significantly lower (by 57+/-36 bpm) than the HR threshold for alternation of action potential depolarization. The magnitude (range, 2.7 to 47.0 mV) and HR threshold (range, 171 to 272 bpm) of repolarization alternans varied substantially between cells across the epicardial surface. T-wave alternans on the surface ECG was explained primarily by beat-to-beat alternation in the time course of cellular repolarization. Above a critical HR, membrane repolarization alternated with the opposite phase between neighboring cells (ie, discordant alternans), creating large spatial gradients of repolarization. In the presence of discordant alternans, a small acceleration of pacing cycle length produced a characteristic sequence of events: (1) unidirectional block of an impulse propagating against steep gradients of repolarization, (2) reentrant propagation, and (3) the initiation of ventricular fibrillation.Conclusions-Repolarization alternans at the level of the single cell accounts for T-wave alternans on the surface EGG. Discordant alternans produces spatial gradients of repolarization of sufficient magnitude to cause unidirectional block and reentrant ventricular fibrillation. These data establish a mechanism linking T-wave alternans of the ECG to the pathogenesis of sudden cardiac death.