Qu Zhilin, Garfinkel Alan, Weiss James N
Department of Medicine Cardiology, David Geffen School of Medicine, University of California, Los Angeles, 90095, USA.
Biophys J. 2006 Aug 1;91(3):805-15. doi: 10.1529/biophysj.106.080952. Epub 2006 May 5.
Unidirectional conduction block of premature extrasystoles can lead to initiation of cardiac reentry, causing lethal arrhythmias including ventricular fibrillation. Multiple extrasystoles are often more effective at inducing unidirectional conduction block and reentry than a single extrasystole. Since the substrate for conduction block is spatial dispersion of refractoriness, in this study we investigate how the first extrasystole modulates this dispersion to influence the "vulnerable window" for conduction block by subsequent extrasystoles, particularly in relation to action potential duration restitution and conduction velocity restitution properties. Using a kinematic model to represent wavefront-waveback interactions and simulations with the Luo-Rudy model in a one-dimensional cable of cardiac cells, we show that in homogeneous tissue, a premature extrasystole can create a large dispersion of refractoriness leading to conduction block of a subsequent extrasystole. In heterogeneous tissue, however, a premature extrasystole can either reduce or enhance the dispersion of refractoriness depending on its propagation direction with respect to the previous beat. With multiple extrasystoles at random coupling intervals, vulnerability to conduction block is proportional to their number. In general, steep action potential duration restitution and broad conduction velocity restitution promote dispersion of refractoriness in response to multiple extrasystoles, and thus enhance vulnerability to conduction block. These restitution properties also promote spatially discordant alternans, a setting which is particularly prone to conduction block. The equivalent dispersion of refractoriness created dynamically in homogeneous tissue by spatially discordant alternans is more likely to cause conduction block than a comparable degree of preexisting dispersion in heterogeneous tissue.
过早期前收缩的单向传导阻滞可导致心脏折返的启动，引发包括心室颤动在内的致命性心律失常。多个期前收缩通常比单个期前收缩更有效地诱导单向传导阻滞和折返。由于传导阻滞的基础是不应期的空间离散，在本研究中，我们探讨第一个期前收缩如何调节这种离散，以影响后续期前收缩导致传导阻滞的“易损窗口”，特别是与动作电位时程恢复和传导速度恢复特性的关系。使用一个运动学模型来表示波前 - 波后相互作用，并在一维心肌细胞电缆中用Luo - Rudy模型进行模拟，我们表明在均匀组织中，过早期前收缩可产生较大的不应期离散，导致后续期前收缩的传导阻滞。然而，在异质组织中，过早期前收缩根据其相对于前一个搏动的传播方向，可减少或增强不应期离散。当多个期前收缩以随机耦合间隔出现时，传导阻滞的易损性与其数量成正比。一般来说，陡峭的动作电位时程恢复和宽泛的传导速度恢复会促进对多个期前收缩反应时的不应期离散，从而增强传导阻滞的易损性。这些恢复特性也促进空间不协调交替，这种情况特别容易发生传导阻滞。在均匀组织中由空间不协调交替动态产生的等效不应期离散比在异质组织中同等程度的预先存在的离散更有可能导致传导阻滞。
