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):793-804. doi: 10.1529/biophysj.106.080945. Epub 2006 May 5.
Spatial dispersion of refractoriness, which is amplified by genetic diseases, drugs, and electrical and structural remodeling during heart disease, is recognized as a major factor increasing the risk of lethal arrhythmias and sudden cardiac death. Dispersion forms the substrate for unidirectional conduction block, which is required for the initiation of reentry by extrasystoles or rapid pacing. In this study, we examine theoretically and numerically how preexisting gradients in refractoriness control the vulnerable window for unidirectional conduction block by a single premature extrasystole. Using a kinematic model to represent wavefront-waveback interactions, we first analytically derived the relationship (under simplified conditions) between the vulnerable window and various electrophysiological parameters such as action potential duration gradients, refractoriness barriers, conduction velocity restitution, etc. We then compared these findings to numerical simulations using the kinematic model or the Luo-Rudy action potential model in a one-dimensional cable of cardiac cells. The results from all three methods agreed well. We show that a critical gradient in action potential duration for conduction block can be analytically derived, and once this critical gradient is exceeded, the vulnerable window increases proportionately with the refractory barrier and is modulated by conduction velocity restitution and gap junctional conductance. Moreover, the critical gradient for conduction block is higher for an extrasystole traveling in the opposite direction from the sinus beat than for one traveling in the same direction (e.g., an epicardial extrasystole versus an endocardial extrasystole).
不应期的空间离散，在心脏病期间会因遗传疾病、药物以及电和结构重塑而加剧，被认为是增加致死性心律失常和心源性猝死风险的主要因素。离散形成了单向传导阻滞的基础，而单向传导阻滞是早搏或快速起搏引发折返所必需的。在本研究中，我们从理论和数值方面研究了预先存在的不应期梯度如何通过单个过早早搏来控制单向传导阻滞的易损窗口。使用一个运动学模型来表示波前 - 波后相互作用，我们首先（在简化条件下）解析推导了易损窗口与各种电生理参数之间的关系，如动作电位时程梯度、不应期屏障、传导速度恢复等。然后，我们将这些结果与在一维心肌细胞电缆中使用运动学模型或罗 - 鲁迪动作电位模型进行的数值模拟结果进行了比较。这三种方法的结果吻合良好。我们表明，可以解析推导传导阻滞的动作电位时程临界梯度，一旦超过这个临界梯度，易损窗口会与不应期屏障成比例增加，并受传导速度恢复和缝隙连接电导的调节。此外，早搏与窦性搏动方向相反时的传导阻滞临界梯度高于同向时（例如，心外膜早搏与心内膜早搏）。
