Lesh M D, Pring M, Spear J F
Cardiovascular Section, University of Pennsylvania, Philadelphia.
Circ Res. 1989 Nov;65(5):1426-40. doi: 10.1161/01.res.65.5.1426.
Although slow conduction is a requirement for the preparation of sustained reentry, it alone is not sufficient for the initiation of reentry. Additionally, unidirectional block and recovery of excitability distal to the site of block must occur. Thus, a comprehensive description of the electrophysiological determinants of reentry must explain both slow conduction and unidirectional block. Although there is a growing body of research exploring the influence of axial resistivity and anisotropy on slow conduction, somewhat less is known about the relation of axial resistivity to spatial dispersion of action potential duration, a condition favorable to the development of unidirectional block. We hypothesized that when cells are well coupled, local differences in intrinsic action potential duration are not evident and that, as axial resistivity increases, local variation in action potential duration becomes manifest. We tested this hypothesis in a numerical model of electrical propagation in a grid of resistively coupled ionic current sources simulating a sheet of ventricular myocardium. Spatial dispersion of intrinsic action potential duration was simulated by varying the magnitude of the fully activated slow inward conductance in Beeler-Reuter membrane ionic kinetics. By then altering coupling resistance, we showed that dispersion of manifest action potential duration is masked in the setting of normal low-resistance cellular coupling and unmasked by increased axial resistance. When nonuniform anisotropy was simulated, dramatic pacing-site-dependent changes in both the pattern of activation and dispersion of action potential duration were noted. These findings may be important in understanding the mechanism of reentrant tachycardia initiation in the border zone of chronic, healed myocardial infarctions where evidence suggests that abnormal cellular coupling is the predominant electrophysiological derangement. In this study, we have shown, using a detailed ionic current-based model of cardiac electrical propagation, that changes in axial resistivity can modulate how spatial dispersion of intrinsic action potential duration is manifest.
虽然缓慢传导是形成持续性折返的必要条件，但仅凭这一点不足以引发折返。此外，还必须发生单向阻滞以及阻滞部位远端兴奋性的恢复。因此，对折返的电生理决定因素进行全面描述必须解释缓慢传导和单向阻滞。尽管有越来越多的研究探讨轴向电阻率和各向异性对缓慢传导的影响，但关于轴向电阻率与动作电位时程空间离散的关系却知之甚少，而动作电位时程空间离散是有利于单向阻滞发展的一种情况。我们假设，当细胞耦合良好时，固有动作电位时程的局部差异并不明显，并且随着轴向电阻率的增加，动作电位时程的局部变化会变得明显。我们在一个电阻耦合离子电流源网格的电传播数值模型中测试了这一假设，该模型模拟了一片心室心肌。通过改变Beeler-Reuter膜离子动力学中完全激活的缓慢内向电导的大小来模拟固有动作电位时程的空间离散。然后通过改变耦合电阻，我们发现，在正常低电阻细胞耦合的情况下，明显动作电位时程的离散被掩盖，而轴向电阻增加时则会显现出来。当模拟非均匀各向异性时，观察到激活模式和动作电位时程离散都有显著的起搏点依赖性变化。这些发现对于理解慢性愈合心肌梗死边缘区折返性心动过速的发生机制可能很重要，有证据表明异常细胞耦合是主要的电生理紊乱。在这项研究中，我们使用基于详细离子电流的心脏电传播模型表明，轴向电阻率的变化可以调节固有动作电位时程的空间离散是如何显现的。
