Spach M S, Dolber P C, Heidlage J F
Department of Pediatrics, Duke University Medical Center, Durham, NC 27710.
Circ Res. 1988 Apr;62(4):811-32. doi: 10.1161/01.res.62.4.811.
Available models of circus movement reentry in cardiac muscle and of drug action on reentrant arrhythmias are based on continuous medium theory, which depends solely on the membrane ionic conductances to alter propagation. The purpose of this study is to show that the anisotropic passive properties at a microscopic level highly determine the propagation response to modification of the sodium conductance by premature action potentials and by sodium channel-blocking drugs. In young, uniform anisotropic atrial bundles, propagation of progressively earlier premature action potentials continued as a smooth process until propagation ceased simultaneously in all directions. In older, nonuniform anisotropic bundles, however, premature action potentials produced either unidirectional longitudinal conduction block or a dissociated zigzag type of longitudinal conduction (a safer type of propagation, similar to transverse propagation). Directional differences in the velocity of premature action potentials demonstrated that anisotropic propagation was necessary for a reentrant circuit to be contained within an area of 50 mm2, even with very short refractory periods. Quinidine produced Wenckebach periodicity, which disappeared after acetylcholine shortened the action potential. Quinidine also produced use-dependent dissociated zigzag longitudinal conduction in the older, nonuniform anisotropic bundles but not in the young, uniform anisotropic bundles. The electrophysiological consequence was that propagation events differed in an age-related manner in response to the same modification of the sodium conductance. The electrical events at microscopic level showed that conditions leading to obliteration of side-to-side electrical coupling between fibers (e.g., aging and chronic hypertrophy) provide a primary mechanism for reentry to occur within very small areas (1-2 mm) due to a variety of propagation phenomena that do not occur in tissues with tight electrical coupling in all directions.
目前关于心肌中 circus 运动折返以及药物对折返性心律失常作用的模型是基于连续介质理论，该理论仅依赖于膜离子电导来改变传导。本研究的目的是表明，微观层面的各向异性被动特性在很大程度上决定了对过早动作电位和钠通道阻断药物引起的钠电导改变的传导反应。在年轻、均匀的各向异性心房束中，逐渐提前的过早动作电位的传导持续进行，是一个平滑的过程，直到在所有方向上同时停止传导。然而，在年老、不均匀的各向异性束中，过早动作电位会产生单向纵向传导阻滞或解离的锯齿状纵向传导（一种更安全的传导类型，类似于横向传导）。过早动作电位速度的方向差异表明，即使在非常短的不应期情况下，各向异性传导对于折返环被限制在 50 mm² 的区域内也是必要的。奎尼丁产生文氏周期，在乙酰胆碱缩短动作电位后消失。奎尼丁还在年老、不均匀的各向异性束中产生使用依赖性解离锯齿状纵向传导，但在年轻、均匀的各向异性束中不产生。电生理结果是，对于相同的钠电导改变，传导事件随年龄呈现不同的反应方式。微观层面的电活动表明，导致纤维间侧向电耦合消失的条件（如衰老和慢性肥大）提供了一种主要机制，使得由于各种在各方向紧密电耦合的组织中不会出现的传导现象，折返能在非常小的区域（1 - 2 mm）内发生。
