Arce Humberto, Xu Aoxiang, Gonzalez Hortensia, Guevara Michael R.
Departamento de Fisica, Facultad de Ciencias, Universidad Nacional Autonoma de Mexico, Apartado Postal 70-542, 04510 Mexico, Distrito Federal, Mexico.
Chaos. 2000 Jun;10(2):411-426. doi: 10.1063/1.166508.
Life-threatening arrhythmias such as ventricular tachycardia and fibrillation often occur during acute myocardial ischemia. During the first few minutes following coronary occlusion, there is a gradual rise in the extracellular concentration of potassium ions (K(+)) within ischemic tissue. This elevation of K(+) is one of the main causes of the electrophysiological changes produced by ischemia, and has been implicated in inducing arrhythmias. We investigate an ionic model of a 3 cmx3 cm sheet of normal ventricular myocardium containing an ischemic zone, simulated by elevating K(+) within a centrally-placed 1 cmx1 cm area of the sheet. As K(+) is gradually raised within the ischemic zone from the normal value of 5.4 mM, conduction first slows within the ischemic zone and then, at higher K(+), an arc of block develops within that area. The area distal to the arc of block is activated in a delayed fashion by a retrogradely moving wavefront originating from the distal edge of the ischemic zone. With a further increase in K(+), the point eventually comes where a very small increase in K(+) (0.01 mM) results in the abrupt transition from a global period-1 rhythm to a global period-2 rhythm in the sheet. In the peripheral part of the ischemic zone and in the normal area surrounding it, there is an alternation of action potential duration, producing a 2:2 response. Within the core of the ischemic zone, there is an alternation between an action potential and a maintained small-amplitude response ( approximately 30 mV in height). With a further increase of K(+), the maintained small-amplitude response turns into a decrementing subthreshold response, so that there is 2:1 block in the central part of the ischemic zone. A still further increase of K(+) leads to a transition in the sheet from a global period-2 to a period-4 rhythm, and then to period-6 and period-8 rhythms, and finally to a complete block of propagation within the ischemic core. When the size of the sheet is increased to 4 cmx4 cm (with a 2 cmx2 cm ischemic area), one observes essentially the same sequence of rhythms, except that the period-6 rhythm is not seen. Very similar sequences of rhythms are seen as K(+) is increased in the central region (1 or 2 cm long) of a thin strand of tissue (3 or 4 cm long) in which propagation is essentially one-dimensional and in which retrograde propagation does not occur. While reentrant rhythms resembling tachycardia and fibrillation were not encountered in the above simulations, well-known precursors to such rhythms (e.g., delayed activation, arcs of block, two-component upstrokes, retrograde activation, nascent spiral tips, alternans) were seen. We outline how additional modifications to the ischemic model might result in the emergence of reentrant rhythms following alternans. (c) 2000 American Institute of Physics.
危及生命的心律失常，如室性心动过速和颤动，常在急性心肌缺血期间发生。在冠状动脉闭塞后的最初几分钟内，缺血组织细胞外钾离子浓度（[K⁺]₀）会逐渐升高。[K⁺]₀的这种升高是缺血导致电生理变化的主要原因之一，并被认为与心律失常的诱发有关。我们研究了一个包含缺血区的3 cm×3 cm正常心室心肌薄片的离子模型，通过升高薄片中心位置1 cm×1 cm区域内的[K⁺]₀来模拟缺血区。随着[K⁺]₀在缺血区内从正常的5.4 mM逐渐升高，传导首先在缺血区内减慢，然后在更高的[K⁺]₀水平时，该区域会出现一个阻滞弧。阻滞弧远端的区域被源自缺血区远端边缘的逆行波前以延迟的方式激活。随着[K⁺]₀进一步增加，最终会出现这样一个点，即[K⁺]₀非常小的增加（0.01 mM）会导致薄片从整体的1期节律突然转变为2期节律。在缺血区的周边部分及其周围的正常区域，动作电位持续时间会交替出现，产生2:2反应。在缺血区的核心部分，动作电位和持续的小幅度反应（高度约为30 mV）会交替出现。随着[K⁺]₀进一步增加，持续的小幅度反应会转变为递减的阈下反应，从而在缺血区的中心部分出现2:1阻滞。[K⁺]₀进一步增加会导致薄片从整体的2期节律转变为4期节律，然后是6期和8期节律，最终缺血核心内的传播完全阻滞。当薄片尺寸增加到4 cm×4 cm（缺血面积为2 cm×2 cm）时，观察到的节律序列基本相同，只是没有看到6期节律。当在一条基本一维传播且不存在逆行传播的细组织条带（3或4 cm长）的中心区域（1或2 cm长）增加[K⁺]₀时，也会看到非常相似的节律序列。虽然在上述模拟中没有遇到类似心动过速和颤动的折返节律，但看到了此类节律的众所周知的先兆（例如，延迟激活、阻滞弧、双成分上升支、逆行激活、新生螺旋尖端、交替现象）。我们概述了对缺血模型的进一步修改如何可能导致交替现象后折返节律的出现。（c）2000美国物理研究所。
