Alternans and higher-order rhythms in an ionic model of a sheet of ischemic ventricular muscle

Abstract

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+](0)) within ischemic tissue. This elevation of [K+](0) 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+](0) within a centrally-placed 1 cmx1 cm area of the sheet. As [K+](0) 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+](0), 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+](0), the point eventually comes where a very small increase in [K+](0) (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 (similar to 30 mV in height). With a further increase of [K+](0), 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+](0) 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+](0) 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. [S1054-1500(00)00102-6].