Reentrant ventricular arrhythmias in the late myocardial infarction period: mechanism by which a short-long-short cardiac sequence facilitates the induction of reentry.

Abstract

The electrophysiological mechanism by which a short-long-short stimulated cardiac sequence facilitates the induction of ventricular tachyarrhythmia was investigated in dogs 4 days after ligation of the left anterior descending coronary artery. In these dogs, reentry develops in the surviving electrophysiologically abnormal epicardial layer that overlies the infarct zone when premature stimulation results in a critically long arc of functional conduction block. The activation wavefront circulates around both ends of the arc, coalesces, and conducts slowly distal to the arc before reactivating sites proximal to the arc to initiate a figure-eight reentrant circuit. Epicardial isochronal activation maps and effective refractory periods (ERPs) were determined during three different stimulation protocols: A, a basic train of eight beats at a cycle length of 300 msec followed by a single premature stimulus (S2); B, a basic train of eight beats at a cycle length of 300 msec with abrupt lengthening of the last cycle of the train before S2 to 600 msec; C, a basic train of eight beats at a cycle length of 600 msec followed by S2. Protocol B was found to result in a differential lengthening of ERP at adjacent sites within the border of the epicardial ischemic zone, whereas protocols A and C induced, respectively, comparable shortening and lengthening of ERPs at the same sites. The differential lengthening of ERPs at adjacent sites resulted in an increased dispersion of refractoriness so that a premature stimulus induced functional conduction block between those sites. The development of a longer arc of conduction block and, hence, a longer reentrant pathway as well as slower conduction of the circulating wavefront during protocol B allowed more time for refractoriness to expire proximal to the arc and for the circulating wavefront to reexcite those sites to initiate reentry. The lengthening of ERP, associated with a single long cycle (protocol B), ranged from 44% to 79% of the total increase in ERP after a series of eight long cycles (protocol C). Epicardial sites with longer ERPs located close to the center of the ischemic zone showed more lengthening of refractoriness during protocol B compared with more normal sites near the border of the ischemic zone. This strongly suggests that the increased dispersion of refractoriness during protocol B is caused by the shorter memory of ischemic myocardium to the cumulative effects of preceding cycle lengths.

Postrepolarization Refractoriness Versus Conduction Slowing Caused by Class I Antiarrhythmic Drugs

“…In this setting, reentry can occur as the result of shortening of activation wavelength below the physical length of a preformed reentry circuit. [35][36][37] Conduction slowing and action potential shortening both shorten activation wavelength. Given little or no change in APD, a fourfold increase in conduction time as observed with propafenone in this study decreases activation wavelength fourfold (Table 4) and possibly below the perimeter of the heart, a setting that allows for macroreentry around the circumference of the whole heart in this model.…”

Discordant Alternans as a Mechanism for Initiation of Ventricular Fibrillation In Vitro

“…As described by Gelzer et al27 and outlined in Figure 1, it is hypothesized that specific sequences of premature stimulus intervals (including SLSS and similar sequences) can, through the influence of APD and CV restitution, cause enhanced spatial dispersion of repolarization, leading to spatially discordant APD alternans, conduction block, reentry, and VF. This sequence of events provides an explanation for the observation that certain patterns of premature complexes, including short‐long‐short,5 long‐short3 and short‐long,4 promote reentry, VT, and VF. In this study, we confirmed that the coupled maps model, when supplied with APD restitution data from canine right ventricles, predicted the presence of discordant alternans, in the form of beat‐to‐beat patterns of sign changes in spatial gradients of APD and DI, when compared with observations from optical mapping data.…”

“…A substantial proportion of sudden cardiac arrests, approximately half in a recent study,2 are associated with ventricular tachycardia (VT) or ventricular fibrillation (VF). It has been observed clinically that sustained VT and VF are often preceded by several irregularly timed premature complexes,3, 4 and studies conducted to explore this phenomenon have shown that specific coupling interval patterns of premature complexes, such as short‐long‐short5 and short‐short‐short,6 tend to lead to reentry and VT. Various researchers have examined the mechanism by which premature complexes or pacing history can interact with electrical restitution properties, including the dependence of action potential duration (APD) and conduction velocity (CV) on the preceding diastolic interval (DI) to produce dynamical heterogeneity of refractoriness, wave break, reentry, and VF7, 8, 9, 10, 11 (see elsewhere12, 13 for reviews).…”

Vulnerability to re-entry in simulated two-dimensional cardiac tissue: Effects of electrical restitution and stimulation sequence

“…[5][6][7] Vulnerability to re-entry is highly influenced by the tissue substrate that a trigger encounters. Heterogeneities naturally exist in the heart 8,9 and are amplified by electrical and structural remodeling in diseased hearts, [10][11][12] by nonuniform cell coupling, [13][14][15] and by inexcitable obstacles. [16][17][18] Heterogeneities can also be induced or modulated by premature extrasystoles or changes in heart rate, 8,9,[19][20][21][22][23][24][25] and thereby affect the VF threshold.…”

“…[16][17][18] Heterogeneities can also be induced or modulated by premature extrasystoles or changes in heart rate, 8,9,[19][20][21][22][23][24][25] and thereby affect the VF threshold. 26 Early experiments in animal and patients 11,[27][28][29][30][31][32] have demonstrated that both dispersion of refractoriness and inducibility of re-entry are affected by the activation sequence of the premature extrasystoles. In the clinical setting, multiple successive extrasystoles are often involved in the initiation of re-entry.…”