RESUMEN
BACKGROUND: Bidirectional ventricular tachycardia (BVT) is a rare type of ventricular tachycardia that is characterized by a beat-to-beat alternation in the QRS axis. Previous studies have shown that it is caused by alternating focal activities from 2 locations. OBJECTIVE: This study proposes a novel mechanism for the formation of spatially discordant alternans (SDA) due to the periodic pacing site alternation that occurs in BVT. METHODS: We used mathematical models of cardiac tissue to understand the dynamic and physiologic mechanisms underlying SDA formation. RESULTS: We found that SDA was formed by periodic pacing site alternation. When tissue was paced from 2 locations alternately, the timing of pacing at distant locations varied, creating a long-short-long-short sequence of pacing periods and thus action potential durations. Importantly, the nodal lines were perpendicular to the wavefront, which is more arrhythmogenic than when nodal lines are parallel to the wavefront. A positive correlation was observed between the separation distance of the 2 sites and the alternans amplitude. SDA patterns can be predicted from the tissue geometry and pacing site locations. CONCLUSION: Periodic pacing site alternation, which occurs in BVT, leads to arrhythmogenic SDA. The nodal lines associated with this phenomenon can be predicted on the basis of tissue geometry and focal locations.
RESUMEN
T-wave alternans (TWA) has been used for predicting the risk of malignant cardiac arrhythmias and sudden cardiac death (SCD) in multiple clinical settings; however, possible mechanism(s) underlying the spontaneous transition from cellular alternans reflected by TWA to arrhythmias in impaired repolarization remains unclear. The healthy guinea pig ventricular myocytes under E-4031 blocking IKr (0.1 µM, N = 12; 0.3 µM, N = 10; 1 µM, N = 10) were evaluated using whole-cell patch-clamp. The electrophysiological properties of isolated perfused guinea pig hearts under E-4031 (0.1 µM, N = 5; 0.3 µM, N = 5; 1 µM, N = 5) were evaluated using dual- optical mapping. The amplitude/threshold/restitution curves of action potential duration (APD) alternans and potential mechanism(s) underlying the spontaneous transition of cellular alternans to ventricular fibrillation (VF) were examined. There were longer APD80 and increased amplitude and threshold of APD alternans in E-4031 group compared with baseline group, which was reflected by more pronounced arrhythmogenesis at the tissue level, and were associated with steep restitution curves of the APD and the conduction velocity (CV). Conduction of AP alternans augmented tissue's functional spatiotemporal heterogeneity of regional AP/Ca alternans, as well as the AP/Ca dispersion, leading to localized uni-directional conduction block that spontaneous facilitated the formation of reentrant excitation waves without the need for additional premature stimulus. Our results provide a possible mechanism for the spontaneous transition from cardiac electrical alternans in cellular action potentials and intercellular conduction without the involvement of premature excitations, and explain the increased susceptibility to ventricular arrhythmias in impaired repolarization. In this study, we implemented voltage-clamp and dual-optical mapping approaches to investigate the underlying mechanism(s) for the arrhythmogenesis of cardiac alternans in the guinea pig heart at cellular and tissue levels. Our results demonstrated a spontaneous development of reentry from cellular alternans, arising from a combined actions of restitution properties of action potential duration, conduction velocity of excitation wave and interplay between alternants of action potential and the intracellular Ca handling. We believe this study provides new insights into underlying the mechanism, by which cellular cardiac alternans spontaneously evolves into cardiac arrhythmias.
Asunto(s)
Nacimiento Prematuro , Fibrilación Ventricular , Animales , Cobayas , Femenino , Humanos , Arritmias Cardíacas , Miocitos Cardíacos , Muerte Súbita Cardíaca , Potenciales de AcciónRESUMEN
In this paper we review two types of dynamic behaviors defined by the bifurcation theory that are found to be particularly useful in describing two forms of cardiac electrical instabilities that are of considerable importance in cardiac arrhythmogenesis. The first is action potential duration (APD) alternans with an underlying dynamics consistent with the period doubling bifurcation theory. This form of electrical instability could lead to spatially discordant APD alternans leading to wavebreak and reentrant form of tachyarrhythmias. Factors that modulate the APD alternans are discussed. The second form of bifurcation of importance to cardiac arrhythmogenesis is the Hopf-homoclinic bifurcation that adequately describes the dynamics of the onset of early afterdepolarization (EAD)-mediated triggered activity (Hopf) that may cause ventricular tachycardia and ventricular fibrillation (VT/VF respectively). The self-termination of the triggered activity is compatible with the homoclinic bifurcation. Ionic and intracellular calcium dynamics underlying these dynamics are discussed using available experimental and simulation data. The dynamic analysis provides novel insights into the mechanisms of VT/VF, a major cause of sudden cardiac death in the US.