Abstract
BackgroundAlternans have been associated with the development of ventricular fibrillation and its control has been proposed as antiarrhythmic strategy. However, cardiac arrhythmias are a spatiotemporal phenomenon in which multiple factors are involved (e.g. calcium and voltage spatial alternans or heterogeneous conduction velocity) and how an antiarrhythmic drug modifies these factors is poorly understood.ObjectiveThe objective of the present study is to evaluate the relation between spatial electrophysiological properties (i.e. spatial discordant alternans and conduction velocity) and the induction of ventricular fibrillation (VF) when a calcium blocker is applied.MethodsThe mechanisms of initiation of VF were studied by simultaneous epicardial voltage and calcium optical mapping in isolated rabbit hearts using an incremental fast pacing protocol. The additional value of analyzing spatial phenomena in the generation of unidirectional blocks and reentries as precursors of VF was depicted. Specifically, the role of action potential duration (APD), calcium transients (CaT), spatial alternans and conduction velocity in the initiation of VF was evaluated during basal conditions and after the administration of verapamil.ResultsOur results enhance the relation between (1) calcium spatial alternans and (2) slow conduction velocities with the dynamic creation of unidirectional blocks that allowed the induction of VF. In fact, the administration of verapamil demonstrated that calcium and not voltage spatial alternans were the main responsible for VF induction.ConclusionsVF induction at high activation rates was linked with the concurrence of a low conduction velocity and high magnitude of calcium alternans, but not necessarily related with increases of APD. Verapamil can postpone the development of cardiac alternans and the apparition of ventricular arrhythmias.
Highlights
The initiation of ventricular arrhythmias is promoted by the presence of (i) dynamic factors and (ii) a heterogeneous substrate, e.g. structurally abnormal hearts or myocardial ischemia, which allows the maintenance and perpetuation of the arrhythmia [1]
The administration of verapamil demonstrated that calcium and not voltage spatial alternans were the main responsible for ventricular fibrillation (VF) induction
VF induction at high activation rates was linked with the concurrence of a low conduction velocity and high magnitude of calcium alternans, but not necessarily related with increases of action potential durations (APD)
Summary
The initiation of ventricular arrhythmias is promoted by the presence of (i) dynamic factors and (ii) a heterogeneous substrate, e.g. structurally abnormal hearts or myocardial ischemia, which allows the maintenance and perpetuation of the arrhythmia [1]. Dynamic factors are related to the ability of a region to show electrophysiological time variations between beats, associated with steep conduction velocity (CV) restitution [2,3] and instability of calcium cycling factors [4,5]. Spatial heterogeneities are due to gradients of expression levels of ion channel and transporter proteins [6] in healthy tissue [7,8], or caused by structural pathologies or ischemia [9], manifesting three-dimensional patterns of action potential durations (APD) and ionic concentration flows, as in intracellular calcium transients (CaT). Cardiac arrhythmias are a spatiotemporal phenomenon in which multiple factors are involved (e.g. calcium and voltage spatial alternans or heterogeneous conduction velocity) and how an antiarrhythmic drug modifies these factors is poorly understood. Tolkacheva, University of Minnesota, UNITED STATES Received: June 18, 2018 Accepted: April 11, 2019 Published: May 14, 2019
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