Early afterdepolarizations and cardiac arrhythmias.
Early afterdepolarizations (EADs) are an important cause of lethal ventricular arrhythmias in long QT syndromes and heart failure, but the mechanisms by which EADs at the cellular scale cause arrhythmias such as polymorphic ventricular tachycardia (PVT) and torsades de pointes (TdP) at the tissue scale are not well understood. Here we summarize recent progress in this area, discussing (1) the ionic basis of EADs, (2) evidence that deterministic chaos underlies the irregular behavior of EADs, (3) mechanisms by which chaotic EADs synchronize in large numbers of coupled cells in tissue to overcome source-sink mismatches, (4) how this synchronization process allows EADs to initiate triggers and generate mixed focal reentrant ventricular arrhythmias underlying PVT and TdP, and (5) therapeutic implications.
Weiss
James N
JN
UCLA Cardiovascular Research Laboratory, Departments of Medicine (Cardiology), Physiology and Integrative Biology and Physiology, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA. jweiss@mednet.ucla.edu
Garfinkel
Alan
A
Karagueuzian
Hrayr S
HS
Chen
Peng-Sheng
PS
Qu
Zhilin
Z
D000200:Action Potentials / Q000502:physiology; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D006329:Heart Conduction System / Q000503:physiopathology; D006801:Humans; D032383:Myocytes, Cardiac / Q000502:physiology; D017711:Nonlinear Dynamics; D017180:Tachycardia, Ventricular / Q000503:physiopathology; D016171:Torsades de Pointes / Q000503:physiopathology; D014693:Ventricular Fibrillation / Q000503:physiopathology; D018879:Ventricular Premature Complexes / Q000503:physiopathology*