Nonstandard abbreviations used: action potential duration (APD); diastolic interval (DI); left ventricle (LV); Luo-Rudy phase 1 (LR1); right ventricle (RV); two-dimensional (2D); ventricular fibrillation (VF).
Conflict of interest:The authors have declared that no conflict of interest exists.
IntroductionIn the normal heart, the wave of electrical activation that triggers synchronized contraction moves in a roughly planar fashion through the ventricular myocardium. In ventricular fibrillation (VF), the most common cause of death from cardiovascular disease, this electrical wave breaks up into multiple wavelets that meander chaotically through the myocardium (1-7), precluding the coordinated contraction that is necessary to maintain blood pressure. This "electrical turbulence" is initiated and maintained by the process of wavebreak, in which new waves are continually generated to replace those that are extinguished because of encounters with each other or with refractory tissue. Traditionally, many cardiac researchers believed that wavebreak was due to external obstacles and focused on the role of anatomical and/or electrophysiological heterogeneities and obstacles, such as built-in gradients of electrophysiological properties, or the presence of infarction, ischemia, and/or fibrosis as the primary causes of wavebreak. However, dynamicists discovered that purely dynamical instabilities, arising from cellular properties such as ion channel dynamics, can also cause wavebreak even in perfectly homogeneous tissue.What drives fibrillation: fixed heterogeneities, dynamical instabilities, or a synergistic interaction between the two? The answer is controversial, because both factors are inevitably present in real cardiac tissue. Indeed, even in normal cardiac tissue without significant fibrosis, infarction, or ischemia, VF can be induced by a sufficiently large electrical stimulus, and it is still unclear what factors cause wavebreak. For example, one important aspect of the gross anatomy of the heart is the shape of the ventricular cavities, the interventricular septum, and the overall geometry of the lower heart (8). Another critical aspect of cardiac gross anatomy is the anisotropy of electrical conduction, which is created by the twisted distribution of cardiac fibers through the myocardial wall (9). This "fiber twist" can play a role in creating wavebreak, as has been shown in models of 3D rectangular slabs of tissue (10, 11). In addition to these fixed factors, one of the key dynamical factors that cause wavebreak is electrical restitution. After an action potential, the cardiac cell must recover ionic balance and replenish calcium stores in the sarcoplasmic reticulum. Ion channels (Na + , K + , or Ca ++ ), having been inactivated or deactivated, must recover to their resting state. These restorative processes take place during the electrical diastolic interval (DI), the interval between repolarization and the next action potential upstroke. Physiologically, it is important for the action potential duration (APD)...