Electromechanical wavebreak in a model of the human left ventricle

Abstract

Keldermann RH, Nash MP, Gelderblom H, Wang VY, Panfilov AV. Electromechanical wavebreak in a model of the human left ventricle. Am J Physiol Heart Circ Physiol 299: H134 -H143, 2010. First published April 16, 2010; doi:10.1152/ajpheart.00862.2009In the present report, we introduce an integrative three-dimensional electromechanical model of the left ventricle of the human heart. Electrical activity is represented by the ionic TP06 model for human cardiac cells, and mechanical activity is represented by the NiedererHunter-Smith active contractile tension model and the exponential Guccione passive elasticity model. These models were embedded into an anatomic model of the left ventricle that contains a detailed description of cardiac geometry and the fiber orientation field. We demonstrated that fiber shortening and wall thickening during normal excitation were qualitatively similar to experimental recordings. We used this model to study the effect of mechanoelectrical feedback via stretch-activated channels on the stability of reentrant wave excitation. We found that mechanoelectrical feedback can induce the deterioration of an otherwise stable spiral wave into turbulent wave patterns similar to that of ventricular fibrillation. We identified the mechanisms of this transition and studied the three-dimensional organization of this mechanically induced ventricular fibrillation. ventricular fibrillation; computer simulations; mechanics; electrophysiology; mechanoelectrical feedback; stretch-activated channels MECHANICAL ACTIVITY of the heart is initiated by electrical waves of excitation that propagate through the heart and initiate cardiac contraction. Abnormal excitation of the heart may result in cardiac arrhythmias and the loss of mechanical pump function, leading to sudden cardiac death. Sudden cardiac death caused by cardiac arrhythmias is the most common cause of death in the industrialized world, and, in most cases, this is due to ventricular fibrillation (VF) (73). It has been shown in clinical and experimental studies (11,17,26,41,46,62,68,70) that VF occurs as a result of the onset of turbulent electrical activation patterns of the heart that are underpinned by multiple reentrant sources of excitation. Mechanisms behind the onset of reentrant sources in the heart and processes resulting in breakup of these sources into complex turbulent activation patterns are of great interest, e.g., in the design of therapeutic strategies to prevent or treat cardiac arrhythmias.One of the important factors that affects electrical excitation of the heart is mechanoelectrical feedback. It has been shown that mechanical deformation alters the electrical properties of myocytes via stretch-activated channels (59), which can change the shape of the action potential in response to stretch (34, 37). Mechanoelectric feedback has been studied in the clinical community for well over a century (for reviews, see Refs. 34,37,38) and may have both proarrhythmic and antiarrhythmic consequences. However, the mechanisms underlying these ph...

Discrete Mechanical Modeling of Mechanoelectrical Feedback in Cardiac Tissue: Novel Mechanisms of Spiral Wave Initiation

“…2.8 III, 32 t.u., 42 t.u., 48 t.u.). Note that this mechanism was first shown in [49] where break occurs to a spiral wave, and also in whole heart whole heart models in [26,28].…”

“…Although this approach can be used as an approximation, and is commonly applied in modeling studies on MEF from generic two-dimensional models to sophisticated whole heart models [28,40,71] it is not formally thermodynamically correct. In a more realistic model, contraction development should be set as an irreversible thermodynamic process.…”

“…They showed that MEF via Isac causes new phenomena, mechanically caused pacemaking activity in a tissue that without deformation is non-oscillatory [48], spiral drift and breakup [49]. From that point on many electromechanical models were created on various levels of complexity, where the most sophisticated account for the heart's anatomy and its complex excitation-contraction coupling [26,28]. For a review on electromechanical models of the heart from single cell to whole organ level see [64].…”

Cardiac Arrhythmias: Mechanistic Knowledge and Innovation from Computer Models

“…Early whole-heart modeling attempts to address the role of SACs in the initiation and termination of arrhythmia by a mechanical impact to the chest used pseudoelectromechanical models, in which mechanical activity was not represented but its effect on ventricular electrophysiology was, through SAC recruitment [74,75]. True electromechanical models of the ventricles have been recently developed [60,67], aimed at investigating the effect of mechanoelectric coupling via SACs on ventricular reentrant wave stability. The study by Hu [60] used an MRI-based electromechanical model of the human ventricles to test the hypothesis that SAC recruitment affects scroll wave stability differently depending on SAC reversal potential and conductance.…”

Stochastic dynamics of phase singularities under ventricular fibrillation in 2D Beeler-Reuter model

“…6 In addition, the initiation of VF in more realistic situations is now commonly investigated. 7 On the other hand, the nature of VF in the steady-state has not yet been elucidated quantitatively.…”