Effect of Na+-channel blockade on the three-dimensional substrate of atrial fibrillation in a model of endo-epicardial dissociation and transmural conduction.

Aims: Atrial fibrillation (AF) is a progressive arrhythmia characterized by structural alterations that increase its stability. Both clinical and experimental studies showed a concomitant loss of antiarrhythmic drug efficacy in later stages of AF. The mechanisms underlying this loss of efficacy are not well understood.

How disruption of endo-epicardial electrical connections enhances endo-epicardial conduction during atrial fibrillation.

Aims: Loss of side-to-side electrical connections between atrial muscle bundles is thought to underlie conduction disturbances predisposing to atrial fibrillation (AF). Putatively, disruption of electrical connections occurs not only within the epicardial layer but also between the epicardial layer and the endocardial bundle network, thus impeding transmural conductions (‘breakthroughs’). However, both clinical and experimental studies have shown an enhancement of breakthroughs during later stages of AF.

P-wave complexity in normal subjects and computer models.

Background: P waves reported in electrocardiology literature uniformly appear smooth. Computer simulation and signal analysis studies have shown much more complex shapes.

Objective: We systematically investigated P-wave complexity in normal volunteers using high-fidelity electrocardiographic techniques without filtering.

Dynamic regulation of atrial coronary blood flow in healthy adult pigs.

Background: There are several indications for a mismatch between atrial oxygen supply and demand during atrial fibrillation (AF), but atrial coronary flow regulation has not been investigated extensively.

Objective: The purpose of this study was to characterize the dynamic regulation of atrial coronary flow in pigs.

Methods: In anesthetized open-chest pigs, Doppler flow probes were placed around left atrial (LA) and left ventricular (LV) branches of the circumflex artery.

Mechano-electrical coupling as framework for understanding functional remodeling during LBBB and CRT.

It is not understood why, after onset of left bundle-branch block (LBBB), acute worsening of cardiac function is followed by a further gradual deterioration of function, whereas most adverse cardiac events lead to compensatory adaptations. We investigated whether mechano-electrical coupling (MEC) can explain long-term remodeling with LBBB and cardiac resynchronization therapy (CRT). To this purpose, we used an integrative modeling approach relating local ventricular electrophysiology, calcium handling, and excitation-contraction coupling to global cardiovascular mechanics and hemodynamics.

Loss of continuity in the thin epicardial layer because of endomysial fibrosis increases the complexity of atrial fibrillatory conduction.

Background: The transition from persistent to permanent atrial fibrillation (AF) is associated with increased complexity of fibrillatory conduction. We have investigated the spatial distribution of fibrillation waves and structural alterations in the atrial free walls in a goat model of AF.

Methods And Results: AF was maintained for 3 weeks (short term [ST], persistent AF) or 6 months (long term [LT], permanent AF).

A computer model of endo-epicardial electrical dissociation and transmural conduction during atrial fibrillation.

Aims: Structural alterations during atrial fibrillation (AF) not only lead to electrical dissociation within the epicardial layer, but also between the epicardial layer and the endocardial bundle network. The aim of the study was to investigate the role of transmural conduction in the stability of AF episodes using a dual-layer computer model.

Methods And Results: A proof-of-principle dual-layer model was developed in which connections between the layers can be introduced or removed at any time during the simulation.

Mechano-electrical feedback explains T-wave morphology and optimizes cardiac pump function: insight from a multi-scale model.

In the ECG, T- and R-wave are concordant during normal sinus rhythm (SR), but discordant after a period of ventricular pacing (VP). Experiments showed that the latter phenomenon, called T-wave memory, is mediated by a mechanical stimulus. By means of a mathematical model, we investigated the hypothesis that slow acting mechano-electrical feedback (MEF) explains T-wave memory.

Atrial septostomy benefits severe pulmonary hypertension patients by increase of left ventricular preload reserve.

At present, it is unknown why patients suffering from severe pulmonary hypertension (PH) benefit from atrial septostomy (AS). Suggested mechanisms include enhanced filling of the left ventricle, reduction of right ventricular preload, increased oxygen availability in the peripheral tissue, or a combination. A multiscale computational model of the cardiovascular system was used to assess the effects of AS in PH.

Modeling cardiac electromechanics and mechanoelectrical coupling in dyssynchronous and failing hearts: insight from adaptive computer models.

Computer models have become more and more a research tool to obtain mechanistic insight in the effects of dyssynchrony and heart failure. Increasing computational power in combination with increasing amounts of experimental and clinical data enables the development of mathematical models that describe electrical and mechanical behavior of the heart. By combining models based on data at the molecular and cellular level with models that describe organ function, so-called multi-scale models are created that describe heart function at different length and time scales.

Mechanoelectrical coupling enhances initiation and affects perpetuation of atrial fibrillation during acute atrial dilation.

Background: Acute atrial dilation increases the susceptibility to atrial fibrillation (AF). However, the mechanisms by which atrial stretch may contribute to the initiation and perpetuation of AF remain to be determined.

Objective: The purpose of this study was to use a novel multiscale model of atrial electromechanics and mechanoelectrical feedback to test the hypothesis that acute stretch increases vulnerability to AF by heterogeneous activation of stretch-activated channels.

Mechanoelectric feedback as a trigger mechanism for cardiac electrical remodeling: a model study.

Regional variation in ionic membrane currents causes differences in action potential duration (APD) and is proarrhythmic. After several weeks of ventricular pacing, AP morphology and duration are changed due to electrical remodeling of the transient outward potassium current (I (to)) and the L-type calcium current (I (Ca,L)). It is not clear what mechanism drives electrical remodeling.

Mechanoelectric feedback leads to conduction slowing and block in acutely dilated atria: a modeling study of cardiac electromechanics.

Atrial fibrillation, a common cardiac arrhythmia, is promoted by atrial dilatation. Acute atrial dilatation may play a role in atrial arrhythmogenesis through mechanoelectric feedback. In experimental studies, conduction slowing and block have been observed in acutely dilated atria.

The role of the hyperpolarization-activated inward current If in arrhythmogenesis: a computer model study.

Atrial fibrillation is the most common cardiac arrhythmia. Structural cardiac defects such as fibrosis and gap junction remodeling lead to a reduced cellular electrical coupling and are known to promote atrial fibrillation. It has been observed that the expression of the hyperpolarization-activated current If is increased under pathological conditions.