Arrhythmogenic effects of ultra-long and bistable cardiac action potentials

Author summary Cardiac fibrillation is a medical condition where normal heart function is compromised as electrical activity becomes disordered. How fibrillation arises spontaneously is not fully understood. It is generally thought to be triggered by premature depolarization of the cardiac action potential in one or more cells. Those premature beats, known as after-depolarizations, subsequently initiate a self-sustaining rotor in the otherwise normal heart tissue. In this study, we propose an alternative mechanism whereby arrhythmias are initiated by cardiac cells that fail to repolarize of their own accord but still operate normally when embedded in functional heart tissue. We find that such cells can act as focal ectopic sources under appropriate conditions of inter-cellular coupling. Moreover, those cells are more prone to initiating arrhythmia when they are located on natural tissue boundaries. This may explain why atrial fibrillation typically originates from the site where the pulmonary vein attaches to the wall of the heart. Contemporary accounts of the initiation of cardiac arrhythmias typically rely on after-depolarizations as the trigger for reentrant activity. The after-depolarizations are usually triggered by calcium entry or spontaneous release within the cells of the myocardium or the conduction system. Here we propose an alternative mechanism whereby arrhythmias are triggered autonomously by cardiac cells that fail to repolarize after a normal heartbeat. We investigated the proposal by representing the heart as an excitable medium of FitzHugh-Nagumo cells where a proportion of cells were capable of remaining depolarized indefinitely. As such, those cells exhibit bistable membrane dynamics. We found that heterogeneous media can tolerate a surprisingly large number of bistable cells and still support normal rhythmic activity. Yet there is a critical limit beyond which the medium is persistently arrhythmogenic. Numerical analysis revealed that the critical threshold for arrhythmogenesis depends on both the strength of the coupling between cells and the extent to which the abnormal cells resist repolarization. Moreover, arrhythmogenesis was found to emerge preferentially at tissue boundaries where cells naturally have fewer neighbors to influence their behavior. These findings may explain why atrial fibrillation typically originates from tissue boundaries such as the cuff of the pulmonary vein.

Automated summary

Traditionally, cardiac arrhythmias like atrial fibrillation are thought to be triggered by after-depolarizations caused by calcium entry or spontaneous release within cells. However, this study proposes an alternative mechanism where arrhythmias are autonomously triggered by cardiac cells that fail to repolarize after a normal heartbeat. These abnormal cells are more likely to cause arrhythmias when located at tissue boundaries, such as the cuff of the pulmonary vein.