The Impact of Mechano-Electric Feedback on Drug- and Stretch- Induced Arrhythmia Using a Computational Model of Cardiac Electromechanics

Mechano-electric feedback (MEF) is thought to be an important factor in the increased arrhythmic risk observed clinically in heart failure and chronic infarct patients. Here, we utilize pathologic stretch as a parameter for investigating the sensitivity of cardiac electrophysiology and mechanics to MEF. To simulate the effects of stretch, we incorporated stretch-activated ion channels (SACs) into a coupled electro-mechanics model based on the well-established O’Hara-Rudy (ORd) (electrophysiology) Land (mechanics) models. We investigated the effect different degrees of stretch had upon electrophysiological parameters such as the action potential duration and calcium transient, as well as functional parameters like force production. We further determined the sensitivity of cardiac cells under stretch to various pro- and anti-arrhythmic drugs to better inform on drug risk classifications and indications. Our results indicate that pathologic stretch may exert a severe pro-arrhythmic effect on cardiac cells, which markedly exacerbates the risk profile of pro-arrhythmic drugs, but one which was mitigated through the action of anti-arrhythmic compounds.