Cell-cell interactions and the role of tissue microarchitecture in cardiac arrhythmias after myocardial infarction

Sudden cardiac death (SCD) is one of the leading causes of death among people who have suffered an acute myocardial infarction (MI), and is the cause of about half of all deaths from cardiovascular diseases. Most SCDs result from ventricular tachyarrhythmias - ventricular tachycardia(VT) and ventricular fibrillation (VF) and, less frequently, bradyarrhythmias. Therefore, identifying and treating areas vulnerable to arrhythmias have clinical relevance for reducing post-MI SCD mortality. Such treatment usually consists of ablation (destruction) of sites that are thought to be the origin of VT. However, the mechanisms responsible for arrhythmia induction remain elusive, related to the complexity of the substrate. Various experimental models have been developed to study the heart muscle’s electrophysiological properties. The whole heart preparations, isolated cells and computational modelling are typically used to study arrhythmogenic events. However, these methods do not allow mechanistic study of the complexity of cardiac tissue. Living myocardial slices (LMS) could help bridge the gap between these conventional models and in vivo studies. LMS is a novel cardiac model with preserved structural and functional properties that can be maintained in vitro for the long term. Ultrathin (100-400 μm) structure allows diffusion of oxygen and other metabolic substrates into all layers of cells within the slice.