Cardiac slices as a predictive tool for arrhythmogenic potential of drugs and chemicals

Abstract

Importance of the field: Cardiac arrhythmia represents one of the primary safety pharmacological concerns in drug development. The most prominent example is drug induced ventricular tachycardia of the Torsade des Pointes type. The mechanism how this type of arrhythmia develops is a complex multi-cellular phenomenon. It can only be insufficiently reflected by cellular or molecular assays. However, organ models – such as Langendorff hearts – or in vivo experiments are expensive and time consuming and not suitable for assays requiring an increased throughput.Areas covered in this review: Here, we describe and review an assay bridging the gap between cardiomyocyte based assays and organ based systems – cardiac slices. This assay is reviewed in direct comparison with established safety pharmacological assays.What the reader will gain: While slices have played an important role in brain research for > 2 decades, cardiac slices are experiencing a renaissance due to the novel challenges in safety pharmacology just in the last few years. Cardiac slices can be cultured and recorded over several days. It is possible to access electrophysiological data with a high number of electrodes – up to 256 electrodes – embedded in the surface of a microelectrode array.Take home message: Cardiac slices close the gap between cellular and organ based assays in cardiac safety pharmacology. The tissue properties of a functional cardiac syncytium are more accurately reflected by a slice rather than a single cell.