A novel adult human ventricle slice preparation for cardiac drug discovery and safety pharmacology

Abstract

The editorial refers to ‘Organotypic slice culture from human adult ventricular myocardium’ by M. Brandenburger et al ., doi:10.1093/cvr/cvr259. Cardiac drug discovery and cardiac safety pharmacology assessment both require new models/methods to advance strategy.1–6 Ventricular arrhythmias are no longer a major focus for therapeutic drug discovery, and to become so again, a range of new preclinical models and a novel experimental strategy will be required for detecting desirable effects on cardiac electrophysiology and rhythm.2,3 In the field of cardiac safety pharmacology, new chemical entities that possess the desired target specificity are entered into high throughput screens (HTS) for safety pharmacology frontloading, including assessment of torsades de pointes liability.4–6 An integrated safety assessment strategy has appeared during the past 10 years, and optimization of the deployment of the numerous available constituent methods continues to evolve.4 Part of this involves the search for more inexpensive, more predictive medium-throughput screens that fit somewhere between the crude HTS methods, and the expensive and technically demanding late-stage safety screens.4–6 In cardiac safety and discovery, the headline goals are the same: to determine what a drug does to cardiac ion channels and how this manifests as an integrated outcome (i.e. effect on action potential configuration, conduction and refractoriness, rhythm and function).1–6 The human ventricular slice preparation described by Brandenburger et al .7 may have a role both in antiarrhythmic drug discovery and in safety assessment going forward. Its potential value arises from several of its aspects. First, it is a human tissue preparation. In research, we justify the use of animals on the basis of the utility of the readout vs. ethical considerations. Readout utility, in drug discovery and safety assessment, …