Preclinical Testing of Drug-Induced Proarrhythmia: Value of Transgenic Models

L.      Fabritz; G.      Breithardt; P.      Kirchhof

Abstract

Drug-induced proarrhythmia is a serious medical problem that causes relevant morbidity and mortality. It is also a relevant problem for the development of novel pharmacological compounds. Therefore, there is a need for sensitive, specific and high-throughput preclinical tests to detect a risk for drug-induced proarrhythmia early in the development of new drugs. The review focuses on the potential role of transgenic models with altered repolarisation but without overt structural heart disease for drug-induced proarrhythmia screening. Today, selected murine models with alterations in K+, Na+ channels and ankyrin are available. In the future, transgenic rabbit and Zebra fish models may also be used.

Keywords: Drug-induced proarrhythmia, repolarisation, long QT syndrome, action potential prolongation, torsades de pointes, transgenic model, experimental model, ion channels