Preclinical testing of drug-induced proarrhythmia: value of transgenic models.
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.
Fabritz
L
L
Department of Cardiology and Angiology, Hospital of the University of Münster, Germany. fabritzl@uni-muenster.de
Breithardt
G
G
Kirchhof
P
P
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D030801:Animals, Genetically Modified; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D004195:Disease Models, Animal; D015195:Drug Design; D006801:Humans; D051379:Mice; D015221:Potassium Channels / Q000235:genetics; D015222:Sodium Channels / Q000235:genetics
D000889:Anti-Arrhythmia Agents; D015221:Potassium Channels; D015222:Sodium Channels