Book of Abstracts - New Frontiers 2022

Abstracts of oral presentations

NEW TRANSGENIC RABBIT MODELS TO PREDICT DRUG-INDUCED ARRHYTHMIAS

I. Baczko

Department of Pharmacology and Pharmacotherapy, Albert Szent- Györgyi Medical School, University of Szeged, Hungary

Drug-induced proarrhythmia represents a potentially lethal adverse effect. This proarrhythmic side effect is often linked to the drug's potential to modulate repolarizing cardiac ion currents thereby causing a lengthening of the QT interval on the ECG. In spite of the sophisticated screening approaches in preclinical and clinical drug development, reliable prediction of proarrhythmia remains a largely unmet need. Drug induced proarr hythmic events are often facilitated by pathological conditions that impair the patient’s repolarization reserve, however, most cellular, tissue, and whole animal model systems used for current preclinical drug safety screening are based on normal, healthy tissues and animals. Several transgenic rabbit models for different types of long QT syndromes (LQTS) cauding impairments in repolarization reserve have been generated recently. The potential use of these models for screening/prediction of drug induced arrhythmia is discussed. Also, the electrophysiological characteristics of the available transgenic LQTS rabbit models are summarized along with proof-of-principle studies in these models – identifying certain advantages and disadvantages of rabbit LQTS models.

Keywords: proarrhythmia, repolarization reserve, long QT syndrome, transgenic rabbit

Funding:Supported by NKFIH-K128851.

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