Transgenic LQT2, LQT5, and LQT2-5 rabbit models with decreased repolarisation reserve for prediction of drug-induced ventricular arrhythmias.

ABSTRACT:

Background and purpose

Reliable prediction of pro-arrhythmic side effects of novel drug candidates is still a major challenge. Although drug-induced pro-arrhythmia occurs primarily in patients with pre-existing repolarisation disturbances, healthy animals are employed for pro-arrhythmia testing. To improve current safety screening, transgenic long QT (LQTS) rabbit models with impaired repolarisation reserve were generated by overexpressing loss-of-function mutations of human HERG (HERG-G628S, loss of I_Kr ; LQT2), KCNE1 (KCNE1-G52R, decreased I_Ks ; LQT5), or both transgenes (LQT2-5) in the heart.

Experimental approach

Effects of K⁺ channel blockers on cardiac repolarisation and arrhythmia susceptibility were assessed in healthy wild-type (WT)

SUBMITTER: Hornyik T 

PROVIDER: S-EPMC7393202 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature