Short-term variability in QT interval and ventricular arrhythmias induced by dofetilide are dependent on high-frequency autonomic oscillations.

ABSTRACT:

Background and purpose

The present study was undertaken to investigate an effect of dofetilide, a potent arrhythmic blocker of the voltage-gated K(+) channel, hERG, on cardiac autonomic control. Combined with effects on ardiomyocytes, these properties could influence its arrhythmic potency.

Experimental approach

The short-term variability of beat-to-beat QT interval (STVQT ), induced by dofetilide is a strong surrogate of Torsades de pointes liability. Involvement of autonomic modulation in STVQT was investigated in healthy cynomolgus monkeys and beagle dogs by power spectral analysis under conditions of autonomic blockade with hexamethonium.

Key results

Increase in STVQT induced by dofetilide in monkeys and dogs was closely associated with an enhancement of endogenou

SUBMITTER: Champeroux P 

PROVIDER: S-EPMC4439882 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature