A novel model of Quinidine induced torsade de pointes arrhythmias in the isolated rabbit heart /

Abstract

Accumulating evidence suggest the underlying danger of Class IA and Class III antiarrhythmic agents in inducing potentially lethal torsade de pointes arrhythmias (TdP) if associated with hypokalemia and slow heart rates. The primary aim of the following study was to examine the proarrhythmic activity of the Class IA agent quinidine in isolated perfused rabbit hearts in an effort towards developing a reliable model of TdP.Thirty five rabbit hearts were perfused with therapeutic quinidine concentrations (2.5 or 5$mu$M) in the presence of hypokalemia (K$sp+$ - 2.7mM) and stimulated at cycle lengths (CLs) ranging from 0.5s-5.5s. Monophasic action potentials (MAPs) were recorded from left endocardial and right epicardial sites along with an ECG.We suggest that the described model of acquired TdP in isolated rabbit hearts can be adapted for the quantitative and qualitative assessment of the proarrhythmic potential of existing and novel antiarrhythmic agents, to test the efficacy of novel therapeutic strategies for the acquired long QT syndrome and/or to clarify the specific mechanism(s) of drug induced TdP. (Abstract shortened by UMI.