In an experimental rabbit heart model of Short QT syndrome, quinidine reduced the inducibility of ventricular fibrillation by 73% (P=0.008) compared to sotalol and flecainide.
Does quinidine reduce the inducibility of ventricular fibrillation in a rabbit heart model of Short QT syndrome compared to sotalol and flecainide?
Quinidine demonstrates superior antiarrhythmic properties compared to sotalol and flecainide in an experimental model of Short QT syndrome by reducing dispersion of repolarization and prolonging postrepolarization refractoriness.
Effect estimate: 73% reduction
p-value: p=0.008
BACKGROUND: Short QT syndrome (SQTS) is a newly described ion channelopathy, characterized by a short QT interval resulting from an accelerated cardiac repolarization, associated with syncope, atrial fibrillation, and sudden cardiac death due to ventricular fibrillation. As therapeutic options in SQTS are still controversial, we examined antiarrhythmic mechanisms in an experimental model of SQTS. METHODS AND RESULTS: Pinacidil, an I(K-ATP) channel opener, was administered in increasing concentrations (50-100 microM) in 48 Langendorff-perfused rabbit hearts and led to a significant reduction of action potential duration and QT interval, thereby mimicking SQTS. Eight simultaneously recorded monophasic action potentials demonstrated an increase in dispersion of repolarization, especially between the left and the right ventricle. During programmed ventricular stimulation with up to two extrastimuli, pinacidil significantly increased the inducibility of ventricular fibrillation (1 heart under baseline conditions, 29 hearts during pinacidil administration; P = 0.0001). Additional treatment with the I(Kr) blocker sotalol (100 microM) and the class I antiarrhythmic drugs flecainide (2 microM) and quinidine (0.5 microM) randomly assigned to three groups of 16 hearts led to prolongation of repolarization as well as refractory period. Sotalol or flecainide did not reduce the rate of inducibility of ventricular fibrillation significantly (P = 0.63; P = 0.219). However, quinidine reduced the inducibility of ventricular fibrillation by 73% (P = 0.008). The antiarrhythmic potential of quinidine was associated with a significantly greater prolongation of MAP duration, refractoriness, and postrepolarization refractoriness (PRR) as compared with sotalol and flecainide. Moreover, quinidine, in contrast to sotalol and flecainide, reduced dispersion of repolarization. CONCLUSION: Pinacidil mimics SQTS via increasing potassium outward currents, thereby facilitating inducibility of ventricular fibrillation. Quinidine demonstrates superior antiarrhythmic properties in the treatment of ventricular fibrillation in this model as compared with sotalol and flecainide because of its effects on refractoriness, PRR, and by reducing dispersion of repolarization.
Milberg et al. (Tue,) conducted a other in Short QT syndrome (experimental model) (n=48). Quinidine vs. Sotalol and flecainide was evaluated on Inducibility of ventricular fibrillation (73% reduction, p=0.008). In an experimental rabbit heart model of Short QT syndrome, quinidine reduced the inducibility of ventricular fibrillation by 73% (P=0.008) compared to sotalol and flecainide.