Ranolazine and Vernakalant Prevent Ventricular Arrhythmias in an Experimental Whole‐Heart Model of Short QT Syndrome

Abstract

In the present pharmacologic model of short QT syndrome treatment with pinacidil led to an increased inducibility of VF in association with a reduction in ERP. Additional treatment with ranolazine or vernakalant reversed this effect and demonstrated potent antiarrhythmic properties based on an increase of ERP.

Modeling Short QT Syndrome Using Human‐Induced Pluripotent Stem Cell–Derived Cardiomyocytes

“…Therefore, an optimal experimental model for SQTS will be useful for studying this rare disease. Recently, an animal model of drug‐induced SQTS has been established to test candidate antiarrhythmic agents that may be effective for treatment of SQTS patients . Because of the differences between animals and humans, animal models are not ideal for drug testing.…”

Considering Ranolazine as a Potential Treatment for K+ Channel Linked Short QT Syndrome

“…We thank Dr. Hancox for his inspiring letter . In the present study, short QT syndrome (SQTS) was simulated by treatment with the K‐ATP channel activator pinacidil leading to an abbreviation of action potential duration, QT‐interval, and effective refractory period . These effects were reversed by treatment with either ranolazine (10 μM) or vernakalant (10 μM).…”

Considering Ranolazine as a Potential Treatment for K+ Channel Linked Short QT Syndrome

“…I read with interest the recent report in the Journal by Frommeyer et al . that showed beneficial actions of ranolazine and vernakalant in an experimental model of short QT syndrome (SQTS) .…”

“…I read with interest the recent report in the Journal by Frommeyer et al . that showed beneficial actions of ranolazine and vernakalant in an experimental model of short QT syndrome (SQTS) . The authors used measurements from Langendorff‐perfused rabbit hearts at baseline and following treatment with the K‐ATP channel activator pinacidil (1 μM).…”

“…Pinacidil abbreviated the duration of ventricular monophasic action potentials (APs) and the QT interval, accompanied by shortening of the effective refractory period (ERP). Application of 10 μM of ranolazine or vernakalant in the maintained presence of pinacidil lengthened AP duration, QT interval, and ERP toward control values . Moreover, while pinacidil increased inducibility of ventricular fibrillation (VF), application of ranolazine or vernakalant reduced this .…”