Key result
Simulated amiodarone administration in human ventricular models provided new insights into its pharmacokinetics and effects on cardiac excitation for treating KCNJ2-linked short QT syndrome.
Why the study?
Does amiodarone improve cardiac excitation parameters in computational models of KCNJ2-linked short QT syndrome?
Does amiodarone improve cardiac excitation parameters in computational models of KCNJ2-linked short QT syndrome?
Computational modeling provides new insights into the potential efficacy and pharmacokinetics of amiodarone for treating KCNJ2-linked short QT syndrome.
May guide amiodarone use in modeled KCNJ2-short QT syndrome; leaves open clinical translation.
Short QT syndrome (SQTS) is associated with ventricular arrhythmias that may lead to cardiac sudden death. However, effective pharmacological treatment for SQTS remains unclear. Amiodarone has emerged as the leading antiarrhythmic therapy for termination and prevention of ventricular arrhythmia in different clinical settings because of its proven efficacy and safety. The aim of this study was to investigate the effects of amiodarone on cardiac excitation of the KCNJ2-linked short QT syndrome. Effects of Kir2.1 D172N mutation-induced changes in IK1 were incorporated into human ventricular cell and tissue models that considered the intrinsic electrical heterogeneity in the left ventricle. Actions of amiodarone were simulated by implementing a simple block pore theory to simulate the drug's effects on ICaL and IKr block for several doses. In cellular simulations, current traces of IKr and ICaL and action potential duration of ENDO, M, and EPI cells were simulated in control, mutant, and amiodarone-in-action conditions. In tissue simulations, the pharmacological effects of amiodarone on the characteristics of ECG were examined. This study provides new insights into the pharmacokinetics of amiodarone for treatment of SQT3 under WT-D172N and D172N conditions.
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Luo et al. (2015) studied KCNJ2-linked short QT syndrome (SQT3). Amiodarone vs. Control and mutant conditions without amiodarone was evaluated on Effects on cardiac excitation (current traces of IKr and ICaL, action potential duration, and ECG characteristics). Simulated amiodarone administration in human ventricular models provided new insights into its pharmacokinetics and effects on cardiac excitation for treating KCNJ2-linked short QT syndrome.
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