Annu Int Conf IEEE Eng Med Biol Soc. 2017 Jul;2017:4273-4276. doi: 10.1109/EMBC.2017.8037800.
The short QT syndrome (SQTS) is a new genetic disorder associated with atrial and ventricular arrhythmias and sudden death. The SQT2, SQTS variant, results from a gain-of-function mutation (V307L) in the KCNQ1-encoded potassium channel. Although pro-arrhythmogenic effects of SQTS have been characterized, less is known about the pharmacology of SQTS. Therefore, this study aims to assess the effects of amiodarone on SQT2.
The ten Tusscher et al. model of the human ventricular action potential (AP) was modified to incorporate changes to I based on experimental data. Cell models were incorporated into heterogeneous one-dimensional (1D) tissue to compute the pseudo-ECG and the corresponding QT interval. The blocking effects of amiodarone on I, I, I, I, I, and I were modeled using n (Hill coefficient) and IC values from the literature. At the cellular level, amiodarone both at low and high doses prolonged the SQT2 AP duration (APD); at the tissue level, amiodarone at a high dose caused QT prolongation to the physiological range, but failed at a low dose.
Amiodarone at a high dose produced better therapeutic effects on SQT2 than at a low dose. This study provides new evidence that amiodarone at a high dose may be a potential pharmacological treatment for SQT2.
短QT综合征（SQTS）是一种与房性和室性心律失常及猝死相关的新型遗传性疾病。SQT2型SQTS变体是由KCNQ1编码的钾通道功能获得性突变（V307L）所致。尽管已经对SQTS的促心律失常作用进行了表征，但对SQTS的药理学了解较少。因此，本研究旨在评估胺碘酮对SQT2的影响。
根据实验数据，对ten Tusscher等人的人类心室动作电位（AP）模型进行修改，以纳入对I的改变。将细胞模型纳入异质性一维（1D）组织中，以计算伪心电图和相应的QT间期。使用文献中的n（希尔系数）和IC值对胺碘酮对I、I、I、I、I和I的阻断作用进行建模。在细胞水平，低剂量和高剂量的胺碘酮均延长了SQT2动作电位时程（APD）；在组织水平，高剂量的胺碘酮使QT延长至生理范围，但低剂量时则无效。
高剂量胺碘酮对SQT2的治疗效果优于低剂量。本研究提供了新的证据，表明高剂量胺碘酮可能是SQT2的一种潜在药物治疗方法。
