Electrophysiologic effects of nicorandil on the guinea pig long QT1 syndrome model

Journal of Cardiovascular Electrophysiology
Zhifang YangYuanmou Liu

Abstract

The slow component of the delayed rectifier K+ current IKs modulates repolarization of the cardiac action potential (AP), and the loss of IKs is known to cause long QT1 (LQT1) syndrome by prolonging action potential duration (APD). In this study, we generated a guinea pig LQT1 syndrome model using the IKs blocker chromanol 293B and then assayed the electrophysiologic effects of the ATP-sensitive potassium channel IK,ATP opener nicorandil on this model. Transmembrane action potentials of perfused right ventricular papillary muscle preparations and both in vitro and in vivo ECGs of guinea pigs were recorded. Blockade of IKs by chromanol 293B (30 microM) prolonged the action potential duration at 90% repolarization (APD90) by 8.5% and QT interval by 16.5% of control values. In addition, proarrhythmic early afterdepolarizations (EADs) and ventricular fibrillation were observed. Venoinjection of chromanol 293B (1 mg/kg) revealed 10.9% QT prolongation. Nicorandil (5-30 microM) dose-dependently shortened APD90 under the control condition, whereas it reversed the AP prolongation effect of chromanol 293B by 7.4% at the 30 microM concentration. Moreover, nicorandil shortened QT intervals both in vitro and in vivo and displayed an inhibit...Continue Reading

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Citations

Jun 15, 2005·Journal of Molecular and Cellular Cardiology·A Jahangir, Andre Terzic
Mar 25, 2008·Acta Pharmacologica Sinica·Zhi-fang YangCi-zhen Li
Nov 6, 2013·Toxicological Sciences : an Official Journal of the Society of Toxicology·Anusak KijtawornratRobert L Hamlin
Mar 1, 2011·Expert Opinion on Emerging Drugs·Keitaro Hashimoto
May 7, 2011·British Journal of Pharmacology·András Varró, István Baczkó
Nov 1, 2006·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Bas A SchoonderwoerdIsabelle C Van Gelder
Apr 9, 2009·Progress in Biophysics and Molecular Biology·Sandeep S HothiChristopher L-H Huang
Nov 26, 2016·British Journal of Pharmacology·Ling-Jun JieYan Wang
Jul 15, 2004·Journal of Cardiovascular Electrophysiology·Kalyanam Shivkumar, Miguel Valderrabano
Oct 12, 2005·Journal of Pharmacological Sciences·Yasue SakaguchiKeitaro Hashimoto
Sep 3, 2021·European Journal of Pharmacology·Ling-Jun JieYan Wang

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