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Electrophysiologic Effects of Nicorandil on the Guinea Pig Long QT1 Syndrome Model
Author(s) -
YANG ZHIFANG,
SHI GUOZHONG,
LI CIZHENG,
WANG HONGWEI,
LIU KAI,
LIU YUANMOU
Publication year - 2004
Publication title -
journal of cardiovascular electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.193
H-Index - 138
eISSN - 1540-8167
pISSN - 1045-3873
DOI - 10.1046/j.1540-8167.2004.03632.x
Subject(s) - medicine , nicorandil , guinea pig , cardiology , electrophysiologic study , atrial fibrillation , anesthesia , tachycardia
The slow component of the delayed rectifier K + current I Ks modulates repolarization of the cardiac action potential (AP), and the loss of I Ks 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 I Ks blocker chromanol 293B and then assayed the electrophysiologic effects of the ATP‐sensitive potassium channel I K,ATP opener nicorandil on this model. Methods and Results: 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 I Ks by chromanol 293B (30 μ M) prolonged the action potential duration at 90% repolarization (APD 90 ) 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 μ M) dose‐dependently shortened APD 90 under the control condition, whereas it reversed the AP prolongation effect of chromanol 293B by 7.4% at the 30 μ M concentration. Moreover, nicorandil shortened QT intervals both in vitro and in vivo and displayed an inhibitory effect on EADs and ventricular fibrillation. Conclusion: The ATP‐sensitive potassium channel opener nicorandil may be an effective drug in the therapy of LQT1 syndrome by shortening APD and the QT interval. (J Cardiovasc Electrophysiol, Vol. 15, pp. 815‐820, July 2004)