Effect of the ATP-sensitive K⁺ channel opener nicorandil in a canine model of proarrhythmia.
Increased action potential duration (APD) induces early afterdepolarization (EAD) in vitro and torsade de pointes in vivo, and ATP-sensitive K(+) channel openers decrease APD in cardiac tissue. We tested whether the ATP-sensitive K(+) channel opener nicorandil has antiarrhythmic effects on class III antiarrhythmic drug-induced ventricular arrhythmia. In 10 anesthetized dogs with chronic atrioventricular block, we recorded monophasic action potentials (MAPs) from the left and right ventricular (LV and RV) endocardium. The class III antiarrhythmic drug nifekalant (1 mg/kg, IV) was administered at 5 minute intervals (total doses; 2-6 mg/kg) until the appearance of EADs, premature ventricular contractions (PVCs), or polymorphic ventricular tachycardias (PVTs). Five minutes after the end of nifekalant administration, nicorandil (1.0 mg/kg) was administered over 5 minutes. Nifekalant decreased the ventricular escape rate from 75 ± 5 beats/minute to 45 ± 10 beats/minute and increased RV-MAP duration (MAPD) from 217 ± 32 msec to 308 ± 2 msec (P < 0.01) and LV-MAPD from 232 ± 32 msec to 353 ± 82 msec (P < 0.01). EADs were recorded in 9 dogs, frequent premature ventricular contractions (PVCs) developed in 10 dogs, incessant PVTs developed in 3 dogs, and monomorphic ventricular tachycardia developed in 3 dogs after nifekalant administration. Nicorandil decreased RV-MAPD to 267 ± 57 msec and LV-MAPD to 279 ± 44 msec. It suppressed EADs, decreased the incidence of PVCs, and abolished PVT. Nicorandil may be clinically useful for treatment of PVCs and PVTs accompanying acquired long QT syndrome.
Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
Ichiro
I
Watanabe
Yasuo
Y
Okumura
Kimie
K
Ohkubo
Koichi
K
Nagashima
Hiroaki
H
Mano
Kazuyuki
K
Sonoda
Masayoshi
M
Kofune
Satoshi
S
Kunimoto
Yuji
Y
Kasamaki
Atsushi
A
Hirayama
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects* / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects*; D054086:KATP Channels / Q000187:drug effects*; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000503:physiopathology*; D020108:Nicorandil / Q000494:pharmacology*; D011744:Pyrimidinones / Q000009:adverse effects*; D016171:Torsades de Pointes / Q000139:chemically induced* / Q000503:physiopathology*; D018879:Ventricular Premature Complexes / Q000139:chemically induced* / Q000503:physiopathology*
D000889:Anti-Arrhythmia Agents; D054086:KATP Channels; D011744:Pyrimidinones; D020108:Nicorandil; C076259:nifekalant