Effects of the ATP-sensitive K channel opener nicorandil on the QT interval and the effective refractory period in patients with congenital long QT syndrome

Aizawa, Yoshifusa; Uchiyama, Hirohide; Yamaura, Masayuki; Nakayama, Tsuneyoshi; Arita, Makoto

doi:10.1016/s0022-0736(98)90042-5

Cited by 27 publications

(19 citation statements)

References 19 publications

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“…We were motivated to examine the effect of HERG overex- pression on the effective refractory period (ERP) because we observed afterhyperpolarizations in cells with high levels of HERG current and because nicorandil, a K + channel opener, provides increased protection against premature stimuli in long Q-T syndrome patients by prolonging the ERP (44). It has also been suggested that HERG may guard against premature beats because of its unique gating properties (45).…”

Section: Sensitivity Of Herg To Block By E-4031mentioning

confidence: 99%

Overexpression of a human potassium channel suppresses cardiac hyperexcitability in rabbit ventricular myocytes

Nuss¹,

Marbán²,

Johns³

1999

J. Clin. Invest.

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The high incidence of sudden death in heart failure may reflect abnormalities of repolarization and heightened susceptibility to arrhythmogenic early afterdepolarizations (EADs). We hypothesized that overexpression of the human K + channel HERG (human ether-a-go-go-related gene) could enhance repolarization and suppress EADs. Adult rabbit ventricular myocytes were maintained in primary culture, which suffices to prolong action potentials and predisposes to EADs. To achieve efficient gene transfer, we created AdHERG, a recombinant adenovirus containing the HERG gene driven by a Rous sarcoma virus (RSV) promoter. The virally expressed HERG current exhibited pharmacologic and kinetic properties like those of native I Kr . Transient outward currents in AdHERG-infected myocytes were similar in magnitude to those in control cells, while stimulated action potentials (0.2 Hz, 37°C) were abbreviated compared with controls. The occurrence of EADs during a train of action potentials was reduced by more than fourfold, and the relative refractory period was increased in AdHERG-infected myocytes compared with control cells. Gene transfer of delayed rectifier potassium channels represents a novel and effective strategy to suppress arrhythmias caused by unstable repolarization.

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Section: Sensitivity Of Herg To Block By E-4031mentioning

confidence: 99%

Overexpression of a human potassium channel suppresses cardiac hyperexcitability in rabbit ventricular myocytes

Nuss¹,

Marbán²,

Johns³

1999

J. Clin. Invest.

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“…30) We did not test low-dose nicorandil in the present study. Thus, the present data could not be applicable to human cases because heart rate was markedly decreased by nifekalant in this model, and the nicorandil dose was more than 10 times higher than that in the clinical dose.…”

Section: )mentioning

confidence: 85%

Effect of the ATP-Sensitive K+ Channel Opener Nicorandil in a Canine Model of Proarrhythmia

et al. 2011

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SummaryIncreased 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. (Int Heart J 2011; 52: 318-322)

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“…19 Nicorandil mimics ischemic preconditioning, which reduce chest pain and ST elevation during PTCA 20 and reduces the infarct size in acute myocardial infarction. 21 In the present study, longacting isosorbide dinitrate was given to patients in both groups to minimize the effect of nitrate and nicorandil alone did not reduce the QT dispersion at baseline.…”

Section: Discussionmentioning

confidence: 99%

Opening of KATP Channel Attenuates the Increase in QT Dispersion Produced by the First Balloon Inflation During Coronary Angioplasty.

Ashikaga

Nishizaki

Arita

et al. 2002

Circ J

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ethal ventricular arrhythmias, which occur more frequently at the first balloon inflation than with subsequent procedures, occur in 1.5-4.4% of patients undergoing percutaneous transluminal coronary angioplasty (PTCA). [1][2][3][4][5][6] Moreover, these arrhythmias develop more often with PTCA of the left anterior descending coronary artery (LAD). 6 Increased QT dispersion is an useful marker of lethal ventricular arrhythmias, 6 but the mechanism and prevention of the lethal ventricular arrhythmias complicating PTCA have not been elucidated.A previous study reported that repeated coronary occlusions during PTCA reduces the occurrence of ventricular arrhythmias, 7 and these phenomenon have been attributed to ischemic preconditioning through the opening of the KATP channel. Tomai et al demonstrated that ischemic preconditioning during PTCA was prevented by glibenclamide, a selective KATP channel blocker, 8 and Garrat et al demonstrated an increased mortality rate in diabetic patients given sulfonylurea during PTCA. 9 Cole et al demonstrated in guinea pigs that blockade of the KATP channel with glibenclamide worsened the electrical and mechanical

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Effects of the ATP-sensitive K channel opener nicorandil on the QT interval and the effective refractory period in patients with congenital long QT syndrome

Cited by 27 publications

References 19 publications

Overexpression of a human potassium channel suppresses cardiac hyperexcitability in rabbit ventricular myocytes

Overexpression of a human potassium channel suppresses cardiac hyperexcitability in rabbit ventricular myocytes

Effect of the ATP-Sensitive K+ Channel Opener Nicorandil in a Canine Model of Proarrhythmia

Opening of KATP Channel Attenuates the Increase in QT Dispersion Produced by the First Balloon Inflation During Coronary Angioplasty.

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