title: Prevention of life-threatening ventricular tachyarrhythmia by a novel and pure class-III agent, nifekalant hydrochloride.
abstract: Nifekalant hydrochloride (NIF) is a novel intravenous class-III antiarrhythmic agent with a pirimidinedione structure that purely blocks the K+ channel without inhibiting beta-adrenergic receptors. The authors investigated the efficacy of NIF for refractory ventricular tachycardia/fibrillation (VT/VF). They studied 30 patients treated with an intravenous infusion of NIF [ 26 men, 4 women; age: 63 +/- 17 (mean +/- SD) years] at a dose of 0.19 +/- 0.14 mg/kg body weight per hour. Sixteen were patients with acute coronary syndrome (ACS), and 14 were patients with chronic structural heart disease (Chr-HD). Amiodarone and sotalol had already been administered to 9 patients with Chr-HD before the administration of NIF. The QT and T peak-end (Tp-e) intervals were measured and corrected by Bazett's method (QTc, cTp-e). The left ventricular ejection fraction was depressed (28 +/- 9%). NIF was effective for preventing VT/VF without proarrhythmia and hemodynamic deterioration in 21 patients (70%; 12 with ACS; 9 with Chr-HD), but ineffective in 4 patients (all with Chr-HD). The QTc prolongation in the responders was more pronounced than in the nonresponders (25% +/- 15% versus 5% +/- 7% increase; P < 0.05). Proarrhythmic torsade de pointes (TdP) developed transiently in the remaining 5 patients in whom the cTp-e was markedly increased compared with that in the responders (93% +/- 49% versus 37% +/- 41% increase; P < 0.05). In conclusion, these findings indicate that the intravenous administration of NIF is useful in the emergent treatment of inhibiting drug-refractory VT/VF, although proarrhythmic TdP owing to an enhancement of transmural dispersion of repolarization needs to be taken into account.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, National Cardiovascular Center, Osaka, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Ohashi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yasuda
authors.forename: Shunichi
authors.initials: S
authors.lastname: Miyazaki
authors.forename: Wataru
authors.initials: W
authors.lastname: Shimizu
authors.forename: Isao
authors.initials: I
authors.lastname: Morii
authors.forename: Takashi
authors.initials: T
authors.lastname: Kurita
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kawamura
authors.forename: Shiro
authors.initials: S
authors.lastname: Kamakura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nonogi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006331:Heart Diseases / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011744:Pyrimidinones / Q000008:administration & dosage / Q000627:therapeutic use*; D012307:Risk Factors; D016896:Treatment Outcome; D014693:Ventricular Fibrillation / Q000503:physiopathology / Q000517:prevention & control*
chemical_list: D000889:Anti-Arrhythmia Agents; D011744:Pyrimidinones; C076259:nifekalant