niferidil and Atrial-Fibrillation

This article reviews experimental and clinical studies of a novel antiarrhythmic agent niferidile. Niferidile, a class III antiarrhythmic agent, blocks potassium outward currents, prolongs repolarization and refractory periods predominantly in atria than in ventricles. Intravenous Niferidile was efficient for interruption of AV-nodal and orthodromic re-entrant tachycardias with rates of 75% to 80%. Niferidile had a conversion rate of up to 87.3% in persistent atrial fibrillation and up to 100% in persistent atrial flutter. Proarrhythmic action of niferidil administration manifested as nonsustained torsade de pointes and monomorphic ventricular tachycardia in 1.2 and 3.7% of cases, respectively. Niferidile can be used for pharmacological cardioversion of persistent atrial fibrillation and flutter as an alternative to electrical cardioversion.

Topics: Animals; Anti-Arrhythmia Agents; Atrial Fibrillation; Dogs; Heart Atria; Humans; Myocytes, Cardiac; Piperidines; Potassium Channel Blockers; Rats; Tachycardia, Supraventricular

To evaluate the efficacy and safety of refralon (niferidil), a new class III antiarrhythmic agent whose activity is related to the block of delayed rectifying potassium current and to the prolongation of atrial and ventricular action potential and refractory periods, when it is used as an agent for pharmacological cardioversion for atrial fibrillation (AF) and atrial flutter (AFL).. The efficacy of the drug as 3 intravenous boluses of 10 μg/kg was evaluated in 134 patients (90 men; 57.8 ± 11 years) with a mean AF duration of 3 (1.5; 6) months. Its effect was controlled by 24-hour Holter ECG monitoring. The criterion for its antiarrhythmic effect was 24-hour sinus rhythm (SR) recovery.. Niferidil restored SR in 47.7% of the patients with AF after administration of bolus 1, in 62% after bolus 2, and in 84.6% after bolus 3. SR was restored in all 100% patients with AFL. With the AF duration of less than 3 months, the efficacy of niferidil was 91.8%. There was nonsustained polymorphic ventricular tachycardia (VT) (torsade de pointes) in 1 (0.7%) patient and nonsustained monomorphic VT was stated in 5 (3.7%) patients. CONCLUSION> Pharmacological cardioversion with niferidil for persistent AF and VT may be regarded as a possible alternative to electrical cardioversion.. Цель исследования. Оценка эффективности и безопасности рефралона (ниферидила) - нового антиаритмического препарата III класса, действие которого связано с блокадой калиевых токов задержанного выпрямления, удлинением потенциала действия и рефрактерных периодов в предсердиях и желудочках, при его применении в качестве средства для медикаментозной кардиоверсии при фибрилляции предсердий (ФП) и трепетании предсердий (ТП). Материалы и методы. Эффективность препарата в виде 3 болюсов по 10 мкг/кг внутривенно оценена у 134 больных (57,8±11 лет, 90 мужчин) при средней длительности ФП 3 (1,5; 6) мес. Действие препарата контролировалось при 24-часовом холтеровском мониторировании электрокардиограммы. Критерием антиаритмического эффекта было восстановление синусового ритма (СР) в течение 24 ч. Результаты. Ниферидил восстановил СР у 47,7% больных с ФП после введения 1-го болюса, у 62% - после введения 2-го и у 84,6% - после введения 3-го болюса. СР восстановлен у всех 100% больных с ТП. При длительности ФП менее 3 мес эффективность ниферидила составила 91,8%. Неустойчивая полиморфная желудочковая тахикардия (ЖТ) типа torsades de pointes отмечена в 1 (0,7%) случае. Неустойчивая мономорфная желудочковая тахикардия (ЖТ) констатирована у 5 (3,7%) больных. Заключение. Медикаментозная кардиоверсия персистирующей ФП и ТП с использованием ниферидила может рассматриваться как возможная альтернатива электрической кардиоверсии.

Topics: Action Potentials; Anti-Arrhythmia Agents; Atrial Fibrillation; Atrial Flutter; Data Interpretation, Statistical; Dose-Response Relationship, Drug; Echocardiography; Electrocardiography, Ambulatory; Female; Heart; Humans; Male; Middle Aged; Piperidines; Potassium Channels; Treatment Outcome

To study the efficacy and safety of the new class III antiarrhythmic agent niferidil for pharmacological cardioversion in patients with persistent atrial fibrillation (AF) and atrial flutter (AFl).. One hundred thirty-four adults (aged 57.8 ± 11 years, 90 males) were included with median AF duration of 3 (1.5-6) months. All patients received a total of 10-30 μg/kg, niferidil, intravenously, in 1-3 (if needed) consecutive boluses at 15-minute intervals. Holter electrocardiogram monitoring was started before infusion and was continued for 24 hours. The criterion for an antiarrhythmic effect was sinus rhythm restoration within 24 hours of the initial bolus. Niferidil converted AF to sinus rhythm in 47.7% of cases after bolus 1, in 62% of cases after bolus 2, and in 84.6% of cases bolus 3. Niferidil induced a 100% recovery rate in patients with AFl and a 91.8% recovery rate in patients with AF of duration from 8 days to 3 months. Nonsustained torsade de pointes occurred in 1 patient (0.7%), and nonsustained monomorphic ventricular tachycardia was observed in 5 patients (3.7%).. The new intravenous class III drug niferidil demonstrated high conversion rates of 84.6% in patients with persistent AF and 100% in patients with persistent AFl. Niferidil may be used as a possible alternative to electrical cardioversion for pharmacological cardioversion of persistent AF/AFl.

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Atrial Flutter; Dose-Response Relationship, Drug; Electrocardiography, Ambulatory; Female; Humans; Male; Middle Aged; Piperidines; Treatment Outcome

A new class III antiarrhythmic drug niferidil (RG-2) has been introduced as a highly effective therapy for cases of persistent atrial fibrillation, but ionic mechanisms of its action are poorly understood. In the present study, the effects of niferidil on action potential (AP) waveform and potassium currents responsible for AP repolarization were investigated in guinea pig atrial myocardium.. APs were recorded with sharp glass microelectrodes in multicellular atrial preparations. Whole-cell patch-clamp technique was used to measure K. Niferidil prolongs APs in guinea pig atrial myocardium via inhibition of I

Topics: Action Potentials; Animals; Anti-Arrhythmia Agents; Atrial Fibrillation; Delayed Rectifier Potassium Channels; Guinea Pigs; Heart Atria; In Vitro Techniques; Male; Microelectrodes; Myocytes, Cardiac; Patch-Clamp Techniques; Piperidines