ABSTRACT
The aim of the study was to evaluate the efficacy and safety of administered intravenously niferidil in doses 10, 20 and 30 mkg per kg in patients with persistent atrial fibrillation (AF) and flutter (AFL) for pharmacological cardioversion. The study included 30 patients (22 male) with persistent AF (n = 28) and AFL (n = 2) without structural heart diseases with median arrhythmia duration 6.1 +/- 4.8 months (2 weeks to 24 months). Niferidil was administered as 3 bolus injections (10 mkg per kg each) performed with the interval of 15 minutes. Antiarrhythmic efficacy of niferidil in dose of 10 mkg per kg was 60%, in dose of 20 mkg per kg it was 70%, and in dose of 30 mkg per kg reached 90% prespectively. The part of the patients, in whom QTc prolongation exceeded potentionally dangerous value of 500 mc, was 22.2% (6 of 27). None of the patients developed proarrhythmic side effect as torsade de pointes.
Subject(s)
Atrial Fibrillation , Atrial Flutter , Heart Rate/drug effects , Piperidines , Aged , Animals , Anti-Arrhythmia Agents/administration & dosage , Anti-Arrhythmia Agents/adverse effects , Anti-Arrhythmia Agents/pharmacokinetics , Atrial Fibrillation/diagnosis , Atrial Fibrillation/drug therapy , Atrial Fibrillation/physiopathology , Atrial Flutter/diagnosis , Atrial Flutter/drug therapy , Atrial Flutter/physiopathology , Depression, Chemical , Disease Models, Animal , Dogs , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Approval , Drug Evaluation, Preclinical , Electrocardiography , Female , Humans , Injections, Intravenous , Male , Middle Aged , Piperidines/administration & dosage , Piperidines/adverse effects , Piperidines/pharmacokinetics , Rabbits , Rats , Time Factors , Torsades de Pointes/chemically induced , Torsades de Pointes/prevention & control , Treatment OutcomeABSTRACT
The electrophysiologic effects of a new drug, RG-2 were studied on anesthetized open-chest dogs and on rabbit right atrial tissue. RG-2 was manufactured in Chemical-Pharmaceutical Institute in Moscow. Dogs (n=12) were anesthetized with sodium pentobarbital (30 mg/kg, i.v.). An ECG lead II, arterial blood pressure, His bundle electrogram, atrial and ventricular bipolar electrograms were continuously monitored, recorded and then analyzed by a computerized complex for electrophysiological study. Electrophysiological variables, ECG parameters, atrioventricular conduction (His electrogram) and blood pressure were determined after sequential i.v. administration of 1, 5, 10, 20, 40 and 80 ug/kg of RG-2. Interval between injections was 60 min. RG-2 had no significant effect on PQ, QRS, S-A, A-H and H-V intervals, but the drug caused dose-dependent increase of R-R and QT intervals. Moreover, RG-2 dose-dependently increased the atrial and ventricular effective refractory periods (AERP and VERP). Maximal increases of AERP and VERP registered at 5 min after administration of RG-2 (40 microg/kg) were 46+/-2% (p<0.001 vs control) and 23+/-6% (p<0.05 vs control), respectively. In the isolated rabbit right atrial tissue RG-2 (0.01 to 1 microM) had no effects on maximal diastolic potential, action potential amplitude and Vmax, but revealed concentration-dependent increase of action potential duration at 90% repolarization level (APD90%). The maximal effects on APD90% obtained after RG superfusion at 1 microM were 26+/-7% (p<0.001 vs control). We conclude that RG-2 has significant effects of class III antiarrhythmic drugs in vivo and in vitro.
Subject(s)
Anti-Arrhythmia Agents/pharmacology , Heart/drug effects , Animals , Arrhythmias, Cardiac/drug therapy , Arrhythmias, Cardiac/physiopathology , Dogs , Electrophysiologic Techniques, Cardiac , Heart/physiology , Heart Conduction System/drug effects , Heart Conduction System/physiology , In Vitro Techniques , Models, Animal , RabbitsABSTRACT
Epicardial mapping (254 unipolar electrodes) of the dog heart both atria was performed to determine spatial distribution of arrhythmic events. The mapping showed that the first atrial premature depolarisation (APD) emerged from ectopic foci, it showed also specific multifocal patterns suggesting a septal source of tachycardia. The data obtained suggests that vagal stimulation (VS) induces focal ectopic APDs, that APDs and escape beats may be due to the same mechanism of spontaneous depolarization in the absence of a reset from dominant rhythm, that a single VS-induced APD is sufficient for initiation of a reentrant atrial fibrillation.
Subject(s)
Atrial Fibrillation/physiopathology , Atrial Function/physiology , Electrophysiologic Techniques, Cardiac/instrumentation , Vagus Nerve/physiology , Animals , Dogs , Electric Stimulation , Electrodes , Electrophysiologic Techniques, Cardiac/methodsABSTRACT
The association between phosphocreatine's antifibrillatory action and its effect on the excitement propagation processes in the ischemic area was investigated under acute coronary arterial occlusion in dogs. Ischemia considerably reduced the amplitude, and increased the duration and time of onset, in local electrograms, and provoked cardiac fibrillation at the time of occlusion or during the recovery of coronary flow. A single intravenous injection of 300 mg/kg phosphocreatine eliminated cardiac fibrillation and largely prevented electrographic changes in the ischemized area. Phosphocreatinine, phosphocreatine's structural analogue, produced a similar effect. It is suggested that antiarrhythmic action of phosphocreatine and phosphocreatinine is mediated by their membrane effects.