Comparison of the in vivo electrophysiological and proarrhythmic effects of amiodarone with those of a selective class III drug, sematilide, using a canine chronic atrioventricular block model.

Amiodarone effectively blocks both the sodium and calcium channels and beta-adrenoceptors, in addition to blocking several potassium currents including IKr, IKs, Ito, IK1, IKACh and IKNa. The incidence of clinical torsade de pointes (TdP) associated with amiodarone has been reported to be low and the present study compared the proarrhythmic potential of amiodarone with that of a selective IKr channel blocker, sematilide, using a canine chronic atrioventrucular block model. Amiodarone or sematilide (3 and 30 mg/kg; n=4 for each group) was administered orally without anesthesia under continuous ECG monitoring. Both drugs prolonged the QT interval, although the onset was faster for sematilide. The high dose of sematilide induced TdP in 3 of 4 animals, which caused their death, but neither the low dose of sematilide nor the 2 dosages of amiodarone induced lethal ventricular arrhythmias. These results suggest that IKr channel inhibition by amiodarone with its additional ion channel blocking action may contribute to the prevention of TdP.

[The effect of metabolic agents on the antiarrhythmic activity of novocainamide and acetylnovocainamide]. / Vliianie metaboliticheskikh sredstv na antiaritmicheskuiu aktivnost' novokainamida i atsetilnovokainamida.

The effects of potassium malate and sodium succinate on the antiarrhythmic activity of novocainamide and acetylnovocainamide during modelling of chlor-calcium-induced arrhythmia as well as in disorders of cardiac rhythm during modelling of pituitrin-isadrine-induced myocardial infarction were studied. The metabolic agents were found to increase the effectiveness of acetylnovocainamide and the toxicity of novocainamide. To interpret the specific features of the mechanism of the anti-arrhythmic action of the compounds there was studied their ability to form complexes with components of biomembranes and ions of biometals.

[New anti-arrhythmia drug. III. Comparative studies of the effects of N-propionylprocainamide, procainamide and N-acetylprocainamide on hemodynamics and cardiac blood flow]. / Nowy lek antyarytmiczny. III. Porównawcze badania wplywu N-propionyloprokainamidu, prokainamidu i N-acetyloprokainamidu na hemodynamike krazenia i ukrwienie serca królików.

Procainamide (PA) often applied in cases of ventricular arrhythmias causes numerous cardiac and extracardiac undesirable symptoms. Its active metabolite, N-acetylprocainamide (NAPA; Acecainide) is known to affect less noxiously the ventriculo-atrial conduction and the intraventricular++ conduction, and it does not impair contractility of the heart muscle. Many drugs with proven antiarrhythmic activity cannot be used in clinical practice because of disadvantageous effects on the function of the left ventricle and on the coronary blood flow, particularly in patients with the recent myocardial infraction. It seems that another acyl derivative of procainamide with potential antiarrhythmic activity, N-propionylprocainamide (NPPA) may be less harmful than PA, and NAPA. Effects of milimolarly equivalent doses of NPPA, NAPA and PA on the cardiac output and the stroke volume index, as well as on the coronary blood flow were investigated in rabbits by the radioisotope method. The obtained results were subjected to statistical analysis. NPPA was found to display no depressive action on the function of the left ventricle. Moreover, it was found to improve the coronary blood flow in rabbits.

[A new anti-arrhythmia drug. II. Comparative studies of the effects of a new acyl derivative of procainamide, procainamide and N-acetylprocainamide on blood pressure and the electrocardiogram in rabbits]. / Nowy lek antyarytmiczny. II. Wplyw nowej N-acylowej pochodnej prokainamidu na cisnienie tetnicze krwi i elektrokardiogram królika w porównaniu z prokainamidem i N-acetyloprokainamidem.

In the recent years a remarkable number of new antiarrhythmic drugs have been introduced, but their side effects limit the application. Procainamide (PA) and N-acetylprocainamide (Acekainide, NAPA) display many undesired side effects, too. It was assumed that N-propionyl-procainamide, having antiarrhythmic activity, might display less unfavourable effects on arterial blood pressure, heart rate and heart conduction system in rabbits, because of blockade of the primary aromatic amine group. The obtained results were subjected to statistical analysis. It has been stated that N-propionylprocainamide decreases the arterial blood pressure in rabbits to a lesser extent than procainamide. Moreover, in contrast with the latter compound, N-propionylprocainamide accelerates the heart rate, but does not influence the atrio-ventricular conduction, and does not prolong the ventricular refraction time. Antiarrhythmic activity of N-propionylprocainamide, not being inferior to that of procainamide and N-acetylprocainamide, and lesser side effects of N-propionylprocainamide indicate for advisability of further studies of this compound.