Prevention of class III-induced proarrhythmias by flecainide in an animal model of the acquired long QT syndrome.

Abstract

The influence of the class Ic agent, flecainide, on the incidence of class III-induced torsades de pointes was examined in an animal model of the acquired long QT syndrome. Twenty-four chloralose-anaesthetized rabbits were pretreated at random with flecainide or vehicle and subsequently given a concomitant infusion of methoxamine and the class III antiarrhythmic agent almokalant. In seven out of eight vehicle-treated rabbits, almokalant induced torsades de pointes which was preceded by a significant lengthening of the JTU interval (used as an indirect measure of ventricular repolarization time) by 55 +/- 9.2 msec. Flecainide dose-dependently reduced the incidence of almokalant-induced torsades de pointes. Hence, in a group of rabbits given a low dose (0.14 mumol/kg + 1.4 mumol/kg/hr) of flecainide, four out of eight animals experienced torsades de pointes (P = 0.1538 versus vehicle) whereas no case (n = 8) was observed after a higher dose (4.8 mumol/kg + 4.8 mumol/kg/hr, P = 0.0007). In the former group almokalant induced a maximal increase in the JTU interval not differing from that seen in the vehicle-treated group (58 + 12.1 msec, P > 0.05). Pretreatment with the high dose of flecainide, however, caused a significant attenuation of the almokalant-induced lengthening of the JTU interval (18 +/- 6.5 msec. P < 0.05). It is concluded that flecainide reduces the risk of proarrhythmia in the setting of delayed repolarization partially by attenuating the primary electrophysiological effect of class III agents.

• Authors: K Hallman, L Carlsson
• Journal: Pharmacology & toxicology (Pharmacol Toxicol) Vol. 77 Issue 4 Pg. 250-4 (Oct 1995) ISSN: 0901-9928 [Print] Denmark
• PMID: 8577635 (Publication Type: Journal Article)

Chemical References

• Adrenergic alpha-Antagonists
• Anti-Arrhythmia Agents
• Propanolamines
• Methoxamine
• almokalant
• Flecainide

Topics

• Adrenergic alpha-Antagonists (administration & dosage, pharmacology, therapeutic use)
• Analysis of Variance
• Animals
• Anti-Arrhythmia Agents (administration & dosage, pharmacology, therapeutic use)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Electrocardiography (drug effects)
• Electrophysiology
• Flecainide (administration & dosage, pharmacology, therapeutic use)
• Male
• Methoxamine (administration & dosage, pharmacology, therapeutic use)
• Propanolamines (administration & dosage, pharmacology, therapeutic use)
• Rabbits
• Torsades de Pointes (prevention & control)