title: Oral clofilium produces sustained lowering of defibrillation energy requirements in a canine model.
abstract: The effect of long-term oral administration of antiarrhythmic drugs on defibrillation energy requirements is not well understood. We examined the effect of clofilium, a drug that prolongs cardiac action potential duration without slowing cardiac conduction, on defibrillation energy requirements and ventricular effective refractory periods in a canine model during a 3-week period. Epicardial patch electrodes were implanted in 12 dogs, and baseline testing was conducted under fentanyl anesthesia on day 7. An oral clofilium (100 mg/day) regimen was started on day 8. Six clofilium-treated and six control dogs underwent repeated testing on days 14, 21, and 28 after surgery. Truncated trapezoidal shocks were given repeatedly at various stored energies in random order; delivered current and impedance were measured; and delivered energy was calculated. The energy and current for 50% success in defibrillation (E50 and I50, respectively) were determined. For control animals, E50 increased by a mean 34 +/- 78%, 60 +/- 83%, and 69 +/- 122% compared with baseline (day 7) on days 14, 21, and 28, respectively. In contrast, E50 in clofilium-treated dogs decreased by 39 +/- 62%, 24 +/- 33%, and 32 +/- 15% on days 14, 21, and 28, respectively. Mean current requirements (I50) remained relatively stable compared with baseline in control animals (-7 +/- 39%, +25 +/- 36%, +40 +/- 75% on days 14, 21, and 28, respectively). After clofilium administration I50 decreased by 36 +/- 22%, 32 +/- 17%, and 33 +/- 17% on days 14, 21, and 28, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, Toronto Western Hospital, Ontario, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Dorian
authors.forename: M
authors.initials: M
authors.lastname: Wang
authors.forename: I
authors.initials: I
authors.lastname: David
authors.forename: C
authors.initials: C
authors.lastname: Feindel
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004285:Dogs; D004554:Electric Countershock; D004567:Electrodes, Implanted; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000628:therapy*
chemical_list: D000889:Anti-Arrhythmia Agents; D000644:Quaternary Ammonium Compounds; C022799:clofilium