ORAL CLOFILIUM PRODUCES SUSTAINED LOWERING OF DEFIBRILLATION ENERGY-REQUIREMENTS IN A CANINE MODEL

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, respectivley. 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. Ventricular refractoriness was not altered in control animals, whereas ventricular effective refractory period increased from 195 +/- 31 msec at baseline to 224 +/- 31, 217 +/- 24, and 221 +/- 9 msec on days 14, 21, and 28, respectively (p < 0.01). For dogs treated with clofilium, the absolute E50 was inversely correlated with ventricular effective refractory period (r = -0.60, p < 0.003) and QTc (r = -0.77, p < 0.001). We conclude that long-term oral clofilium administration lowers defibrillation energy and current requirements; and it increases ventricular refractoriness within 1 week of therapy. These effects persist during a 3-week treatment period. The observed decreases in defibrillation energy requirements may be related to increased ventricular refractoriness.