Proarrhythmic effects of ibutilide in a canine model of pacing induced cardiomyopathy

The authors developed a canine model of pacing induced cardiomyopathy to study the possible mechanisms of ibutilide induced torsades de pointes (TP) in heart failure. Thirteen dogs received intravenous ibutilide after acute AV block for 60 minutes, and after implantation of a VVI pacemaker, with a rate of 270 beats/min for 2-3 weeks. Twelve-lead ECG and right and left ventricle monophasic action potentials were recorded at different right ventricle pacing cycle lengths from 600 ms to 1200 ms during the study. The results showed ibutilide could significantly prolong ventricular repolarization and increase the dispersion in a dose dependent and reverse use dependent manner. Furthermore, after ibutilide administration, cardiomyopathic dogs had a greater dispersion of ventricular repolarization, and also had higher incidences of early after depolarizations and spontaneous or pacing induced TP than acute AV block dogs.