Caffeine induces ventricular tachyarrhythmias possibly due to triggered activity in rabbits in vivo

Caffeine induces delayed afterdepolarizations (DADs) and triggered activity in isolated cardiac tissue. We investigated the ability of caffeine to induce triggered ventricular arrhythmias in rabbits in vivo. During continuous infusion of caffeine at doses of 0.3 or 1.0 mg/kg per min, ventricular pacing was performed with 50 stimuli with a cycle length of 220 msec (basic pacing train) every 5 min until ventricular tachycardia (VT) was induced. The effects of programmed stimulation and pharmacologic agents on the induction of ventricular ectopic beats (VEBs) were examined. Pacing protocols were carried out in the presence of vagal-induced slowing of sinus rhythm. VT was induced by a basic pacing train during the infusion of caffeine at 1.0 mg/kg per min, but not at 0.3 mg/kg per min. An increase in the pacing rate or the number of stimuli resulted in 1) a decrease in the first postpacing interval, and 2) an increase in the number of postpacing VEBs. Induction of VT was suppressed by intravenous bolus injections of verapamil, propranolol and adenosine. At the time of the initial induction of VT, the plasma concentration of caffeine was 87 +/- 2 micrograms/ml and the plasma level of norepinephrine increased from 666 +/- 166 pg/ml at baseline to 1121 +/- 245 pg/ml. These results suggest that catecholamine-associated triggered activity may be responsible for caffeine-induced VT.