Caffeine and dobutamine challenge induces bidirectional ventricular tachycardia in normal rats

Bidirectional ventricular tachycardia (BD-VT) is an intriguing arrhythmia, characterized by a beat-to-beat alternation of the QRS polarity on electrocardiogram. Currently there is no simple BD-VT animal model.

We report a simple animal model of BD-VT induced by caffeine and dobutamine (C+D) challenge in normal rats in which the arrhythmia can be attenuated by dantrolene (a ryanodine receptor stabilizer) treatment, but not by the pacemaker channel blocker ivabradine treatment.

Adult (4-5 months old) Sprague-Dawley rats (both sexes) were randomized into C+D (n = 8, received caffeine 120 mg/kg intraperitoneally [IP] and dobutamine 60 μg/kg IP, sequentially) and control (n = 8) groups. In addition, a group of 7 rats were pretreated with dantrolene (10 mg/kg, IP) 30 minutes before the C+D challenge and another group of 8 rats were pretreated with ivabradine (5 mg/kg, IP) 30 minutes before the C+D challenge.

C+D challenge induced spontaneous premature ventricular contractions (PVCs) in 7 of 8 rats and BD-VT (lasted 4.3 ± 2.9 minutes, terminated spontaneously) in 6 of 8 (75%) rats. No ventricular arrhythmia was induced in the control group (P < .05 vs C+D group). Dantrolene treatment significantly decreased BD-VT (1 of 7 rats in the Dantrolene+C+D group vs 6 of 8 rats in C+D group, P < .05). Ivabradine treatment did not affect C+D-induced BD-VT (7 of 8 rats in the Ivabradine+C+D group vs 6 of 8 in the C+D group, P > .05).

Caffeine and dobutamine challenge induces BD-VT in a majority of normal rats. Stabilizing cardiac ryanodine receptors with dantrolene treatment can significantly decrease the occurrence of BD-VT, but pacemaker channel blocker ivabradine treatment does not have effect in this animal model.