Ventricular arrhythmias triggered by alerting stimuli in conscious rabbits pre-treated with dofetilide

Abstract.

We tested whether normally benign alerting/arousing stimuli provoke cardiac arrhythmias in conscious rabbits with electrically unstable myocardium. Alerting stimuli (loud sound, tapping and moving the cage, pinprick, inhalation of formaldehyde vapour) were presented before and after administration of dofetilide to conscious unrestrained rabbits (New Zealand White). Dofetilide (0.28–3.0 mg/kg i. v.) caused prolongation of QT interval (from 131 ± 9 to 217 ± 11 ms; p < 0.01, n = 6) and Tpeak-Tend interval (from 34 ± 5 to 81 ± 9 ms; p < 0.01, n = 6), altered ventricular conductance, and caused appearance of spontaneous ventricular ectopic beats. Alerting stimuli elicited ventricular ectopic beats in 18/30 trials in all dofetilide-treated animals, with a short latency (3.1 ± 0.4 s). Formaldehyde vapour, in addition, elicited profound bradycardia, and precipitated non-sustained polymorphic ventricular tachycardia (torsades de points) lasting 0.6–8.5 s in 5/6 animals. These arrhythmias occurred also with a short latency (mean 8.7 ± 1.6 s). Betaadrenergic blockade with propranolol (1.5 mg/kg i. v.) abolished spontaneous ventricular ectopy, suppressed torsades de points precipitated by formaldehyde, and significantly (p < 0.05) reduced the number of ventricular ectopic beats triggered by alerting stimuli. In predisposed hearts, alerting stimuli precipitate arrhythmias by producing transient increases in sympathetic discharge in the ventricular myocardium. Vagally induced bradycardia with concurrent ventricular beta-adrenoreceptor activation may underlie development of torsades de points in patients with long QT syndrome precipitated by swimming, diving or facial immersion.