Basic Res Cardiol 99: 142 – 151 (2004) DOI 10.1007/s00395-003-0448-1 ORIGINAL CONTRIBUTION Eugene Nalivaiko Carmine G. De Pasquale William W. Blessing 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, pin- prick, 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 stim- uli 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). Beta- adrenergic blockade with propranolol (1.5 mg/kg i.v.) abolished spontaneous ventricular ectopy, suppressed torsades de points precipitated by formalde- hyde, and significantly (p < 0.05) reduced the number of ventricular ectopic beats triggered by alerting stimuli. In predisposed hearts, alerting stimuli pre- cipitate arrhythmias by producing transient increases in sympathetic dis- charge in the ventricular myocardium. Vagally induced bradycardia with concurrent ventricular beta-adrenoreceptor activation may underlie devel- opment of torsades de points in patients with long QT syndrome precipitated by swimming, diving or facial immersion.  Key words Long QT syndrome – ventricular repolarization – sudden death – ECG, ventricular arrhythmia BRC 448 Dr. E. Nalivaiko () · W. W. Blessing Department of Medicine Flinders Medical Centre Bedford Park 5042 SA, Australia Tel.: +61-8/82044107 Fax: +61-8/82045450 E-Mail: eugene.nalivaiko@flinders.edu.au C. G. De Pasquale Department of Cardiology Flinders Medical Centre Adelaida, Australia Received: 8 September 2003 Returned for revision: 24 September 2003 Revision received: 6 October 2003 Accepted: 23 October 2003 Published online: 29 November 2003 Introduction Malignant cardiac arrhythmias are more likely to be trig- gered by acute psychological stress when there is pre- existing myocardial electrical instability, and when there is a background of chronic psychological stress or dep- ression [11, 21, 29, 30]. Holter monitors and implantable cardioverters/defibrillator studies have documented the relationship between acute psychological stress and ventricular arrhythmias in predisposed individuals, as exemplified by the cardiac events precipitated by the Marmara earthquake [18] and the World Trade Center terrorist attack [20]. In patients with long QT syndrome, sudden arousing stimuli may precipitate ventricular arrhythmias within seconds [8, 43], suggesting that they are neurally triggered. The acute proarrhythmic effects of brain stimulation have been clearly demonstrated in anesthetized animals (see [28] for review). Perhaps surprisingly, there have