Poster Presentation 6th Australian Health and Medical Research Congress 2012

Riluzole reduces aconitine induced arrhythmias in an in-vivo­­ rat model (#466)

David G Morris 1 , Steven Weiss 2 , David Saint 1
  1. Department of Physiology, University of Adelaide, Adelaide, SA, Australia
  2. School of Medicine, Australian National University, Caberra, ACT, Australia

INTRODUCTION: It has been sugggested that block of the cardiac persistent sodium current (INaP) is antiarrhythmic. However, previous studies suggested that the INaP blocker riluzole was ineffective against aconitine-induced arrhythmias (Mestre et al., 2000) We re-investigated the anti-arrhythmic effect of riluzole in an anesthetized rat aconitine-induced arrhythmia model.

METHODS:  Male Spraque-Dawley rats (330-400g) were anesthetized with ketamine and domitor.  IV (jugular) and arterial (carotid) catheters were inserted.  Continuous recordings of BP and a 3 lead ECG were made throughout each experiment, starting 1 minute prior to treatment infusion. Animals were randomly given either control, (n=5), vehicle IV (n=6), 2 mg/kg riluzole IV (n=6), 4 mg/kg riluzole IV (n=6) or + 34µg.3mL-1.15min-1 infusion lidocaine (n=6) immediately prior to starting IV infusion of aconitine (15µg/3mL at 0.2mL/min).  ECG recordings were divided into 30 second epochs and the presence/absence of differing arrhythmias (PVC/Bigeminy/Salvo/AT/AF/AVblock/VT/VF) noted and scored, based on the scheme suggested by Curtis et al., 1988.

RESULTS: Lidocaine, and riluzole decreased aconitine induced arrhythmias compared to control (P<0.05) but showed no significance compared to each other for the same measurement. In agreement with Mestre et al., there was no difference observed for any treatment in time until first aconitine induced arrhythmia.

CONCLUSION: The novel INaP blocker riluzole significantly reduces the severity and incidence of aconitine induced arrhythmias, reinforcing the appeal of INaP as a novel antiarrhyhtmic target.  

  1. Mestre, M, Djellas, Y, Carriot, T & Cavero, I 2000, 'Frequency-independent blockade of cardiac Na+ channels by riluzole: comparison with established anticonvulsants and class I anti-arrhythmics', Fundam Clin Pharmacol, vol. 14, no. 2, Mar-Apr, pp. 107-117.
  2. Curtis, MJ & Walker, MJ 1988, 'Quantification of arrhythmias using scoring systems: an examination of seven scores in an in vivo model of regional myocardial ischaemia', Cardiovasc Res, vol. 22, no. 9, Sep, pp. 656-665.