15 research outputs found
Relevance of anaesthesia for dofetilide-induced torsades de pointes in α1-adrenoceptor-stimulated rabbits
Background and purpose: No information is available concerning the
effects of anaesthetics in the most frequently used in vivo
pro-arrhythmia model. Accordingly, in this study we examined the effect
of pentobarbital, propofol or alpha-chloralose anaesthesia on the
pro-arrhythmic activity of the class III anti-arrhythmic dofetilide in
alpha(1)-adrenoceptor-stimulated rabbits.
Experimental approach: Rabbits anaesthetized intravenously with
pentobarbital, propofol or alpha-chloralose were infused simultaneously
with the alpha(1)-adrenoceptor agonist phenylephrine (15 mu g kg(-1)
min(-1), i.v.) and dofetilide (0.04mg kg(-1) min(-1), i.v.). The
electrocardiographic QT interval, the T-peak-T-end interval and certain
QT variability parameters were measured. The heart rate variability and
the baroreflex sensitivity were utilized to assess the vagal nerve
activity. The spectral power of the systolic arterial pressure was
calculated in the frequency range 0.15-0.5 Hz to assess the sympathetic
activity.
Key results: Pentobarbital considerably reduced, whereas propofol did
not significantly affect the incidence of dofetilide-induced torsades
de pointes (TdP) as compared with the results with alpha-chloralose
(40%(P=0.011) and 70% (P=0.211) vs 100%, respectively). In additional
experiments, neither doubling of the rate of the dofetilide infusion
nor tripling of the rate of phenylephrine infusion elevated the
incidence of TdP to the level seen with alpha-chloralose. None of the
repolarization-related parameters predicted TdP. The indices of the
parasympathetic and sympathetic activity were significantly depressed
in the alpha-chloralose and propofol anaesthesia groups.
Conclusions and implications: In rabbits, anaesthetics may affect
drug-induced TdP genesis differently, which must be considered when
results of different studies are compared