Relevance of anaesthesia for dofetilide-induced torsades de pointes in alpha(1)-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 clas...

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Elmentve itt :
Bibliográfiai részletek
Szerzők: Vincze D
Farkas Attila
Rudas László
Makra Péter
Csík Norbert
Leprán István
Forster Tamás
Csanády Miklós
Papp Gyula
Varró András
Farkas András
Dokumentumtípus: Cikk
Megjelent: 2008
Sorozat:BRITISH JOURNAL OF PHARMACOLOGY 153 No. 1
Tárgyszavak:
doi:10.1038/sj.bjp.0707536

mtmt:1132583
Online Access:http://publicatio.bibl.u-szeged.hu/22862
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520 3 |a 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. 
650 4 |a Klinikai orvostan 
700 0 1 |a Farkas Attila  |e aut 
700 0 1 |a Rudas László  |e aut 
700 0 1 |a Makra Péter  |e aut 
700 0 1 |a Csík Norbert  |e aut 
700 0 1 |a Leprán István  |e aut 
700 0 1 |a Forster Tamás  |e aut 
700 0 1 |a Csanády Miklós  |e aut 
700 0 1 |a Papp Gyula  |e aut 
700 0 1 |a Varró András  |e aut 
700 0 1 |a Farkas András  |e aut 
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