Anesthesia and arrhythmogenesis in the chronic atrioventricular block dog model.
BACKGROUND
Drug-induced torsade de pointes (TdP) arrhythmias can readily be induced in anesthetized dogs with remodeled hearts [chronic complete atrioventricular block (CAVB) dogs]. Similar studies in conscious CAVB dogs reveal lower TdP incidences. Regulations forced us to reconsider our anesthetic regimen, which consist of pentobarbital followed by halothane (P + H). We investigated the relevance of anesthesia for this enhanced susceptibility (part 1) and compared 3 anesthetic regimens (part 2).


METHODS
Part 1-Ten CAVB dogs paced from the high septum at 1000 milliseconds were challenged with dofetilide (25 microg x kg(-1) x 5 min(-1)) twice: once under anesthesia and once awake. Anesthesia consisted of P + H (n = 5) and thiopental maintained by isoflurane (T + I). Part 2-In CAVB dogs (n = 6) with spontaneous idioventricular rhythm, the electrophysiological and arrhythmogenic consequences of different anesthetic regimens (P + H, T + I, and P + I) were serially compared.


RESULTS
Part 1-In paced dogs, dofetilide-induced TdP was higher under anesthetized than in conscious circumstances, with the more severe outcome seen after T + I as compared with P + H or control (2x): 5/5, 2/5, 0/5, and 0/5, respectively; P < 0.05. Part 2-Electrophysiologically, T accelerated idioventricular rhythm, increased QTc, and transiently induced polymorphic ventricular tachycardias in 2 of 6 dogs. This was not seen after P. At 120 minutes (end of the preparation), QTc increase was highest after T + I, intermediate with P + I, and the smallest after P + H. Dofetilide in combination with T + I induced the most severe arrhythmogenic outcome.


CONCLUSIONS
Thiopental anesthesia causes arrhythmias sec, whereas anesthesia in general predisposes for drug-induced TdP in the CAVB dog. In combination with dofetilide, T + I has a more arrhythmic outcome than P + I or P + H.
Dunnink
Albert
A
Department of Medical Physiology, Division of Heart and Lungs, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands.
Sharif
Shahnam
S
Oosterhoff
Peter
P
Winckels
Stephan
S
Montagne
Denise
D
Beekman
Jet
J
van der Nagel
Roel
R
van der Heyden
Marcel A G
MA
Vos
Marc A
MA
D000758:Anesthesia / Q000009:adverse effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D054537:Atrioventricular Block; D004285:Dogs; D005260:Female; D006221:Halothane / Q000009:adverse effects; D006327:Heart Block / Q000209:etiology / Q000503:physiopathology*; D007530:Isoflurane / Q000009:adverse effects; D008297:Male; D010627:Phenethylamines; D013449:Sulfonamides; D013874:Thiopental / Q000009:adverse effects; D016171:Torsades de Pointes / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology
D010627:Phenethylamines; D013449:Sulfonamides; D007530:Isoflurane; D013874:Thiopental; C063533:dofetilide; D006221:Halothane