Role of the vagus nerve in the antidysrhythmic effect of dexmedetomidine on halothane/epinephrine dysrhythmias in dogs.
BACKGROUND
Dexmedetomidine, an alpha 2-adrenergic agonist, can prevent the genesis of halothane/epinephrine dysrhythmias through the central nervous system. Because stimulation of alpha 2 adrenoceptors in the central nervous system enhances vagal neural activity and vagal stimulation is known to inhibit digitalis-induced dysrhythmias, dexmedetomidine may exert the antidysrhythmic property through vagal stimulation. To address this hypothesis, the effect of dexmedetomidine in vagotomized dogs was examined and compared with that in intact dogs. In addition, the effect of vagotomy on the antidysrhythmic action of doxazosin, an alpha 1 antagonist, was studied.


METHODS
Adult mongrel dogs were anesthetized with halothane (1.3%) and monitored continuously for systemic arterial pressure and premature ventricular contractions. Animals were divided into two groups receiving bilateral vagotomy or sham operation. The dysrhythmia threshold was expressed by the dysrhythmogenic dose of epinephrine, defined as the smallest dose producing four or more premature ventricular contractions within a 15-s period, and plasma concentration of epinephrine at the time when the dysrhythmogenic dose was reached. The threshold was determined in the presence of dexmedetomidine (a selective alpha 2 agonist that crosses the blood-brain barrier) and doxazosin (a selective alpha 1 antagonist that does not penetrate the blood-brain barrier) in the two groups. In addition, the effect of dexmedetomidine in the presence of atropine methylnitrate instead of vagotomy was examined.


RESULTS
Vagotomy did not affect the basal vulnerability to halothane/epinephrine dysrhythmias significantly. Although dexmedetomidine dose-dependently prevented the genesis of the dysrhythmias in intact dogs, the beneficial effect of dexmedetomidine was abolished in both the vagotomized and the atropine-treated dogs. On the other hand, vagotomy did not change the antidysrhythmic property of doxazosin.


CONCLUSIONS
The vagus nerve plays an important role in the prevention of halothane/epinephrine dysrhythmias by dexmedetomidine in dogs. However, resting vagal tone neither modulates the onset of halothane/epinephrine dysrhythmias nor affects the antidysrhythmic action of doxazosin.
D000316:Adrenergic alpha-Agonists / Q000097:blood / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000633:toxicity*; D000818:Animals; D004285:Dogs; D017292:Doxazosin / Q000494:pharmacology; D004347:Drug Interactions; D004837:Epinephrine / Q000097:blood / Q000633:toxicity*; D005260:Female; D006221:Halothane / Q000633:toxicity*; D006439:Hemodynamics / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D020926:Medetomidine; D011897:Random Allocation; D014628:Vagotomy; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*; D018879:Ventricular Premature Complexes / Q000139:chemically induced* / Q000517:prevention & control*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D018685:Anesthetics, Inhalation; D007093:Imidazoles; D020926:Medetomidine; D017292:Doxazosin; D006221:Halothane; D004837:Epinephrine