DEXMEDETOMIDINE PREVENTS EPINEPHRINE-INDUCED ARRHYTHMIAS THROUGH STIMULATION OF CENTRAL ALPHA-2 ADRENOCEPTORS IN HALOTHANE-ANESTHETIZED DOGS

Since alpha-2-adrenergic agonists have important effects on the adrenergic system that have recently been applied to the anesthetic setting, we investigated the effect of stimulation of alpha-2 adrenoceptors on epinephrine-induced arrhythmias in halothane-anesthetized dogs. The arrhythmogenic threshold for epinephrine was determined during halothane anesthesia in the presence of dexmedetomidine, a selective alpha-2 agonist, and L-medetomidine, a stereoisomer of medetomidine that lacks alpha-2-agonist activity. Dexmedetomidine increased the arrhythmogenic threshold for epinephrine in a dose-dependent manner during halothane anesthesia. At the highest dose of dexmedetomidine, 0.5-mu-g . kg-1 . min-1, there was a three-fold increase in both the arrhythmogenic dose of epinephrine and the plasma epinephrine concentration that was reached at this dose. On the other hand, L-medetomidine over the same dose range did not effect the arrhythmogenic dose of epinephrine. Atipamezole, a central alpha-2 antagonist that crosses the blood-brain barrier, blocked the antiarrhythmic action of dexmedetomidine. L-659,066 a peripheral alpha-2 antagonist that does not penetrate the blood-brain barrier, did not affect the antiarrhythmic action of dexmedetomidine. Thus, dexmedetomidine's antiarrhythmic effect on epinephrine-induced arrhythmias during halothane anesthesia appears to be mediated at least in part by stimulation of central alpha-2 adrenoceptors.