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 microgram.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 crossed 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.
Department of Anesthesiology, National Cardiovascular Center, Osaka, Japan.
Y
Y
Hayashi
K
K
Sumikawa
M
M
Maze
A
A
Yamatodani
T
T
Kamibayashi
M
M
Kuro
I
I
Yoshiya
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000769:Anesthesia, Inhalation; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000517:prevention & control*; D001794:Blood Pressure; D004285:Dogs; D004837:Epinephrine / Q000037:antagonists & inhibitors* / Q000097:blood; D005260:Female; D006221:Halothane; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D020926:Medetomidine; D013237:Stereoisomerism
D000316:Adrenergic alpha-Agonists; D007093:Imidazoles; D020926:Medetomidine; D006221:Halothane; D004837:Epinephrine