Role of potassium channels in halothane-epinephrine arrhythmias.
It has been reported that antiarrhythmic drugs possessing the property of potassium channel blockade were most effective in preventing halothane-epinephrine induced arrhythmias. Recent attention has focused on ATP-sensitive potassium (K(ATP)) channels because of their contribution to the cardiovascular actions of volatile anesthetics. The present study was designed to evaluate whether K(ATP) channels or transient outward potassium channels (Ito) were involved in the mechanism of halothane-epinephrine arrhythmias in rat. Rats were anesthetized with halothane (1.5%), and the lungs were mechanically ventilated. The arrhythmogenic thresholds of epinephrine during halothane anesthesia were determined in 74 rats receiving saline or one of tested agents. The arrhythmogenic dose of epinephrine (ADE) was significantly increased by a K(ATP) channel opener, JTV506 (P < 0.01), and had a tendency to be increased by other K(ATP) channel openers, cromakalim, nicorandil, KRN2391 and Y 26763, but were not affected by a K(ATP) channel blocker, glibenclamide. The Ito blocker, 4-aminopyridine, also significantly increased the ADE. Epinephrine produced second-degree or complete atrioventricular block in 4 out of 7 rats receiving glibenclamide. These results suggest that Ito but not K(ATP) channels might be involved in the mechanism in producing halothane-epinephrine arrhythmias.
Zhang
S
S
Department of Anesthesiology, Nagasaki University School of Medicine, Japan.
Todoroki
S
S
Urechino
H
H
Morooka
H
H
Makita
T
T
Shibata
O
O
Sumikawa
K
K
D000255:Adenosine Triphosphate / Q000378:metabolism; D018685:Anesthetics, Inhalation / Q000633:toxicity*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000517:prevention & control*; D001794:Blood Pressure / Q000187:drug effects; D004837:Epinephrine / Q000633:toxicity*; D006221:Halothane / Q000633:toxicity*; D006327:Heart Block / Q000139:chemically induced / Q000517:prevention & control; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D018685:Anesthetics, Inhalation; D015221:Potassium Channels; D000255:Adenosine Triphosphate; D006221:Halothane; D004837:Epinephrine