Halothane sensitizes the canine heart to pharmacological IKr blockade.
The effects of halothane and pentobarbital on the cardiovascular system were compared using the in vivo canine models. The ventricular repolarization process was longer under the halothane-anesthesia than pentobarbital-anesthesia. Intravenous administration of a selective blocker of rapidly activating delayed rectifier K+ currents (I(Kr)) sematilide prolonged the ventricular repolarization period without affecting the intraventricular conduction under both anesthesia; however, the potency was about 1.5-folds greater under the halothane-anesthesia than pentobarbital-anesthesia. These results suggest that halothane can more effectively sensitize the heart to pharmacological I(Kr) blockade, resulting in the excessive QT interval prolongation. Thus, the halothane-anesthetized canine model can be useful for predicting the in vivo I(Kr) blocking property of new drugs.
Takahara
Akira
A
Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Tamaho-cho, Nakakoma-gun, Yamanashi 409-3898, Japan.
Sugiyama
Atsushi
A
Satoh
Yoshioki
Y
Wang
Kai
K
Honsho
Sachiko
S
Hashimoto
Keitaro
K
D000818:Animals; D027682:Cation Transport Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D051668:Delayed Rectifier Potassium Channels; D004285:Dogs; D051638:Ether-A-Go-Go Potassium Channels; D005260:Female; D006221:Halothane / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D008297:Male; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors* / Q000502:physiology
D027682:Cation Transport Proteins; D051668:Delayed Rectifier Potassium Channels; D051638:Ether-A-Go-Go Potassium Channels; C092509:KCNH6 protein, human; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D006221:Halothane