title: Halothane sensitizes the canine heart to pharmacological IKr blockade.
abstract: 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.
authors.affiliation: Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Tamaho-cho, Nakakoma-gun, Yamanashi 409-3898, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Takahara
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sugiyama
authors.forename: Yoshioki
authors.initials: Y
authors.lastname: Satoh
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Sachiko
authors.initials: S
authors.lastname: Honsho
authors.forename: Keitaro
authors.initials: K
authors.lastname: Hashimoto
mesh_terms: 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
chemical_list: 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