title: Antiviral drug vidarabine possessing cardiac type 5 adenylyl cyclase inhibitory property did not affect cardiohemodynamic or electrophysiological variables in the halothane-anesthetized dogs.
abstract: Vidarabine has been used for the treatment of patients with local and systemic herpes virus infection; moreover, it was recently reported that it inhibits cardiac type 5 adenylyl cyclase. Furthermore, vidarabine has been shown to suppress atrial fibrillation and improve congestive heart failure in experimental models of mice induced by the isoproterenol infusion. Since information that can explain its experimentally demonstrated efficacy against congestive heart failure and atrial fibrillation remains limited, in this study we precisely assessed cardio-electropharmacological effect using the halothane-anesthetized canine model. Vidarabine was intravenously administrated in three escalating doses of 1, 10, 100 mg/kg over 10 min with a pause between the doses (n = 4). Meanwhile, the vehicle dimethyl sulfoxide in volumes of 0.033, 0.033 and 0.33 mL/kg was intravenously administrated in the same manner as was vidarabine (n = 4). No significant difference was detected in any cardiohemodynamic or electrophysiological variables between the vehicle- and vidarabine-treated groups, which indicates that effective doses of vidarabine adequately inhibiting type 5 adenylyl cyclase did not affect the cardiovascular variables in vivo at all, showing its cardiac safety profile under physiological condition. Thus, the clinical utility of vidarabine might be limited to the pathological situation including congestive heart failure with increased adrenergic tone and/or sympathetic nerve-dependent atrial fibrillation.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Toho University.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Wada
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Xin
authors.initials: X
authors.lastname: Cao
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohara
authors.forename: Hiroko
authors.initials: H
authors.lastname: Izumi-Nakaseko
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ando
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakazato
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sugiyama
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000769:Anesthesia, Inhalation; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001281:Atrial Fibrillation / Q000188:drug therapy; D004285:Dogs; D055724:Electrophysiological Phenomena / Q000187:drug effects*; D006221:Halothane; D006333:Heart Failure / Q000188:drug therapy; D006439:Hemodynamics / Q000187:drug effects*; D007262:Infusions, Intravenous; D008297:Male; D023421:Models, Animal; D014740:Vidarabine / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D000998:Antiviral Agents; D014740:Vidarabine; D006221:Halothane