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.