Oral administration of dl-sotalol (10 mg/kg) to atrioventricular-block Microminipigs prolonged the QT interval and frequently induced dangerous ventricular premature beats, establishing its utility as a proarrhythmia model.
Does oral dl-sotalol induce QT prolongation and ventricular arrhythmias in an AV-block Microminipig model compared to vehicle?
The AV-block Microminipig provides a sensitive and specific non-rodent in vivo model for detecting drug-induced long QT syndrome and proarrhythmia.
A new in vivo proarrhythmia model of drug-induced long QT syndrome was developed using the Microminipig, an incredibly small minipig established by Fuji Micra Inc. (Shizuoka). The atrioventricular (AV) node of the Microminipig of either sex weighing approximately 6 - 7 kg was ablated under halothane anesthesia, and proper care was taken for them. Proarrhythmic effects of drugs were assessed at >2 months after the onset of AV block using a Holter recording system. Oral administration of dl-sotalol (10 mg/kg) to the AV-block Microminipig prolonged the QT interval; moreover, it frequently induced dangerous ventricular premature beats, whereas no arrhythmia was detected after the vehicle administration (n = 4). Such dl-sotalol-induced ventricular arrhythmias were not detected in the intact Microminipig with sinus rhythm, although significant QT prolongation was observed (n = 4). Thus, the sensitivity and specificity of the AV-block Microminipig for detecting the drug-induced long QT syndrome can be considered to be comparable to previously established AV-block animal models of dogs and monkeys.
Sugiyama et al. (Sat,) conducted a other in Drug-induced long QT syndrome (n=8). dl-sotalol vs. Vehicle was evaluated on Induction of ventricular arrhythmias (ventricular premature beats, R on T phenomenon, slow ventricular tachycardia). Oral administration of dl-sotalol (10 mg/kg) to atrioventricular-block Microminipigs prolonged the QT interval and frequently induced dangerous ventricular premature beats, establishing its utility as a proarrhythmia model.