Microminipig, a non-rodent experimental animal optimized for life science research: in vivo proarrhythmia models of drug-induced long QT syndrome: development of chronic atrioventricular block model of microminipig.
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.
Department of Pharmacology, School of Medicine, Toho University, Tokyo 143-8540, Japan. atsushi.sugiyama@med.toho-u.ac.jp
Atsushi
A
Sugiyama
Yuji
Y
Nakamura
Yasuki
Y
Akie
Hiroyuki
H
Saito
Yasukatsu
Y
Izumi
Hiroshi
H
Yamazaki
Naoki
N
Kaneko
Katzuhiko
K
Itoh
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D054537:Atrioventricular Block / Q000139:chemically induced*; D001947:Breeding; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D008133:Long QT Syndrome / Q000139:chemically induced*; D008297:Male; D013015:Sotalol / Q000633:toxicity*; D013552:Swine; D013556:Swine, Miniature
D013015:Sotalol