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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
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نویسنده
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sugiyama a. ,nakamura y. ,akie y. ,saito h. ,izumi y. ,yamazaki h. ,kaneko n. ,itoh k.
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منبع
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journal of pharmacological sciences - 2011 - دوره : 115 - شماره : 2 - صفحه:122 -126
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چکیده
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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. © the japanese pharmacological society.
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کلیدواژه
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Atrioventricular block; dl-sotalol; Long QT syndrome; Microminipig; Torsades de pointes
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آدرس
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department of pharmacology,school of medicine,toho university,5-21-16,omori-nishi,ota-ku,tokyo 143-8540,japan,yamanashi research center of clinical pharmacology,73-5 hatta,isawa-cho,fuefuki-city,yamanashi 406-0023, Japan, department of pharmacology,school of medicine,toho university,5-21-16,omori-nishi,ota-ku,tokyo 143-8540,japan,yamanashi research center of clinical pharmacology,73-5 hatta,isawa-cho,fuefuki-city,yamanashi 406-0023, Japan, department of pharmacology,school of medicine,toho university,5-21-16,omori-nishi,ota-ku,tokyo 143-8540,japan,sugi institute of biological science,10221 kobuchizawa-cho,hokuto-city,yamanashi 408-0044, Japan, sugi institute of biological science,10221 kobuchizawa-cho,hokuto-city,yamanashi 408-0044, Japan, department of pharmacology,osaka city university medical school,1-4-3 asahimachi,abeno-ku,osaka 545-8585, Japan, laboratory of drug metabolism and pharmacokinetics,showa pharmaceutical university,3-3165 higashitamagawagakuen,machida-city,tokyo 194-8543, Japan, fuji micra inc.,260 miyabara,fujinomiya-city,shizuoka 418-0005, Japan, fuji micra inc.,260 miyabara,fujinomiya-city,shizuoka 418-0005, Japan
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Authors
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