title: Effect of sodium channel blocker, pilsicainide hydrochloride, on net inward current of atrial myocytes in thyroid hormone toxicosis rats.
abstract: To investigate effect of pilsicainide hydrochloride (pilsicainide) on electrocardiogram (ECG) signals and action potentials (APs) of atrial myocytes, levo-thyroxine (T4, 500 microg/kg body weight) was daily injected into peritoneal cavity of Sprague-Dawley rats for 14 days. T4-treatment significantly shortened RR interval, P wave, and QRS complex durations on ECG. Although pilsicainide did not affect the heart rate, P wave and corrected QT interval (QTc) was increased in T4-treated rats. AP recordings revealed that AP durations at 20%, 50%, and 90% repolarization were significantly shortened and maximal rate of rise (Max dV/dt) was significantly increased in T4-treated rat atrial cells. Pilsicainide significantly decreased AP amplitude (APA) and Max dV/dt in both control and T4-treated rat atrial cells. Concentration-inhibition study demonstrated that pilsicainide significantly inhibited net inward current of T4-treated rats at lower concentration (IC50 of 29.2 microg/mL) than that of control rats (133 microg/mL). In conclusion, pilsicainide could decrease the conduction velocity in T4-treated rat atrium by decreasing the Max dV/dt and net inward current, which could be a possible treatment of thyrotoxicosis-induced arrhythmia.
authors.affiliation: Department of Endocrinology and Metabolism, University of the Ryukyus, Okinawa, Japan.
authors.forename: Munesada
authors.initials: M
authors.lastname: Yamakawa
authors.forename: Masanori
authors.initials: M
authors.lastname: Sunagawa
authors.forename: Michio
authors.initials: M
authors.lastname: Shimabukuro
authors.forename: Namio
authors.initials: N
authors.lastname: Higa
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takasu
authors.forename: Tadayoshi
authors.initials: T
authors.lastname: Kosugi
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000209:etiology*; D004562:Electrocardiography; D006325:Heart Atria / Q000166:cytology; D008012:Lidocaine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D013971:Thyrotoxicosis / Q000139:chemically induced / Q000150:complications*; D013974:Thyroxine
chemical_list: D026941:Sodium Channel Blockers; D008012:Lidocaine; D012964:Sodium; C042288:pilsicainide; D013974:Thyroxine