Pharmacological β-adrenoceptor blockade can augment torsadogenic action of IKr inhibitor: Comparison of proarrhythmic effects of d-sotalol and dl-sotalol in the chronic atrioventricular block dogs

• Main Authors: Ai Goto, Mihoko Hagiwara-Nagasawa, Koki Chiba, Ryuichi Kambayashi, Yoshio Nunoi, Hiroko Izumi-Nakaseko, Akio Matsumoto, Yasunari Kanda, Atsushi Sugiyama
• Format: Article
• Language: English
• Published: Elsevier 2019-09-01
• Series: Journal of Pharmacological Sciences
• Online Access: http://www.sciencedirect.com/science/article/pii/S1347861319357123

Information is still limited whether β-blockade may augment or attenuate the onset of torsade de pointes in patients with IKr inhibitor-induced labile repolarization process. We compared the proarrhythmic effects of d-sotalol with those of dl-sotalol using the chronic atrioventricular block dogs, since d- and l-isomers share a similar blocking action on IKr but β-blocking activity resides only in l-isomer. dl-Sotalol (3 mg/kg, p.o.) induced torsade de pointes in 3 out of 4 animals, whereas d-sotalol (3 mg/kg, p.o.) induced it in only 1 out of 4 animals. Thus, β-blockade can augment torsadogenic action of IKr inhibitor. Keywords: IKr inhibitor, β-blockade, Torsade de pointes