Journal of Pharmacological Sciences (Sep 2019)

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

  • Ai Goto,
  • Mihoko Hagiwara-Nagasawa,
  • Koki Chiba,
  • Ryuichi Kambayashi,
  • Yoshio Nunoi,
  • Hiroko Izumi-Nakaseko,
  • Akio Matsumoto,
  • Yasunari Kanda,
  • Atsushi Sugiyama

Journal volume & issue
Vol. 141, no. 1
pp. 86 – 89

Abstract

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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