Inhibition of Delayed Rectifier K^+ Current by Dofetilide and E-4031 Differentially Affects Electrical Cardiac Responses to Vagus Stimulation in Anesthetized Dogs

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Author(s)

Abstract

Vagal activation influences various cardiac functions as well as occurrence of arrhythmias. Inhibition of a rapid type of delayed rectifier K<SUP>+</SUP> current (I<SUB>Kr</SUB>) has been reported to be effective for the treatment of both ventricular and supraventricular arrhythmias. However, it is unknown how I<SUB>Kr</SUB> inhibition modulates the cardiac responses to vagal activation in situ. We analyzed the effects of I<SUB>Kr</SUB> inhibitors, dofetilide and E-4031, and a class I antiarrhythmic agent, disopyramide, on electrical cardiac responses to vagus stimulation in anesthetized dogs. Dofetilide (0.003 – 0.3 μmol/kg, i.v.), E-4031 (0.01 – 1 μmol/kg, i.v.) and disopyramide (2.9 – 29 μmol/kg, i.v.) prolonged sinus cycle length (SCL), right atrial effective refractory period (AERP) and ventricular effective refractory period (VERP) dose-dependently. During cervical vagus stimulation-induced prolongation of SCL, atrio-His (AH) interval and VERP and shortening of AERP, dofetilide and E-4031 inhibited the prolongation of SCL but potentiated the shortening of AERP. Dofetilide and E-4031 did not affect prolongations of AH interval and VERP. On the other hand, disopyramide inhibited all electrical cardiac responses to vagus stimulation. These results suggest that I<SUB>Kr</SUB> inhibition differentially modulate cardiac responses to vagus activation probably due to a different role of I<SUB>Kr</SUB> in each cardiac function in the heart in situ.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 76(1), 31-37, 1998-01

    The Japanese Pharmacological Society

References:  30

Cited by:  1

Codes

  • NII Article ID (NAID)
    10008191008
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    00215198
  • NDL Article ID
    4395855
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
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