Effects of verapamil, diltiazem and disopyramide on sinus function: a comparison with bepridil.
Cardiac drugs known to affect sinus function mostly exhibit negative chronotropic activity. However, impulse conduction within the sinus node can also be influenced. Recently we studied the direct effects of bepridil on rabbit sinus function. It appeared that sinoatrial impulse conduction was depressed markedly with drug concentrations that did not affect sinus automaticity. In the present study the direct effects of verapamil, diltiazem and disopyramide on rabbit sinus function and atrial conduction properties were studied. Verapamil (8.8 x 10(-8) M) reduced the sinoatrial impulse conduction velocity by 35% and prolonged sinoatrial refractoriness by 36%. On the other hand, the sinus rate and atrial conduction parameters were hardly affected. Diltiazem (5 x 10(-6) M) exerted similar actions on the sinoatrial impulse conduction velocity and caused a simultaneous reduction in the sinus rate of 48%. Atrial conduction remained unaffected. Disopyramide (5 x 10(-5) M) depressed both the atrial and nodal conduction properties markedly, whereas the sinus rate was reduced moderately, by almost 20%. Thus, verapamil, diltiazem and disopyramide act differently on sinus function and atrial conduction, whereby the predominant effect of verapamil and diltiazem on sinoatrial conduction properties favours the occurrence of a sinus exit block.
Kirchhof
C J
CJ
Department of Physiology, University of Limburg, Maastricht, The Netherlands.
Bonke
F I
FI
Allessie
M A
MA
D000818:Animals; D015764:Bepridil; D004110:Diltiazem / Q000494:pharmacology*; D004206:Disopyramide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D011759:Pyrrolidines / Q000494:pharmacology*; D011817:Rabbits; D012849:Sinoatrial Node / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology*
D011759:Pyrrolidines; D015764:Bepridil; D014700:Verapamil; D004110:Diltiazem; D004206:Disopyramide