Effects of bepridil on conduction properties of the isolated rabbit sinus node and atrial myocardium.
In the isolated rabbit sinus node and right atrial myocardium, the effects of bepridil (1-6 x 10(-6) M) on impulse formation, impulse conduction, and tissue refractoriness were examined. In the sinus node, drug concentrations between 1 and 3 x 10(-6) M were tested. In the border zone of the sinus node, bepridil (3 x 10(-6) M) reduced impulse conduction velocity by 65% and prolonged the effective refractory period by 81% (n = 11). In the center of the sinus node, bepridil in a concentration of 2.5 x 10(-6) M decreased impulse conduction velocity by 78% and prolonged effective refractory period by 77% (n = 9), whereas a drug concentration of 3 x 10(-6) M blocked impulse conduction systematically. Despite these marked effects on nodal conduction properties, only limited effects on sinus rate were found. Conduction properties in the atrium were affected by bepridil as well, but higher concentrations (4-6 x 10(-6) M) were needed. Impulse conduction velocity was decreased by 57%, and the effective refractory period was prolonged by 73% (6 x 10(-6) M; n = 8). At these higher drug concentrations, sinus automaticity decelerated and ceased abruptly, after which only subthreshold oscillations were detectable. From these findings, we concluded that (a) bepridil reduces impulse conduction velocity and prolongs refractoriness in the sinus node, less markedly in the atrial myocardium; (b) bepridil affects nodal impulse conduction prior to nodal impulse formation; and (c) bepridil possesses both "fast channel" and "slow channel" inhibitory properties.
Kirchhof
C J
CJ
Department of Physiology, University of Limburg, Maastricht, Netherlands.
Bonke
F I
FI
Allessie
M A
MA
Huijberts
M S
MS
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D015764:Bepridil; D005260:Female; D006321:Heart / Q000187:drug effects*; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D011759:Pyrrolidines / Q000494:pharmacology*; D011817:Rabbits; D012849:Sinoatrial Node / Q000187:drug effects*
D000889:Anti-Arrhythmia Agents; D011759:Pyrrolidines; D015764:Bepridil