Effects of verapamil and diltiazem on the ventricular rate during simulated atrial flutter in isolated guinea pig hearts.
To compare the direct effects of verapamil and diltiazem on the ventricular rate during atrial flutter, we developed an atrial flutter model in guinea pig isolated hearts. Atrial flutter was simulated by rapid atrial pacing (cycle length = 50 ms). At this atrial pacing cycle length, the shape of the frequency of distribution of the ventricular cycle lengths was comparable to that during spontaneous atrial flutter. Verapamil (0.01, 0.03 microM) and diltiazem (0.03, 0.09 microM) caused a comparable prolongation of the atrioventricular conduction time and atrioventricular refractoriness. Also, the anterograde Wenckebach cycle length was increased to a comparable degree by both substances. The mean ventricular cycle length during atrial flutter was comparable prolonged by both substances. The prolongation of the maximal ventricular cycle length was significantly more pronounced in the presence of verapamil. The time dependence of drug-induced alterations in atrioventricular conduction time during abrupt changes of heart rate is significantly more pronounced in the presence of verapamil compared to diltiazem. In conclusion, the more pronounced effect of verapamil on the maximal ventricular cycle length compared to the action of diltiazem may be explained by the slow binding kinetic of this drug to the Ca2+ channel resulting in a longlasting blockade of the Ca2+ channel.
Stark
U
U
Department of Internal Medicine, Karl-Franzens-University, Graz, Austria.
Stark
G
G
Kasper
K
K
Decrinis
M
M
Domanovits
H
H
Sterz
F
F
Belardinelli
L
L
Tritthart
H A
HA
D000818:Animals; D001282:Atrial Flutter / Q000503:physiopathology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology*; D004195:Disease Models, Animal; D004562:Electrocardiography; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects; D016276:Ventricular Function / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D014700:Verapamil; D004110:Diltiazem