Quinidine/quinine: stereospecific electrophysiologic and antiarrhythmic effects in a canine model of ventricular tachycardia.
The two major electrophysiologic effects of quinidine are prolongation of refractoriness and prolongation of conduction time. To determine which of these effects contributes to its antiarrhythmic effect, we compared the electrophysiologic effects of quinidine and its stereoisomer quinine (which was expected to prolong conduction time but not refractoriness) in 24 dogs with inducible sustained ventricular tachyarrhythmia late after ischemic injury. Conscious but sedated animals were randomly assigned to receive infusions of saline, quinidine, or quinine. Serum concentrations of quinidine and quinine were 18 +/- 9 and 23 +/- 8 microM, respectively. Both drugs prolonged conduction times to a similar extent, but quinidine prolonged local repolarization times and refractoriness much more than quinine. Sustained ventricular tachyarrhythmia was consistently inducible during placebo (saline) studies. Antiarrhythmic efficacy was observed with quinidine (3 of 12) but not quinine (0 of 15) or saline (0 of 13) (p less than 0.05, Chi-square test). Quinidine also significantly prolonged monomorphic ventricular tachycardia (VT) cycle length (157 +/- 33 ms on quinidine vs. 129 +/- 26 ms at baseline, p less than 0.001) whereas quinine had no significant effect. Thus, prolonging refractoriness is important in preventing the induction of ventricular tachyarrhythmias and in prolonging VT cycle length.
Sheldon
R S
RS
Cardiovascular Research Group, University of Calgary, Alberta, Canada.
Rahmberg
M
M
Duff
H J
HJ
D000818:Animals; D004285:Dogs; D006329:Heart Conduction System / Q000187:drug effects* / Q000502:physiology; D011802:Quinidine / Q000494:pharmacology* / Q000627:therapeutic use; D011803:Quinine / Q000494:pharmacology* / Q000627:therapeutic use; D012032:Refractory Period, Electrophysiological / Q000187:drug effects*; D013610:Tachycardia / Q000188:drug therapy / Q000503:physiopathology*
D011803:Quinine; D011802:Quinidine