title: Frequency-dependent electrophysiologic effects of d,l-sotalol and quinidine and modulation by beta-adrenergic stimulation.
abstract: BACKGROUND
  Frequency-dependent electrophysiologic actions of oral quinidine and oral sotalol may be clinically important, but these properties and their modulation by beta-adrenergic sympathetic stimulation have not been determined.
  
  
  RESULTS
  The frequency-dependent effects of oral quinidine (n = 17) and oral d,l-sotalol (n = 17) were determined at: (1) drug-free baseline; (2) during steady-state drug dosing; and (3) during isoproterenol infusion to patients receiving quinidine or d,l-sotalol. The monophasic APD90 and RVERP were prolonged 12% to 17% (P < 0.001) during pharmacologic therapy, and frequency-dependent effects were only observed for the RVERP during sotalol. In both drug groups, isoproterenol significantly reduced the sinus cycle length and reduced the RVERP to a greater extent at longer than at shorter paced cycle lengths. While isoproterenol fully reversed quinidine's effects on the APD90 and RVERP, sotalol-induced APD90 prolongation was reduced by only 2% to 4%, and the RVERP was unaffected. Isoproterenol attenuated the frequency-dependent effects of quinidine on QRS duration by a relatively fixed amount of 7% to 10%. Isoproterenol fully reversed quinidine-induced, but did not affect sotalol-induced prolongation in the sustained VT cycle length.
  
  
  CONCLUSIONS
  (1) Over the range of examined cycle lengths, oral quinidine and d,l-sotalol did not exert frequency-dependent effects on ventricular repolarization. (2) Isoproterenol fully reversed quinidine's effects on refractoriness, repolarization, and prolongation of VT cycle length, whereas d,l-sotalol's effects were largely preserved, despite significant reductions in sinus cycle length. (3) These results suggest that beta-blockade is important in preventing reversal of antiarrhythmic drug effects by augmented sympathetic nervous system tone.
authors.affiliation: Division of Cardiology, Veterans Affairs Medical Center of West Los Angeles, CA 90073, USA.
authors.forename: P T
authors.initials: PT
authors.lastname: Sager
authors.forename: M
authors.initials: M
authors.lastname: Behboodikhah
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000284:Administration, Oral; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage; D000704:Analysis of Variance; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage*; D001341:Autonomic Nervous System / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D004562:Electrocardiography; D006801:Humans; D007545:Isoproterenol / Q000008:administration & dosage; D008875:Middle Aged; D011446:Prospective Studies; D011802:Quinidine / Q000008:administration & dosage*; D013015:Sotalol / Q000008:administration & dosage*; D017180:Tachycardia, Ventricular / Q000188:drug therapy / Q000503:physiopathology*
chemical_list: D000318:Adrenergic beta-Agonists; D000889:Anti-Arrhythmia Agents; D013015:Sotalol; D011802:Quinidine; D007545:Isoproterenol