title: Differential effects of isoproterenol on sustained ventricular tachycardia before and during procainamide and quinidine antiarrhythmic drug therapy.
abstract: BACKGROUND
  Autonomic modulation, especially increased sympathetic activity may play a role in the genesis of ventricular arrhythmias. The purpose of this study was to determine whether beta-sympathetic stimulation with isoproterenol would alter sustained ventricular tachycardia (VT) circuits similarly during the drug-free and antiarrhythmic drug-treated states.
  
  
  RESULTS
  Twenty-five patients with repeatedly inducible, hemodynamically stable, sustained VT were evaluated by programmed ventricular stimulation. In the antiarrhythmic drug-free state, isoproterenol (0.03 microgram/kg per minute) shortened the following intervals (in milliseconds; mean +/- SEM; 25 patients; paired t test): sinus cycle length (792 +/- 37 to 568 +/- 18; (p < 0.001), ventricular paced QT interval (386 +/- 8 to 348 +/- 6; p < 0.001), ventricular paced QRS duration (185 +/- 4 to 182 +/- 4; p = 0.014), ventricular effective (238 +/- 5 to 208 +/- 4; p < 0.001) and functional (261 +/- 6 to 227 +/- 5; p < 0.001) refractory periods, and the VT cycle length (VTCL) (311 +/- 9 to 291 +/- 9; p < 0.001). Isoproterenol (0.03 microgram/kg per minute) was administered during 31 antiarrhythmic drug trials (procainamide, n = 18; quinidine, n = 13) in 22 patients. Isoproterenol shortened the sinus cycle length, QT interval during ventricular pacing, and ventricular effective and functional refractory periods before and during procainamide and quinidine therapy (ANOVA; isoproterenol effect, p < or = 0.0002 for all). The amount of decrease in these intervals with isoproterenol was the same before and during procainamide and quinidine therapy (ANOVA interaction, p = NS for all). The QRS duration during ventricular pacing and VTCL were also shortened by isoproterenol before and during procainamide (baseline, n = 17; QRS, 182 +/- 4 to 178 +/- 4 msec; VTCL, n = 18, 314 +/- 11 to 291 +/- 11 msec; during procainamide, QRS, 218 +/- 7 to 197 +/- 6 msec; VTCL, 422 +/- 15 to 359 +/- 11 msec) and quinidine (baseline, n = 13; QRS, 190 +/- 6 to 185 +/- 5 msec; VTCL, n = 12, 298 +/- 10 to 280 +/- 9 msec; during quinidine, QRS, 223 +/- 9 to 208 +/- 8 msec; VTCL, 415 +/- 14 to 355 +/- 10 msec) (isoproterenol effect p < or = 0.0003 for all). However, the amount of decrease in QRS duration and VTCL with isoproterenol was greater during procainamide and quinidine than in the drug-free state (ANOVA interaction, p < or = 0.02 for all). These changes continued to be significant when normalized for the initial QRS duration and VTCL (p < or = 0.03 for all).
  
  
  CONCLUSIONS
  Isoproterenol affects presumed reentrant sustained VT circuits less in the absence of antiarrhythmic drugs but markedly attenuates the antiarrhythmic drug-induced slowing of sustained VT. To the extent that the change in QRS duration reflects a change in conduction within the VT circuit, these data imply that the attenuation of drug-induced slowing of VT by isoproterenol is due to a greater change in conduction rather than refractoriness.
authors.affiliation: Krannert Institute of Cardiology, Indianapolis, Ind.
authors.forename: M L
authors.initials: ML
authors.lastname: Markel
authors.forename: W M
authors.initials: WM
authors.lastname: Miles
authors.forename: J C
authors.initials: JC
authors.lastname: Luck
authors.forename: L S
authors.initials: LS
authors.lastname: Klein
authors.forename: E N
authors.initials: EN
authors.lastname: Prystowsky
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D002304:Cardiac Pacing, Artificial; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D005260:Female; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D011342:Procainamide / Q000627:therapeutic use*; D011802:Quinidine / Q000627:therapeutic use*; D012032:Refractory Period, Electrophysiological; D017180:Tachycardia, Ventricular / Q000188:drug therapy / Q000503:physiopathology*
chemical_list: D011802:Quinidine; D011342:Procainamide; D007545:Isoproterenol