title: The class III antiarrhythmic effect of sotalol exerts a reverse use-dependent positive inotropic effect in the intact canine heart.
abstract: OBJECTIVE
  We sought to study the rate related effects of sotalol on myocardial contractility and to test the hypothesis that the class III antiarrhythmic effect of sotalol has a reverse use-dependent positive inotropic effect in the intact heart.
  
  
  BACKGROUND
  Antiarrhythmic drugs exert significant negative inotropic effects. Sotalol, a beta-adrenergic blocking agent with class III antiarrhythmic properties, may augment contractility by virtue of its ability to prolong the action potential duration (APD).
  
  
  METHODS
  In 10 anesthetized dogs, measurements of left ventricle (LV) peak (+)dP/dt and simultaneous endocardial action potentials were made during baseline conditions and after sequential administration of esmolol and sotalol. In addition, electrical and mechanical restitution curves were constructed at a basic pacing cycle length of 600 ms by introducing a test pulse of altered cycle length ranging from 200 ms to 2,000 ms.
  
  
  RESULTS
  In the steady state pacing experiments, sotalol prolonged the APD in a reverse use-dependent manner; such an effect was not seen with esmolol. At cycle lengths exceeding 400 ms, LV (+)dP/dt was significantly higher with sotalol than it was with esmolol. There was a direct relation between APD and LV (+)dP/dt with sotalol (r = 0.46, p < 0.001), but there was no significant relation between APD and LV (+)dP/dt with esmolol (r = 0.27, p = NS). Results in the single beat (restitution) studies were qualitatively similar to the steady state results; APD (at cycle length >400 ms) and LV (+)dP/dt (at cycle length >600 ms) were significantly higher with sotalol than they were with esmolol.
  
  
  CONCLUSIONS
  The reverse use-dependent prolongation of APD by sotalol is associated with a positive inotropic effect.
authors.affiliation: Section of Cardiovascular Medicine and Laser Research Laboratory, Lahey Clinic Medical Center, Burlington, Massachusetts, USA.
authors.forename: A O
authors.initials: AO
authors.lastname: Peralta
authors.forename: R M
authors.initials: RM
authors.lastname: John
authors.forename: W H
authors.initials: WH
authors.lastname: Gaasch
authors.forename: P I
authors.initials: PI
authors.lastname: Taggart
authors.forename: D T
authors.initials: DT
authors.lastname: Martin
authors.forename: F J
authors.initials: FJ
authors.lastname: Venditti
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000503:physiopathology*; D004195:Disease Models, Animal; D004285:Dogs; D004594:Electrophysiology / Q000379:methods; D005260:Female; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D011412:Propanolamines / Q000627:therapeutic use; D013015:Sotalol / Q000627:therapeutic use*
chemical_list: D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D013015:Sotalol; C036604:esmolol