title: Effects of verapamil and propranolol on early afterdepolarizations and ventricular arrhythmias induced by epinephrine in congenital long QT syndrome.
abstract: OBJECTIVE
  This study used monophasic action potentials to investigate the effects of verapamil and propranolol on epinephrine-induced repolarization abnormalities in congenital long QT syndrome.
  
  
  BACKGROUND
  Early afterdepolarizations have been suggested to play a significant role in QT prolongation and ventricular arrhythmias in congenital long QT syndrome. Calcium channel blocking as well as beta-adrenergic blocking agents are reported to be effective in the management of this syndrome.
  
  
  METHODS
  Monophasic action potentials from 2 to 4 sites were recorded simultaneously in eight patients with the long QT syndrome (22 sites) and in eight control patients (23 sites) and were obtained during constant atrial pacing 1) before epinephrine infusion; 2) during epinephrine infusion (0.1 microgram/kg body weight min); 3) after verapamil injection (0.1 mg/kg) during epinephrine infusion; and 4) after both propranolol (0.1 mg/kg) and verapamil injections.
  
  
  RESULTS
  Early afterdepolarizations were recorded in two of the eight patients (2 of 22 sites) during the control state. During epinephrine infusion, early afterdepolarizations were recorded in six patients (six sites), and ventricular premature complexes were induced in three and torsade de pointes in one. Epinephrine prolonged 90% monophasic action potential duration from 348 +/- 48 (mean +/- SD) to 381 +/- 49 ms (22 sites, p < 0.0005) and increased the dispersion of action potential duration (difference between the longest and shortest action potential duration) from 36 +/- 20 to 64 +/- 34 ms (p < 0.005). Verapamil eliminated (two sites) or reduced (four sites) early afterdepolarizations and abolished ventricular premature complexes in two of the three patients as well as suppressing torsade de pointes. Verapamil shortened the action potential duration to 355 +/- 28 ms (p < 0.01 vs. epinephrine) and decreased the dispersion to 44 +/- 19 ms (p < 0.05 vs. epinephrine). Propranolol further eliminated (two sites) or reduced (two sites) early after depolarizations, abolished ventricular premature complexes in the remaining one patient and further shortened the action potential duration to 337 +/- 32 ms (p = 0.09 vs. verapamil). In the control patients, none of the early afterdepolarizations, ventricular arrhythmias or marked prolongations of action potential duration were induced by epinephrine, and neither verapamil nor propranolol changed repolarization variables.
  
  
  CONCLUSIONS
  These results indicate that both verapamil and propranolol can improve repolarization abnormalities induced by epinephrine in congenital long QT syndrome.
authors.affiliation: Department of Internal Medicine, National Cardiovascular Center, Osaka, Japan.
authors.forename: W
authors.initials: W
authors.lastname: Shimizu
authors.forename: T
authors.initials: T
authors.lastname: Ohe
authors.forename: T
authors.initials: T
authors.lastname: Kurita
authors.forename: M
authors.initials: M
authors.lastname: Kawade
authors.forename: Y
authors.initials: Y
authors.lastname: Arakaki
authors.forename: N
authors.initials: N
authors.lastname: Aihara
authors.forename: S
authors.initials: S
authors.lastname: Kamakura
authors.forename: T
authors.initials: T
authors.lastname: Kamiya
authors.forename: K
authors.initials: K
authors.lastname: Shimomura
mesh_terms: D000200:Action Potentials; D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D001794:Blood Pressure; D002648:Child; D002675:Child, Preschool; D004347:Drug Interactions; D004837:Epinephrine / Q000009:adverse effects*; D006801:Humans; D008133:Long QT Syndrome / Q000151:congenital / Q000188:drug therapy / Q000503:physiopathology*; D008875:Middle Aged; D011433:Propranolol / Q000627:therapeutic use*; D014693:Ventricular Fibrillation / Q000139:chemically induced / Q000188:drug therapy*; D014700:Verapamil / Q000627:therapeutic use*
chemical_list: D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D011433:Propranolol; D014700:Verapamil; D004837:Epinephrine