title: Electrophysiological characteristics of canine superior vena cava sleeve preparations: effect of ranolazine.
abstract: BACKGROUND
  In addition to extrasystoles of pulmonary vein (PV) origin, those arising from the superior vena cava (SVC) can precipitate atrial fibrillation (AF). The present study evaluates the electrophysiological properties of canine SVC sleeve preparations and the effect of ranolazine on late phase 3 early and delayed afterdepolarization (EAD and DAD)-induced triggered activity in SVC sleeves and compares SVC and PV sleeve electrophysiological properties.
  
  
  RESULTS
  Action potentials (APs) were recorded from superfused SVC and PV sleeves using microelectrode techniques. Acetylcholine (1 μmol/L), isoproterenol (1 μmol/L), high calcium ([Ca(2+)](o)=5.4 mmol/L), or a combination were used to induce EADs, DADs, and triggered activity. A marked diversity of action potential characteristics was observed in the SVC sleeve, including action potentials with short and long APs, with and without phase 4 depolarization. Rapid pacing induced hyperpolarization, accentuating the slope of phase 4 depolarization. Phase 4 depolarization and rapid pacing-induced hyperpolarization were reduced or eliminated after atropine (10 μmol/L) or ranolazine (10 μmol/L). APs displaying phase 4 depolarization (n=19) had longer APDs, smaller amplitude and V(max), and a more positive take-off potential than APs lacking phase 4 depolarization (n=15). Ranolazine (5-10 μmol/L) eliminated late phase 3 EAD- and DAD-induced triggered activity as well as isoproterenol-induced automaticity elicited in SVC sleeves. Compared with PV, SVC sleeves display phase 4 depolarization, smaller V(max), and longer APs.
  
  
  CONCLUSIONS
  Autonomic influences promote spontaneous automaticity and triggered activity in SVC sleeves, thus generating extrasystolic activity capable of initiating atrial arrhythmias. Ranolazine can effectively suppress these triggers.
authors.affiliation: Masonic Medical Research Laboratory, Utica, NY 13501-1787, USA. sicouris@mmrl.edu
authors.forename: Serge
authors.initials: S
authors.lastname: Sicouri
authors.forename: Jonathan
authors.initials: J
authors.lastname: Blazek
authors.forename: Luiz
authors.initials: L
authors.lastname: Belardinelli
authors.forename: Charles
authors.initials: C
authors.lastname: Antzelevitch
mesh_terms: D000083:Acetanilides / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001281:Atrial Fibrillation / Q000503:physiopathology / Q000517:prevention & control; D001285:Atropine / Q000494:pharmacology; D004285:Dogs; D055724:Electrophysiological Phenomena / Q000187:drug effects* / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D023421:Models, Animal; D010042:Ouabain / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D011667:Pulmonary Veins / Q000187:drug effects / Q000502:physiology; D000069458:Ranolazine; D014683:Vena Cava, Superior / Q000187:drug effects* / Q000502:physiology*
chemical_list: D000083:Acetanilides; D000889:Anti-Arrhythmia Agents; D004791:Enzyme Inhibitors; D010879:Piperazines; D010042:Ouabain; D001285:Atropine; D000069458:Ranolazine