Electrophysiological Characteristics of Canine Superior Vena Cava Sleeve Preparations Effect of Ranolazine

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. Methods and Results-Action potentials (APs) were recorded from superfused SVC and PV sleeves using microelectrode techniques. Acetylcholine (1 mu mol/L), isoproterenol (1 mu mol/L), high calcium ([Ca2+](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 mu mol/L) or ranolazine (10 mu mol/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 mu mol/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. (Circ Arrhythm Electrophysiol. 2012;5:371-379.)