The effect of vernakalant (RSD1235), an investigational antiarrhythmic agent, on atrial electrophysiology in humans.
OBJECTIVE
To determine the acute effects of vernakalant (RSD1235) on electrophysiologic (EP) properties in humans.


BACKGROUND
Vernakalant is an investigational mixed ion channel blocker that can terminate acute atrial fibrillation (AF) in humans at 2 to 5 mg/kg and may be more "atrial-selective" than available agents.


METHODS
Patients (N=19; 53% male; age, 48+/-11 years) underwent EP study before and after 25 minutes of intravenous vernakalant administration: 2 mg/kg over 10 min+0.5 mg/kg/hr for 35 min or 4 mg/kg over 10 min+1 mg/kg/hr for 35 min. EP measurements, including atrial refractory period (AERP) and ventricular refractory period (VERP), were obtained.


RESULTS
The lower dose prolonged AERP at 600, but not at 400 or 300 msec paced cycle length. The higher dose significantly prolonged AERP from 203+/-31 msec to 228+/-24 msec at 600 msec, 182+/-30 msec to 207+/-27 msec at 400 msec, and 172 msec+/-24 to 193+/-21 msec at 300 msec. There was no significant prolongation of VERP at either dose or at any cycle length. There was a small but significant prolongation of AV nodal refractoriness; Wenckebach cycle length prolonged by 18+/-12 msec (from baseline 343+/-54 msec) at the higher dose (P<0.05). Sinus node recovery time also increased by 123+/-158 msec (from baseline 928+/-237 msec) at the higher dose (P<0.05). There was a slight prolongation of QRS duration at the higher dose, during ventricular pacing at CL=400 msec (15+/-15 msec, P=0.0547). QT and HV intervals were unchanged.


CONCLUSIONS
At doses similar to those tested clinically, vernakalant dose-dependently prolonged atrial refractoriness, prolonged AV nodal conduction and refractoriness, and slightly prolonged QRS duration, but it had no effect on ventricular refractoriness.
Dorian
Paul
P
St. Michael's Hospital, and University of Toronto, Toronto, Ontario, Canada. dorianp@smh.toronto.on.ca
Pinter
Arnold
A
Mangat
Iqwal
I
Korley
Victoria
V
Cvitkovic
Suzan S
SS
Beatch
Gregory N
GN
D000328:Adult; D000840:Anisoles / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D016275:Atrial Function / Q000187:drug effects*; D001283:Atrioventricular Node / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D004594:Electrophysiology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D012032:Refractory Period, Electrophysiological; D012849:Sinoatrial Node / Q000187:drug effects; D016276:Ventricular Function / Q000187:drug effects
D000840:Anisoles; D000889:Anti-Arrhythmia Agents; D011759:Pyrrolidines; C524581:vernakalant