title: Atrial selective effects of intravenously administered vernakalant in conscious beagle dogs.
abstract: Vernakalant is a relatively atrial-selective antiarrhythmic drug approved for the conversion of recent onset atrial fibrillation in Europe and is under regulatory review in the United States. In this study, we examined the effects of intravenously administered vernakalant (5, 10, and 20 mg/kg) on blood pressure, heart rate, and the electrocardiogram in conscious male beagle dogs and compared them with those of orally administered dl-sotalol (32 mg/kg). Vernakalant had no consistent dose-dependent effects on the heart rate or mean arterial pressure. Although vernakalant inhibits I(Kr), it tended to decrease the QTc interval but only at the top dose and later time points. The most striking effect of vernakalant on the electrocardiogram was a dose-dependent and selective slowing of atrial conduction (P-wave duration), with no effect on ventricular conduction (QRS duration). In contrast, treatment with dl-sotalol resulted in a marked and statistically significant prolongation of PR and QTc intervals with no effect on QRS or P-wave duration, consistent with its known class II and III antiarrhythmic actions. These results provide further evidence that vernakalant is unlikely to alter ventricular refractoriness or conduction at plasma concentrations in excess of those necessary for conversion of atrial fibrillation to sinus rhythm in patients.
authors.affiliation: Cardiome Pharma Corp, Vancouver, Canada. jbechard@cardiome
authors.forename: Jeff
authors.initials: J
authors.lastname: Bechard
authors.forename: Marc
authors.initials: M
authors.lastname: Pourrier
mesh_terms: D000818:Animals; D000840:Anisoles / Q000008:administration & dosage*; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage; D016275:Atrial Function / Q000187:drug effects* / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003243:Consciousness / Q000187:drug effects* / Q000502:physiology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007262:Infusions, Intravenous; D008297:Male; D011759:Pyrrolidines / Q000008:administration & dosage*
chemical_list: D000840:Anisoles; D000889:Anti-Arrhythmia Agents; D011759:Pyrrolidines; C524581:vernakalant