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Dronedarone effects on atrial and ventricular electrophysiology in conscious dogs
Author(s) -
Neves Liomar A. A.,
Buening James,
Huang Jinbao,
Senese Peter B.,
Gralinski Michael R.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1053.3
Subject(s) - medicine , refractory period , dronedarone , cardiology , electrophysiology , atrial fibrillation , anesthesia , atrium (architecture) , beagle , amiodarone
Atrial and ventricular electrophysiological assessments in conscious dogs are relevant models to interrogate the selectivity of potential antiarrhythmic drugs. We investigate the selective effects of dronedarone (DRO) on atrial and ventricular effective refractoriness using a conscious dog model. Male beagle dogs (n=5, 8–11Kg) were surgically instrumented with telemetry devices and two sets of bipolar electrodes placed on the right atrium and the right ventricular outflow tract to determine the atrial and ventricular effective refractory periods (AERP and VERP). One week after surgery, dogs received vehicle (β‐cyclodextrin/mannitol 0.033 mL/kg/min) and DRO (0.033, 0.067 and 0.167 mg/kg/min) every 30 minutes. Dose dependent prolongation of AERP, but not VERP, was observed with DRO administration. At 300 msec cycle length, AERP was significantly increased by 19%, 31% and 46% with 1, 2 and 5 mg/kg of DRO respectively, compared to vehicle. At 400 msec cycle length, a significant increase of 44% in AERP was observed only with 5mg/kg DRO as compared to vehicle. Arterial blood pressure, heart rate, P‐wave duration, and QTc interval values were unchanged throughout the experiment. Both vehicle and DRO (1, 2 and 5 mg/kg) had no significant effect on any of these cardiovascular parameters except P‐wave duration which was significantly increased by 5% with 5mg/kg DRO as compared to vehicle. In summary, dose‐dependent prolongations of AERP, but not VERP, were observed with DRO. This model possesses utility as a paradigm to determine the differential efficacy of test articles on atrial and ventricular refractoriness.