January 1, 2006Journal of Cardiovascular Pharmacology
Characterization of the In Vivo and In Vitro Electrophysiological Effects of the Novel Antiarrhythmic Agent AZD7009 in Atrial and Ventricular Tissue of the Dog
Key result
AZD7009 potently and predominantly increased atrial refractoriness in dogs (AERP increased by 48 +/- 7 milliseconds, P<0.001 versus vehicle) compared to ventricular refractoriness.
Why the study?
Does AZD7009 selectively increase atrial refractoriness compared to ventricular refractoriness in a canine model?
Population
Anesthetized dogs (in vivo) and dog atrial and ventricular tissue (in vitro)
Comparison
AZD7009 infused to produce three pseudo… vs Azimilide and vehicle
Design
Preclinical
Authors
Discussion
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Member takes
Implication
May inform atrial-selective antiarrhythmic development; leaves open translation to human AF trials.
Structured PICO
Does AZD7009 selectively increase atrial refractoriness compared to ventricular refractoriness in a canine model?
P
Population
Anesthetized dogs and dog atrial/ventricular tissue used to evaluate the electrophysiological effects of the novel antiarrhythmic agent AZD7009.
I
Intervention
AZD7009 (novel antiarrhythmic agent) infused to produce three pseudo steady-state plasma concentrations in vivo, and applied in vitro
C
Comparator
Azimilide and vehicle
O
Outcome
Atrial and ventricular effective refractory period (ERP), action potential duration (APD), QT interval, and Vmaxsurrogate
Main Result
p-value: p=<0.001
AZD7009 demonstrates atrial-selective prolongation of refractoriness in a canine model, driven by combined effects on repolarization and the Na+-current system.
Cite This Study
Carlsson et al. (2006) studied this question. AZD7009 vs. azimilide and vehicle was evaluated on Atrial effective refractory period (AERP) (p=<0.001). AZD7009 potently and predominantly increased atrial refractoriness in dogs (AERP increased by 48 +/- 7 milliseconds, P<0.001 versus vehicle) compared to ventricular refractoriness.