A modification of the in vitro canine Purkinje fiber repolarization assay using variable frequency pacing

The in vitro canine cardiac Purkinje fiber (CCPF) assay used to predict drug-induced QT prolongation typically employs trains of constant frequency stimulation. We describe a modification of the model using a variable pacing protocol that mimics the sinus arrhythmia of living dogs. Using this model, Sotalol (10 and 50 μM) elicited a dose-dependent shift of the variable frequency pacing return curve in a dose dependent manner to lower diastolic intervals. The shift and increased variability of the return curve with the high Sotalol concentration represents greater electrophysiologic instability. Further investigations are needed to assess the utility of the variable pacing protocol to evaluate electrophysiologic instability as a surrogate marker for proarrhythmia in the CCPF model.