Effect of action potential duration and conduction velocity restitution and their spatial dispersion on alternans and the stability of arrhythmias

Introduction: The slope of the action potential duration (APD) restitution curve has been used to explain wavebreaks during arrhythmia initiation and maintenance. This hypothesis remains incomplete to fully describe the experimental data. Other factors contributing to wavebreaks must be studied to further understand arrhythmia dynamics. Methods and Results: Control APDs were measured from isolated rabbit hearts using a monophasic action potential probe. APD and conduction velocity (CV) restitution were quantified over the heart surface for two drugs, diacetyl monoxime (DAM) and cytochalasin D (CytoD), using a dual camera video imaging system. For all pacing intervals: (1) control APDs were shorter than for CytoD but longer than for DAM; and (2) CV was greater for CytoD compared with DAM. APD dispersion increased as pacing interval decreased for both drugs. For DAM, increased dispersion was due to a difference in APD restitution between the right and left ventricle. For CytoD, increased dispersion was due to discordant alternans, with no significant spatial variation in restitution. Fibrillation was sustained only in the control hearts; with DAM, stable reentry was sustained with shorter APD and cycle length compared with CytoD for which only nonsustained unstable reentry occurred. Conclusion: Alternans and arrhythmia dynamics are affected by the spatial dispersion of APD restitution as well as CV restitution, not simply the slope of APD restitution. Therefore, a direct link of the APD restitution slope to alternans and arrhythmia dynamics in rabbit heart does not exist. Designing antiarrhythmic drugs to alter only the restitution slope may not be appropriate.