| The rate dependence of action potential duration (APD), i.e., restitution, has been proposed as a possible mechanism for the development of alternans and ventricular arrhythmias. Changes in cycle length are associated with the initiation of arrhythmias, but the resulting APD variations may not only result from the preceding diastolic interval (DI), but also from memory effects. Therefore other factors contributing to wavebreaks must be studied to further understand arrhythmias.; Using a dual-camera video imaging system, APD was measured for isolated rabbit hearts with the electro-mechanical uncoupler Cytochalasin D (CytoD) or diacetyl monoxime (DAM) and for isolated pig hearts with CytoD. During steady state pacing (SSP) in the rabbit heart, APDs were shorter with DAM and longer with CytoD compared to controls. With DAM, increased APD dispersion as pacing interval decreased was due to a difference in APD restitution between the RV and LV. For CytoD, increased dispersion was a result of discordant alternans. Mathematical models constructed from the APD and conduction velocity (CV) restitution exhibited sustained spiral wave reentry without breakup despite an APD restitution slope >1 for CytoD. In experiments, sustained stable spiral wave reentry was observed with DAM, APD and cycle length were the same as those in the model; however, sustained arrhythmias were not observed with CytoD. In pig hearts, abrupt cycle length changes applied to SSP demonstrated an initial rapid APD decrease followed by a slower decrease. Arrhythmia induction or decremental pacing moved restitution above and to the left of the SSP restitution curve with an overall shortening of APD. Restitution during steady state ventricular fibrillation was below the SSP restitution curve. On the other hand, defibrillation shocks moved restitution below and to the right of the curve with an overall prolongation of APD.; 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. Memory also plays an important role in the restitution characteristics when cycle length is changed abruptly. Analysis of arrhythmia induction and termination indicates both short and long-term memory effects that provide insight into the mechanism of ventricular fibrillation. |
