Introduction: Cytochalasin D (cyto-D) has been used as an excitation-contraction uncoupler during optical mapping studies. However, its effects on action potential duration restitution (APDR) and dynamics during ventricular fibrillation (VF) are unclear. Methods and Results: Langendorff-perfused rabbit hearts (N = 6) were immersed in a tissue chamber. Transmembrane potential was recorded using glass microelectrodes. APD measured to 90% repolarization (APD90) was used to construct the APDR curve. During regular pacing at 300-msec cycle length, increasing concentrations of cyto-D resulted in progressively prolonged APD90 (131 ± 26 msec, 171 ± 14 msec, and 177 ± 14 msec) and steepened maximum slope of the APDR curve (1.1 ± 0.2, 1.3 ± 0.2, and 1.6 ± 0.4 for control, 5 μM, and 10 μM, respectively; P < 0.01). Resting membrane potential, AP amplitude, and maximum dV/dt did not change. Cyto-D lengthened VF cycle length and APD90, and steepened the maximum slope of the APDR curve. However, cyto-D did not significantly change the diastolic interval. The dominant frequency of pseudoelectrocardiogram progressively decreased with increasing concentrations of cyto-D (15.2 ± 0.6 Hz, 11.1 ± 2.4 Hz, and 9.8 ± 3.2 Hz for control, 5 μM, and 10 μM, respectively; P < 0.01). Sustained (>1 min) VF was repeatedly inducible at baseline and with 5 or 10 μM of cyto-D. Conclusion: Continuous perfusion of cyto-D at 5 or 10 μM prolonged APD90, steepened APDR slope, and reduced dominant frequency in rabbit ventricles. Cyto-D at these concentrations allowed induction of sustained VF.
- Action potentials