Effects of cytochalasin D on electrical restitution and the dynamics of ventricular fibrillation in isolated rabbit heart

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 (APD(90)) was used to construct the APDR curve. During regular pacing at 300-msec cycle length, increasing concentrations of cyto-D resulted in progressively prolonged APD(90) (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 muM, and 10 muM, respectively; P < 0.01). Resting membrane potential, AP amplitude, and maximum dV/dt did not change. Cyto-D lengthened VF cycle length and APD(90), 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 muM, and 10 muM, respectively; P < 0.01). Sustained (>1 min) VF was repeatedly inducible at baseline and with 5 or 10 muM of cyto-D. Conclusion: Continuous perfusion of cyto-D at 5 or 10 muM prolonged APD(90), steepened APDR slope, and reduced dominant frequency in rabbit ventricles. Cyto-D at these concentrations allowed induction of sustained VF.