Effects of diacetyl monoxime and cytochalasin D on ventricular fibrillation in swine right ventricles

1 Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center, and 2 Division of Cardiology, Departments of Medicine and Physiology and Physiological Science, University of California School of Medicine, Los Angeles, California 90048; and 3 Department of Physics and Astronomy, Vanderbilt University, Nashville, Tennessee 37235 Whether or not the excitation-contraction (E-C) uncoupler diacetyl monoxime (DAM) and cytochalacin D (Cyto D) alter the ventricular fibrillation (VF) activation patterns is unclear. We recorded single cell action potentials and performed optical mapping in isolated perfused swine right ventricles (RV) at different concentrations of DAM and Cyto D. Increasing the concentration of DAM results in progressively shortened action potential duration (APD) measured to 90% repolarization, reduced the slope of the APD restitition curve, decreased Kolmogorov-Sinai entropy, and reduced the number of VF wave fronts. In all RVs, 15-20 mmol/l DAM converted VF to ventricular tachycardia (VT). The VF could be reinduced after the DAM was washed out. In comparison, Cyto D (10-40 µmol/l) has no effects on APD restitution curve or the dynamics of VF. The effects of DAM on VF are associated with a reduced number of wave fronts and dynamic complexities in VF. These results are compatible with the restitution hypothesis of VF and suggest that DAM may be unsuitable as an E-C uncoupler for optical mapping studies of VF in the swine RVs. action potentials; defibrillation; electrophysiology; reentry; tachyarrhythmias