The Effects of Excitation-Contraction Uncouplers on the Dynamics of Ventricular Fibrillation in Isolated Swine Right Ventricles

ABSTRACT

BACKGROUND: Whether or not the excitation-contraction (EC) uncoupler, diacetyl monoxime (DAM) and cytochalacin D (Cyto D) alter the ventricular fibrillation activation patterns is unclear. METHODS: We recorded single cell action potentials and performed optical mapping in isolated perfused swine right ventricles at different concentrations of DAM and cyto D during ventricular fibrillation and dynamic pacing. RESULTS: Increasing concentration of DAM results in progressively shortened action potential duration measured to 90% repolarization (APD90), reduced slope of the action potential duration restitution(APDR) curve, decreased Kolmogorov-Sinai entropy, and reduced number of ventricular fibrillation wavefronts. In all right ventricles, 15 to 20 mmol/l DAM converted ventricular fibrillation to ventricular tachycardia. The ventricular fibrillation could be reinduced after the DAM was washed out. In comparison, cyto D (10 to 40 mol/l) has no effects on APDR curve or the dynamics of ventricular fibrillation. The effects of DAM on ventricular fibrillation are associated with reduced number of wavefronts and dynamic complexities in ventricular fibrillation. CONCLUSION: These results are compatible with Restitution Hypothesis of ventricular fibrillation and suggest that DAM may be unsuitable as an EC uncoupler for optical mapping studies of ventricular fibrillation in the swine right ventricles.