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

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.

Wavebreak Mechanism During Ventricular Fibrillation in Isolated Swine Right Ventricle

BACKGROUND: Several different patterns of wavebreak have been described by mapping of the tissue surface during fibrillation. However, it is not clear whether these surface patterns are caused by multiple distinct mechanisms or by a single mechanism. METHODS: To determine the mechanism by which wavebreaks are generated during ventricular fibrillation, we conducted optical mapping studies and single cell transmembrane potential recording in 6 isolated swine right ventricles. RESULTS: Among 763 episodes of wavebreak (0.75 times/sec/cm2), optical maps showed 3 patterns: 80% due to a wavefront encountering the refractory waveback of another wave, 11.5% due to wavefronts passing perpendicularly each other and 8.5% due to a new (target) wave arising just beyond the refractory tail of a previous wave. Computer simulations of scroll waves in 3-D tissue showed that these surface patterns could be attributed to two fundamental mechanisms: head-to-tail interactions and filament break. CONCLUSION: We conclude that during sustained ventricular fibrillation in swine RV, surface patterns of wavebreak are produced by two fundamental mechanisms: head-to-tail interaction between waves and filament break.