Pure Na+-current inhibition terminated all atrial fibrillation at 65% block in a mathematical model by enlarging the center of rotation and reducing secondary wavelets.
Does pure sodium channel blockade terminate atrial fibrillation in mathematical models and isolated sheep hearts?
Pure sodium channel inhibition terminates atrial fibrillation by enlarging the center of rotation, decreasing anchoring, and reducing secondary wavelets, providing mechanistic insight into class I antiarrhythmic drugs.
The mechanisms by which Na+-channel blocking antiarrhythmic drugs terminate atrial fibrillation (AF) remain unclear. Classical "leading-circle" theory suggests that Na+-channel blockade should, if anything, promote re-entry. We used an ionically-based mathematical model of vagotonic AF to evaluate the effects of applying pure Na+-current (I(Na)) inhibition during sustained arrhythmia. Under control conditions, AF was maintained by 1 or 2 dominant spiral waves, with fibrillatory propagation at critical levels of action potential duration (APD) dispersion. I(Na) inhibition terminated AF increasingly with increasing block, terminating all AF at 65% block. During 1:1 conduction, I(Na) inhibition reduced APD (by 13% at 4 Hz and 60% block), conduction velocity (by 37%), and re-entry wavelength (by 24%). During AF, I(Na) inhibition increased the size of primary rotors and reduced re-entry rate (eg, dominant frequency decreased by 33% at 60% I(Na) inhibition) while decreasing generation of secondary wavelets by wavebreak. Three mechanisms contributed to I(Na) block-induced AF termination in the model: (1) enlargement of the center of rotation beyond the capacity of the computational substrate; (2) decreased anchoring to functional obstacles, increasing meander and extinction at boundaries; and (3) reduction in the number of secondary wavelets that could provide new primary rotors. Optical mapping in isolated sheep hearts confirmed that tetrodotoxin dose-dependently terminates AF while producing effects qualitatively like those of I(Na) inhibition in the mathematical model. We conclude that pure INa inhibition terminates AF, producing activation changes consistent with previous clinical and experimental observations. These results provide insights into previously enigmatic mechanisms of class I antiarrhythmic drug-induced AF termination. The full text of this article is available online at http://circres.ahajournals.org
Kneller et al. (Fri,) conducted a other in Atrial fibrillation. Pure Na+-current (I(Na)) inhibition vs. Control conditions was evaluated on Atrial fibrillation termination and activation changes. Pure Na+-current inhibition terminated all atrial fibrillation at 65% block in a mathematical model by enlarging the center of rotation and reducing secondary wavelets.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: