Excitation Wave Detachment from Structural Discontinuities Leading to Generation of Rotors by Enhancement of Gap Junctional Coupling in Rabbit Ventricles

Abstract

Introduction: We have reported that enhancement of gap junctional (GJ) coupling destabilizes 2-D spiral-wave reentry and facilitate its termination through the inhibition of wavefront propagation with high curvature. However the effect of GJ enhancement on excitation waves in ventricles with structural discontinuities is unknown. Methods: 2-D ventricular myocardium of perfused rabbit hearts (n=9) was prepared, and a linear cryolesion was made parallel to the fiber orientation. Electrical stimulation was applied next to the lesion (2.5–12 Hz) and the dynamics of U-turning excitation waves were analyzed by high-resolution optical mapping. Results: Rotigaptide (RG, 0.1 µM) significantly increased conduction velocity (by 12±3% and 13±6% along and across the fiber direction at 6.7 Hz, n=10) in ventricles without cryolesion. In the presence of RG, high frequent stimulation (8–12 Hz) increased the incidence of wavefront-detachments from the edge of the incision compared to controls (5/9 hearts vs. 2/9 hearts) and rotors were formed behind the barrier. Conclusions: The enhancement of GJ coupling facilitates detachment of excitation waves from structural discontinuities and creates rotors. Wavefront detachment may help termination of anatomical reentry, whereas rotor generation may initiate functional reentry.