Destabilization and early termination of spiral-wave reentry by a class III antiarrhythmic agent, nifekalant, in a perfused two-dimensional layer of rabbit ventricular myocardium.

Nifekalant (NF) is a novel class III antiarrhythmic agent that is effective in preventing recurrent life-threatening ventricular tachycardia/fibrillation (VT/VF). However, because the mechanism underlying the antiarrhythmic action of NF is unknown, we investigated the effects of NF on the dynamics of functional reentry in rabbit hearts. A 2D subepicardial myocardial layer was prepared in 21 Langendorff-perfused rabbit hearts by cryoablation of the left ventricular cavity. Action potential signals were recorded and analyzed by a high-resolution optical mapping system. During basic stimulation, NF (0.1 mol/L) significantly prolonged action potential duration without affecting conduction velocity. VTs induced by DC stimulation in the presence of NF had a longer cycle length (188 31 ms, NF, versus 154 16 ms, control, P 0.05) and were of shorter duration (VTs 30 s: 2/54, NF, versus 19/93, control). Spiral-wave excitations after NF were characterized by a greater meandering with longer lines of functional block and more frequent wavefront–tail interactions, resulting in either breakup of the spiral-wave or a sudden spatial jump of the phase singularity. In controls, rotors terminated spontaneously, mostly as a result of mutual annihilation of counter-rotating wavefronts. With NF, rotors frequently terminated by wavefront collision with the atrioventricular groove or by trapping the spiral tip in a refractory zone. This modification was the result of the limited proportion of excitable tissue in the ventricles. NF destabilizes spiral-wave reentry in the heart through modulation of repolarization, leading to early termination or breakup. (Circ Res. 2006;98:0-0.)