A mechanism of transition from ventricular fibrillation to tachycardia - Effect of calcium channel blockade on the dynamics of rotating waves

Abbreviation of the action potential duration and/or effective refractory p eriod (ERP) is thought to decrease the cycle length of reentrant arrhythmia s. Verapamil, however, paradoxically converts ventricular fibrillation (VF) to ventricular tachycardia (VT), despite reducing the ERP. This mechanism remains unclear. We hypothesize that the size and the dynamics of the core of rotating waves, in addition to the ERP, influence the arrhythmia manifes tation (ie, VF or VT). The objectives of this study were (1) to demonstrate functional reentry as a mechanism of VF and VT in the isolated Langendorff -perfused rabbit heart in the absence of an electromechanical uncoupler and (2) to elucidate the mechanism of verapamil-induced conversion of VF to VT . We used high-resolution video imaging with a fluorescent dye, EGG, freque ncy and 2-dimensional phase analysis, and computer simulations. Activation patterns in 10 hearts were studied during control, verapamil perfusion (2x1 0(-6) mol/L), and washout. The dominant frequency of VF decreased from 16.2 +/-0.7 to 13.5+/-0.6 Hz at 20 minutes of verapamil perfusion (P<0.007), Con comitantly, phase analysis revealed that wavefront fragmentation was reduce d, as demonstrated by a 3-fold reduction in the density of phase singularit ies (PSs) on the ventricular epicardial surface (PS density: control, 1.04/-0.12 PSs/cm(2) verapamil, 0.32+/-0.06 PSs/cm(2) [P=0.0008]). On washout, the dominant frequency and the PS density increased, and the arrhythmia rev erted to VF. The core area of transiently appearing rotors significantly in creased during verapamil perfusion (control, 4.5+/-0.6 mm(2) verapamil, 9.2 +/-0.5 mm(2) [P=0.0002]). In computer simulations, blockade of slow inward current also caused an increase in the core size. Rotating waves underlie V F and VT in the isolated rabbit heart. Verapamil-induced VF-to-VT conversio n is most likely due to a reduction in the frequency of rotors and a decrea se in wavefront fragmentation that lessens fibrillatory propagation away fr om the rotor.