A Mechanism of Transition From Ventricular Fibrillation to Tachycardia

Abstract

Abbreviation of the action potential duration and/or effective refractory period (ERP) is thought to decrease the cycle length of reentrant arrhythmias. 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 manifestation (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, ECG, frequency and 2-dimensional phase analysis, and computer simulations. Activation patterns in 10 hearts were studied during control, verapamil perfusion (2x10(-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). Concomitantly, phase analysis revealed that wavefront fragmentation was reduced, as demonstrated by a 3-fold reduction in the density of phase singularities (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 reverted to VF. The core area of transiently appearing rotors significantly increased 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 VF and VT in the isolated rabbit heart. Verapamil-induced VF-to-VT conversion is most likely due to a reduction in the frequency of rotors and a decrease in wavefront fragmentation that lessens fibrillatory propagation away from the rotor.

Ionic mechanisms of arrhythmogenesis

“…Ionic currents affecting intracellular Ca 2+ cycling ([Ca 2+ ] i ), such as L-type Ca 2+ current, I CaL , also influence the APD, and are thus likely to influence the spiral wave dynamics. In a previous study, verapamil (a partial blocker of I CaL ), reduced the excitation frequency of VF, the core meander was increased, and VF was converted to ventricular tachycardia (VT) [47]. However, these results must be interpreted with caution, since at the concentrations of verapamil used in this study, verapamil blocks both I CaL , as well as I Kr [48].…”

Gene therapies for arrhythmias in heart failure

“…Strategies designed to genetically modulate Ca 2+ channel subunits selectively in the heart could, therefore, represent a novel and useful therapeutic strategy that complements existing calcium channel blockers. Moreover, as conduction around the core of reentrant “spiral waves” is driven by Ca 2+ , blocking I Ca-L might convert or at least slow down these arrhythmias [58]. …”

Universal scaling law of electrical turbulence in the mammalian heart

“…Previously, ventricular tachycardia and VF were attributed to rotors spinning with invariant angular velocity around a core of characteristic size (22). Recent data, however, suggest that the core size may be different in different species (13,23,24). We therefore investigated the effect of body size on the core perimeter, with the idea of investigating the underlying basis of VF frequency scaling.…”