© 2000 American Heart Association, Inc.
Integrative Physiology |
A Mechanism of Transition From Ventricular Fibrillation to Tachycardia
Effect of Calcium Channel Blockade on the Dynamics of Rotating Waves
From the Department of Pharmacology (F.H.S., R.M., C.Z., J.B., J.J.) and Pediatrics (Cardiology) (R.M.), SUNY Upstate Medical University, Syracuse, NY; Department of Biomedical Engineering (R.A.G.), University of Alabama, Birmingham, Ala; and Cardiovascular Institute (Y.W.), Fujita Health University, Japan.
Correspondence to José Jalife, Department of Pharmacology, SUNY Upstate Medical University, 766 Irving Ave, Syracuse, NY 13210. E-mail jalifej{at}mail.upstate.edu
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/cm2; verapamil, 0.32±0.06 PSs/cm2 [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 mm2; verapamil, 9.2±0.5 mm2 [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.
Key Words: arrhythmia • fibrillation • tachycardia • verapamil • optical mapping
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