NONLINEAR-ANALYSIS OF THE PHARMACOLOGICAL CONVERSION OF SUSTAINED ATRIAL-FIBRILLATION IN CONSCIOUS GOATS BY THE CLASS IC DRUG CIBENZOLINE

Methods from nonlinear dynamics were applied to test the hypothesis th at the dynamics of sustained atrial fibrillation (AF) is modified by t he class Ic drug cibenzoline during pharmacological conversion. The ex periments were performed in conscious goats in which sustained AF was induced by continuous maintenance of AF via programmed electrical stim ulation. Data were collected from electrophysiological experiments in five goats to terminate sustained AF by continuous infusion of cibenzo line. Sets of five unipolar epicardial electrograms of one minute dura tion were recorded from the left and right atrial free wall during sus tained AF (control), and at three episodes during infusion of cibenzol ine, when the mean AF interval had been prolonged to 25%, 50% and 85% with respect to control. Ventricular far-field potentials were removed from atrial electrograms by a coherent averaging procedure. Using the Grassberger-Procaccia method, the dynamics of the local atrial electr ograms was investigated by estimating the (coarse-grained) correlation dimension and correlation entropy from the correlation integral. The results were related to a recently proposed classification (types I-II I) of AF based on the degree of complexity of atrial activation patter ns. The coarse-grained correlation dimension D-cg and entropy K-cg ind icated that sustained AF corresponded to type Il. During drug administ ration the coarse-grained parameters were not significantly different from control. Scaling regions in the correlation integral were observe d after infusion of cibenzoline (3 out of 5 goats) suggesting that the drug introduced low-dimensional features (type I) in the dynamics of AF (correlation dimension D ranging from 2.8 to 4.4 and correlation en tropy K from 1.6 to 6.2 nats/s). Sinus rhythm recorded shortly after c ardioversion was very regular (D<2 and K<3 nats/s). The hypothesis tha t the electrograms during AF and sinus rhythm were generated by a stat ic transformation of a linear Gaussian random process was rejected usi ng a test for time reversibility. The nonlinear analysis revealed that cibenzoline does not significantly alter the dynamics of sustained AF during pharmacological conversion other than a slowing down of the at rial activation and a somewhat increasing global organization of the a trial activation pattern. The sudden change in the dynamical behavior at cardioversion suggests a mechanism that is reminiscent of a bifurca tion. (C) 1997 American Institute of Physics.