Ibutilide decreases defibrillation threshold by the reduction of activation pattern complexity during ventricular fibrillation in canine hearts

Background  Ibutilide has been commonly used for pharmacologic cardioversion of atrial fibrillation and flutter in clinical settings. The objective of this study was to investigate the effects of ibutilide on the defibrillation threshold (DFT), restitution properties, dispersion of refractoriness and activation patterns during ventricular fibrillation (VF).

Methods  Ibutilide was administrated intravenously in six open-chest beagles. Before and after the drug administration, 20-second episodes of VF were electrically induced and recorded with a 10×10 unipolar electrode plaque sutured on the lateral epicardium of the left ventricle. DFT and VF activation patterns, including type of epicardial activation maps, VF cycle length (VF-CL), conduction velocity, wavelength (WL) and reentry incidence, were measured. Restitution properties and dispersion of refractoriness were estimated from activation recovery intervals (ARI) during pacing.

Results  Compared to baseline, ibutilide markedly decreased the DFT by 31% ((491±14) V vs. (337±59) V, P <0.01). The drug significantly reduced the maximal slope of the restitution curve (1.34±0.08 vs. 0.76±0.06, P <0.01) and its epicardial dispersion (0.36±0.09 vs. 0.21±0.06, coefficient of variation, P=0.03). The dispersion of refractoriness was enhanced at the pacing cycle length of 300 ms to 160 ms by ibutilide. The drug significantly increased the VF-CL ((96±19) ms vs. (112±20) ms, P <0.01) and the WL ((41±9) mm vs. (52±14) mm, P=0.02) during VF, and reduced the reentry incidence by 25% (0.08±0.02 vs. 0.06±0.02, P <0.01). In the epicardial activation maps, ibutilide significantly reduced the percentage of more complex activation maps during VF.

Conclusions  Intravenous ibutilide significantly decreased the DFT. It might be due to reduction of activation pattern complexity during VF.