Nicotine Increases Spatiotemporal Complexity of Ventricular Fibrillation Wavefront on the Epicardial Border Zone of Healed Canine Infarcts

BACKGROUND: The influence of a pharmacologic agent on wavefront dynamics during ventricular fibrillation (VF) in a setting of remodeled and healed myocardial infarction (MI) remains poor explored. We hypothesized that nicotine, by virtue of its complex direct and indirect cardiovascular effects, increases wavefront complexity during VF. Specifically, we sought to determine whether nicotine increases the number and complexity (approximate entropy) of wavelets during stage II VF in hearts with healed MI. METHODS AND RESULTS: The left anterior descending coronary artery was permanently occluded in five mongrel dogs and wavefront dynamics during VF studied 5 to 6 weeks after occlusion in the open-chest anesthetized state. VF was induced by rapid pacing and the activation pattern mapped on the surviving epicardial border zone (EBZ) of the left ventricle with a plaque (3.2 x 3.8 cm) having 477 bipolar electrodes 1.6 mm apart. VF was mapped before and 20 minutes after 5 µg/kg/min nicotine infusion. Nicotine with a mean arterial plasma concentration of 127 +/- 76 ng/mL (range 57 to 240 ng/mL) significantly (P <.01) increased the number of wavelents from 3.8 +/- 0.4 to 5 +/- 0.41. The increased number of wavelets was caused by an increase (P <.01) in the spontaneous breakup of wavefronts from 4.1 +/- 0.9 times/s to 6.9 +/- 1.1 times/s. Wavebreak over the EBZ was functional in nature as no breakup occurred during normal sinus rhythm. Approximate entropy, a measure of complexity, significantly (P <.01) increased after nicotine administration from 0.23 +/- 0.02 to 0.28 +/- 0.01. CONCLUSIONS: Nicotine increases the number of wavelets and their complexity during VF by promoting spontaneous wavebreak over the EBZ of healed MI.