Effect of botulinum toxin on inducibility and maintenance of atrial fibrillation in ovine myocardial tissue

BackgroundAberrant vagal stimulation may promote the generation and propagation of atrial fibrillation (AF). Researchers have suggested that botulinum toxin (BTX), a neurotoxin that decreases neural vagal stimulation, may decrease the incidence of postoperative AF. The exact electrophysiologic mechanism underlying the observations and histopathologic alterations associated with BTX are unclear. ObjectiveTo investigate the electrophysiologic, functional, and histopathologic effects of BTX on fibrillation induction in ovine atria. MethodsEight sheep underwent BTX injections into their pulmonary veins, atrial fat pads, and ventricular walls. Electrophysiology with pacing was performed at baseline and 7 days after injection to evaluate the atrial effective refractory period (ERP) and vulnerability to AF with and without vagal stimulation. Echocardiography was performed at baseline and day 7. After euthanasia, histopathologic analysis was performed. ResultsSeven sheep completed the study. For both atria, there was significant shortening in the ERP with vagal stimulation versus no stimulation on day 0 but not on day 7. More aggressive pacing was required to induce AF in the left atrium on day 7 than on day 0. Echocardiography on day 7 showed no significant changes in ejection fraction or new wall-motion abnormalities of the left and right ventricle. Histopathologic analysis showed no significant adverse effects. ConclusionThe subacute BTX effect reduced the vulnerability of atrial tissue to AF induction and reduced the vagal influence on atrial ERP shortening compared to baseline levels. Direct BTX injection did not cause myocardial dysfunction or histologic adverse effects.