Alireza Nazeri1,2, Anand V Ganapathy1,2, Ali Massumi1, Mehran Massumi1,2, Egemen Tuzun3, Raymond Stainback1, Ana-Maria Segura4, Macarthur A Elayda5, Mehdi Razavi1,2. 1. Department of Cardiology, Texas Heart Institute, Houston, Texas. 2. Department of Internal Medicine, Section of Cardiology, Baylor College of Medicine, Houston, Texas. 3. Cardiovascular Research Laboratories, Texas Heart Institute, Houston, Texas. 4. Department of Cardiovascular Pathology, Texas Heart Institute, Houston, Texas. 5. Department of Biostatistics and Epidemiology, Texas Heart Institute, Houston, Texas.
Abstract
BACKGROUND: Aberrant 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. OBJECTIVE: To investigate the electrophysiologic, functional, and histopathologic effects of BTX on fibrillation induction in ovine atria. METHODS: Eight 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. RESULTS: Seven 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. CONCLUSION: The 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.
BACKGROUND: Aberrant 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. OBJECTIVE: To investigate the electrophysiologic, functional, and histopathologic effects of BTX on fibrillation induction in ovine atria. METHODS: Eight 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. RESULTS: Seven 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. CONCLUSION: The 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.
Authors: Peter Hanna; Eric Buch; Stavros Stavrakis; Christian Meyer; John D Tompkins; Jeffrey L Ardell; Kalyanam Shivkumar Journal: Cardiovasc Res Date: 2021-06-16 Impact factor: 10.787
Authors: Seungyup Lee; Alexander Khrestian; Albert L Waldo; Celeen M Khrestian; Alan Markowitz; Jayakumar Sahadevan Journal: J Am Heart Assoc Date: 2019-05-21 Impact factor: 5.501
Authors: David Sergeevichev; Vladislav Fomenko; Artem Strelnikov; Anna Dokuchaeva; Maria Vasilieva; Elena Chepeleva; Yanina Rusakova; Sergey Artemenko; Alexander Romanov; Nariman Salakhutdinov; Alexander Chernyavskiy Journal: Mar Drugs Date: 2020-08-02 Impact factor: 5.118