Vol. 19 No. 4 (2015)
HEART RHYTHM DISORDERS

Endocardial botulinum toxin injection into ganglionated plexi in order to reduce atrial fibrillation inducibility

PDF (Русский)
  • A. Strel'nikov,
  • A. Yakubov,
  • D. Sergeevichev,
  • S. Artemenko,
  • I. Mikheenko,
  • S. Abashkin,
  • A. Romanov,
  • E. Pokushalov
A. Strel'nikov
Academician Ye. Meshalkin Novosibirsk Research Institute of Circulation Pathology, Ministry of Health Care of Russian Federation, 15 Rechkunovskaya St., 630055 Novosibirsk, Russian Federation
A. Yakubov
Academician Ye. Meshalkin Novosibirsk Research Institute of Circulation Pathology, Ministry of Health Care of Russian Federation, 15 Rechkunovskaya St., 630055 Novosibirsk, Russian Federation
D. Sergeevichev
Academician Ye. Meshalkin Novosibirsk Research Institute of Circulation Pathology, Ministry of Health Care of Russian Federation, 15 Rechkunovskaya St., 630055 Novosibirsk, Russian Federation
S. Artemenko
Academician Ye. Meshalkin Novosibirsk Research Institute of Circulation Pathology, Ministry of Health Care of Russian Federation, 15 Rechkunovskaya St., 630055 Novosibirsk, Russian Federation
I. Mikheenko
Academician Ye. Meshalkin Novosibirsk Research Institute of Circulation Pathology, Ministry of Health Care of Russian Federation, 15 Rechkunovskaya St., 630055 Novosibirsk, Russian Federation
S. Abashkin
Academician Ye. Meshalkin Novosibirsk Research Institute of Circulation Pathology, Ministry of Health Care of Russian Federation, 15 Rechkunovskaya St., 630055 Novosibirsk, Russian Federation
A. Romanov
Academician Ye. Meshalkin Novosibirsk Research Institute of Circulation Pathology, Ministry of Health Care of Russian Federation, 15 Rechkunovskaya St., 630055 Novosibirsk, Russian Federation
E. Pokushalov
Academician Ye. Meshalkin Novosibirsk Research Institute of Circulation Pathology, Ministry of Health Care of Russian Federation, 15 Rechkunovskaya St., 630055 Novosibirsk, Russian Federation
DOI: https://doi.org/10.21688/1681-3472-2015-4-99-107

Published 2016-01-11

Keywords

  • atrial fibrillation,
  • ablation,
  • pulmonary vein,
  • botulinum toxin,
  • ganglionated plexi,
  • autonomic nervous system
    • ...More
    Less

How to Cite

Strel’nikov, A., Yakubov, A., Sergeevichev, D., Artemenko, S., Mikheenko, I., Abashkin, S., Romanov, A., & Pokushalov, E. (2016). Endocardial botulinum toxin injection into ganglionated plexi in order to reduce atrial fibrillation inducibility. Patologiya Krovoobrashcheniya I Kardiokhirurgiya, 19(4), 99–107. https://doi.org/10.21688/1681-3472-2015-4-99-107

Copyright (c) 2016 Strel'nikov A.G., Yakubov A.A., Sergeevichev D.S., Artemenko S.N., Mikheenko I.L., Abashkin S.A., Romanov A.B., Pokushalov E.A.

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Abstract

Objective. Prior animal studies suggest that botulinum toxin injection into the epicardial fat pads can suppress atrial fibrillation (AF) inducibility. The purpose of the present study was to assess the efficacy and safety of endocardial botulinum toxin injection into epicardial fat pads and intramyocardial left atrial ganglionated plexi (GP) for preventing AF.
Methods. Twenty-four dogs were separated into 3 groups: endocardial approach for botulinum toxin (Xeomin, Germany) injection into epicardial fat pads and intramyocardial GPs; endocardial approach for placebo injection (0.9% normal saline; control 1; n = 8) and epicardial approach for botulinum toxin injection (control 2; n = 8).
Results. A mean of 6.9±1.7 intramyocardial injections (10 U/0.2 mL at each) and 3 injections (50 U/1 mL at each) were administered into each site exhibiting a positive vagal response and into each epicardial fat pad in all groups (p>0.05 between groups).
The injections of botulinum toxin demonstrated dramatic prolongation of ERP in all PV-atrial junctions. This effect correlated with less pronounced ERP shortening in response to vagal nerve stimulation. Suppression of AF inducibility was observed at 7 days after endocardial botulinum toxin injections. The level of AF inducibility was: at 7 days – 57% (p<0.001 vs placebo; p<0.001 vs baseline); at 14 days – 61% (p<0.001 vs placebo; p<0.001 vs baseline); at 1 month – 38% (p<0.001 vs placebo; p<0.001 vs baseline); at 3 months – 23% (p = 0.003; p = 0.06 vs baseline). There were no differences between botulinum groups (p>0.05 for all). The effect of AF suppression disappeared at 3 months. No procedure-related complications occurred.
Conclusion. Botulinum toxin injection into intramyocardial GPs and epicardial fat pads by an endocardial approach is feasible and safe. It provides complete removal of cardiac vagal responses and reliably reduces vulnerability to atrial fibrillation.

PDF (Русский)

References

  1. Schauerte P., Scherlag B.J., Pitha J., Scherlag M.A., Reynolds D., Lazzara R., Jackman W.M. Catheter ablation of cardiac autonomic nerves for prevention of vagal atrial fibrillation // Circulation. 2000. Vol. 102. P. 2774–2780.
  2. Scherlag B., Nakagawa H., Jackman W. Yamanashi W.S., Patterson E., Po S., Lazzara R. Electrical Stimulation to Identify Neural Elements on the Heart: Their Role in Atrial Fibrillation // J. Cardiovasc Electrophysiol. 2005. Vol. 13. P. 37–42.
  3. Hou Y., Scherlag B.J., Lin J., Zhang Y., Lu Z., Truong K., Patterson E., Lazzara R., Jackman W.M., Po S.S. Ganglionated plexi modulate extrinsic cardiac autonomic nerve input: effects on sinus rate, atrioventricular conduction, refractoriness, and inducibility of atrial fibrillation // J. Am. Coll. Cardiol. 2007. Vol. 50 P. 61–68.
  4. Bettoni M., Zimmermann M. Autonomic tone variations before the onset of paroxysmal atrial fibrillation // Circulation. 2002. Vol. 23. P. 2753–2759.
  5. Amar D., Zhang H., Miodownik S., Kadish A. Competing autonomic mechanisms precedes the onset of postoperative atrial fibrillation // J. Am. Coll. Cardiol. 2003. Vol. 42. P. 1262–1268.
  6. Ogawa M., Zhou .S, Tan A.Y., Song J., Gholmieh G., Fishbein M.C., Luo H., Siegel R.J., Karagueuzian H.S., Chen L.S., Lin S.-F., Chen P.-S. Left stellate ganglion and vagal nerve activity and cardiac arrhythmias in ambulatory dogs with pacing-induced congestive heart failure // J. Am. Coll. Cardiol. 2007. Vol. 50. P. 335–343.
  7. Patterson E., Po S.S., Scherlag B., Lazzara R. Triggered firing in pulmonary veins initiated by in vitro autonomic nerve stimulation // Heart Rhythm. 2005. Vol. 2. 624–631.
  8. Po S.S., Nakagawa H., Jackman W.M. Localization of left atrial ganglionated plexi in patients with atrial fibrillation // J. Cardiovasc. Electrophysiol. 2009. Vol. 20. P. 1186–1189.
  9. Armour J.A., Murphy D.A., Yuan B.X., Macdonald S., Hopkins D.A. Gross and microscopic anatomy of the human intrinsic cardiac nervous system // Anat. Rec. 1997. Vol. 247. P. 289–298.
  10. Pauza D.H., Skripka V., Pauziene N., Stropus R. Morphology, distribution, and variability of the epicardiac neural ganglionated subplexuses in the human heart // Anat. Rec. 2000. Vol. 259. P. 353–382.
  11. Lu Z., Scherlag B.J., Lin J., Niu G., Fung K.M., Zhao L., Ghias M., Jackman W.M., Lazzara R., Jiang H., Po S.S. Atrial fibrillation begets atrial fibrillation: autonomic mechanism for atrial electrical remodeling induced by short-term rapid atrial pacing // Circ. Arrhythm. Electrophysiol. 2008. Vol. 1. P. 184–192.
  12. Lin J., Scherlag B.J., Zhou J., Lu Z., Patterson E., Jackman W.M., Lazzara R., Po S.S. Autonomic mechanism to explain complex fractionated atrial electrograms (CFAE) // J. Cardiovasc. Electrophysiol. 2007. Vol. 18. P. 1197–1205.
  13. Pokushalov E., Romanov A., Artyomenko S., Shirokova N., Turov A., Karaskov A., Katritsis D.G., Po S.S. Ganglionated plexi ablation directed by high-frequency stimulation and complex fractionated atrial electrograms for paroxysmal atrial fibrillation // Pacing. Clin. Electrophysiol. 2012. Vol. 35. P. 776–84.
  14. Katritsis D.G., Giazitzoglou E., Pokushalov E., Po S.S., Camm A.J. Rapid pulmonary vein isolation combined with autonomic ganglia modification: a randomized study // Heart Rhythm. 2011. Vol. 8. P. 672–8.
  15. Montecucco C., Schiavo G., Tugnoli V., de Grandis D. Botulinum neurotoxins: mechanism of action and therapeutic applications // Mol. Med. Today. 1996. Vol. 2. P. 418–424.
  16. Rossetto O., Seveso M., Caccin P., Schiavo G., Montecucco C. Tetanus and botulinum neurotoxins: turning bad guys into good by research // Toxicon. 2001. Vol. 39. P. 27–41.
  17. Yu L., Scherlag B., Dormer K., Nguyen K.T., Pope C., Fung K.M., Po S.S. Autonomic Denervation With Magnetic Nanoparticles // Circulation. 2010. Vol. 122. P. 2653–2659.
  18. Oh S., Choi E., Zhang Y., Mazgalev T. Botulinum Toxin Injection in Epicardial Autonomic Ganglia Temporarily Suppresses // Circ. Arrhythm. Electrophysiol. 2011. Vol. 4. P. 560–565.
  19. Стрельников А.Г., Лосик Д.В., Сергеевичев Д.С., Зыков И.С., Абашкин С.А., Романов А.Б., Покушалов Е.А. Нейротоксическая денервация автономной нервной системы левого предсердия в целях лечения и профилактики фибрилляции предсердий: экспериментальное исследования на животных // Патология кровообращения и кардиохирургия. 2015. Т. 19. № 3. C. 94–99.
  20. Кливер Е.Н., Чернявский А.М., Романов А.Б., Покушалов Е.А., Терехов И.Н. Трехлетние результаты эндокардиальной имплантации аутологических клеток костного мозга пациентам с ишемической болезнью сердца с нормальной фракцией выброса левого желудочка // Патология кровообращения и кардиохирургия. 2015. Т. 19. № 1. C. 59–65.
  21. Liu X., Yan Q., Li H., Tian Y., Su J., Tang R., Lu C., Dong J., Ma C. Ablation of ligament of marshall attenuates atrial vulnerability to fibrillation induced by inferior left atrial fat pad stimulation in dogs // J. Cardiovasc. Electrophysiol. 2010. Vol. 21. P. 1024–30.
  22. Danik S., Neuzil P., Avila A., Malchano Z.J., Kralovec S., Ruskin J.N., Reddy V.Y. Evaluation of catheter ablation of periatrial ganglionic plexi in patients with atrial fibrillation // Am. J. Cardiol. 2008. Vol. 102. P. 578–583.
  23. Pokushalov E. The role of autonomic denervation during catheter ablation of atrial fibrillation // Curr. Opin. Cardiol. 2008. Vol. 23. P. 55–9.
  24. Pokushalov E., Romanov A., Katritsis D.G., Artyomenko S., Shirokova N., Karaskov A., Mittal S., Steinberg J.S. Ganglionated Plexi Ablation vs Linear Ablation in Patients Undergoing Pulmonary Vein Isolation for Persistent/Longstanding Persistent Atrial Fibrillation: A Randomized Comparison // Heart Rhythm. 2013. Vol. 10. P. 1280–6.
  25. Katritsis D.G., Pokushalov E., Romanov A., Po S.S. Camm A.J., Ioannidis J.P. Autonomic Denervation Added to Pulmonary Vein Isolation for Paroxysmal Atrial Fibrillation: A Randomized Clinical Trial // J. Am. Coll. Cardiol. 2013. Vol. 62. P. 2318–25.
  26. Pokushalov E., Kozlov B., Romanov A., Strelnikov A., Bayramova S., Sergeevichev D., Bogachev-Prokophiev A., Zheleznev S., Shipulin V., Salakhutdinov N., Lomivorotov V.V., Karaskov A., Po S.S., Steinberg J.S. Botulinum toxin injection in epicardial fat pads can prevent recurrences of atrial fibrillation after cardiac surgery: results of a randomized pilot study // J. Am. Coll. Cardiol. 2014. Vol. 64. P. 628–9.