The influence of the vagus nerve and indole derivative SS-68 on excitation processes in the SA node

Anatoliy A. Nechepurenko; Pavel A. Galenko-Yaroshevsky; Vladimir M. Pokrovskiy; Anait V. Zelenskaya; Konstantin F. Suzdalev; Svetlana A. Lebedeva; Natalia M. Makhnova; Alexandr V. Maksemyuk; Ivan A. Minenko; Roman V. Nikitin; Valeriy G. Abushkevich†

doi:10.18413/rrpharmacology.9.10054

Authors

Anatoliy A. Nechepurenko Federal Center for Cardiovascular Surgery https://orcid.org/0000-0001-5722-9883
Pavel A. Galenko-Yaroshevsky Kuban State Medical University https://orcid.org/0000-0001-6856-1777
Vladimir M. Pokrovskiy Kuban State Medical University https://orcid.org/0000-0003-3138-2075
Anait V. Zelenskaya Kuban State Medical University https://orcid.org/0000-0001-9512-2526
Konstantin F. Suzdalev Southern Federal University https://orcid.org/0000-0003-4879-0577
Svetlana A. Lebedeva I.M. Sechenov First Moscow State Medical University https://orcid.org/0000-0001-8769-1040
Natalia M. Makhnova Kuban State Medical University
Alexandr V. Maksemyuk Kuban State Medical University
Ivan A. Minenko Kuban State Medical University
Roman V. Nikitin Kuban State Medical University
Valeriy G. Abushkevich† Kuban State Medical University https://orcid.org/0000-0002-1483-0131

DOI:

https://doi.org/10.18413/rrpharmacology.9.10054

Abstract

Introduction: Atrial fibrillation (AF) is the most common form of cardiac arrhythmias. Studying the pathogenesis of this pathological process will make it possible to look for new methods of treating AF and to predict its occurrence in a more targeted way. The aim of the study was to identify the components of the takeover process of central rhythmogenesis by the SA node in the conditions of atrial fibrillation when stimulating the vagus nerve and using substance SS-68.

Materials and Methods: The experiments were conducted on 30 frogs and 90 cats. In frogs, the activity of the regions of the medulla oblongata synchronous with the heart rhythm was determined in a high-frequency electromagnetic field. In cats, proximal and distal foci of luminescence in the vagus nerve (VN) and pools of pacemaker cells (PCs) in the sinoatrial node were visualized under topical and general anesthesia, using a KELSY scanner with a microscope video capture unit while stimulating VN and using SS-68.

Results and Discussion: The stimulation of VN with volleys of electrical impulses and the introduction of SS-68 increase the foci of luminescence in the nerve and unite the PC pools. This way, under general anesthesia in comparison with topical anesthesia, the area of the proximal focus of VN luminescence decreased by 83.8%, and the distal focus – by 44.9%. Against the background of general anesthesia, the area of the proximal focus of luminescence when stimulating VN with volleys of electrical impulses was by 76.0% larger than before stimulation, and the distal focus – by 72.5%. After the administration of SS-68, there was an increase in the foci of luminescence: under general anesthesia, when compared with topical anesthesia, the area of the proximal foci of luminescence decreased by 86.8%, and the distal one – by 67.1%. Under general anesthesia, the area of the proximal focus of luminescence under conditions of stimulating VN with volleys of electrical impulses was by 82.2% larger than before stimulation and the distal one – by 78.2%. When signals from the brain arrive simultaneously through VN at the PC pools, they are absorbed by the PC pools; the focus of early depolarization becomes wide, which prevents the development of AF. The increased synchronizing influence of VN may be one of the methods for treating autonomic AF, and if its influence decreases, it can be a prognostic factor for the occurrence of recurrent AF.

Conclusion: The tonic effect of VN on the heart rhythm through electrical stimulation of the former and the use of SS-68 is manifested in a decreased heart rate: the difference between the initial heart rhythm and the minimal synchronization range boundary. A decrease in the heart rate under the influence of VN prevents paroxysms of AF, but does not completely eliminate the influence of ectopic foci on it.

Graphical Abstract

Keywords:

substance SS-68, pacemaker cells, sinoatrial node, brain rhythm

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Author Contribution

Anatoliy A. Nechepurenko, Federal Center for Cardiovascular Surgery

Candidate of Medical Sciences, Head of the Department of Surgical Arrhythmology, Federal Center for Cardiovascular Surgery, Astrakhan, Russia; e-mail: vestik@mail.ru; ORCID ID https://orsid.org/0000-0001-5722-9883. The author made a significant contribution to the concept of mechanisms for preventing atrial fibrillation by simultaneously exciting pools of cells in the sinoatrial region.

Pavel A. Galenko-Yaroshevsky, Kuban State Medical University

Corresponding Member of the Russian Academy of Sciences, Doctor Habil. of Medical Sciences, Professor, Head of the Department of Pharmacology, Kuban State Medical University, Krasnodar, Russia; e-mail: Galenko.Yaroshevsky.@gmail.com; ORCID ID http://orsid.org/0000-0001-6856-1777. The author made a significant contribution to the concept of the effect of substance SS-68 on cardiac rhythmogenesis.

Vladimir M. Pokrovskiy, Kuban State Medical University

Doctor Habil. of Medical Sciences, Professor, Professor of the Department of Normal Physiology, Kuban State Medical University, Krasnodar, Russia; e-mail: PokrovskyVM@ksma.ru; ORCID ID https://orcid.org/0000-0003-3138-2075. The author made a significant contribution to the concept of assimilation of the rhythm coming from the brain via the vagus nerves by autogenous structures of the sinoatrial node.

Anait V. Zelenskaya, Kuban State Medical University

Candidate of Medical Sciences, Associate Professor of the Department of Pharmacology, Kuban State Medical University, Krasnodar, Russia; e-mail: anait_06@mail.ru; ORCID ID https://orcid.org/0000-0001-9512-2526. The author participated in the processing of the obtained data.

Konstantin F. Suzdalev, Southern Federal University

Candidate of Chemical Sciences, Associate Professor of the Department of Chemistry of Natural and Macromolecular Compounds of Southern Federal University, Rostov-on-Don, Russia; e-mail: konsuz@gmail.com; ORCID ID https://orcid.org/0000-0002-6818-084. The author made a significant contribution to the concept of the effect of substance SS-68 on cardiac rhythmogenesis.

Svetlana A. Lebedeva, I.M. Sechenov First Moscow State Medical University

Doctor of Biological Sciences, Associate Professor, Professor of the Department of Pharmacology of A.P. Nelyubin Institute of Pharmacy, I.M.Sechenov First Moscow State Medical University, Moscow, Russia; e-mail: Lebedeva502@yandex.ru; ORCID ID https://orcid.org/0000-0001-8769-1040. The author analyzed, processed and interpreted the data.

Natalia M. Makhnova, Kuban State Medical University

Graduate student, Department of Normal Physiology, Kuban State Medical University, Krasnodar, Russia; e-mail: agapinata6a1@mail.ru. The author participated in the collection of material on the visualization of luminescence (excitation) in the areas of the medulla oblongata.

Alexandr V. Maksemyuk, Kuban State Medical University

Graduate student, Department of Normal Physiology, Kuban State Medical University, Krasnodar, Russia; e-mail: Maks23rus@mail.ru. The author participated in the collection of material on visualization of the luminescence of pacemaker cell pools of the sinoatrial node.

Ivan A. Minenko, Kuban State Medical University

Graduate student, Department of Normal Physiology, Kuban State Medical University, Krasnodar, Russia; e-mail: Dr-evan@mail.ru. The author participated in the collection of material on the visualization of luminescence (excitation) in the cardiac fibers of the vagus nerve.

Roman V. Nikitin, Kuban State Medical University

Postgraduate student, Department of Normal Physiology, Kuban State Medical University, Krasnodar, Russia; e-mail: nikitinrv@mail.ru. The author participated in the collection of material on the visualization of luminescence (excitation) in the areas of the medulla oblongata.

Valeriy G. Abushkevich†, Kuban State Medical University

Valeriy G. Abushkevich^†, Doctor Habil. of Medical Sciences, Professor, Professor of the Department of Normal Physiology, Kuban State Medical University, Krasnodar, Russia; e-mail: Abushkevich_v@mail.ru; ORCID ID https://orcid.org/0000-0002-1483-0131. The author analyzed and interpreted the data.