Role of indole derivative SS-68 in increasing the frequency range of cardiac rhythm control (reflex stimulation of the sinoatrial node)

Pavel A. Galenko-Yaroshevsky; Anatoly A. Nechepurenko; Tatiana G. Pokrovskaya; Nikolay L. Shimanovsky; Alexander S.  Dukhanin; Konstantin F. Suzdalev; Polina D. Maslova; Natalia M. Makhnova; Vadim V. Sheivais; Valery G. Abushkevich; Anait V. Zelenskaya; Valeria V. Seletskaya; Saida K. Akhedzhak-Naguse; Konstantin G. Korotkov

doi:10.3897/rrpharmacology.7.75337

Authors

Pavel A. Galenko-Yaroshevsky Kuban State Medical University https://orcid.org/0000-0001-6856-1777
Anatoly A. Nechepurenko Federal Center for Cardiovascular Surgery https://orcid.org/0000-0001-5722-9883
Tatiana G. Pokrovskaya Federal Center for Cardiovascular Surgery https://orcid.org/0000-0001-6802-5368
Nikolay L. Shimanovsky Pirogov Russian National Research Medical University https://orcid.org/0000-0001-5722-9883
Alexander S. Dukhanin Pirogov Russian National Research Medical University https://orcid.org/0000-0001-5722-9883
Konstantin F. Suzdalev Southern Federal University
Polina D. Maslova Kuban State Medical University
Natalia M. Makhnova Kuban State Medical University
Vadim V. Sheivais Kuban State Medical University
Valery G. Abushkevich Kuban State Medical University https://orcid.org/0000-0002-1483-0131
Anait V. Zelenskaya Kuban State Medical University https://orcid.org/0000-0001-9512-2526
Valeria V. Seletskaya Kuban State Medical University https://orcid.org/0000-0002-0007-1971
Saida K. Akhedzhak-Naguse Kuban State Medical University https://orcid.org/0000-0002-1573-9970
Konstantin G. Korotkov St. Petersburg Research Institute of Physical Culture https://orcid.org/0000-0001-9043-1012

DOI:

https://doi.org/10.3897/rrpharmacology.7.75337

Abstract

Introduction: Cardiac pacing is indicated for sick sinus syndrome. It is performed with a pacemaker via electrodes implanted in the heart. This technique has several disadvantages. The search for alternative methods of cardiac pacing is underway. One of them is control of heart rhythm through stimulation of the tragus.

Objective: To perform the reflex stimulation of the sinoatrial node and to study the influence of the SS-68 substance on it.

Materials and methods: Two electrodes were fixed in the reflexogenic zone of rabbits’ auricles, volleys of electrical impulses from an electrical stimulator were applied to the electrodes, and the synchronization range of volley frequency and cardiac contractions was recorded. This range was re-recorded again after injecting the SS-68 substance (2-phenyl-1-(3-pyrrolidine-1-cyclopropyl)-1H-indole hydrochloride) intravenously at a dose of 50 µg/kg. In other experiments on frogs in a high-frequency electromagnetic field, the process of excitation of the area of the medulla oblongata associated with the heart rhythm was visualized. After the application of SS-68 (50 μM) to the surface of this zone, the process of its excitation was recorded.

Results and discussion: Stimulation of the auricular reflexogenic zone of rabbits produced a synchronization of volley frequency and heart rate in the range from 173.5 ± 2.0 to 214.0 ± 1.8 per minute. SS-68 extended this range from 168.2 ± 1.9 to 219.4 ± 1.5 per minute. In the frog’s medulla oblongata, an area synchronous to the heart rhythm glowed in the high-frequency electromagnetic field. SS-68 increased the area of glow by 131.0%.

Conclusion: The substance SS-68 increases the frequency range of heart rhythm control by activating reflex stimulation of the sinoatrial node. The main point of application of SS-68 is the medulla oblongata. Glow in the high-frequency electromagnetic field reflects the process of neuron excitation. The increase in the glow zone under the influence of SS-68 indicates synchronously excited neurons, which leads to the assimilation of the central heart rhythm generation by the sinoatrial node.

Keywords:

SS-68 substance, visualization of excitation in the brain, reflex cardiostimulation

Author Contribution

Pavel A. Galenko-Yaroshevsky, Kuban State Medical University

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

Anatoly A. Nechepurenko, Federal Center for Cardiovascular Surgery

MD, PhD, Head of the Department of Surgical Arrhythmology, Federal Center for Cardiovascular Surgery, Astrakhan, Russia, e-mail: vestik@mail.ru, ORCID ID http://orcid.org/0000-0001-5722-9883. The author made a significant contribution to the concept of mechanisms of reflex control of heart rhythm.

Tatiana G. Pokrovskaya, Federal Center for Cardiovascular Surgery

Dr. habil. of Medical Sciences, Professor of the Department of Pharmacology and Clinical Pharmacology of the Institute of Medicine, head of the Clinical Research Laboratory of the Research Institute of Pharmacology of Living Systems of Belgorod State University, Belgorod, Russia, e-mail: tpokrovsky@yandex.ru, ORCID ID http://orcid.org/0000-0001-6802-5368. The author made a significant contribution to the concept of the effect of SS-68 on cardiac rhythmogenesis.

Nikolay L. Shimanovsky, Pirogov Russian National Research Medical University

Corresponding Member of the Russian Academy of Sciences, Dr. habil. of Medical Sciences, Professor, Head of the Department of Molecular Pharmacology and Radiobiology, Pirogov Russian National Research Medical University, Moscow, Russia, e-mail: shimannn@yandex.ru, ORCID ID http://orcid.org/0000-0001-5722-9883. The author analyzed and interpreted the results of the study.

Alexander S. Dukhanin, Pirogov Russian National Research Medical University

Dr. habil. of Medical Sciences, Professor, Department of Molecular Pharmacology and Radiobiology, Pirogov Russian National Research Medical University, Moscow, Russia, e-mail: das03@rambler.ru, ORCID ID http://orcid.org/0000-0001-5722-9883. The author analyzed and interpreted the results of the study.

Konstantin F. Suzdalev, Southern Federal University

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

Polina D. Maslova, Kuban State Medical University

Assistant of the Department of Nervous Diseases and Neurosurgery with a course of nervous diseases and neurosurgery of the Faculty of Pedagogical Problems of Kuban State Medical University, Krasnodar, Russia, e-mail: polinamaslova@mail.ru. The author participated in obtaining reflex control of heart rhythm in rabbits.

Natalia M. Makhnova, Kuban State Medical University

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

Vadim V. Sheivais, Kuban State Medical University

postgraduate student, Department of Normal Physiology, Kuban State Medical University, Krasnodar, Russia. e-mail: shneyways@yandex.ru. The author participated in obtaining reflex control of heart rhythm in rabbits.

Valery G. Abushkevich, Kuban State Medical University

Dr. habil. of Medical Sciences, Professor, Chair of the Department of Normal Physiology, Kuban State Medical University, Krasnodar, Russia, e-mail: Abushkevich_v@mail.ru, ORCID ID http://orcid.org/0000-0002-1483-0131. The author performed an analysis and interpretation of the study results.

Anait V. Zelenskaya, Kuban State Medical University

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

Valeria V. Seletskaya, Kuban State Medical University

M.D., PhD, assistant of the Department of Pharmacology, Kuban State Medical University, Krasnodar, Russia, e-mail: seleckaya.v@mail.ru, ORCID ID http://orcid.org/0000-0002-0007-1971. The author participated in the processing of the obtained data.

Saida K. Akhedzhak-Naguse, Kuban State Medical University

PhD, Assistant Professor of the Department of Public Health, Healthcare and History of Medicine, Kuban State Medical University, Krasnodar, Russia, e-mail: naguzesk@mail.ru, ORCID ID http://orcid.org/0000-0002-1573-9970. The author participated in the processing of the data obtained.

Konstantin G. Korotkov, St. Petersburg Research Institute of Physical Culture

PhD, Professor, Lead Researcher of St. Petersburg Research Institute of Physical Culture, St. Petersburg, Russia. e-mail: korotkov2000@gmail.com, ORCID ID http://orcid.org/0000-0001-9043-1012. The author participated in the creation of the excitation visualization setup.