A group of SSU scientists and their colleagues from Saratov State Medical University develop new methods to assess cardiovascular system failure in people with COVID-19, considering their biological signals. To do this, you can even use a household device – fitness bands, smart watches, and other portable devices.
NOW EXTENSIVE MONITORING IS AVAILABLE FOR PUBLIC
These methods were developed by specialists from the Department of Dynamic Modelling and Biomedical Engineering of Saratov State University. They offered their approach to the rapid and mass assessment of the cardiovascular system in patients with COVID-19. Their colleagues from the Saratov State Medical University became interested in this approach, together they develop and test new methods for assessing severity cardiovascular system score in a person with COVID-19 considering biological signals.
Last year, we witnessed that the whole world with its most powerful epidemiological and virological centres and advanced medicine found itself in a situation where we had to develop new approaches to cure and diagnose coronavirus infection and its complications. The problem of prompt mass monitoring of cardiovascular system has become more relevant than ever, and its disorders can cause complications after exposing to COVID-19.
The studies in this field are based on the long-term developments of the scientists from the Saratov branch of the Institute of Radio Technology and Electronics, RAS, and the Institute of Physics, SSU (a large scientific group led by the permanent scientific supervisor for over 30 years, Doctor of Physics and Mathematics, Professor Boris Bezruchko). Back in the Soviet Union, they produced radiophysical applications, including defence ones, and created special communication systems (satellite communication, microwave communication, etc.). But in the 1990s, when the situation changed, they had to new ways how to apply those developments, and the team leader proposed to repurpose them for solving biomedical problems. It brought about not only new development perspectives were opened up but long-term cooperation with medical scientists from the Research Institute of Cardiology (the research team headed by Associate Professor, Doctor of Medical Sciences Vladimir Gridnev) and several departments of Saratov State Medical University.
New techniques appeared as a result of continuing research of the development of methods for diagnosing the interaction of elements of the circulatory system and mathematical modelling of the dynamics of these elements [1-7].
QUITE ROMANTIC PRE-HISTORY
How did people understand that they need to pay attention to the work of autonomic regulation systems? It all started with the development of space medicine. When Yuri Gagarin flew into space, the technology made it possible to install only one electrocardiograph in the spacecraft, which recorded his electrocardiogram. When physicians began to study this unique recording of the first man in space, they were at first even disappointed, as they saw an ordinary electrocardiogram of a healthy heart. How else? Considering that Yuri Alekseevich is a healthy and physically strong person, a test pilot. But this answer did not satisfy the specialists, because it is obvious that significant changes take place with the body in conditions of weightlessness and overload. Therefore, the recording was analyzed like no other in the world. And it turned out that although in general the shape of the electrocardiogram did not change, the distribution between the sequence of moments of heart contractions changed significantly. These changes were so striking, so clear and radical in relation to what is observed in people in the usual "ground" situations, that it became clear that it is in them, in these intervals between heartbeats, that information about what happens to the body is hidden.
A well-known scientist, specialist in space cardiology R.M. Baevsky, founder of the theory of interaction of autonomic regulation systems.
Paradoxically, the heart of a healthy person, in fact, does not work rhythmically. It beats rhythmically only in cases of severe pathologies, psychoemotional or physical overload. In these states, the body must provide completely different needs for oxygen and nutrients for the brain, and the heart must work in a completely different mode. In such situations, it is much more effective for the body to raise the pressure in order to pump the required amount of blood. The so-called mechanisms of regulation of blood circulation are engaged in this, they also regulate the tone of blood vessels, the rhythm and strength of heart contractions. The vasomotor muscles are located in the walls of the vessels, and the system sends signals to compress these muscles and raise the pressure. Other regulatory mechanisms work to raise or lower the heart rate as needed, thereby regulating blood pressure. And these mechanisms of regulation of the heart and blood vessels must do everything in a coordinated manner.
HOW TO FIND INFORMATION?
The purpose of the development of physicists at SSU is to learn how to assess the degree of coordination of all these elements of blood circulation regulation. They figured out how from various biological signals (electrocardiogram, photoplethysmogram, respiration, etc.) to "get" information about the work of regulation circuits and evaluate in one digit the degree of their interaction.
It turned out that in people who have had myocardial infarction, the degree of coordination of regulatory systems shows the severity of damage to the heart and blood vessels and allows personalized choice of drug therapy, which is very important in the early stages of a heart attack. The same technique has shown itself in the diagnosis of arterial hypertension. A number of applications have also been created. Scientists have also worked with newborn children; there are a number of interesting results of a fundamental nature. Prospects have emerged using a new method to assess the degree of "maturity" of these regulatory elements, because specific disorders in newborns can cause health problems.
A complex of different systems was developed, computer programs were prepared that implement these methods, they work in conjunction with standard, certified and serial medical recorders. There is an area where SSU scientists are developing their own devices, including small ones, that can read such indices in the long-term monitoring mode. Such prototypes have already been created, this direction is being mastered by graduate students.
YOUTH FOCUSES ON PROCESSING
‘Young scientists and graduate students are actively involved in the research,’ says Victoria Skazkina, a graduate student of the Department of Dynamic Modeling and Biomedical Engineering. ‘We work with medical specialists to help us receive patient signals and interpret observation results. We were very fortunate to have met medical colleagues with whom we developed companionship and learned how to effectively interact within the framework of interdisciplinary research. When the very idea of new screening methods appeared, we won two youth grants, and personally I - the scholarship of the President of the Russian Federation.’
Government agencies are interested in the development of methods for screening diagnostics of the condition of patients with Covid-19, which is being developed by Saratov physicists, and tested in practice by physicians.
In the direction of diagnostics of connections between elements of the cardiovascular system, Saratov scientists have a number of world-class achievements. And according to some of them they are "ahead of the whole planet." SSU scientists closely interact with foreign experts. In 2017, a postgraduate student, assistant of the Institute of Physics Viktoria Skazkina won the first grant from the Innovation Support Fund to work on the project "Development of a Methodology for Assessing the Degree of Interaction of Infant Respiratory and Blood Circulation Regulatory Circuits for the Diagnosis of Autonomic Disorders." In 2019, she trained for six months in Germany (Potsdam) under a project funded by the Ministry of Higher Education and Science of the Russian Federation and DAAD.
UNION OF PHYSICISTS AND DOCTORS
Doctor of Physics and Mathematics, Professor of the Department of Dynamic Modeling and Biomedical Engineering Anatolii Karavayev said that over the past two decades, cooperation with colleagues from Saratov State Medical University and Saratov Research Institute of Cardiology of SSMU (group of Associate Professor, Doctor of Medical Sciences V.I. Gridnev and Associate Professor A.R. Kiseleva, Doctor of Medicine) made it possible to form a powerful groundwork in the study of the state of autonomic regulation of the cardiovascular system and the development of biomedical applications. Physicists offered doctors several methods for analyzing the individual and collective dynamics of the contours of the autonomic regulation of the heart and blood vessels, the state of which is a sensitive indicator of the general state of the body.
‘We have developed a set of methods that are focused on diagnosing severe pathologies of the cardiovascular system,’ the scientist continued. ‘This is recovery after heart attacks, diagnostics of the severity of the state of arterial hypertension. As a result, we came to the solution of the problems of personalized therapy. Our approach will allow in some cases to individually select the type and dosage of drugs, which is now considered a very promising and important area of modern medicine. Based on these developments, we decided to move on, since Covid-19 made its own adjustments, the epidemic literally forced us to solve new problems.
We began to actively interact with our medical colleagues from Saratov State Medical University in the spring of 2020, as soon as it became clear that the problem was very significant and the first restrictions began in our country and in the world. Over the course of a year, we managed to accumulate a serious base of experimental records and develop a methodology that allows us to analyse them. Today we are actively cooperating with the research team of Alexander Kuligin, Doctor of Medical Sciences, in terms of studying the features of circulatory physiology disorders in different categories of patients with Covid-19, and a scientific school under the leadership of Doctor of Medical Sciences, Professor-Cardiologist Yurii Schwartz, in terms of analysing the peculiarities of the course of cardiovascular diseases in Covid-19.’
WHAT IS INTRIGUING?
According to Anatolii Karavayev, the intrigue is as follows: it turns out that agents-viruses infect some specific proteins ACE-2, which affect the functioning of the systems of autonomic regulation of the heart. The systems sense that proteins are damaged by the virus and begin to work differently.
The achievement of the Saratov scientists lies in the fact that they were the first to invent and learn how to quantitatively determine the degree of interaction of these regulatory systems. And this is an indirect sign of the degree of harmful effects of a viral infection on the human body - changes in the autonomic regulation system are considered a very sensitive marker of various pathologies.
With the help of these approaches, it was possible to diagnose a fairly pronounced difference in the degree of interaction between regulatory systems in patients with Covid-19 and in healthy people of comparable age. Interesting data were also obtained on the features of autonomic dysfunction in patients with Covid-19 and concomitant cardiovascular pathology.
New techniques can prove to be very useful for solving the problems of mass screening. The development lies in the fact that according to the recorded signals of the same electrocardiograms, which are easily recorded with cheap devices from the surface of the body, and even with the help of smartphones, smart watches, bracelets, it is possible to register signals of interest to specialists.
At present, SSU scientists are improving the methodology, implementing it in the form of computer programs that can be used by medical specialists in the future, using well-known devices or those devices that are created by physicists.
How does it look in practice? Here's one of the options. A person with Covid-19 at home registers signals from the cardiovascular system, sends them to the data center at the clinic, where a computer program processes these signals and instantly gives a result about the general severity of disorders in the cardiovascular system. Of course, so far this is only a beautiful idea, but it may well be implemented in the near future in practice. At the moment, the stage of laboratory testing is being completed, scientists are preparing publications on the current results. In the future - the introduction of new methods and clinical trials at the clinical base of Saratov State Medical University.
It is important that the approach being developed is applicable not only to Covid-19, but also to other diseases. And this means that even after the end of the current epidemic, the method will be useful, it will be possible to effectively use it for solving other clinical problems.
The achievement of the Saratov scientists lies in the fact that they were the first to invent and learn how to quantitatively determine the degree of interaction of regulatory systems. And a continuous series of breakthroughs in technology and technology has made it possible to create small-sized household devices such as smart watches, into which a full-fledged computer or very sensitive sensors can be introduced - everything that previously fit in a doctor's office and required special equipment and personnel.
Text by: Tamara Korneva
Translated by: Lyudmila Yefremova
Photos by: Gennadii Savkin
Articles about the main method:
Karavaev A.S., Ishbulatov Yu.M., Prokhorov M.D., Ponomarenko V.I., Kiselev A.R., Runnova A.E., Hramkov A.N., Semyachkina-Glushkovskaya O.V., Kurths J., Penzel T. Simulating dynamics of circulation in the awake state and different stages of sleep using non-autonomous mathematical model with time delay // Frontiers in Physiology. 2021. V. 11. P. 612787.
Ishbulatov Yu.M., Karavaev A.S., Kiselev A.R., Simonyan M.A., Prokhorov M.D., Ponomarenko V.I., Mironov S.A., Gridnev V.I., Bezruchko B.P., Shvartz V.A. Mathematical modeling of the cardiovascular autonomic control in healthy subjects during a passive head-up tilt test // Scientific Reports. 2020. V. 10. P. 16525
Kiselev A.R., Borovkova E.I., Shvartz V.A., Skazkina V.V., Karavaev A.S., Prokhorov M.D., Ispiryan A.Y., Mironov S.A., Bockeria O.L. Low-frequency variability in photoplethysmographic waveform and heart rate during on-pump cardiac surgery with or without cardioplegia // Scientific Reports. 2020. V. 10. P. 2118
A.S. Karavaev, M.D. Prokhorov, V.I. Ponomarenko, A.R. Kiselev, V.I. Gridnev, E.I. Ruban, and B.P. Bezruchko Synchronization of low-frequency oscillations in the human cardiovascular system // Chaos 19, 033112 (2009).
Karavaev A.S., Ishbulatov J.M., Ponomarenko V.I., Prokhorov M.D., Gridnev V.I., Bezruchko B.P., Kiselev A.R. Model of human cardiovascular system with a loop of autonomic regulation of the mean arterial pressure // Journal of the American Society of Hypertension. 2016. V. 10. Iss. 3. P. 235-243.
Kiselev A.R., Mironov S.A., Karavaev A.S., Kulminskiy D.D., Skazkina V.V., Borovkova E.I., Shvartz V.A., Роnomarenko V.I., Prokhorov M.D. A comprehensive assessment of cardiovascular autonomic control using photoplethysmograms recorded from earlobe and fingers // Physiological Measurement. 2016. V. 37. P. 580-595.
Karavaev A.S., Skazkina V.V.,Borovkova E.I., Kiselev A.R., Ponomarenko V.I., Kulminskiy D.D.,Gridnev V.I., Prokhorov M.D., Bezruchko B.P. Statistical properties of the phase synchronization index of cardiovascular autonomic control contours // Russian Open Medical Journal. 2018. V.7. I.4. e0403. (DOI: 10.15275/rusomj.2018.0403)
