Open access e-journal Cardiometry - No.6 May 2015

No.6 May 2015

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CARDIOMETRY Basic and applied research.

Theory, practice, therapy, engineering, philosophy & methodology.

ISSN 2304-7232 e-Journal www.cardiometry.net

Editorial board EDITOR-IN-CHIEF Prof. Vladimir A. Zernov, RUS EXECUTIVE EDITORS Prof. Mikhail Y. Rudenko, RUS

EDITORIAL ADVISORY BOARD Prof. Yury V. Gulyaev, RUS

Prof. Howard Robert Horvitz, USA

Prof. Roman M. Baevsky, RUS

Prof. Peter Mansfield, GBR

Prof. Sergey G. Chefranov, RUS

Dr. Christian Muller, AUT

Dr. Sergey V. Kolmakov, FIN

Dr. Olga K. Voronova, RUS

Prof. Jorge Moreno-Lopez, SWE

Prof. Vladimir A. Vecherkin, RUS

Prof. Vitaly S. Polikarpov, RUS

Prof. Sergey N. Zaguskin, RUS

Prof. Jury P. Stupakov, RUS

Dr. Zied ben El hadj, TUN

Prof. Vyacheslav M. Tyutyunnik, RUS

Dr. Marwan Refaat, LBN

Prof. Boris I. Leonov, RUS

Dr. Chandra Mani Adhikari, NPL

Prof. Mohammad Aleem, EGY

Dr. Saad Al Bugami, SAU

Dr. Alberto Alfie, ARG

Prof. Alejandro Barbagelata, USA

Dr. Pablo Avanzas, ESP

Dr. Nancy Aggeli, GRC

Dr. Marko Banovic, SRB

Prof. Dimitrios Karakitsos, USA

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Founded and published by Russian New University www.rosnou.ru

Editorial Front Office: Radio Street, 22 Moscow Russia 105005 Phone/Fax: +7 (495) 925-03-83

Editorial Back Office: Alexandrovskaya Street, 47 Taganrog Russia 347900 Phone/Fax: +7 (8634) 31-24-03 E-mail: journal@cardiometry.net

An official peer-reviewed journal. Frequency: 2 issues/year. First issue: 2012.

Managing editor: T. Kharchenko. Datawarehouse manager: S. Rudenko.

Design developer: Т. Fedosova. Content manager: K. Kamyshev

Š All rights reserved.

No.6 May 2015

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CARDIOMETRY No.6 May 2015 12 April 1961: the Birthday of Space Telemedicine Roman М. Baevsky

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Artificial heart creation: what problems are to be solved?

Vladimir A. Zernov

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Application of principles of space medicine to health monitoring of the aging population Roman М. Baevsky, Azaliya P. Berseneva, Peter A. Baevsky, Maia Master

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Development of space technologies and problems of “home medicine” Roman M. Baevsky, Aleksey R. Baevsky, Evgenie Y. Bersenev, Olga N. Isaeva, Vadim I. Pougachev, Anna G. Chernikova

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Studies of natural changes in diastolic pressure in each cardiac cycle on the basis of digitally processed ECG and Rheo Olga K. Voronova

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Biophysical phenomena in blood flow system in the process of indirect arterial pressure measurement Mikhail Y. Rudenko, Olga K. Voronova, Vladimir A. Zernov

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Correction of the recording artifacts and detection of the functional deviations in ECG by means of syndrome decoding with an automatic burst error correction of the cyclic codes using periodograms for determination of the code component spectral range.

Part 1: Basic principles of the novel approach Evgenie D. Adamoviс, Pavel L. Aleksandrov, Oleg V. Gradov, Leonid M. Mamalyga, Maksim L. Mamalyga

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The course of very severe aortic stenosis due to bicuspid aortic valve calcinosis in a young man Regina Jonkaitiene, Egle Rumbinaite, Egle Kazakauskaite

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Diagnostic value of measured hemodynamic parameters: cardiac output, minute volume and a complete set of phase-related volumes of blood Nikolay E. Sapuntsov, Olga K. Voronova, Vladimir A. Zernov, Konstantin K. Mamberger

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Effects of total table salt restriction on blood pressure Francisco Jose Chacon-Lozsan, Juan Sebastian Peinado-Acevedo

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Cardiometry practice

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Dear readers!

Let me introduce the 6th issue of our journal to you. Its cover presents three milestones in science to mark the list of the greatest discoveries: DNA structure, model of atom, and … the specific blood flow regime in a human body. The last discovery is demonstrated for the first time, but we hope it will hold a firm place in the list considering its contribution to understanding of importance of cardiometry as a new fundamental science.

It would be of interest to our reader to learn more about the latest results from research of biophysical processes related to occlusive blood flow when non-invasively measuring arterial pressure. The research led to a new officially registered scientific discovery that laid the groundwork for development of the cardiac cycle phase analysis theory. The respective theoretical and practical concepts facilitating pioneering effective investigations in cardiometry have been originated from that research.

Cardiometry reveals a number of problems in cardiology which could not be solved before. Their solutions have become possible only due to a high scientific potential of cardiometry.

Original devices developed on the basis of cardiometry for cardiac signal recording and analysis are an absolutely new class of medical instrumentation supported by the latest advancements in metrology, and they make it possible to detect any responses of the cardiovascular system performance to external and internal effects.

In this issue you will find a unique story presenting Memoirs written by Prof. Roman M. Baevsky about Y.A. Gagarin, the first cosmonaut in the history of mankind. In fact, the 12th of April 1961 is the birthday of telemetry and space telemedicine, the new era of medicine. It is very exciting to read about the emotions of the man who was among the pioneers and developers of space cardiology diagnostics and who was responsible for remote medical control of the first cosmonaut during his space mission. Besides, two scientific articles by prof. Roman M. Baevsky are published by us herein.

In April this year, the 16th Congress of the Russian Society of Holter Monitoring and Noninvasive Electrophysiology (ROHMINE) took place in Russia. Within its framework, the 8th All-Russian Congress CLINICAL ELECTROCARDIOLOGY was traditionally held. It should be noted that this ROHMINE Congress has initiated a process of the 1st All-Russian Conference of Pediatric Cardiologists of FMBA of Russia. Very interesting reports were presented by the “Sports cardiology” section.

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In this connection, the ROHMINE Congress paper “Anatomy and physiology of the sinoatrial node: modern concepts� by Prof. N.A. Tarsky should be highlighted. To our mind, it is an original research report which proves for the first time our suggestion that no links between the SA and AV nodes exist.

In fact, it is the second law of cardiometry. However, Prof. Tarsky did not state that the SA node is a baroreceptor, but he has given excellent proof that there are no links between the said nodes.

Time shows that the potential of our research school being involved in development of cardiometry as a new scientific field is the most advanced in the world. We are ready tp prove it not barely in word but truly in deed. Our journal deals with new developments in the cardiovascular system research.

We hope they will attract attention of not only academicians, but also medical practitioners.

With best wishes, Cardiometry Editorial Board

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Editor’s note

12 April 1961: the Birthday of Space Telemedicine Roman М. Baevsky1* 1 Institute

of Biomedical Problems of the Russian Academy of Sciences Russia 123007 Moscow, Khoroshevskoye sh. 76A

Imprint

Roman М. Baevsky. 12 April 1961: the Birthday of Space Telemedicine; Cardiometry; No.6; May 2015; p.8-17 ; doi: 10.12710/cardiometry.2015.6.817 Available from: www.cardiometry.net/no6-may-2015/space-telemedicine

Introduction

Roman M. Baevskiy Roman M.Baevskiy, academician and one of the pioneers of space cardiology, systems of computer pre-nosology diagnosis; he personally developed biotelemetry systems, performed evaluation and creation of medical control devices for the space flight of Yuriy Gagarin

On the morning of April 12th, 1961, the day of the first human space flight, I went to the Remote Space Communication Center located at 3 Stroiteley Street, in Leninsky Prospect. This is where first ever telemedicine session for receiving information on the cosmonauts’ physical condition during space flight was scheduled. Grigory Zlotin, a recognized expert in the field of telecommunications,

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founded the Cente and I, as a leader of our medical control team, was responsible for receiving the cosmonauts’ physical condition from space and then analyzing it. In essence, this was the first Space Flight Medical Control Center that led to the formation of the present-day medical control system for space missions. That day, we had an extremely critical task. We were responsible for monitoring the status of the medical equipment aboard the Vostok spacecraft, from the moment it was turned on when Yuri Gagarin entered the spacecraft in its ready-for-launch position and connected his spacesuit to the communication network. It was vital not only to assess the quality of the received information and possibilities of its analysis, but even more importantly, to continuously observe the cosmonaut’s physical condition during his space mission.

All of the people involved in this task were stressed and anxious, despite the fact that we had already tested the telemetry system of data transmission from the spacecraft twice when we had sent our control group of dogs, Chernushka and Zvyozdochka into space. This was especially challenging for me, because I was one of the leading developers of the system of sensors and electrodes used for medical monitoring in that first manned space mission. By April 1961, I only had a little over a year of experience in space medicine. In 1959, after serving 5 years at the Air Force on Sakhalin Island, in the far eastern part of Russia, I was transferred to the Institute of Aviation and Space Medicine in Moscow, where I was immediately assigned to prepare medical equipment that would monitor the physical condition of dogs in space. The first medical system called “Sector” was prepared in record time, and was successfully implemented as early as August 1960 when dogs Belka and Strelka flew into space. They were the first living creatures that had travelled into space and safely returned to Earth. After that we had to urgently start developing data transmission systems that would control the physical condition of cosmonauts during their flight into space. There were only six month left before the first space manned mission.

Fortunately, we had already laid the groundwork for the system that would monitor the human physical condition in space. A small research team that was responsible for physiological measuring under my supervision was also working on developing and testing new sensors and electrodes that would be used to study cosmonauts in space [1,2]. One of the members of that team was the famous inventor of vectoelectrocardioscope, Ivan Akulinichev. We proposed to record the ECG using two new leads applied with electrodes placed on the upper and lower parts of the breast as well as to the left and right on the breast. This allowed us to get a high-quality stable ECG signal even when the cosmonaut was actively moving around. Keeping the electrodes attached to the skin in space for a prolonged period of time (and in future flights, for several days) was a serious challenge.

We needed to avoid skin irritation and discomfort after a prolonged contact of the electrodes with the cosmonaut’s skin. The most suitable electrodes turned out to be those made in the form of silver discs 0.3-0.5 mm thick with a diameter of 15-20 mm. We used a special conductive paste in order to achieve a constant and reliable contact of the electrodes with the skin. The electrodes were fixed in place with gauze pad stickers. To keep electrodes in place for a long period of time, we designed a special removable halter system. The respiratory sensor was attached to that same system. The measurement of respiratory rate and depth was achieved using a resistive transducer by smoothly changing its resistance around the breast circumference. The transducer was designed as a thin elastic rubber tube filled with coal powder that was integrated into the medical breast belt.

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Ivan Akulinichev and I along with other researchers from our lab conducted many tests of this new system of biomedical data acquisition for space flights. That system was tested not only by staff test pilots and researchers, but also by future cosmonauts. Yuri Gagarin and German Titov visited our lab several times, where we customized their individual medical chest belts and made initial reference recordings with onboard instrumentation mock-ups.

In addition to ECG and respiration recordings, we planned to obtain data on redistribution of blood in the lower part of the human body during the first manned flight. А special transducer in the shape of an elastic rubber tube, similar to the respiratory sensing element, was designed and positioned around the circumference of the lower portion of shin. The transducer connected to the electrocardiographic channel input and was able to successfully record pulse waves associated with filling of the blood vessels in the lower extremities.

A few hours before the “Vostok” spaceship launch, we had already established regular phone communication between our Telemedicine Center in Moscow and the launch site. Ivan Akulinichev, who was responsible for pre-launch testing of our medical equipment and the proper placement of the sensors, transducers and electrodes left for the Baikonur Cosmodrome. I stayed in Moscow where I was responsible for the medical data support.

It is almost time for the launch and we are waiting for it anxiously. We started to worry an hour before the launch when we saw the signals transmitted by the telemetry system from Vostok displayed on our monitors. As soon as they appeared, it became immediately obvious that the sensing element placed on the cosmonaut’s shin surface was not working. The most likely explanation is that the tops of the cosmonaut’s boots were on too tight and they has disturbed the proper operation of that unique sensing element. Since it was impossible to resolve this problem so late in the process, after a discussion with Ivan Akulinichev we had decided not to raise the alarm. In any case, that particular telemetry channel was a backup that we enabled by our own initiative.

Nowadays, half a century later, it would not be possible to put even spare electrodes on board of a spacecraft, not to mention an entire new sensor. Every wire in each device, every napkin in supplies are clearly described in the preapproved documentation and had been properly tested and accompanied by the relevant test certificates and records. Back in those years, everything was much simple, though not necessarily better. For example, a day before the launch of the spaceship with dogs, Pchyolka and Mushka in December 1960, I connected a new seismocardiogram sensor to the on-board instrumentation set called “Sector” [3]. The sensor was attached to the dog’s “spacesuit”.

This was how we had obtained the first ever seismocardiogram from space. Naturally, the space flight management had to approve everything, but there was no need to create any sort of special documents.

So, let us return to the events on April 12, 1961. At our Telemedicine Center in Moscow, we were capable of receiving telemetry recordings and TV images sent from the Vostok spacecraft. The data was transmitted via the ground receiving stations located along the space flight path over the Russian Far East, as well as ships in the Pacific and the Atlantic oceans. We anxiously waited in between shorttime interruptions in signal transmission from the spaceship caused by the transition from one receiving station area to another. My duty was to provide running commentary on the incoming data quality and content. It was vital to determine that there are no arrhythmias, to make sure the T-wave

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on the ECG was not going down and that the ST-interval was not moving down. Afterwards, the experts on ECG, cardiologists, would assess the data. During the space mission, however, we had to review the data as it was coming. I did not have the necessary clinical experience, so there were two clinical cardiologists in the room with me. Now I cannot remember their names, but at that time, it was a desirable and necessary insurance.

Yuri Gagarin’s heart rate during launch was quite fast: up to 110 beats per minute. During the space flight, the heart rate decreased to 70-80 beats per minute, but just before landing, it again quickened to 100-120 beats per minute. We did not detect any alarming changes in the cosmonaut’s ECG. Live communication between the Earth and the spaceship also made it also possible to assess the cosmonaut’s psycho-emotional state. I should note that during the entire flight, we heard Yuri Gagarin’s resolute and cheerful voice trying to calm down everyone back on Earth who was following his mission. He constantly reported on what he saw in space and what he felt. Ever session he would repeat, “I feel fine, I am in good spirits. The space flight is going well.” The video feed from space, of rather poor quality at the time, showed him smiling every time it was established, providing additional confirmation that he was in good health.

The most stressful period for all of us was the landing. It took about one hour after sending the command to land to receive confirmation that Yuri Gagarin landed successfully close to the village Smelovka in the Saratov Region in Russia. All of us knew that the landing was the most critical and dangerous stage of the space flight, but we were confident everything would go well.

After the successful completion of the first human space flight, I was involved in the organization and management of many other manned space flights aboard the spaceships Vostok, Voskhod and Soyuz as well orbital stations Salyut, Mir and the ISS. But I think that my participation in the preparation and the execution of the Yuri Gagarin’s space flight remains one the greatest events in my life. I received the Order of the Red Star in recognition of my involvement in this historic event, which I keep to this day. At that time I was 33 years old, whereas Yuri Gagarin was 27. That makes us contemporaries. I am extremely proud that I had the opportunity to participate together with him in one of the most important events in the 21st century: the first human flight in space.

In conclusion – about telemedicine. On that day, April 12, 1961, I of course did not yet understand that I was contributing to the birth of a new applied research field: space telemedicine. This new direction made great impact on the advancements of telemedicine research on the Earth. Among the first “invasions” of space telemedicine into the Earth-based health care problems happened in 1982, with the development of a new mobile computerized lab system called “Autosun-82”. This lab used the same medical monitoring system as the orbital station Salyut, but added a computer to automate the assessment of health of the patients [2]. The mobile lab Autosan-82 began a new pioneering area in preventive health care. We conducted mass health screenings in different industrial enterprises across the various regions of the USSR [4]. In 1996-97, Corresponding Member of the Russian Academy of Sciences O.I. Orlov established the “Telemedicine” fund that promoted telemedicine services in Russia. A “Telemedicine” course was taught to students and physicians, and a textbook on the subject was written and published. That is how the space telemedicine, that started with the first manned space travel, where remote monitoring of health of human in space began, furthers the development of our Earth medicine.

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In the Atlas of Telemedicine History [5], the section “Biotelemetry and space telemedicine” contains photographs and short biographies of the scientists that participated in the creation of this new applied science. It includes Vasilly V. Parin, the Academic who was at that time the chief scientist responsible for medical & biological research in space. Over the next 10 years, he was my direct research supervisor including for my master’s and PhD dissertations. Other pioneers include Vladimir I. Yazdovsky, Chief of the Department, and Oleg G. Gazenko, Chief of the Laboratory at the Research Institute of Aviation and Space Medicine, where they led the medical support program for use in manned space flight. In that Atlas you can also find the photographs of Ivan T. Akulinichev and Roman M. Baevskiy. My research is described as follows: “…he personally developed biotelemetry systems and was responsible for the methods of evaluation and for creation of medical support devices for the space flight of Yuriy Gagarin” [5].

The public recognition and acknowledgement of my contribution to the history-making event in science, namely, the first human spaceflight in the history of the mankind, are very important and prestigious to me. Not everybody is lucky enough to be in the right place at the right time. It was so for me. And although my life was filled with not only success, but also with obstacles, difficulties and misfortunes as well. I have had my share of friends and enemies. For all this, I am grateful, for it is known: per aspera ad astra - Through hardships to the stars. As a famous Brazilian writer Paolo Coelho once said: “To realize one's destiny is a person's only real obligation and when you want something, all the universe conspires in helping you to achieve it.”

Vasiliy V.Parin (1903-1971) Academician and one of the pioneers of medical electronics and cybernetics, creator of classical methods of biotelemetry and computerbased mathematical analysis of biological information.

Editor of the book «Biological Telemetry» published in 1971.

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Vladimir I.Jazdovskiy (1913-1999) Academician, founder and first leader of Space Biology and Medicine Research Program (background, planning and usage of medical control systems for the space flights)

Oleg G.Gazenko (1918-2007) Oleg G.Gazenko, academician and one of the pioneers of space biology and medicine, creator of medical support and control systems for the cosmonauts, director of the Institute of Medical and Biological Problems (Moscow, USSR/Russia). In the1980s he took part in the organization of telemedical “space bridges� between USSR and USA

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Ivan T. Akulinichev (1915-2000) Ivan T.Akulinichev, academician and one of the pioneers of medical radioelectronics, head of the research programs for space flights’ telemetry medical control systems (MCS), he personally provided the MCS functions to Yuriy Gagarin

3 November 1957 – first transmission of biological information from space to Earth (during space flights of Layka). The dog had transmitted blood pressure, ECG, pneumogramma motions activity indicators

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In the first human space flights onboard the “Vostok” space ships, the “Vega-A” set were used. They allowed to perform ECG telemetry and to collect breath rate and pulse signals. In the following flights, the list of telemetry indicators broadened constantly (cinetocardiogram, electroencephalogram, electrooculogram, skin-galvanic reactions, seismocardiogram etc). For general control and psychological examinations, radio and television were used

Medical examination of Yuriy Gagarin by Doctors I.T.Akulinichev, A.R.Kotovskaya and F.D.Gorbov (11 April 1961)

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Yuriy Gagarin (1934-1968).

First cosmonaut (picture before first human space flight 12.04.1961)

Academician Oleg Gazenko on the doctor’s stand at the Center for Space Flights medical control (1970s)

Boris B.Egorov (1937-1994). First medical doctorcosmonaut (space ship “Voskhod-1”, 1964)

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References 1. Akulinichev IT, Baevsky RM, Zazykin KP, Freidel VP. Radioelectronics in space medicine. люoscow:Energiya; 1964. 50 pages.

2. Adamovich BA, Baevsky RM, Berseneva AP, et al. Problem of automated evaluation of functional condition of organism in cosmonautics and preventive medicine at current stage. Cosm. biol. and aviation & space med. 1990;6:23-31.

3. Baevsky RM. Physiological measurements in space and problem of their automation.

Moscow:Nauka; 1970. 256 pages.

4. Grigoryev AI, Baevsky RM. Health concept and space medicine. Moscow:Slovo; 2007. 208 pages.

5. Dumanskyy YV, Vladzimirsyy AV, Lobas VM, Lievens F. Atlas of the Telemedicine History.

Donetsk:Knowledge; 2013. 72 pages.

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Editorial

Artificial heart creation: what problems are to be solved?

Vladimir A. Zernov1* 1 Russian

New University Russia 105005 Moscow, Radio str. 22 Corresponding author phone: +7 (8634) 312-403, e-mail: cardiocode@mail.ru

*

Keywords

Artificial heart • ECG • Hemodynamics • Cardiometry • Cardiac disease prevention

Imprint

Vladimir A. Zernov. Artificial heart creation: what problems are to be solved?; Cardiometry; No.6; May 2015; p.18-21; doi: 10.12710/cardiometry.2015.6.1821 Available from: www.cardiometry.net/no6-may-2015/artificial-heart-creation

Introduction Attempts to create an artificial heart were highlighted by our journal one year ago [1-3]. Now we can say that there is no break-through news in this field: no technological progress, no pioneering research and no spectacular advancements are reported. An imperfect understanding of the cardiovascular system performance hinders any progress in the R & D activities aimed at the artificial heart creation. But from our point of view, all the existing design & engineering difficulties can be mastered. However in this connection another question comes to mind: is it reasonable in principle to design and produce an artificial heart? Let us leave this question open for future discussions and offer our list of issues to be solved as given below: 1. A lack of knowledge on the performance of half of the cardiac cycle phases.

In this context it is just cardiometry that is capable of providing the most precise concept of the performance and significance of all of the 10 cardiac cycle phases [1, 4-6]. But unfortunately the recognized American and French artificial heart developers do not take this novel concept into account [7-12]. As a rule they use only 5 cardiac cycle phases which are incompletely and inconsistently described and interpreted in the classical research. Is it possible to solve a problem based on 50% of incomplete and inconsistent data basis? It is doubtful. Fig.1 illustrates ECG related data used by the above developers versus the data provided by cardiometry.

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Figure 1. Identification of the boundaries in each cardiac cycle phase based on the laws of cardiometry (b) or by ignoring them and using generally accepted concepts (a): point L to indicate the beginning of the rapid ejection phase cannot be identified; the location of the j point as the beginning of the slow ejection phase cannot be found; significance of the U wave as the interval of the coronary blood flow filling is not understood. Cardiometry is capable of accurately identifying all the phase boundaries and properly locating all significant points on the ECG.

The knowledge on the cardiac cycle phase pattern is build upon the relevant axiomatic and logic system. And it is the basis for any science, including cardiometry. Moreover, cardiometry offers its own original mathematical description of all hemodynamic processes in a human body. It is just the thing that is urgently required for the American and French scientists who are involved in research and development of artificial heart. The above figure shows the ST segment ST on the ECG which consists of four most important systolic phases. In fact the conventional cardiology is not capable of delivering such valuable information. Ignoring the valuable information is the most critical deterrent to make progress in engineering of artificial heart.

This problem did not appear at once. Victor Froelicher and John P.A. Ioannidis have clearly defined the problematic topics in their papers [13, 14]. Our intention is to suggest new ways how to handle this challenging task in research [3, 4].

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The latest research results and methodology initiate re-consideration and re-evaluation of the existing expertise. The same is applicable to our case with cardiology and cardiometry. Upon the fresh expertise, taking into account original comprehensive capabilities in the modern cardiac diagnostics, we are inclined to believe that it is not reasonable to create artificial heart today and that we should pay more attention to cardiac disease prevention and treatment. Following this way, it is vital to establish a system of preventive children’s cardiology based on monitoring, screening and effective correction measures. We should address interdependence between the heart performance and health as a whole. Every effort should be made to maximize the health of children because children’s health is a prerequisite for the future nation’s wealth. As our practice shows, unfortunately, not so many healthcare officers share this opinion. And sometimes some health care officers think the creation of an artificial heart will automatically resolve all the health care problems.

We are very interested to hear our readers’ opinion: what advantages does the artificial heart creation have? Or is it better to improve the efficiency of diagnostics and prevention instead?

References 1. Rudenko MY, Krstacic G. New philosophy of validation and verification for cardiology: classical proof theory imported from natural sciences.

Cardiometry.

2014;4:16-30. doi:10.12710/cardiometry.2014.4.1630 2. Rudenko MY, Voronova OK, Zernov VA. ECG periodic table: a new ECG classification based on heart cycle phase analysis. Cardiometry. 2013;2:19-28.

3. Rudenko MY, Zernov VA, Mamberger KK, Rudenko SM. Heart and aortic baroreceptors: operation in providing hemodynamic processes in cardiovascular system. Cardiometry. 2013;3:31-44.

4. Rudenko MY, Voronova OK, Zernov VA. Theoretical Principles of Heart Cycle Phase Analysis.

Frankfurt a/M, Munich, London, New York: Fouqué Literaturverlag; 2009. 336 p. ISBN 9783937909578.

5. Rudenko MY, Zernov VA, Voronova OK. Study of hemodynamic parameters using phase analysis of the cardiac cycle. Biomedical Engineering. 2009;43(4):151-5.

6. Rudenko MY, Zernov VA, Voronova OK. Fundamental research on the mechanism of cardiovascular system hemodynamics self-regulation and determination of the norm-pathology boundary for the basic hemodynamic parameters and analysis of the compensation mechanism as a method of revealing the underlying causes of disease. Heart Rhythm. 2012;9(11):1909-10.

7. Verbovaia TA, Gritsenko VV, Davydenko VV, et al. On the history of creation and introduction of the first compact artificial heart valves in Russia. Vestnik khirurgii imeni I. I. Grekova. 2009;168(3):947.

8. Spiliopoulos S, Koerfer R, Tenderich G. A first step beyond traditional boundaries: Destination therapy with the SynCardia total artificial heart. Interactive Cardiovascular and Thoracic Surgery.

June 2014;18(6):855-6.

9. Torregrossa G, Morshuis M, Varghese R. Results with syncardia total artificial heart beyond 1 year.

ASAIO Journal. 2014;60(6):626-34.

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10. Slepian MJ, Alemu Y, Soares JS. The Syncardia™ total artificial heart: In vivo, in vitro, and computational modeling studies. Journal of Biomechanics. 18 January 2013;46(2):266-75.

11. MĂŠnard J. Keys to the success of the CARMAT project? Medecine/Sciences. February 2014;30(2):204-5.

12. Arabia FA, Moriguchi JD. Machines versus medication for biventricular heart failure: Focus on the total artificial heart. Future Cardiology. 1 September 2014;10(5):593-609.

13. Yong CM, Froelicher V, Wagner G. The electrocardiogram at a Crossroads. Circulation.

2013;128:79-82. doi:10.1161/CIRCULATIONAHA.113.003557 14. Ioannidis JPA. How to make more published research true. PLoS Med. 2014;11(10): e1001747. doi:10.1371/journal.pmed.1001747.

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Report

Application of principles of space medicine to health monitoring of the aging population Roman М. Baevsky1*, Azalia P. Berseneva1, Peter A. Baevsky2, Maia Master3 Institute of Biomedical Problems of the Russian Academy of Sciences Russia 123007 Moscow, Khoroshevskoye sh. 76A

1

Company «Autosun Health Technology Inc» Canada, Toronto 2

Resort “Mishpacha” Canada, Ontario 3

Corresponding author phone: +7 (499) 193-62-44, e-mail: rmb1928@mail.ru

*

Submitted: 17 March 2015 Accepted: 10 April 2015 Published online: 16 May 2015 Abstract

Monitoring the health of astronauts based on the assessment of the functional state of the body within the realms of norm and pathology. The area of functional states qualifies as the yellow score of health on a notional scale "traffic light of health": Modern medicine is particularly interested in studying the health of the yellow score, because of the preventative measures that could still be taken before making contact with the healthcare system. This method has been used in a study of a group of people (mean age >70) during their stay at a resort in northern Ontario. Data were obtained by a spectral analysis of HRV. High-frequency oscillations (HF,%), indicating the increased activity of the parasympathetic system, which protects the body from stress was significantly increased. Centralization of control of autonomic functions (IC) was decreased as well as heart rate. All these changes indicate growth of functional reserves, aimed at increasing protection against stress’ effect due to environmental factors. This research shows that the method based on space medicine assessment in health can be successfully utilized within various fields of physiology and medicine, particularly in gerontological practice to dynamically monitor and research ways to improve the health of the elderly.

Keywords

Health • Functional states • Stress • Space medicine • Heart rate variability • Aging • Spectral analysis • Risk of disease • Functional reserves • Gerontology

Imprint

Roman М. Baevsky, Azalia P. Berseneva, Peter A. Baevsky, Maia Master.

Application of principles of space medicine to health monitoring of the aging population; Cardiometry; No.6; May 2015; p.22-29; doi: 10.12710/cardiometry.2015.6.2229 Available from: www.cardiometry.net/no6-may-2015/principles-of-space-medicine

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Introduction Recently a company «Autosun Health Technologies» has developed a new approach to objectively measuring the psychological level of stress through analysis of heart rate rhythm [1]. This project was done in collaboration with Institute of Biomedical Problems; the leading organization in Russia that is conducting and monitoring research on the Russian segment on the international space station. The new approach is called “Traffic Light of Health”, this approach is grounded in theory based on space medicine which was established in the 1970’s [2,6]. The concept of the theory is that the health index is signified through a three-color scale: green - normal, yellow - requires attention to present health, red - initial signs of pathology are evident. In the forefront of this scale is the yellow score, as it borders between health and disease. It is this border state that is studied in space medicine, as the astronauts are practically healthy people who have been specially selected, through a vigorous process, and trained to work in difficult conditions and in constant stress. Even in those cases fatigue, sleep disturbances, decreased appetite and irritability is evident. These are signs of adaptation caused by stress and the demands placed to adapt to the vastly different conditions of space. Such changes are not dangerous, as they are a sign of the adaptive capacity and are thus in the yellow score of the scale. Experiment “Pneumocard” had the objective to acquire new data that would expand our knowledge of the mechanisms by which the cardiovascular system adapts to the conditions of long-duration space mission.

Regular modern medicine is particularly interested in studying the health of the yellow score on the scale, because it is a bordering state of health and disease. Once pathology becomes symptomatic, it is then brought to the attention to physicians and specialists. There are no clear-cut diagnosis of the disease, and physicians are known to engage patients only when a definitive diagnosis of a disease is to be made. Thus, as long as the person does not see a physician, doesn’t undergo certain laboratory tests (chemistry, microbiology, complete blood count to name a few), they generally practice "home medicine". “Home medicine” has in recent years became quite widespread. It is to practice medicine, apply therapies and usage of diagnostic equipment in the home environment. For example, measuring blood pressure by a store-bought device or by accessing the internet for health related information to be used to treat a health issue at home without guidance by regulated medical personnel.

On board a spacecraft, all crew members are also able to use their own rather complex medical equipment, designed for regular medical monitoring and medical research. There are clearly traced analogies between space medicine and home medicine. But there is one more important analogy to be discussed. It refers to the “yellow” score of health on the scale. People utilizing this scale are healthy individuals interested in sustaining their health. While in space, the crew investigated are regarded as "very healthy" people with a large margin of functional reserves in the body, home medicine deals with a decrease of the functional reserves in people who are on the verge of transition from health to disease, in both cases we have to talk about the “yellow score” of health. Below are figures from the book by AI Grigoriev and RM Baevsky «Problem of Health Evaluation and Conception of Norm (M., 2006) [6], which shows the relationship of the "Traffic Light of Health" with the different kinds of standards (Figure 1) and the dependence of the functional reserves and the degree of tension of the regulatory systems (Fig. 2).

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Figure 1. Various kinds of norms and classifications of functional states SN – statistical norm; IN – ideal norm; PN – physiological norm; CN – clinical norm

Figure 2. Decrease of the functional reserves as a function of risk

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These figures show that astronauts who belong to the “green score of health” are very healthy, with large capacity to withstand stress and show no symptoms of pathology. People with reduced functional reserves are considered to be relatively healthy, and are so so-called within the "clinical norm." As can be seen from Figure 1. The range of "clinical norm" occupies almost all the yellow score, almost reaching its border with the red score. What this means is well illustrated by Figure 2, which shows a reduction of functional reserves of the body due to the increase of tension of regulatory systems and the development of stress. It is now generally accepted that excessive stress is one of the leading causes of the decrease of functional reserves and depletion mechanism of vegetative regulation. Prolonged or intense stress is the main cause of the transition from yellow to the red score of health.

Assessment of the level of stress in space medicine, starting with the first manned flight, began with a method of analysis named heart rate variability. This concept that is used in space medicine, can also be applied to today’s modern medicine. In 1970-1990’s, first in Russia and then in the United States and Europe, analysis of heart rate variability (HRV) has become widely used in various fields of physiology and medicine [6,7]. In recent years this method has been greatly improved to meet the challenges in space medicine. Developed as a probabilistic approach to the assessment of the level of stress and adaptation of the organism [3]. This introduced the concept of adaptive risk. The concept of adaptive risk holds 10 categories of risk, of which only the 4th category presents the concept of development of hazardous situations to health [4]. It is this improved version of the method of analysis of HRV that is used in the above-mentioned "traffic light of health” concept. Thus, space medicine, again, as in the 1970s, becomes the source of a new methodology for assessing health, which is now based on the experience and findings made within space research which includes longitudinal research of healthy individuals living and working in conditions of chronic stress. This research, of course, may be useful in everyday modern medicine, where large numbers of people, particularly the elderly are in need of simple and affordable methods of evaluation and monitoring of their health.

Research methodology The "Traffic Lights of Health" concept has been implemented on smartphone platforms such as "Android", which ensures the accessibility to this new method. In order to evaluate its validity and reliability, a study of this methodology has been conducted on the elderly at a resort in northern Ontario, Canada. In this study, there were no attempts made to diagnose or treat any of the participants. The participants were merely observed using the “Traffic Light of Health” concept. The study was conducted on a strictly voluntary basis.

The research methodology has been greatly simplified, and included the following three steps: 1) A questionnaire about the health and general lifestyle 2) measurement of body weight and blood pressure, 3) ECG. Special analysis of heart rate variability according to the ECG and the "Traffic Light of Health" allows objective measurement of the level of stress. Immediately upon arrival to the resort, surveys were conducted in 20 people aged 60 to 85 years (5 males and 15 females, mean age 79.1 years). After 7 days, another follow up examination was completed, which was attended by 14 people.

According to the survey results, each participant was assigned to one of the groups of health. It was found that among those surveyed, not one participant could be attributed to the “Green” group. 75%

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of those surveyed were "Yellow" (50% of them in a state of functional stress and 25% in the premorbid state). The premorbid state is indicated by the orange score of health. Only 25% were in the "red" group (in the initial stages of various diseases).

Results Analysis of the repeated surveys showed quite unexpected results. Most notably, it showed an improvement of health in 10 of 14 participants. The distribution of participants by health groups has shown significant improvement. Some of the participants moved into the green group, the number of persons in the yellow group decreased as did the number of people in red group (see. Figure 3) The majority of participants had less complaints in regards to the various manifestations of sickness or discomfort. A significant decrease in blood pressure was also noted. HRV parameters and dynamics are shown below.

Figure 3. Changes in the structure of health after a 10-days vacation

With repeated measurements there was an increase in the stress index (SI, decreased rates of total variability (SDNN) and the total power of HRV spectrum (TP). All these changes point to increased activity of the sympathetic level of regulation, which is typical of mobilization of functional reserves in various treatments.

Data obtained by spectral analysis of HRV strength significantly increased high-frequency oscillations (HF,%), indicating that the increased activity of the parasympathetic system (which protects the body from stress). Increased activity of vascular regulation (LF,%) and energyregulation of metabolic processes (VLF,%). Decreased centralization of control of autonomic functions (IC), slightly decreased heart rate. All these changes indicate an increase of functional reserves, aimed at increasing protection against stress caused by environmental factors. The diagram in Figure 4 illustrates the dynamics described.

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Results of the analysis of heart rate variability in participants at resort "Mishpaha".

Indicator

Result 1

Result 2

HR

67,53

65

SDNN, ms SI

25,67 215,22

22,1 279,2*

ТР, ms2

677,56

482,38*

HF, % LF, %

29,78 19,72

47,2* 27,1*

VLF, % IC

22,06 1,83

26,1* 1,56

Note: *- significant difference (р>0,05)

Figure 4. Changes in the spectral indicators of HRV after subsequent measurement

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Discussion and conclusions The research comes to two important conclusions: 1) “Vacation� for elderly people at a resort increases their level of health, as evidenced by positive changes in the structure of health parameters; 2) Increases the level of health according to the analysis of HRV is accompanied by mobilization and increase of functional reserves. Should be to say that these results could be significant for both scientific and practical conclusions.

The scientific research of this study is of some value as it is possible to obtain distinct objective data on the simultaneous increase in activity of both sympathetic and parasympathetic autonomic regulation. Such an outcome is possible if the main regulator of activation (the hypothalamus) that "controls" both divisions of the autonomic nervous system. This is consistent with current knowledge of the mechanisms of aging and is a good scientific rationale for the use of HRV as criteria for evaluating the effectiveness of restorative processes [5].

The practical usefulness of the results is also obvious. We have confirmed that the "Traffic Light Health" and methods of HRV analysis in monitoring the health of older people and are now openly available and accessible.

Modern space technology assessment in health can be successfully used in various fields of physiology and medicine, particularly in gerontological practice to monitor the health of the elderly.

Statement on ethical issues Research involving people and/or animals is in full compliance with current national and international ethical standards.

Acknowledgements We are grateful to S.I. Anisimov, G.S. Golitsin, V.P. Goncharov, E.A. Novikov, and N.A. Inogamov for useful comments and interest to the work.

Conflict of interest None declared.

Author contributions RMB, APB, PAB prepared the manuscript and analyzed the data. APB and MM coordinated and helped to draft the manuscript. All authors have equally contributed to the manuscript, read and approved the final manuscript.

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References 1. Baevsky RM, Baevsky AR, Bersenev EY, et al. Use of space technologies of HRV analysis for creation of the operative health control system on the basis of the smartphone. 13th Annual International Gravitational Physiology Meeting; Waterloo, Canada; 16-20 June 2014.

2. Baevsky RM. Non-invasive methods in space cardiology. J. Cardiovasc. Diagn. a. Proced.

1997;14(3):1-11.

3. Baevsky R, Chernikova A, Funtova I, Tank J. Assessment of Individual Adaptation to Microgravity during long term space flight based on stepwise Discriminant Analysis of Heart Rate Variability Parameters. Acta Astronautica. 2010;69:1148-1153.

4. 小hernikova A, Baevsky R, Funtova I, Tank J. Adaptation risk in space medicine. 63-th IAC; Italy; 2012.

5. Dilman VM. The law of deviation of homeostasis and diseases of aging. Boston: John Wrigth; 1981.

380 p.

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Report

Development of space technologies and problems of “home medicine” Roman M. Baevsky1, Aleksey R. Baevsky2, Evgenie Y. Bersenev1, Olga N. Isaeva1, Vadim I. Pougachev3, Anna G. Chernikova1 Institute of Biomedical Problems of the Russian Academy of Sciences Russia 123007 Moscow, Khoroshevskoye Ch. 76A

1

Company «Autosun Health Technology Inc» Canada, Toronto 2

Company «Biocom Technologies» USA 98370 WA Poulsbo, Bond Road NE 20301 Suite 100 3

Corresponding author phone: +7 (499) 193-62-44, e-mail: rmb1928@mail.ru

*

Submitted: 19 March 2015 Accepted: 13 April 2015 Published online: 16 May 2015 Abstract

Experience of cosmonauts’ health monitoring shows that in the study of healthy subjects clinical approach to the evaluation of various medical and physiological data is almost less effective than the evaluation of organism adaptive abilities. The idea of prenosological diagnosis and the concept of adaptive risks develop in space medicine last years. These new space technologies are being actively tested in terrestrial studies in systems as "home medicine".

The report presents three variants of systems, respectively, designed to work with a) home PC ("Ecosan-2007" and "Ecosan-TM"), b) Internet connections ("Delta 2013"), c) mobile communication channels ("Traffic Lights of Health"). The main method of functional conditions evaluation in all these systems is the heart rate variability (HRV) analysis. HRV indices allow us to construct a mathematical model and to compute the stress degree of regulatory systems, their functional reserve and adaptive risk.

Keywords

Space technologies • “Home medicine” • Health, adaptation • Heart rate variability • Ear photopltetismogram • Prenosological diagnose • Stress • Functional states • Ecosan • Telemedicine

Imprint

Roman M. Baevsky, Aleksey R. Baevsky, Evgenie Y. Bersenev, Olga N. Isaeva, Vadim I. Pougachev, Anna G. Chernikova. Development of space technologies and problems of “home medicine”; Cardiometry; No.6; May 2015; p.30-40; doi: 10.12710/cardiometry.2015.6.3040 Available from: www.cardiometry.net/no6may-2015/space-technologies

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Introduction Till recently the major household medical tools have been a tonometer, a thermometer and, though not universally, a glucosimeter. Now the situation is changing in leaps and bounds. A variety of pulse and step meters, physical load measuring devices and so on have gained an extensive use in everyday life. The majority of consumers are essentially healthy people who would like to have personal devices and systems to keep under control their diet, fitness training program or quality of sleep. So far all these are from the realm of wishes. Yet, these is a vast area of scientific and technological progress where almost every fancy of domestic medicine gave been realized or are taking shape. It is the area of space medicine or, more specifically, medical support to space crews. Members of space crews make their own choice among numerous available devices and technologies intended for health monitoring. Purpose of this paper is to discuss some of the existing space technologies in the context of their suitability for domestic use.

Materials and methods We shall consider only few systems that embody methods of heart rate variability analysis (HRV) [1].

This analysis allows mathematical modeling of functional states of the organism and thereupon calculating levels of regulatory systems tension, their functional reserve and adaptation risk [2-4].

Each of these indices was validated in long-term space flights and demonstrated effectiveness for evaluation of cosmonauts’ health and reactions in different periods of space flight, including in the course of working in the outer space, and during descent and landing3. The hard-software system “Ecosan-2007”, which has been developed from on-board device “Pneumocard”, was used for monthly health control for groups of volunteers (120 males) in longitudal medical-ecological investigations in different regions of the world in MARS-500 project. For weekly investigations in home conditions the device “Heart Wizard” was applied [5,6].

The leading place among the newly defined evaluative criteria is occupied by the index of adaptation risk that characterizes probability of functional state deterioration from prenosologic to premorbid and consequent disease. Evaluation of the adaptation risk is the end result of investigation performed using hard- and software Ekosan-ТМ2 and Delta-2013 spun off from space technologies[7].

Ekosan-TM2 serves to population-wide and individual examination of essentially healthy people.

Ekosan-ТМ is a midget computer unit enabling registration of electrocardiogram and filling out questionnaire about health, well-being, complaints and life style. Body mass and blood pressure measurements made with the help of respective devices are entered additionally. Results of the quick examination are used to release “a health passport” that includes information about estimated degree of tension and functional reserve of regulatory systems, as well as adaptation risk; it also contains rating of patient’s functional state and provides a precise individual recommendation concerning steps toward better life style and disease prevention [6].

Delta-2013, an Internet-analog of the system, is a tiny aural clip-type photoplethysmograph with a computer interface that makes possible simultaneous filling-out the questionnaire and analysis of photoplethysmographic HRV. Data processing and analysis are performed remotely via the Internet channels.

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Figure 1. Diagram of operation of the complex «ECOSAN-TM2»

With this device the health passport can be obtained sitting in front of home computer either displayed on the PC screen or printed out, if necessary [6,7].

Another HRV-based system for domestic medicine has been integrated in android smartphone. The smartphone still camera reads pulse signals from patient’s finger. The system was called Health Lights, as it rates health state awarding one of three color: green – physiological norm, yellow prenosology, red – premorbidity or highly probable pathology.

That is conceptually the approach to health evaluation is same as in the previously described devices; however, in view of slow signal reading by the still camera a simpler algorithm is used to rate the functional state of organism.

Results Analysis of Ekosan-2007 data gathered in the extended eco-medical survey of normal people from different regions showed that monthly examination combining HRV analysis with filling-out the questionnaire and anthropometric measurements was sufficient to identify people in prenosologic and premorbid states, to monitor dynamics of these states, to detect changes due to seasonal weather variations or stresses associated with social, everyday and work-related factors.

Study participants were classified into 4 groups according to their averaged risk categories for 1.5 years. The comparing of group and individual dynamics of HRV parameters has shown in many cases the presence of pronounced individual patterns of functional conditions, which confirms the need for personalization of prenosological control.

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Group1

Individual1 80,00

Group3

Individual3

SDNN, ms

70,00

60,00

50,00 HR, bmp 40,00 40,00

50,00

60,00

70,00

80,00

90,00

100,00

110,00

30,00

20,00

Figure 2. Changes of functional status of persons with different risk categories (low risk -1-th group, the high risk-group – 3-rd group). Examples 1,5-annual monitoring during medico-ecological studies "Mars-500"

According to the results of “Ecosan-2007” and “Heart Wizard” use in MARS-500 project [5,8], algorithms, data entry and processing and issuing documentation of the survey results have been modified. It allowed to create new hardware and software systems.

Figure 3. The hardware-software complex «ECOSAN-TM2»

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"Ecosan-TM" is designed for use during public prenosological examinations to classify groups of individuals with prenosological and premorbid states, evaluate the degree of deviation of the analyzed parameters in the observed contingents (see Fig. 4), as well as for individual prenosological control.

Figure 4. The example of risk factors assessment in one of experimental groups HRV parameters: 1- HR, 2- SDNN, 3- pNN50, 4- SI, Total risks: 5'- lifestyle, 6' - mental health, 7' physical health. Risks for diseases: 8" - cardiovascular systemб 9"- gastro-intestinal tract, 10"musculoskeletal system, 11" - nervous system.

Testing of a specialized system for individual prenosological control of the functional state was conducted in "Mars-500" project on the basis of the «Heart Wizard » device, designed jointly by the IBMP and the American company «Biocom Technologies».

Analysis of the results of the investigation showed that functional state of these largely healthy people was extremely sensitive to any stress factor from weather change to work environment[7,8].

Figure 5.

A. The device «Delta2013»; B. Mount photoplethysmographic sensor on the ear lobe

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The experimental results laid the ground for development of medico-engineering specifications for Delta-2013. Testing of the Delta-2013 prototype demonstrated its friendliness and usability equally at workplace and home, and utility for getting timely information about health deviation. The system automatically generates and issues individual health-improving and preventive recommendations, or, if necessary, advises do not delay with consulting a doctor [7].

Testing of the system "Delta 2013" in terms of weekly regular use for individual prenosological control based on HRV analysis confirmed the effectiveness of its application for the evaluation and control of the functional state. Fig. 7 shows an example of the dynamics of individual risk assessments disadaptative two panelists.

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Figure 6. Screenshots of the examination session with ÂŤDelta 2013Âť

Figure 7. Risks of adaptation disorder represented by volunteers A, B.

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The Health Lights system as a smartphone mobile application was developed cooperatively by IBMP (Russia) and Autosun Health Technoligies Inc. (Canada). Medico-physiological testing of the system had the aim to identify HRV indices that the smartphone microprocessor would calculate with a minimal error, and to search for original evaluating criteria. It was proven that cellular communication for functional state evaluation in real-time can become part and parcel of the system of telemedical health monitoring and “domestic medicine”.

A

B

C

D

Figure 8. Appearance of working screens of system «Health Traffic light».

A - General screen, B - Finger-photopletismogram, C - Cardiointervalogram, D - Histogram of RR-intervals

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We develop unique system of personification of the data, allowing to consider specific features of vegetative regulation of functions at each concrete patient-user. On the basis of estimations of adaptable risk and results of personification of the data the orientation of changes of a functional state is defined during dynamic supervision and the decision on necessary preventive actions is made or the recommendation about the urgent reference to the doctor is given. Results of the conducted research can be transferred to the set e-mail address or in the special analytical centre.

Now three variants of "a health Traffic light» are developed: 1) For prenosological control (an estimation of a current functional state); 2) For an estimation of adaptable risk (the forecast of an orientation of changes); 3) For management of health. (With delivery of improvingly-preventive recommendations).

Conclusion Plans to further the development and transfer of health monitoring systems to domestic medicine envisage creation of specialized analytical centers, both local and regional, for on-line servicing some categories of patients. A single network could combine all types of system presented above. These centers could cooperate with large outpatient clinics and hospitals in formation of groups with different adaptation risk categories and, therefore, simplify significantly planning of medical care and services.

Statement on ethical issues Research involving people and/or animals is in full compliance with current national and international ethical standards.

Conflict of interest None declared.

Author contributions All authors prepared the manuscript and analyzed the data. All authors read the ICMJE criteria for authorship and approved the final manuscript.

References 1. Heart Rate Variability. Standards of Measurement, Physiological Interpretation and Clinical Use. Circulation. 1996;93:1043 – 1065.

2. Baevsky RM, Berseneva AP. Introduction in Prenosological Diagnostics. Moscow:Slovo; 2008. 220 p. [in Russian] 3. Baevsky RM, Chernikova AG. To the Problem of Physiological Norm: the Mathematical Model of Functional States on the Base of Heart Rate Variability Analysis. Aviaspace and Ecological Medicine.

2002;5:34–7. [in Russian] 4. Сhenikova AG, Baevsky RM, Funtova I, Tank J. Adaptation risk in space medicine. 63-th IAC; Italy; 2012.

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5. Pougatchev VI, Baevsky RM, Berseneva AP, Chernikova AG, Baevsky AR, Isaeva ON. Long-term Medico-ecological Studies in North America Based on the Use «Heart Wizard Mars500» system.

Aviaspace and ecological medicine. 2013;47(6):39–45. [in Russian] 6. Orlov O, Pougatcev V, Berseneva A, et al. Telemedical System for Individual Prenosological Health Assessment. Luxembourg: Med-e-Tel. Global Telemedicine and eHealth updates: Knowledge resources. Volume 5; pp. 433-7. 2012.

7. Assessment of health healthy people, working in conditions of prolonged exposure to stress factors. Methodological manual on the use of hardware-software complex "ECOSAN-TM".

Moscow:SLOVO; 2014.

8. Isaeva ON, Orlov OI, Baevsky RM, et al. First Experience in Using Telemedical System Heart Wizard DELTA in Individual Prenosological Health Monitoring in Russia. Luxembourg: Med-e-Tel. Global Telemedicine and eHealth updates; pp. 476-483. 2013.

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Report

Studies of natural changes in diastolic pressure in each cardiac cycle on the basis of digitally processed ECG and Rheo Olga K. Voronova1* 1 Voronezh

State University Russia 394006 Voronezh, Universitetskaya pl. 1 Corresponding author phone: +7 (473) 220-85-93, e-mail: office@main.vsu.ru

*

Submitted: 15 January 2015 Accepted: 6 February 2015 Published online: 16 May 2015 Abstract

Conventional methods for arterial pressure (AP) measurement are not capable of identifying it in each cardiac cycle. Besides, they ignore many significant factors. The paper reports on an innovative method based on cardiac cycle phase analysis for detecting systolic and diastolic AP changes in each cardiac cycle using synchronous digitally processed ECG and Rheo recordings. Considered is the phase mechanism of the natural diastolic pressure regulation. The diastolic AP changes referred to the physiological norm and aortic dilatation status are also assessed.

Keywords

Arterial pressure • Systolic • Diastolic • Hemodynamics • Cardiac cycle phase • ECG • Rheo

Imprint

Olga K. Voronova. Studies of natural changes in diastolic pressure in each cardiac cycle on the basis of digitally processed ECG and Rheo; Cardiometry; No.6; May 2015; p.41-48 ; doi: 10.12710/cardiometry.2015.6.4148 Available from: www.cardiometry.net/no6-may-2015/natural-changes-in-diastolic-pressure

Introduction The most widely used hemodynamic parameter is arterial pressure (AP). It is easy to measure it for everybody and there upon to take necessary steps to normalize AP. Taking into account the fact that any measurement in cardiology relates to the field of cardiometry, it is reasonable to consider the natural mechanism of AP self-regulation in more detail. The more so as the widely used indirect method of AP measurements identifies the AP parameter not in each cardiac cycle, but by measuring separately the systolic pressure in one cardiac cycle and the diastolic pressure in the other cardiac cycle. This procedure ignores many factors which must be taken into consideration. First of all, it is an influence of respiratory rhythm. Cardiometry allows considering AP changes in every cardiac cycle. Besides, it is possible to detect and trace mutual relationship between systolic and diastolic AP changes, based on the cardiac cycle phase analysis. It is very important as the practice shows that the

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most critical mistake in medical practice is to decide on reducing high systolic pressure, while not taking into account the diastolic pressure changes [1-9].

Matherials and methods Let us consider an ECG and a Rheo synchronously recorded with the Cardiocode device. It is the only PC-assisted device which is capable of detecting phase changes in each cardiac cycle and, that is important in our case, recording an AP characteristics curve and plus an ECG synchronously. In doing so, all the processes of the ascending aorta are traced, so that we can obtain the most spectacular picture of the actual cardiovascular system performance.

Fig.1 shows synchronously recorded ECG and Rheo curves which may be conditionally ccepted as reference ones. The respective reactions of AP in the aorta captured by the Rheo and the ECG synchronously recorded can be accurately identified in each phase.

Figure 1. Synchronous recordings of AP changes and ECG of aorta made with the Cardiocode device

It is fundamentally important that the recorded ECG and Rheo curves are synchronized by the point S, i.e., by the point in the beginning of the cardiac muscle tension phase. The synchronization is required to define the Rheo curve isoline that makes possible to trace any Rheo changes in the cardiac muscle tension phase S-L. If an AP curve is of the same type as shown in Fig.1, then it corresponds to the norm. As a rule, the normal value is from 65 to 70 mm Hg. The cardiac muscle tension phase ends at the point L. This point is described in the previous issue of our journal [10]. We have pioneered in describing this ECG point. That has been the idea of the authors hereof to introduce this new ECG point in order to complete the ECG analysis. It is impossible to evaluate biophysical processes in the cardiovascular system not using this point. Fig.1 shows the

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L point in each cardiac cycle. According to our novel interpretation concept, the beginning of the rapid ejection phase corresponds to the point L. During the said phase the aortic valve opens, and blood starts entering the aorta. Pressure rising takes place. The L point indicates the very moment when the diastolic pressure is evaluated and measured with all known conventional indirect methods [1117].

Let us note that the end of the rapid ejection phase on the ECG corresponds to point j (Fig.2). The location of this point as well as the specified sequence of the cardiac cycle phases remains fixed and unchanged under any conditions.

Figure 2. The Rheo derivative is added to the ECG and Rheo curves shown in Fig.1, and the derivative maximum indicates the rapid ejection phase end at the point j.

The point of inflection of the Rheo front edge corresponds to the point j on ECG

The diastolic pressure is a pressure when aorta filling is completed in the beginning of the rapid ejection phase, to be more exact, at the time marked as point L on the ECG. It is a must to provide the completion of the filling procedure in the aorta, and any spaces not filled with blood are out of the question. Thus, both the phase mechanism of the heart performance and the heart anatomy are so designed that they sequentially generate and maintain the specific blood flow pattern in the aorta, fill the aorta with the specified volume of blood, that corresponds to the diastolic pressure, and provide the systolic pressure level by adding of stroke volume to the diastolic volume of blood.

Reaching the required systolic pressure fires the baroreceptors that makes possible to move blood to the periphery.

It is important to know what is the primary factor in the development of hypertension: an improper rise in systolic or diastolic pressure?

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The systolic pressure is required to provide a difference in pressures between the aorta and the venous blood flow circuit to organize blood circulation in the body. When the blood vessel resistance changes, the systolic pressure increases. But the pressure rising cannot be infinitely provided with increasing systolic AP only. The normal upper limit of the AP is 140 mm Hg in case if the diastolic AP remains at a level of 70 mm Hg. The systolic AP over 140 mm Hg is an indicator of pathology in blood vessels. In this case it is necessary to examine the situation and decide on an appropriate therapy. As a rule, an abnormally high AP is lowered by dilatation of blood vessels, i.e., by reduction of their resistance to blood flow.

At the same time, it is necessary to control the diastolic AP. It is allowed to lower the systolic AP until the diastolic one starts rising. It is not acceptable to continue lowering the systolic AP if the diastolic pressure starts its uncontrollable increase.

Fig.1 shows the diastolic pressure in S-L tension phase. It should be noted that the diastolic AP can naturally change in this phase, but the change is not significant, approximately 5 mm Hg. Fig. 3 gives a segment in the said phase, where the Rheo curve segment is elevated and not straight as it is the case in Fig.1. It is the very rise in the diastolic pressure. Let us note again that the Rheo isoline location has been identified by the point S. The S-point synchronization is a prerequisite for an extensive analysis and assessment of a huge volume of data which can be delivered with the Cardiocode device only.

Figure 3. Insignificant natural changes of 5 mm Hg in the diastolic AP in the cardiac muscle tension phase S-L. Sometimes it may be detected during orthostatic test.

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Let us consider a more complicated case with the diastolic AP rising (Fig.4). The diastolic AP starts rising at the point Q. Actually, it is 100 mm Hg. Such Rheo behavior may indicate the weakness of the aortic valve. There are some causes to explain the abnormality: 1. Significant increase in the blood vessel resistance to blood flow; 2. Significant dilatation of the aorta; 3. Some specific changes in valve anatomy.

Due to an increase in the blood vessel resistance to blood flow, a specified amount of blood is naturally expelled from the blood vessels. Of course, this amount of blood is an integral part of the full blood volume within the circulatory system because it is a closed circuit. Therefore, during the diastolic phases the specified blood amount is pumped into the ventricles increasing load applied thereon, and prior to opening of the aortic valve, the total blood amount in question should penetrate through the closed aortic valve. It is very important since the initial pressure, namely: the diastolic pressure must reach a specified pressure level to overcome the elevated resistance to the blood flow.

After the point L, the total ejected blood volume should be considered as stroke volume. But this volume is added to the diastolic volume. In this case, the systolic pressure will be higher than the normal one. Therefore, it is necessary not to reduce the systolic AP because it results in elevating of the diastolic pressure and dilatation of blood vessels that in its turn may cause even greater problems. Naturopathic clearing of blood vessels can eliminate this problem, and it is the only appropriate therapy.

Figure 4. Early rise in the diastolic AP

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Special attention should be paid to a “step” on the Rheo curve in the S-L phase representing the cardiac muscle tension as shown in Fig.4 herein. It reflects a natural reduction in blood flow through the valve when the valve area is narrowing under the influence of cardiac muscle tension. This “step” may serve as an indicator of an abnormally elevated diastolic AP. Another cause of the diastolic AP elevation is a significant aortic dilatation. Two signs indicate this case. The first sign is an early AP elevation detected on the Rheo curve, that is similar to case one as described above, and the second sign is a not bell-shaped, but cusped peak on the Rheo curve. It indicates a greater blood flow with an increased diameter of the aorta. At the same time, the T wave on the ECG shows smaller amplitude (Fig.5). In the case illustrated it is not available at all. We can detect just the final stage of the wave as the systolic end.

Figure 5.

A combination of the low T-wave amplitude and the normal bell-shaped Rheo peak may very often occur.

To treat the third cause with specific aortic valve anatomy problems, as indicated above, it should be stated that a small blood volume ejection into the aorta is observed owing to blood flow regurgitation.

On the Rheo curve it can be found as a small slope angle of the curve segment in the L-j rapid ejection phase. There is no such sign available in Fig.5. Thus, we deal with the aortic dilatation.

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Conclusions We have considered the phase mechanism of the natural diastolic pressure regulation. Many cardiovascular system functions are involved therein, therefore the presented analysis may offer much useful information. Primarily, the following information can be extracted: 1. Assessment of actual diastolic AP changes referred to the physiological norm; 2. Aortic dilatation status assessment; 3. Control & monitoring of the therapy efficacy, when lowering the systolic pressure.

Statement on ethical issues Research involving people and/or animals is in full compliance with current national and international ethical standards.

Conflict of interest None declared.

Author contributions The author prepared the manuscript, analyzed the data, read the ICMJE criteria for authorship and approved the final manuscript.

References 1. Lehman LWH, Saeed M, Talmor D, Mark R, Malhotra A. Methods of blood pressure measurement in the ICU. Critical Care Medicine. January 2013;41(1):34-40.

2. Park M, Kang H, Huh Y, Kim KC. Cuffless and noninvasive tonometry mean arterial pressure measurement by physiological characteristics and applied pressure. Annual International Conference of the IEEE Engineering in Medicine and Biology – Proceedings 2006, Article number 4030037, Pages 6418-6421.

3. Douniama C, Sauter CU, Couronne R. Acquisition of parameters for noninvasive continuous blood pressure estimation - Review of the literature and clinical trial. IFMBE Proceedings.

2009;25(4):2151-4.

4. Raamat R, Talts J, Jagomägi K, Kivastik J. Errors of oscillometric blood pressure measurement as predicted by simulation. Blood Pressure Monitoring. October 2011;16(5):238-45.

5. Barbara J. The source of errors in the oscillometric blood pressure measurements. Metrology and Measurement Systems. 2008;15(4):539-49.

6. Hansen S., Staber M. Oscillometric blood pressure measurement used for calibration of the arterial tonometry method contributes significantly to error. European Journal of Anaesthesiology.

September 2006;23(9):781-7.

7. Turner MJ, Baker AB, Kam PC. Effects of systematic errors in blood pressure measurements on the diagnosis of hypertension. Blood Pressure Monitoring. October 2004;9(5):249-53.

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8. Vlachopoulos C, O'Rourke M. Diastolic pressure, systolic pressure, or pulse pressure? Current Hypertension Reports. 2000;2(3):271-9.

9. Smulyan H, Safar ME. The diastolic blood pressure in systolic hypertension. Annals of Internal Medicine. 1 February 2000;132(3):233-7.

10. Rudenko SM. A new point on ECG: point L as identifier of rapid and slow ejection phases boundary. Cardiometry. May 2013;2:30-9; doi: 10.12710/cardiometry.2013.2.3039.

11. Rudenko MY, Voronova OK, Zernov VA. ECG periodic table: a new ECG classification based on heart cycle phase analysis. Cardiometry. 2013;2:19-28. doi: 10.12710/cardiometry.2013.2.1928.

12. Rudenko MY, Zernov VA, Voronova OK. Study of hemodynamic parameters using phase analysis of the cardiac cycle. Biomedical Engineering. 2009;43(4):151-5.

13. Rudenko MY, Zernov VA, Voronova OK. Fundamental research on the mechanism of cardiovascular system hemodynamics self-regulation and determination of the norm-pathology boundary for the basic hemodynamic parameters and analysis of the compensation mechanism as a method of revealing the underlying causes of disease. Heart Rhythm. 2012;9(11):1909-10. http://dx.doi.org/10.1016/j.hrthm.2012.09.091 14. Makedonsky DF, Mamberger KK, Rudenko SM, Rudenko MY. Law of interdependent change of amplitude and phase modes of heart performance as a hemodynamic self-regulation mechanism.

IZVESTIYA SFedU. ENGINEERING SCIENCES. 2004;6(41):98-100. [in Russian] 15. Voronova OK, Zernov VA, Kolmakov SV, Mamberger KK, Makedonsky DF, Rudenko MY, Rudenko SM. Cardiac cycle phase analysis as a noninvasive method for volumetric hemodynamic parameters accurate measurement. Policlinica. 2008;6:56-8. [in Russian] 16. Rudenko MY, Voronova OK, Zernov VA. Theoretical Principles of Heart Cycle Phase Analysis.

Frankfurt a/M, Munich, London, New York: FouquĂŠ Literaturverlag; 2009. 336 p. ISBN 9783937909578.

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Reprinted from Intech

Biophysical phenomena in blood flow system in the process of indirect arterial pressure measurement Mikhail Y. Rudenko1*, Olga K. Voronova2, Vladimir A. Zernov1 1 Russian

New University Russia 105005 Moscow, Radio str. 22

2 Voronezh

State University Russia 394006 Voronezh, Universitetskaya pl. 1 Corresponding author phone: +7 (8634) 312-403, e-mail: cardiocode@mail.ru

*

Keywords

Biophysics • Blood flow • Arterial pressure •Measurement • Cardiovascular diagnostics

Imprint

Mikhail Y. Rudenko, Olga K. Voronova, Vladimir A. Zernov. Biophysical phenomena in blood flow system in the process of indirect arterial pressure measurement; Cardiometry; No.6; May 2015; p.49-64; doi: 10.12710/cardiometry.2015.6.4964 Available from: www.cardiometry.net/no6-may-2015/indirect-arterial-pressuremeasurement

Introduction Diagnostic parameter “arterial pressure” known in medical practice from the earliest times is now widely used for assessment of body state. Indirect occlusive methods are the most popular measurement techniques. Although the indirect method of measurement is more than one hundred years old there is no precise understanding of biophysical processes taking place in compressed blood flow.

The idea of indirect arterial pressure measurement with the help of occlusive cuff belongs to RivaRocci. However, the phenomenon of noise appearing and disappearing in the blood flow distal of the brachial artery compression during the equality moments of occlusive, systolic and diastolic pressure was called Korotkov sounds. The origin of the sounds is considered from different viewpoints [1].

But it is important to mention that their identification has no valid criteria. If their appearance corresponds to the systolic pressure, their disappearance is not always characteristic for the diastolic pressure. Thus, during the Olympic Games in Mexico continuous sounds were recorded with the swimmers. But this fact didn’t mean that they had zero diastolic pressure.

In case of measurement method computerization more reliably recorded biosignals in the form of oscillogram are used [1]. Nowadays Korotkov sounds are out of use in case of computerization of the arterial pressure measurement. The oscillometrical method of measurement is more reliable. But this method has no explanation from the point of view of biophysics as well.

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The authors of the present research work have studied biophysics of the processes in the occlusive blood flow for a long time. The study resulted in discovery of the objective law concerning the origin of arterial pressure waves interference in occlusive blood flow. It enabled to understand the processes taking place in occlusive blood flow and find the criteria which systolic pressure and diastolic pressure correspond to.

Biophysical processes of origin of the arterial pressure waves interference in occlusive blood flow Let us consider the occlusive method of the arterial pressure measurement. Big blood vessels are compressed with occlusive pressure artificially produced in the rubber cuff put as a rule on one of the patient’s arms. Then the pressure is measured at the moments of its balance with the arterial pressure using the corresponding criteria. This method enables the measurement of two parameters – systolic arterial pressure and diastolic arterial pressure.

Which criteria can be used for accurate measurement?

In practice the method of Korotkov sounds and the oscillometrical method are used. In case of the measurement process computerization the sounds method is not used. It is not reliable for noise recording. Oscillometrical method seems to be more reliable. Oscillogram is the signal of pulse wave oscillations modulated by the occlusive pressure. When recorded, these oscillations are extracted from the pressure signal in the cuff as a variable component with the help of the filtering method.

This process is technically simple and reliable.

To understand the biophysics of occlusive blood flow it is necessary to have at least its hypothetical model. We propose to study the model ‘living body–mechanic system’. It can help to define the real biophysical processes. In this case the model is represented by the ‘artery–cuff’ system.

Electronic converters quite accurately register the processes taking place in the system. However different existing theories of biophysical processes give ambiguous characteristic of the criteria of arterial and occlusive pressure balance [3]. This prevents the provision of electronic arterial pressure measuring instruments with the corresponding metrology. Practically metrology of the indirect method of arterial pressure measurement does not exist.

Although the problem is quite serious we will try to study it. Let us consider the biophysical phenomena in the system of the proposed ‘artery–cuff’ hypothetical model in the process of indirect arterial pressure measurement [4].

Figure 1 shows the simplified version of this model. For convenience only a half of the cuff is shown, it is conventionally in contact with the artery. Pulsating blood flow contacting with the cuff influences it which is recorded in the form of the corresponding signals.

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a. beginning of phase 1; b. end of phase 1, beginning of phase 2; c. transitory moment of phase 2; d. end of phase 2, beginning of phase 3; e. the first inflection moment in phase 3; f. the second inflection moment in phase 3. → travel direction of the arterial pressure wave; −−→ changed travel direction of the arterial pressure wave influenced by the occlusive pressure.

Figure 1. Changes in the ‘artery–cuff’ contact profile during different phases of arterial pressure measurement.

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Figure 2 shows the synchronous record of decompression occlusive pressure. The oscillogram (Fig.2, b) is received by means of filtration in the frequency band and increase of the oscillations which exist against the background of occlusive pressure as pulsations with small amplitudes (Fig.2, a). Several heart cycles of the oscillogram and its derivatives can be more closely seen in Fig.3. The extreme values of one cardiac cycle and the corresponding derivatives are marked by points 1, 2 and 3.

Figure 2. Synchronous record of decompression occlusive blood pressure (a); oscillogram of first-order derivative (b); oscillogram of second-order derivative (c); oscillogram of the part of the second derivative (d); oscillogram of the plethysmogram (e). The explanation is to be found in the text

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Figure 3. Synchronous record of several cardiac cycles in the first phase of occlusive pressure (a); oscillogram (b); first-order derivative (c); second derivative (d); part of the second derivative (e) and photoplethysmogram (f). 1, 2, 3 are extreme values of one cardiac cycle and their corresponding derivatives

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In the process of modulation of blood flow by occlusive pressure additional characteristic vessel impedance is needed. Its value is calculated in compliance with the formula: Z=

ρ⋅c S

where: ρ – blood density; c – arterial pressure wave velocity; S – vessel area.

Increase of the additional characteristic vessel impedance causes the appearance of standing wave proximal the occlusive place. Designed in such a manner interference pattern is registered by the cuff against the background of the occlusive blood pressure (see Fig. 2, a).

We should mention that reflected waves emergence in physiological blood flow is considered from a perspective of characteristic impedance disagreement in vessel branching and curving points [2]. In scientific literature this approach is based on research in rigid pipes imitating blood vessels. The received results are not proved by the experiments over the living bodies [3]. Theoretic calculations of the arterial wave reflection level in case of vessel branching for physiological blood flow can be found in [2]. It is marked that even in case of 10% mismatch of the vessel impedances which significantly exceeds the real one, the reflected waves are imperceptible and can not considerably influence the falling pressure wave. Scientific literature does not provide the investigation of the process in case of local increase of the characteristic vessel impedance which cuff occlusion under condition of arterial pressure measurement is. Thus, the study of the phenomena in case of maximum impedance change range arouses interest.

Deviation in extreme points amplitude by the falling wave is characteristic for interference [5]. This phenomenon is presented on the second derivative (see Fig. 2,d; 3,d).

For convenience we shall divide the process of arterial pressure measurement into three phases (see Fig. 1).

During the first phase (see Fig.1, a, b) the occlusive pressure exceeds the systolic pressure and the characteristic impedance is maximum. In case of decompression in one phase it remains constant.

Increase of the ‘cuff-artery’ contact area leads to cuff elasticity growth (see Fig. 1, a, b). As a result the amplitudes of the recorded oscillations on the oscillogram rise (see Fig. 2, b). Herewith the deviations of the extreme points remain maximum. This fact is proved by the first and second derivatives character (see Fig. 2, c, d). Distal of the occlusion place the arterial pressure oscillations are not to be found (see Fig. 2, f).

The second measurement phase starts from the moment of occlusive and systolic pressure balance when the oscillating part of the arterial pressure wave begins to recover distal of the occlusion place (see Fig., b, c; Fig.2, f) and finishes at the moment of occlusive and systolic pressure balance (see Fig.1, d; Fig.2, b, d).

There exist two characteristic features of this phase. Firstly, the elasticity and area of the ‘artery–cuff’ contact continue to increase when the occlusive pressure falls. As a result condition for continuous oscillation amplitudes growth on the oscillogram is created.

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Secondly, characteristic impedance remains maximum for the arterial pressure values that are lower than those of the occlusive pressure. For the values that exceed the occlusive pressure ones the impedance is proportional to difference of the current occlusive and systolic pressure values. This fact is related to the alteration of the straight-line travel direction of arterial pressure wave influenced by the occlusion (see Fig.1). The reflected wave amplitude will decrease proportionately with the decrease of the vessel characteristic impedance for the arterial pressure wave layers the values of which exceed the occlusive pressure. This will lead to decrease of the corresponding layers amplitude offset against the overall interference background. As a result offset of the indicated extreme points will proportionally decrease.

For the described process of layer-by-layer vessel characteristic impedance alteration for the arterial pressure falling waves the corner of triangle (marked with 2 in Fig.2, d, e) with a definite error can serve as a criterion for systolic pressure measurement. In Fig. 2 ,e a part of the second derivative shown in Fig.2 ,d can be seen. Point 2 characterizes the amplitude offset of the dicrotic oscillogram part in case of interference of falling and reflected arterial pressure waves during the occlusion.

Figure 3 shows that point 2 being extreme corresponds with the dicrotic oscillogram part.

Along the same line consideration of the extreme values of the oscillogram and its derivatives indicated with 1 and 3 in Fig. 3 enables to mark similar triangles with the corresponding corners (see Fig.2, d).

The triangle corner indicated with point 1 corresponds to the moment of diastolic pressure and occlusive pressure balance (see Fig.1, d and Fig.2, d). At this moment the oscillating blood flow part is fully recovering distal of the occlusion (Fig. 2,f). On the oscillogram the oscillation with maximum amplitude and maximum leading edge steepness which corresponds to the maximum of the first derivative conforms to the described process (see Fig.2, c).

The considered model of biophysical processes enables the pressure measurement of different arterial wave layers according to characteristic maximums of oscillogram derivatives, in particular, systolic and diastolic pressure.

The beginning of the third measurement phase is the moment of diastolic and occlusive pressure balance (see Fig.1, d). This phase is characterized by the two inflections of enveloping oscillogram, defined by the alteration of the cuff shape and elasticity as a result of occlusive pressure fall (see Fig.1, e, Fig.2, b).

For the oscillating part of arterial pressure characteristic impedance is defined only by the alteration of the arterial wave travel direction influenced by the occlusive pressure. At the moment of enveloping oscillogram inflection (see Fig.2, b) the cuff loses its shape rigidness (see Fig.1, d). At the same time characteristic impedance changes rapidly. During the period preceding the second inflection (see Fig.1, f) the cuff takes almost the same shape as it would have without the creation of the occlusive pressure. After the second inflection the cuff perceives the arterial pressure oscillations at the expense of the occlusive pressure. Herewith the cuff elasticity does not change.

The described biophysical phenomena allow concluding that indirect method can be used to measure systolic and diastolic pressure with a definite error in the process of the oscillogram and its derivatives recording. To accomplish this it is necessary to search and record the first oscillogram

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derivative maximum (see Fig.2,b) and a part of the second oscillogram derivative maximum (see Fig.2, e).

The described process of falling and reflected arterial pressure waves interference is accompanied by turbulence distal of the occlusion place. Let us consider the equation of continuity:

υ1⋅ S1 = υ2 ⋅ S2 = υ3 ⋅ S3 where: υ1 − stands for velocity proximal of the occlusion place; υ2 − is velocity at the place of occlusion; υ3 − is velocity distal of the occlusion place; S1,2,3 – artery cross-section area at the corresponding places.

Considering the equation of continuity it is possible to state that if S2 at the place of occlusion tends to zero velocity υ2 should tend to infinity. Velocity υ2 in Reynolds number equation defining the interrelation of inertial and viscous forces in the blood flow is found in numerator: Re =

where: υ − velocity; d − vessel diameter;

υ⋅d ν

ν − kinematic viscosity coefficient.

As velocity υ2 is found in the numerator of the above equation then during the systolic time interval Reynolds number will exceed the value of 2500 which corresponds to turbulence emersion.

Turbulence promotes the acoustic noise called Korotkov sounds.

Synchronous record of occlusive decompression pressure is shown in Figure 4. According to considered above criteria of occlusive and arterial pressure balance Korotkov sounds appearance corresponds to the moment of systolic pressure measurement. The peak amplitude of the sounds corresponds to the moment of diastolic pressure measurement and the disappearance of sounds occurs during the second presented inflection of the enveloping oscillogram. The connection of Korotkov sounds disappearance with the moment of their maximum amplitude and the diastolic pressure measurement criterion is possible using the ‘cuff–artery’ contact measurement. To achieve this, the cuff should not bear against the patient’s arm. As a result the second inflection almost matches the peak amplitude and a drastic decrease of the enveloping oscillation and the sounds is registered.

Measurement criteria of systolic and diastolic arterial pressure based on recording by the oscillogram derivative extreme point The peculiarities of oscillogram recording In the first part of this chapter the biophysical processes forming the oscillogram were considered.

It was proved that the oscillogram is a reflection of arterial pressure waves interference process in the place of artery occlusion. The process of falling and reflected waves interference modulated by external pressure can be investigated only with the help of mathematical derivatives. In this case we used the first-order and second-order derivatives. We should notice that the first derivative reflects the process of the object alteration. The extreme points of the first derivative always indicate the moment of transformation of an object’s state or its function to a different state or function. The second derivative is a result of interaction of the object or its functions with ambient environment.

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Here the extreme points are also informative. But their amplitude indicates the end result i.e. the fact of interaction and its result.

Figure 4. Synchronous record of decompression occlusive pressure (a); oscillogram (b); the first derivative (c); the second derivative (d) and Korotkov sounds (e)

In the process of investigation the authors faced an interesting problem. We would name it “take something – not known what”. The fact is that both the engineers and the doctors worked on the development of ECG and other bioelectric signals recording. The engineers tried to provide the doctors with the instruments that show “a fine signal”. They were unaware of the degree of distortion during the filtration process and its difference from the real processes. Our research showed that these distortions are significant and reach 25% [5]. This situation could be improved but the received distorted ECG have for a long time served for creation of cardiological standards in diagnostics.

Moreover, the theory which was formed had many “blank spaces”.

That is why here we shall reveal a secret. It is essential that the lower cut-off band in the filter should be equal: FH = 0,35 Hz.

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The signal upper this value is differentiated, the signal lower the value is integrated. If the frequencies differ from the indicated ones it would be very difficult to understand what happens in the occlusive blood flow. The same could be said about rheography.

For the engineers we should note that for the filtration process the rate of signal increase is important as well. Different ECG phases have different amplitudes. In case of incorrect choice of filtration band R deflection can be integrated increasing the RS phase to a considerable extent. This process is influenced by the upper cut-off band. Inserting this phase time in G.Poedintsev–O.Voronova hemodynamics equation we shall obtain “fantastic” results which will be different from the real results.

Criteria of systolic and diastolic arterial pressure measurement The considered above criteria of systolic and diastolic arterial pressure measurement using the oscillometric method and Korotkov sounds method allow to obtain identical values. But these methods have considerable discrepancies concerning diastolic pressure measurement. When the oscillometric method is used diastolic pressure is measured by the maximum of the first oscillogram derivative. When Korotkov sounds method is used diastolic pressure is measured by the sounds disappearance. Figure 5,c shows these discrepancies in points 2 and 3.

The study showed that the difference approximately accounts for 15 mm.Hg (Fig.5, points 2 and 3).

How do the engineers solve this problem when developing commercial arterial pressure measuring instruments?

1. The oscillogram is recorded (Fig.5, b). At the beginning of its amplitude’s increase comparator threshold is selected. Thus, systolic pressure is recorded.

2. Diastolic pressure is recorded when the oscillogram amplitude decreases below the comparator threshold.

3. In automatic devices the oscillogram resembles the first derivative. It occurs due to minimization of transient phenomena influence in the process of pumping pressure into cuff.

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Figure 5. Diastolic pressure measurement using the moment of Korotkov sounds disappearance: a – occlusive pressure; b – oscillogram; c –first-order derivative; d – second derivative; e – Korotkov sounds

Thus, all automatic machines with comparator threshold of signal amplitude do not measure diastolic pressure accurately. The measuring instrument developed by the authors of the present research work makes it possible to solve the problem in the following way. Figure 6 shows the signal records received from the commercially produced instrument. These signals are used to record systolic and diastolic pressure by derivatives maximum. After the measurement 15 mm.Hg. are deducted from diastolic pressure value.

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Figure 6. Synchronous record of processed oscillogram derivatives and signals of amplitudes relation analyses unit. The amplitudes were extracted from the commercially produced measuring instrument based on arterial pressure waves interference. a –first-order derivative; b – search of diastolic pressure measurement criterion; c - search of systolic pressure measurement criterion; d –second-order derivative

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The end result will correlate with Korotkov sounds method and will not leave the doctors asking questions. Thus, the measuring instrument provides two variants of the measurement results presentation: 1) systolic pressure and average pressure (average pressure conforms to the time of maximum of the first derivative and maximum sounds amplitude i.e. true diastolic pressure (point 2 on Fig.5,b); 2) systolic pressure and diastolic pressure (diastolic pressure conforms to the second inflection of the enveloping oscillogram or the moment of Korotkov sounds disappearance (point 3 on Fig. 5,b). It is close to the value of comparator threshold in the measuring instruments produced by different firms.

Conclusion 1. The conditions of local increase of vessel characteristic impedance leading to interference of falling and reflected arterial pressure waves are considered. Criteria of systolic and diastolic pressure measurement compared with the used in practice Korotkov sounds are revealed.

2. The described method enables to measure systolic and diastolic arterial pressure accurately.

3. Commercially produced automatic arterial pressure measuring instruments using comparator functioning as criteria for diastolic arterial pressure measurement during oscillogram amplitude decrease do not measure diastolic pressure accurately; they rather show the value which is 15 mm.Hg lower than the true value.

Acknowledgements The problem of arterial pressure measurement is given much attention in the world scientific literature. Specialized magazines are published. Scientific subpanels formed at symposiums study the results of research in this scientific field. Having studied in Radiotechnical institute the authors of the present research work took interest in the popular at that time idea of computerization of arterial pressure measurement process. In the 1970s the problem of pressure measurement in the place of brachial artery and temporal artery was set. Their magnitude relation should be equal to two. This coefficient was supposed to indicate good physical fitness of the sportsmen. The young authors started to work enthusiastically. We could not know then that the study of this problem would become a foundation for considerable scientific research the authors would devote their life to. A group of professionals would carry on research and develop medical instruments. Many of the researchers would found their schools of thought and achieve good results in business. Thirty years later the authors would receive a diploma for scientific discovery “Objective laws of arterial pressure waves propagation in blood-vessels in the areas of their impedance local increase�.

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Figure 7. Mikhail Y. Rudenko is in the hostel soldering the pressure–voltage transformation junction.

The strain indicator is glued to the shoe cream box.

Thus, the Big Science started (1978).

An outstanding school of thought with distinguished scientists was formed. Over the past twenty years more than 150,000 copies of books were published. There emerged a need in system research of human biophysics. All of the research works found practical use.

Figure 8. The first in the world commercial instrument for indirect arterial pressure measurement based on artery pressure waves interference (1986).

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Figure 9. The documents of the official registration of scientific discovery “Objective laws of arterial pressure waves propagation in blood-vessels in the areas of their impedance local increase� (2005).

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Statement on ethical issues Research involving people and/or animals is in full compliance with current national and international ethical standards.

Conflict of interest None declared.

References 1. Savitsky N.N. Biophysical principles of circulation and clinical methods of hemodynamic study. – 3-d ed. – Л., 1974.

2. Caro, C.; Padley, T.; Shroter, R.& Sid,W. (1981). Blood Circulation Mechanics. - Mir. М.

3. Eman А.А. Biophysical principles of arterial pressure measurement. – Л., 1983.

4. Rudenko, M.; Voronova, O.; & Zernov, V. (2009). Study of Hemodynamic Parameters Using Phase analyses of the Cardiac Cycle. Biometrical Engineering. Springer New York. ISSN 0006-3398 (Print) 1573-8256 (Online). Volume 43, Number 4 / July 2009. P. 151-155.

5. Rudenko, M.; Voronova, O.; & Zernov, V. (2009). Theoretical Principles of Heart Cycle Phase Analyses. Fouqué Literaturverlag. ISBN 978-3-937909-57-8, Frankfurt a/M. München – London – New York.

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Original research

Correction of the recording artifacts and detection of the functional deviations in ECG by means of syndrome decoding with an automatic burst error correction of the cyclic codes using periodograms for determination of the code component spectral range Part 1: Basic principles of the novel approach Evgenie D. AdamoviŃ 1, Pavel L. Aleksandrov1, Oleg V. Gradov1, Leonid M. Mamalyga2, Maksim L. Mamalyga3 1 Institute

of Energy Problems of Chemical Physics, Russian Academy of Sciences Russia 119334 Moscow, Leninsky prosp. 28, building 2

2 Institute

of Biology and Chemistry, Moscow Pedagogical State University Russia 129164 Moscow, Kibalchicha str. 6, building 1

3 Bakulev

Scientific Center of Cardiovascular Surgery Russia 121552 Moscow, Rublevskoe shosse 135

Corresponding author phone: +7 (915) 492-29-43, e-mail: neurobiophys@gmail.com

*

Submitted: 1 April 2015 Accepted: 30 April 2015 Published online: 16 May 2015 Aims

This paper describes a novel approach to the analysis of electrocardiographic data based on the consideration of the repetitive P, Q, R, S, T sequences as cyclic codes. In Part I we introduce a principle similar to the syndrome decoding using the control numbers, which allows correcting the noise combinations.

Materials and methods

We propose to apply the burst-error-correcting algorithms for automatic detection of the ECG artifacts and the functional abnormalities, including those compared to the reference model. Our approach is compared to the symbolic dynamics methods.

During the automated search of the code components (i.e. point values and spectral ranges one-to-one corresponding to P, Q, R, S, T) considered in Part II, the authors apply the Lomb-Scargle periodogram method with the phase control which allows to determine the code components not only from the main harmonics, but also using the sidebands, avoiding the phase errors.

Results

The results of the method testing on rats with the heart failure using a simplified telemetric recording from the implantable chips are given in Part III. A complete independence of the results of the determination of the code points (fingerprints) from the variables for which the calculation is performed is shown. We also prove the

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robustness of the above approach with respect to the most types of the non-adaptive filtration.

Conclusion

The above method can be useful not only for experimental medicine, but also for veterinary and clinical diagnostic practice. This method is adequately reproduced both on animals and human ECG, except for some constant values.

Keywords

ECG • Cyclic codes • Error corrections • Syndrome decoding • Control numbers • Lomb-Scargle periodogram methods • Fingerprinting

Imprint

Evgenie D. Adamoviс, Pavel L. Aleksandrov, Oleg V. Gradov, Leonid M. Mamalyga, Maksim L. Mamalyga. Correction of the recording artifacts and detection of the functional deviations in ECG by means of syndrome decoding with an automatic burst error correction of the cyclic codes using periodograms for determination of the code component spectral range. Part 1: Basic principles of the novel approach; Cardiometry; No.6; May 2015; p.65-76; doi: 10.12710/cardiometry.2015.6.6576 Available from: www.cardiometry.net/no6-may-2015/functional-deviations-in-ecg

Is it rational to use the cyclic codes in ECG interpretation?

It is well known that a normal sinus rhythm is characterized by the periodicity and regularity of the P, Q, R, S, T components, while any deviations from the cycle (beat-to-beat interval) belong to HRV (Heart Rate Variability) and are usually considered as the cycle length variability, RR variability, heart period variability, etc. Thus, any method based on the detection of the cyclicity, iteration interval or the period of the signal (including a single component shifted one) can be successfully applied for the periodicity analysis and diagnostics of the functional abnormalities (especially for arrhythmias) using ECG, as well as for the detection and correction of the artifacts of the electrocardiographic data computer identification associated with the improper fixation of the electrodes on the patient's body leading to the changes in the waveform or periodicity of the cardiac cycle components. In particular, this recognition process with the parallel correction is very useful both for telemetric electrocardigraphic analysis in experimental veterinary medicine and for Holter monitoring on the active patient, since the dynamics of the monitored organism inevitably affects the ECG waveform and periodicity [1,2].

The automatic decomposition of the ECG signal into the principal P, Q, R, S, T components makes it possible to establish one-to-one correspondence between them and the computer font symbols which allow to perform fingerprinting of the functional states and organic disorders changing the heart rhythm. A similar approach can be implemented within symbolic dynamics where the electrophysiological activity of the heart is considered as a dynamic system with the points of the phase space represented by the sequential set (a so-called alphabet, e.g. P-Q-R-S-T), and the certain disruptions in the heart rhythm can be considered as the sequential shift [3]. In this context we deliberately define the PQRST-alphabet in terms of the digital sequential logic, since it considers the operation background of the systems modeled in a discrete form, which is important for diagnostics and researches with the check experiments. From the mathematical standpoint it would be more accurate to define it using the Bernoulli automorphism, invariant closed subsets and invariant

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measures, but it is almost useless for the purposes of this methodical paper, while the application of the classical analytical tools – the asymptotic methods and the perturbation theory series, does not satisfy this task from the metrological positions.

The first application of symbolic logic to the cardiographic data analysis dates back to the late 1970s – early 1980s [4,5] and becomes methodologically complete during the period from 1982 to 1986 which resulted in the development of the symbolic logic notation (language and "alphabet") describing the sinoatrial node activity and its rhythm as a regulator of the contractile frequency [6], symbolic systems of analysis and visualization for electrical mapping of the heart with the predicate elements being the symbols of the spatiotemporal mapping [7] and for automatic interpretation of the myocardial scintigrams [8] based on the mathematical logic predicates of the Horn clause in the logic programming language PROLOG. This laid a physico-technical basis for the spatio-temporal, and hence, morphophysiological interpretation of the cardiological data within symbolic logic and at the same time resulted in the publication of several papers combining morphological measurements with the computer-assisted symbolic logic analysis (e.g., see a well known paper on the myocardial vascular microangiopathy [9]). However, being directly related to the progress and spread of the computer technology, a full introduction of symbolic diagnostics to the routine medical practice became possible only in the 1990-th, particularly due to the required transition from symbolic logic to symbolic dynamics necessary for identification of the transient cardiac syndromes associated with the nonlinear phenomena determined from the ECG. The very first complex application of symbolic dynamics in cardiology for the above purpose dates back to the middle 1990-th [10], while nonlinear, chaotic and noise phenomena in HRV have been quantitatively studied earlier [11]. To date the application of symbolic dynamics in HRV analysis has already become a routine procedure [12]. A significant advantage of symbolic dynamics is the simplicity of its mathematical algorithms involved in detection of the correlations between the cardiac and respiratory syndromes and factors [13], as well as in the determination of the cardioneurological correlations and cause-and-effect relationships (in the framework of the predicate logic) including significantly nonlinear HRV measurements [14,15]. To date it does not make any difficulties, since the parameters causing nonlinearity of the HRV curves are well studied [16] and the regimes corresponding to the transient phenomena and rhythmic (amplitude-frequency) distorsions can be easily expressed in terms of symbolic dynamics [17]. It is also essential that application of symbolic dynamics allows to detect and analyze the natural modulations of the cardiac activity independently of their source and origin [18,19]. One of the most clinically relevant applications of the above approach is a long-term monitoring of the cardiac rhythm change in the age physiology and pathology [20,21], starting from the fetal stage of development [22,23].

The possibility of the multi-scale analysis of the cardiac activity and HRV using symbolic dynamic techniques [24,25] provides broad prospects for diagnostics. Thus, the application of symbolic dynamics to the classification of electrocardiographic signals [26] allows to diagnose various diseases, including those difficult to be identified at the early stages due to the lack of a clear clinical picture, such as dilated cardiomyopathy [27]. As for the mathematical foundations of the above classification, one should consider different existing approaches to HRV analysis in symbolic

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dynamics [28]. This diversity results from the difference of variables, boundary conditions and confidence intervals of the accurate parameter detection and quantization determining the so-called "pathological" values. Of special interest is the correlation adjustment of the data typical for cardiorespiratory comparative (i.e. comparison of the syndromes) and correlation studies. For example, the known relationship between the cardiac and respiratory cycles expressed in terms of symbolic dynamics [29] provides an automatic detection (without any external models [30]) of the deviations from the above function indicating the presence of either functional disorders or organic pathologies. This method (with the known cardiorespiratory interactions expressed in the symbolic dynamics notation [31]) allows to detect a number of diseases, such as hypoxia / ischemia effects [32], obstructive sleep apnea [33], interactions between the cardiac and respiratory oscillators associated with the stages of sleep in healthy children [34], etc. It is noteworthy that in such cases a similar respiration pattern variability analysis is also performed and the corresponding optimized symbolic dynamics approaches for the pattern analysis and calibration are also developed [35,36].

All the above methods are based on the monitoring of the deviations from the beat-to-beat interval and HRV – cycle length variability, RR interval variability and heart period variability, e.g. symbolic dynamic analysis of beat-to-beat interactions of heart rate and systolic blood pressure [37], assessment of the RR versus QT relation by the symbolic dynamics method [38], and the classical concepts about the heart rhythm are quite sufficient for analysis at this level [39]. Another positive aspect of the electrocardiographic PQRST-sequence analysis using symbolic dynamics methods is the possibility of the casuality analysis within the cycle and in its relevant repeats [40] despite the fact that in the framework of symbolic dynamics hidden Markov models are also developed without any dependence of the current parameter value from the previous state of the system [41], which seem to be regarded as the Bayesian belief networks. In this regard one can conclude that symbolic dynamics in cardiology operates both at the state-space of a periodic PQRST-oscillator / pacemaker [42] with a high determinism inherent to the healthy heart [43] and at a noisy case [44] with an indeterminism caused by a number of states with a various degree of proximity of the real PQRST to the model one according to the Hamming theory [45]. However, it is important to find out which symbolic dynamics can operate in presence of the intermediate or "parasitic" (considered as artifacts) states?

Many authors and users try to minimize the bit depth of the data under processing reducing the point phase space of symbolic dynamics to the binary trigger simulation: methods for analysis of the binary sequences are adapted to the cardiac activity analysis [46], the information entropy of such sequences is also calculated and fitted [47] and the special systems based on the above binary approach for HRV pattern biomedical classification at the autonomic modulation are also developed [48]. However, this approach reduces both the diagnostic accuracy at the registration stage and the robustness of the signal processing.

At the same time for dynamical systems which can be attributed to symbolic dynamics mapping is defined as a sequence shift by a single symbol which is described by either Markov or Bernoulli shift conditions, so the shift in a reduced phase space (with a reduced symbol alphabet) decreases the quality of the mapping compared to those of the standard full alphabet (P, Q, R, S, T). Thus, we do not claim that the above cited works are not correct, but we postulate the need for an alternative method / approach which, on the one hand, will take into account the cyclic nature, regularity and periodicity

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of the ECG, and, at the other hand, will be able to detect the arrhythmia and the recording artifacts (i.e. the delay and “outrunning” in a readback mode).

A biomathematical approach proposed We propose to solve the above problems by using a mathematical apparatus of the cyclic codes' decoding [49]. A regular iteration of the PQRST-sequence (P−wave, QRS−complex, T−wave) in the Einthoven's triangle suggests that the above cyclic dynamics can be described by cyclic codes. In general, a cyclic code at the ECG is a linear block ( n , k ) − code which being shifted by a single step to the left produces a code word which belongs to the same code, and the manifold of the code words is a set of polynomials degree n−1 and less, dividing by the generator polynomial g ( x ) degree r = n − k , which is a factor of the binomial x n + 1 , and the code words in this code are represented as polynomials: v( x) = v n−1 x

n −1

+ vn−2 xn−2 + K + v1x1 + v0 xo , where n− is the code length; vi − coefficients

from the field GF ( q ) . If we interpret the heart rhythm as a stable code (due to the automatism of the heart muscle and autonomous regulation) with the errors indicating physiological abnormalities, one can represent a PQRST sequence as a “code over a field GF ( PQRST ) ” analogous to the binary code being a code over a field GF (2) . From the technical positions, the code shift either to the left or to the right will determine the cyclic window, but this will not be included in a statistical analysis. This is consistent with the symbolic dynamics theory in a shift context [50].

An error detection with respect to the reference code range with the normal rhythm, pulse interval, force and tension, and the absence of the rhythm failures can be achieved using an error polynomial e( x) and a syndrome polynomial S ( x ) . An error polynomial can be determined from the equation:

e(x) = v• (x) + v(x) , where v• (x) and

v( x) are polynomials representing an accepted (with an error) and transmitted code words, respectively, with non-zero coefficient positions in e( x) corresponding

to the errors. An essential feature of some cyclic codes is the ability to correct burst errors. In the case of the cardiac activity this function is performed due to the bioelectric heart automatism and compensatory homeostatic effects.

A syndrome polynomial used in cyclic code decoding is given by a remainder of the division of the code

word

by

S j ( x ) = R g ( x )  v • ( x ) + e j ( x )  = R

the g ( x)

generator

polynomial:

S j ( x ) = Rg ( x ) v • ( x )

or

 e j ( x )  , i.e. directly depends on the error polynomial e( x) , and

hence, can be applied to the generation of a syndrome table which is used in the decoding process and contains a list of the error polynomials as well as the list of syndromes determined from the expression S j ( x ) = Rg ( x )  e j ( x )  . Automatic correction of the recording artifacts can be performed by means of a table search of the polynomial e( x) , which after summation with the code word gives a • new corrected code word: v j ( x) = v j ( x) + e j ( x)

From the standpoint of the algebraic block code theory, the code cyclicity imposes serious restrictions on the code word set, which simplifies the decoding procedure in electrocardiography, since both Bose-Chaudhuri-Hocquenghem (BCH) codes capable of correcting several independent errors and Golay codes which correct single, double and triple errors are sufficient enough in this

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case, as nothing more is required. The length of a primitive cyclic code, when n = q −1 over m

GF ( PQRST ) may be quite sufficient for interference-free data interpretation. The proximity of

interpretation and pointedness of the mathematical apparatus (formalism) allows to use the cyclic code decoding methods in the same manner as the symbolic dynamics methods with the ECG sequences recognition as algebraic curves [51]. This is facilitated by the presence of several systolic architectures for cyclic code decoding [52] which allows to perform the coding even in the extremely simplified case – within the classical binary sequences' analysis discussed above [46].

Moreover, there is a number of quasi-cyclic codes [53,54] which include in the framework of this approach the ECG codes over the field GF ( PQRST ) . This is promoted by the existence of the quaternary quasi-cyclic codes [55]: if we consider one of the wave components as a “punctuation mark” in the structural numeration of the ECG components [56] (which corresponds to the consideration of the heart automatism as the analog "sequential machine" [57] but is not applicable to any other non-systematic irregular electrophysiological sequences [58]), so codes over the field GF ( PQRST ) will appear to be ternary ones with a fixed point. This requires an automatic determination of the heart rate as a cyclic code rate [59] and beating [60] with automatic positioning (fingerprinting) of the “punctuation point”. For this purpose computer analysis of cyclic codes applies the weight spectra [61] which may be successfully used in cardiography where symbolic dynamics analysis is often combined with the spectral analysis [62], especially for the search of distortions [63].

The feasibility of introduction of the above approach to the clinical practice at the current stage can be proved by the already accomplished (within the US and the EU) implementation of the combined spectral frequency, pulse-time and symbolic dynamic methods of the heart rhythm variability in hepatology [64], gender fingerprinting using combined spectral and symbolic dynamic techniques both in the prevention and clinical examination [65], combination of the morphometric, ultrastructural, optical microscopic and symbolic-logical analysis in cardioendocrinology at myocardial microangiopathy and experimental diabetes [66]. In the areas where spectral analysis is traditionally used, such as the analysis and detection of ventricular tachycardia [67], symbolic dynamics approaches are implemented to perform the same functions [68]. One of the current trends is combined multiparameter analysis using wavelet-based symbolic representations [69] which does not allow to make a clear distinction between the spectral and symbolic approaches. In this regard, we propose a novel approach where the elements of symbolic dynamics are determined by the computer rather than by a physician / operator, automatically performing "fingerprinting" of the ECG signal with the subsequent comparison to the statistically relevant recognizable spectral components (and the related harmonics) in the indicator dynamics (e.g. in the form of cumulative spectral decay), indicating their belonging to the certain components of the cyclic code over a field GF ( PQRST ) . The statistical deviation values [70] in this case will indicate the heart rate variability in symbolic dynamics [71], and the presence of nonlinear phenomena after detection and detrending of the fluctuations will indicate certain biophysical mechanisms rather than the recording artifacts [72].

From the standpoint of the cyclic code mathematics substituting symbolic dynamics, detection of the ectopic pulses in nonlinear dynamics of the heart rhythm [73], will be an essential part of the code error detection procedure [74].

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Thus, the main aim of this paper was to demonstrate the possibilities and the prospects of the concept proposed (i.e. spectrally-mediated determination and fluctuating code range specification during ECG interpretation). For this purpose it is also necessary to demonstrate the stability of the frequency components' determination (fingerprinting) and the independence of their values from the discrimination and filtration types, as well as from the variables used. These problems will be considered in the next part of this work.

Acknowledgements We are grateful to S.I. Anisimov, G.S. Golitsin, V. P. Goncharov, E.A. Novikov, and N.A. Inogamov for useful comments and interest to the work.

Conflict of interest None declared.

Author contributions All authors prepared the manuscript and analyzed the data, E.D.A. drafted the manuscript. All authors read the ICMJE criteria for authorship and approved the final manuscript.

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Case report

The course of very severe aortic stenosis due to bicuspid aortic valve calcinosis in a young man Regina Jonkaitiene1, Egle Rumbinaite1*, Egle Kazakauskaite1 1 Department

of Cardiology, Lithuanian University of Health Sciences, Kauno Klinikos Lithuania 50009 Kaunas, Eiveniu g. 2A

Corresponding author phone: +370 688-11-387, e-mail: egle.rumbinaite@gmail.com

*

Submitted: 25 November 2014 Accepted: 8 December 2014 Published online: 16 May 2015 Abstract

In the young patients with bicuspid aortic valve, manifestation of aortic stenosis (AS) often remains silent. Asymptomatic very severe AS makes medical decisions challenging. For the better evaluation of AS severity and estimation the indications for the surgical treatment any stress test is preferable.

We report a case history of a 46 year old male patient with successfully treated critical AS with severe heart failure (HF) that demonstrates effectiveness of the surgical treatment. Successful aortic valve replacement (AVR) was beneficial and guided to increase functional class, improve LV systolic function, normalization of the heart chambers, decreased pulmonary hypertension (PH), determined reversible left ventricle (LV) hypertrophy. Summarizing our experience, we hypothesize that surgical treatment of this patient with asymptomatic very severe AS would be helpful in increasing quality of life and avoiding manifestation of AS with critical severe HF.

Keywords

Aortic stenosis • Bicuspid aortic valve • Aortic valve replacement • Reversible left ventricle hypertrophy• Severe heart failure

Imprint

Regina Jonkaitiene, Egle Rumbinaite, Egle Kazakauskaite. The course of very severe aortic stenosis due to bicuspid aortic valve calcinosis in a young man; Cardiometry; No.6; May 2015; p.77-82; doi: 10.12710/cardiometry.2015.6.7782 Available from: www.cardiometry.net/no6-may-2015/bicuspid-aortic-valve-calcinosis

Introduction Management of asymptomatic very severe or critical aortic stenosis (AS) is controversial and often challenging. Unselected premature aortic valve replacement (AVR) carries the risks of cardiac surgery, but delayed AVR due to unrecognized symptoms can result in unfavorable outcome [1].

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Materials and methods The medical records of a patient were analyzed and presented as a case report. We have analyzed the data of the patient during the eight years period and follow-up 9 months after AVR. The patient refused surgery in the first time, but later the indication for surgery was based on the latest existing valvular heart disease (VHD) guidelines.

Results History began in 2005, when asymptomatic very severe AS was diagnosed for 46 year old man. The bicuspid calcified aortic valve (AV) was revealed with parameters of very severe AS. AS jet velocity 6.3 m/s, mean gradient - 96 mmHg, aortic valve area (AVA) was 0.71 cm2, valve area index - 0.36 cm2, LV diastolic diameter was 56 mm, concentric left ventricle (LV) hypertrophy was revealed (LV mass index 184.5 g/m2). LV ejection fraction (EF) was evaluated as 57%. The patient had no symptoms despite his active lifestyle. Nevertheless, despite the heart team (cardiologists, heart surgeons) have explained possible medical, interventional, surgical opportunities and the complicated course of the uncorrected AS, but the patient refused surgical treatment and, moreover, he had never came for the planned TTE and consultation of cardiologist in the outpatient department during 8 years.

The patient was hospitalized urgently on 29th of February, 2012 with severe IV class (according to New York Heart Association (NYHA)) HF. The patient had severe dyspnea at rest, pulmonary stasis, pleural fusion, ascites, hepatocellular insufficiency. During that admission, TTE was performed.

Echocardiographic signs of disease progression were obvious: critical AS was accompanied with reduced LV EF – 10%, restrictive diastolic LV function and dilated LV (LV diastolic diameter - 64 mm.), dilated left atrium (LA) - 60 mm, pulmonary hypertension (systolic pulmonary artery pressure (sPAP) was 51 mmHg), dilated right ventricle (RV) – 40 mm, dilated right atrium (RA) - 67 mm, relative IV° tricuspid regurgitation (TR), severely reduced RV function (tricuspid annular plane systolic excursion (TAPSE) - 8 mm), pericardial and pleural fusion. He underwent coronary angiography, no significant stenoses of the coronary arteries were found.

The indications for the AV surgery were discussed by the heart team. The patient agreed with the surgical treatment. AV replacement with mechanical prosthesis and tricuspid valve repair were performed during that hospitalization.

On the follow-up, the vital signs, electrocardiographic (ECG), echocardiographic parameters of the patient were evaluated every three months (Table 1) (Figure 1).

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Table 1. Echocardiographic parameters before and after aortic valve replacement (AVR)

10 Jan 2005

29 Feb 2012

6 Jun 2012 3 month after surgery

LV diastolic diameter (cm) Septal wall thickness (cm)

5,6 1,56

6,4 16

5,4 13

5,2 12

Posterior wall thickness (cm) LV mass index (g/m2) Ejection fraction (%)

1,36 184,5

1,4 202

1,25 148,5

1,14 124

57 49

10 60

40 45

50 45

85

116

74

74

RA diameter (cm) SPAP (mmHg)

35 25

67 75

48 25

46 30

Aortic jet velocity (m/s) Mean pressure gradient (mmHg)

6,3 96

5,9 59

2,5 13

2,5 13

Aortic valve area Tricuspid regurgitation degree

0,71 I

0,62 IV

1,86 I

1,86 I

LA diameter (cm) LA volume

18 Dec 2012 6 month after surgery

LV − left ventricle; LA − left atrium; RA − right atrium; SPAP − systolic pulmonary artery pressure

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Figure 1. A, B, C, D are ECG samples that was taken during admission to the hospital, before aortic valve replacement (AVR); A’, B’, C’, D’ are ECG samples that was taken 9 months after surgical treatment; A, A’ reveals I, II, III ECG derivations; B, B’ – aVR, aVL, aVF derivations; C, C’ – V1, V2, V3; D, D’ – V4, V5, V6. The positive ECG dynamics demonstrates significantly decreased LV hypertrophy and pressure overload after the AVR.

Discussion and conclusions This fortunate case of successfully cured very severe critical AS demonstrates effectiveness of the surgical treatment. Despite manifestation of the AS by severe HF, all parameters dramatically changed after the successful surgery: increased functional class, echocardiography revealed improved LV systolic function, the size of heart chambers normalized, and moreover, reversible LV hypertrophy was detected not only on echocardiography but on ECG also. According to Villari et al, LV hypertrophy in patients with AS is associated with an increase in interstitial fibrosis, which is more pronounced in male (2). Previous investigators showed an increased collagen I and III, as well as matrix metalloproteinase expression, in predominantly male patients undergoing aortic valve

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surgery (3). Few clinical studies investigated LV mass regression after AVR (4,5,6). Christakis et al (4) found a significant decrease in LV mass of â&#x2030;&#x2C6;14% in <5 days after surgery; Djavidani et al (5) showed after AVR a 13% decrease in LVM in the early postoperative period and a further. Petrov et al, show that regression of LVH after AVR is different in women and men (6). Future studies are needed to show the exact mechanisms of reversible LVH after AVR. Nevertheless, the optimal time and possibility for AVR in such asymptomatic patients remains unclear. Recent studies have revealed the importance of the initial AV jet velocity. According to Rosenhek et al., the patients with an initial AV jet velocity more than 5.5 m/s had a higher likelihood (52%) of severe symptom onset compared to AV jet velocity between 5.0 and 5.5 m/s (27%; P=0.03) [7]. As it is mentioned previously, our patientâ&#x20AC;&#x2122;s initial AV jet velocity was 6.3 m/s.

The other important issue in evaluation of AS is evaluation of symptoms such as dyspnea that remains subjective. The principal role of exercise testing is to unmask patients with critical AS who claim to be asymptomatic [8]. For the more precise evaluation of AS during the first time of diagnosis, exercise testing was suggested for our patient as well, however, he refused any further investigation.

Current guidelines of valvular heart disease [9] support the role of exercise testing in asymptomatic AS patients, with first class recommendations for AS surgery to those with exercise-induced symptoms or abnormal blood pressure response. Recent studies emphasized the usefulness of exercise stress echocardiography (ESE) in asymptomatic patients with AS [5, 6]. The exerciseinduced increase in transvalvular gradient may be helpful to improve risk stratification in asymptomatic AS patients with normal exercise response. So, ESE may provide additional prognostic information over that obtained from standard exercise tests and rest echocardiography [10].

Evidence of improved LV systolic function, normalization of the heart chambers and reversible LV hypertrophy in 46 year male patient with critical AS after the AVR surgery hypothesize that surgical treatment of very severe AS may be useful for increasing quality of life and avoiding progression of HF. According to VHD guidelines, stress testing for asymptomatic patients is preferable for the better evaluation of AS severity and estimation of indications for the surgical treatment of AS.

Statement on ethical issues Research involving people and/or animals is in full compliance with current national and international ethical standards.

Conflict of interest None declared.

Author contributions RJ, ER and EK prepared the manuscript, analyzed the data and reviewed the recent literature. RJ was the responsible doctor of this patient, done 9 month follow-up and suggested to write the report. ER and EK have equally contributed to the manuscript. All authors read and approved the final manuscript.

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References 1. Rosenhek, R., et al., Natural history of very severe aortic stenosis. Circulation, 2010. 121(1): p. 1516.

2. Villari B, Campbell SE, Schneider J, Vassalli G, Chiariello M, Hess OM. Sex-dependent differences in left ventricular function and structure in chronic pressure overload. Eur Heart J. 1995; 16: 1410– 1419.

3. Fielitz J, Hein S, Mitrovic V, Pregla R, Zurbrugg HR, Warnecke C, Schaper J, Fleck E, Regitz-Zagrosek V. Activation of the cardiac renin-angiotensin system and increased myocardial collagen expression in human aortic valve disease. J Am Coll Cardiol. 2001; 37: 1443–1449 4. Christakis GT, Joyner CD, Morgan CD, Fremes SE, Buth KJ, Sever JY, Rao V, Panagiotopoulos KP, Murphy PM, Goldman BS. Left ventricular mass regression early after aortic valve replacement. Ann Thorac Surg. 1996; 62: 1084–1089.

5.Djavidani B, Schmid FX, Keyser A, Butz B, Seitz J, Luchner A, Debl K, Feuerbach S, Nitz WR. Early regression of left ventricular hypertrophy after aortic valve replacement by the Ross procedure detected by cine MRI. J Cardiovasc Magn Reson. 2004; 6: 1–8.

6. George Petrov, Vera Regitz-Zagrosek, Lehmkuhl, Thomas Krabatsch, Anne Dunkel, Michael Dandel, Elke Dworatzek, Shokoufeh Mahmoodzadeh, Carola Schubert, Eva Becher, Hannah Hampl, and Roland Hetzer. Surgery for Valvular Heart Disease: Regression of Myocardial Hypertrophy After Aortic Valve Replacement: Faster in Women? Circulation. 2010;122:S23-S28.

7. Picano, E., et al., The emerging role of exercise testing and stress echocardiography in valvular heart disease. J Am Coll Cardiol, 2009. 54(24): p. 2251-60.

8. Vahanian, A., et al., Guidelines on the management of valvular heart disease (version 2012). Eur Heart J, 2012. 33(19): p. 2451-96.

9. Marechaux, S., et al., Usefulness of exercise-stress echocardiography for risk stratification of true asymptomatic patients with aortic valve stenosis. Eur Heart J, 2010. 31(11): p. 1390-7.

10. Lancellotti, P., et al., Determinants and prognostic significance of exercise pulmonary hypertension in asymptomatic severe aortic stenosis. Circulation, 2012. 126(7): p. 851-9.

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Report

Diagnostic value of measured hemodynamic parameters: cardiac output, minute volume and a complete set of phase-related volumes of blood Nikolay E. Sapuntsov1, Olga K. Voronova2*, Vladimir A. Zernov3, Konstantin K. Mamberger3 Southern Federal University Russia 344006 Rostov-on-Don, Bolshaya Sadovaya str. 105/42 1

Voronezh State University Russia 394006 Voronezh, Universitetskaya pl. 1 2

Russian New University Russia 105005 Moscow, Radio str. 22 3

Corresponding author phone: +7 (473) 220-85-93, e-mail: office@main.vsu.ru

*

Submitted: 18 February 2015 Accepted: 4 March 2015 Published online: 16 May 2015 Abstract

The paper reviews the existing methods for hemodynamic parameters measurement, namely the Fick method, the thermodilution technique and the Cardiocode technology. Comparative analysis of the above methods is presented. Strong and weak points in each method and their informative values are identified. Distinctive features of the Cardiocode method, as the only noninvasive one, are described.

Keywords

Hemodynamics • The Fick method • Thermodilution • Cardiocode

Imprint

Nikolay E. Sapuntsov, Olga K. Voronova, Vladimir A. Zernov, Konstantine K. Mamberger.

Diagnostic value of measured hemodynamic parameters: cardiac output, minute volume and a complete set of phase-related volumes of blood; Cardiometry; No.6; May 2015; p.83-95; doi: 10.12710/cardiometry.2015.6.8395 Available from: www.cardiometry.net/no6-may-2015/diagnostic-value-of-measured-hemodynamicparameters

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Introduction It is commonly believed that cardiac output and minute volume of blood are most indicative signs of the cardiovascular system performance which may be used as reliable functional diagnostics tools [1-3].

Up to now, the above parameters have been measuredusingeither directmethod oran indirect one.

The thermodilution technique with the Swan-Ganz catheter is classified as a direct, an invasive method to measure cardiac output in patients [4,5]. But it should be stressed that the thermodilution technique is always associated with a huge volume of preparatory workin patientswhichsometimes may takeeven several days. The cardiac catheterization techniques a special thermistor-tipped catheter (Swan-Ganz catheter) to be inserted from a peripheral vein into the pulmonary artery. A cool indicator of known temperature and volume is injected into the right atrium from a catheter port. The indicator is mixed with the blood, thus cooling the blood. The blood temperature is measured by a thermistor at the catheter, and the changes in blood temperature are calculated with a computer obtaining from the data the respective cardiac output parameters from the right ventricle.

An echocardiographic imaging technique being an indirect methodcan also be usedto determine cardiac output for the purpose of diagnostics. It estimates real-time changes in ventricular dimensions. Then the volumetric parameterscanbe computed according to somespecific formulas.

But why have these parametric indicatorsnot gained the popularity in practical cardiology despite the fact theyare really needed for diagnostics?

It has been just cardiometry that has offered new instrumentationtoimprove accuracy in noninvasive measuring of phase-related blood volumes and simplify themeasuring procedures, when obtaining these key diagnostic parameters. But it should be mentioned that unfortunately classical cardiologists ignore thisunique opportunity increasing the value of diagnostics.

It seems that there is anexpertisemythology inthe cardiological communitywhorelieson the commonly recognized diagnostic effectiveness of estimation ofcardiac output and minute volumetric parameters that is practically always associated with supposedly inevitable difficulties both in their invasive procedural measuring and their real information value for the diagnostic purposes.

That has been the driving force for us to submit our own review to address this critical issue.

Materials and methods It is known that used are two direct methods of measuring cardiac output: the Fick method and the thermodilution technique [6,7]. Let us consider their basics in general.

The Fick method This method is based on the Fick principle according to which â&#x20AC;&#x153;the total uptake of (or release of) a substance by the peripheral tissues is equal to the product of the blood flow to the peripheral tissues and the arterial-venous concentration difference (gradient) of the substance." [Fick A. Uber die messung des Blutquantums in den Hertzventrikeln.SitzberPhysik Med Ges Wurzburg. July 9th: 36, 1870]. Following this principle, we can calculate the cardiac output as the quotient of oxygen uptake

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(AVDO2, ml/100 ml) and the difference of the arterial and mixed venous oxygen content.The Fick technique supplies us with a blood flow rate in liters per minute. The arteriovenous difference is computed by receiving samples of arterial blood and mixed venous blood, and the said venous blood is received via a catheter reaching up to the right ventricular / the pulmonary artery [1].

The consumption of oxygen by the blood in the lungs per unit of time (VO2, ml/min) can be reliably determined with spirometry only. In fact, theoxygen consumption is often calculated by empirical formulasusingvariables likethe body surface area (KO, m2) and age of the patient. The body surface area is calculatedaccordingto a special chart (nomogram)prepared on the basis of the Du Boisformula, taking into accountthe body height and weight. Sure it is a source of errors in calculations and measuring minute-related volumeVO2.

The minute volume measurements according to the Fick method should be conducted adhering to the following procedure: • Blood sampling from the pulmonary artery to determine the concentration of oxygen in the mixed venous blood • Blood sampling from the left ventricle or the aortaline to identify the concentration of oxygen in the arterial blood • Calculation of the oxygen content in both blood samples taking into account hematocrit (Hb, g/dl).

Since 1 g of hemoglobin binds 1.34 ml of oxygen, the hemoglobin index Hb is multiplied by 1.34 (Hüfner's number as oxygen binding capacity).

• Calculation of the arteriovenous oxygen content difference (AVDO2).

• Calculation of the amount of oxygen (VO2) taken up by blood in the lungs using the empirical formulas taking into account the body surface area and the patient's age: VO2= KO (161 – 0,54 • age) VO2= KO(147,5 – 0,47 • age)

(for males) (1) (for females)

Minute blood volumeMVis calculatedby the formula given below: MV= VO2 / 10 • AVDO2, l/min (2) Despite the fact that the Fick method is a well-known routine procedure utilized for a long time and considered to be one of the most accurate methods for CO measurements, there are many factors that mayproduce errors in the Fick technique application. In this connection, the following factors should be listed [1]: 1. The use of the empirical formulas with many conditional coefficients like KO, data to be taken from the nomograms and other variables involves as a rule risks of obtaining erroneous results.

2. The Fick method provides us withan integrated value of the MV and is not capable of deliveringactual blood volume data in each cardiac cycle.

3. This method has limitations: it is not suitable for use in patients with lung abnormalities provoking oxygen diffusion disorders.

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4. The direct Fick technique cannot be used for measuring cardiac output in case of intra-cardiac shunt, aortic or mitral regurgitation, sincea fraction of blood bypasses the pulmonary circuit that also leads to measurement errors.

5. The Fick method demonstrates its highest accuracyin case with low minute volume at a large arteriovenous oxygen difference, but in patients with high minute volume this techniquebecomes more and more inaccurate.

Thermodilution method The method of thermodilution is a derivation of the Fick principle [1, 6-10]. The only difference is that not oxygen, but a cold solution at a temperature below the body temperature, for example, isotonic sodium chloride solution or 5% glucose solutionis used as an indicator.

The procedure of minute blood volume measurements with the use of the thermodilution technique covers the following steps: • A standard quantity of coldsolutionis injected into the right atrium from a proximal catheter port.

The cold solution causes a decrease in blood temperature which is measured by a thermistor inserted into the pulmonary artery catheter.Temperature change is detected by a thermistor tip at the end of the catheter in the pulmonary artery. Resultant changes in blood temperatures arerecorded, producing a curve (similar to an indicatordilutioncurve). Multi-lumen catheters are utilized for this purpose.

• Changes in pulmonary artery blood temperature over time are plotted, producing thermodilution curves. The area under the curves is inversely related to the flow rate. Cardiac output can be accurately computed provided that a practically ideal thermodilution curve is produced. Irregular or slurred curves should be discarded to exclude inaccuracy in measurements.

• The CO computer provides for integration of the area under the thermodilution curve.

• The cardiac minute volume (MV) is derived from the Stewart-Hamilton equation as follows: MV= [K • VI• (TH – TI)] / S, l/min (3) where: VI— injected volume; TH − blood temperature; TI − injectate temperature; K − empirical corrections for specific heat and density of the injectate and for blood and dead space volume; S − the area under the thermodilution curve This technique should consider a numberof factors which may cause errors in minute blood volume measurements [1] similar to the Fick method: 1. It is essential to provide a rapid and even injection technique (>4 seconds), otherwise a slow or uneven mixing of the injectate with blood in the right atrium and the right ventricle may induce erroneous measurements.

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2. Another problematic factor: extrasystole during measurement procedure.

3. As opposed to the Fick method, the thermodilution technique shows the greatest error in case of low cardiac output (<3,5 l/min).

Cardiocode method As to cardiometry, there is a new method of heart cycle phase analysis offered. It has been successfully implemented with a new type of medical equipment: the Cardiocode device. Cardiocode utilizes a non-invasive measuring technology based on digital processing of a single channel ECG recorded [2]. This technique allows measuring not only the stroke and minute blood volumes, but also a complete set of phase-related volumetric data as listed below: SV − stroke volume, ml; PV1 − volume of blood entering the ventricle in the phase of early diastole that characterizes the ventricular suction function, ml; PV2 − blood volume entering the left ventricle during the phase of atrial systole that characterizes the atrial contractile function, ml; PV3 − blood volume ejected by the ventricle during the phase of rapid ejection, (ml); PV4 − blood volume ejected by the ventricle during the phase of slow ejection, (ml); PV5 − blood volume (a part of SV) pumped by the ascending aorta operating as a peristaltic pump,characterizing the tonus of the aorta, (ml).

Minute blood volumes according to the Cardiocode technology are non-invasively measured as described below: 1. An ECG of the ascending aorta is recorded. In principle, it is enough to record one cardiac cycle only in order to obtain all necessary hemodynamic data upon ECG digital processing. But as a rule10 to15 cardiac cycles are recorded and digitally processed to get the complete hemodynamic picture.

2. Durationsof the phases and cardiac cycle intervals are digitally measured according to the actually producedECG: QRS;RS;Q−T; PQsegment;T−T (s).

3. The phase-related hemodynamic parameters are calculated by substituting the cardiac cycle phase durations into the Poyedintsev – Voronova equations. In addition to the phase durations,as mentioned above, the following values are also involved into the equations: a – sound velocity in blood; g – gravity acceleration; Sa – ascending aorta lumen area foradults.

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Functional dependence between the stroke volume (SV), minute volume (MV)and cardiac cycle phase durations can be described as follows: SV= f (a, g, Sa, QRS, RS, Q-T), ml; (4) MV= 0.06 SV / (T-T),l/min (5) Sources of possible errors when measuring minute volume according the above technique are as follows: 1. Sa being the area of the lumen of the ascending aorta utilized in the calculations is defined as an average value for adults. For this purpose, the area of the lumen of the ascending aorta isaccepted to bea constant value. This may lead toan error in the measurements of the absolute values of the minute and stroke volumes, but it does not affect the dynamics of changes in these parameters with time under an influence of internal or external factors.

2. The novel technology demonstratesits high accuracy in measurements of the cardiac cycle phases, but at the same time it is very sensitive. This advanced technique is capable of capturing the slightest changes in the patientâ&#x20AC;&#x2122;s cardiovascular system performance, including those in the patientâ&#x20AC;&#x2122;s emotional state affecting hemodynamics.

Comparative data study A comparative study of values obtained with the three considered methods was carried out. The results are presented in Fig. 1 with the Bland - Altman statistics analysis [11]. It is evident that when comparing the two methods, namely, the Fick technique and thermodilution, which are the same in their essence, they demonstrate a difference in their results similar to that when comparing the Cardiocode hemodynamic data with each of them.

At the same time it should be mentioned that the Cardiocode method is a non-invasive technology, and it is capable of measuring not only the minute and the stroke volumes, but also 5phase-related volumetric parameters as well. To obtain this huge amount of information, no special clinical preparatory measures are required. The complete set of hemodynamic parameters is computed for each cardiac cycle recorded. The Cardiocode technology is absolutely safe for patients, and that is of great importance, too. In this connection, it should be noted that the application of the above invasive measuring techniques involves high risks of complications for patients, and the associated lethality rate is evaluated to be about 5 % [12].

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Figure 1. Comparative analysis of results for the three methods: Cardiocode vs. thermodilution, and Fick method vs.thermodilution.

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This is decisive evidence that the Cardiocodetechnology demonstrates its indisputable advantages.

However, unfortunately the unique capabilities of this advanced technology have not found a wide application in practice yet. Therefore, our idea is to summarize herein the basics of the novel technology and the hemodynamic data interpretation concept.

Practical informative value of the hemodynamic phase-related parameters: phase-related volumes SV, MV, PV1, PV2, PV3, PV4, and PV5 The significance of each of the cardiac cycle phases was presented herein above. Let us discuss how to interpret them basically.

SV is stroke volume of blood (ml). It is a sum of two volumes: PV1 and PV2. Parameter PV1 is the blood volume which is supplied to the ventricle in the phase of early diastole, and it is an indicator of the suction function of the ventricle (ml). PV2 is the blood volume which is delivered to the left ventricle of the heart during the phase of atrial systole, andit is indicator of the atrial contractility performance (ml). The stroke volume SV is always equal to the sum of two diastolic blood volumes PV3 and PV4. It corresponds to the energy conservation law, i.e. the volume at inlet of the circulation system should be equal to that at outlet thereof. It is an axiomatic statement. Therefore, the stroke volume SV should be interpreted as the total result indicating the performance of all other cardiac cycle phases in integrative manner. The volume in question is generated during two phases: within the rapid and slow ejection phase. The normal value of this parameter is 55 ml. Some changes in the parametric value can be observed during orthostatic test. But in well-conditioned athletes no changes in the stroke volume under orthostatic test conditions are reported. It is important to take into account that the said normal value may show acceptable deviations with increase in body weight and age. The more the weight, the higher is the stroke volume, and vice versa. The same is applicable to the age of patients: the less it is, the less is the stroke volume. The Cardiocode technique provides for such age and BMI corrections when digitally processing the data. These relationships are presented in Fig. 2 and 3 below.

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Figure 2. Relationship between stroke volume SV and age

Figure 3. Relationship between stroke volume SV and body weight

But what values of parametersSV and MV are considered to be normal? In order to answer this question, a number of factors should be taken into account, not only age and BMI of a patient. The Cardiocode technology takes into consideration the multitude of factors which might influence the final parameter value which is accepted to be the normal one. For the purpose of application of the Cardiocode technique, the following normal values have been taken as the norms for a middle-aged person with an average BMI: SV=55 ml and MV= 3,7l/min. But these values might show some changes during the orthostatic test. Another important issue should be addressed in this connection: the norm should betaken lower inpatients aged under 15. The normal value may have differences from the above norm in some patients who show some specific physiological parameters. So, it is a must for a physician to properly interpret the actual measured value and deviations thereof considering influence of all factors involved. It is essential to know the actual range of the norm for a given patient to make effective diagnostics. Theoretical calculations and clinical studies have shown that the deviations+30 % are judged to be within the norm. If the said deviation is exceeded by 50%, such

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measured value within the transition area between the norm and pathology is considered to be still acceptable.

The Cardiocode device displays these ranges in the form of dark and light green fields on the monitor (Fig.4). To be more precise, the calculation of the boundary values located in the green fieldis always a more complicated thing. We can say that the deviation of +30 % is an approximate acceptable value.

In fact, it is computed more accurately with complex mathematical equations of hemodynamics taking into account actual durations of the phases in each cardiac cycle [13-17].

Minute volume MV is computed by multiplication of the actual SV parameter by the HR. The MV parameter is measured in liters per minute. The computation results are displayed by Cardiocode similarly to the SV indication. The MV is regulated by variable heart rate. For the purpose of the proper diagnostics, this feature should be taken into account, too.

Phase-related diastolic blood volumes PV1 and PV2 are significant markers of the relaxation of heart muscle fibers in the early diastole phase and their elasticity in the atrial systole. Interpreting the above hemodynamic parameters from the point of view of biophysics, we can say that PV1 (ml) is the volume of blood which enters the ventricle in the early diastole phase;the parameter in question characterizes the suction function of the ventricle. PV2 (ml) is the volume of blood which enters the left ventricle in the atrial systole, and itis an indicator of the contractility performance of the heart muscle fibers.

a)

b)

c) Figure 4. Example: Stroke value SV: actual measured value displayed as red indicator bar in the dark green field,within the norm. Details: a)and b) red indicator bar shows the norm, 0.00% deviation from the norm; c) red indicator bar shows the actual measured value which is within the norm, but with an acceptable deviation of 14.28% (exceeding the norm)

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a)

b)

c) Figure 5. Hemodynamic parameter PV2: the volume of blood entering the left ventricle in the atrial systole; the given data were obtained during monitoring of a patient. Measurements were taken every hour. Observed is a growth of the PV2 parameter with increasing deviation from the norm from 32.64% to 73.62%. It is a marker of increased atrial preloading and reduced elasticity of heart muscle fibers

Hemodynamic parameter PV3 (ml) showing the volume of blood ejected by the ventricle in the rapid ejection phase and another hemodynamic parameter PV4 (ml) demonstrating the volume of blood ejected by the ventricle in the slow ejection phase are displayed by Cardiocode in the same way as it is the case with the other hemodynamic parameters.

For the purpose of computations, the following simple rule is applicable: the sum of the diastolic blood volumes must always be equal to that of the systolic volumes, and any of the sums must be equal to stroke volume SV as given below: SV=PV1+PV2=PV3+PV4 The Cardiocode device software is capable of digitally processing the ECG based on the above mathematics and deriving the complete set of the hemodynamic parameters for each cardiac cycle which may be effectively used for diagnostics.

Hemodynamic parameter PV5 is the volume of blood (a fraction of SV) which is pumped by the ascending aorta operating as peristaltic pump. It characterizes the aortic tonus and is measured in ml, too. But actually, under the real conditions, only a certain fraction of the total blood volume circulates in our organism. The PV5 parameter corresponds just to the circulating (â&#x20AC;&#x153;movingâ&#x20AC;?) fraction of blood. Functionally, it depends on energy of the blood volume supplied to the aorta. If the blood volume is high, the aorta is additionally loaded in order to support blood circulation in the blood vessels.

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Conclusions 1. Blood volumes non-invasively measured on the basis of the cardiac cycle phase analysis by digital processing of ECG are true circulation volumetric parameters.

2. The informative value of the obtained phase-related blood volume parameters as indicators of the performance of the cardiovascular system is considerably higher as compared tothe informative value of parameters produced by any other existing hemodynamic data equipment.

3. Cost-effectiveness of the new non-invasive technology capable of obtaining a huge volume of new information about the performance of the cardiovascular system in accordance with the novel cardiac cycle phase analysis concept outperforms all conventional measuring methods applied now in cardiology diagnostics.

Statement on ethical issues Research involving people and/or animals is in full compliance with current national and international ethical standards.

Conflict of interest None declared.

Author contributions All authors participated in the manuscript preparation and data analysis. N.E.S. drafted the manuscript. All authors read the ICMJE criteria for authorship and approved the final manuscript.

References 1. Harald Lapp. Das Herzkatheterbuch: Diagnostische und Interventionelle Kathetertechniken Gebundene Ausgabe. December 2013.

2. Rudenko MY, Voronova OK, Zernov VA. Theoretical Principles of Heart Cycle Phase Analysis.

Frankfurt a/M, Munich, London, New York: FouquĂŠ Literaturverlag; 2009. 336 p. ISBN 9783937909578.

3. Agostoni PG, Wasserman K, Perego GB,et al. Non-invasive measurement of stroke volume during exercise in heart failure patients. Clinical Science. 2000;98(5):545-51.

4. Gawlikowski M, Pustelny T. The influence of limited dynamic response of the indicator detector in a Swan-Ganz catheter on the overestimation of cardiac output measurement by means of thermodilution. Metrology and Measurement Systems. 2012;19(4):751-8.

5. Wang ZH, Zhou GH,QiaoW. Comparison between pulse-indicated continuous cardiac output catheter and Swan-Ganz catheter in evaluating blood volume.Chinese Critical Care Medicine.

2012;24(8):495-6.

6. Baylor P. Lack of agreement between thermodilution and fick methods in the measurement of cardiac output. Journal of Intensive Care Medicine. 2006;21(2):93-8.

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7. Engoren M, Barbee D. Comparison of cardiac output determined by bioimpedance, thermodilution, and the fick method. American Journal of Critical Care. 2005;14(1):40-5.

8. Ložek M,Nedvědová B, Havlík J. Mechanical model of cardiovascular system: Determination of cardiac output by thermodilution method. International Conference on Applied Electronics. 17 October 2013; Article number 6636507.

9. Dhingra VK, Fenwick JC, Walley KR, Chittock DR, Ronco JJ. Lack of agreement between thermodilution and Fick cardiac output in critically ill patients. Chest. 2002;122(3):990-7.

10. Özbek M, Özel HF, Ekerbiçer N, Zeren T. A physical model of the thermodilution method: Influences of the variations of experimental setup on the accuracy of flow rate estimation.

Biomedizinische Technik. 2011;56(1):59-64.

11. Lang T, Secic M. How To report Statistics in Medicine. Philadelphia: American college of physicians; 2006. 480 p.

12. Zhao Z, Wang L, Poon CC, Zhang YT. Measurement principles and development of cardiac output monitoring. Chinese Journal of Biomedical Engineering. 2010;29(4):619-26.

13. Rudenko MY, Voronova OK, Zernov VA. ECG periodic table: a new ECG classification based on heart cycle phase analysis. Cardiometry. 2013;2:19-28.

14. Rudenko MY, Zernov VA, Mamberger K, Rudenko SM. Heart and aortic baroreceptors: operation in providing hemodynamic processes in cardiovascular system. Cardiometry. 2013;3:31-44.

15. Rudenko MY, Zernov VA, Voronova OK. Study of hemodynamic parameters using phase analysis of the cardiac cycle. Biomedical Engineering. 2009;43(4):151-5.

16. Rudenko MY, Zernov VA, Voronova OK. Fundamental research on the mechanism of cardiovascular system hemodynamics self-regulation and determination of the norm-pathology boundary for the basic hemodynamic parameters and analysis of the compensation mechanism as a method of revealing the underlying causes of disease. Heart Rhythm. 2012;9(11):1909-10.

17. Voronova OK, Zernov VA, Kolmakov SV, Mamberger KK, Makedonsky DF, Rudenko MY, Rudenko SM. Cardiac cycle phase analysis as a noninvasive method for volumetric hemodynamic parameters accurate measurement. Policlinica. 2008;6:56-8. [in Russian]

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Young investigators section Original research

Effects of total table salt restriction on blood pressure Francisco Jose Chacon-Lozsan1*, Juan Sebastian Peinado-Acevedo2 1 Resident

Critical Care, Placido Rodriguez Hospital-Venezuela, Universidad Centroccidental Lisandro Alvarado Venezuela 3023 Lara, Street 4 with 8th transversal, El Paraiso

2 Medical

Student. Autonomous University of Bucaramanga Colombia 680001 Bucaramanga, Avenida 42 # 48-11 Corresponding author phone: +57 (7) 643-62-61, e-mail: franciscojlk@hotmail.com

*

Submitted: 22 March 2015 Accepted: 17 April 2015 Published online: 16 May 2015 Aims

The aim of the study was to evaluate the effect of total omission of dietary salt intake on BP.

Material and methods

The effects of total omission on the consumption of dietary salt over the BP, were evaluated for this study in a group of 30 hypertensive patients between 40-60 years old, uncontrolled, with monotherapy with angiotensin converting enzyme inhibitors or angiotensin II receptor antagonists. BP was recorded over three days at the same time, according to the guidelines of the American Heart Association for correct BP measurement in humans. The average of the three registers measurement was taken as baseline for comparison of the data. The only intervention was the total restriction of table salt and sauces with salt. The patients were followed monthly during the first five months recording BP under the same conditions that basal measurement, after this, were indicated to all the patients the consumption of salt 5g/day (provided by the researchers) and were followed for another five months in the same measurement conditions above.

Results

Total restriction of consumption of dietary salt caused highly significant reduction (P<0.0001) of SBP, which was progressive and was evident from the first week of follow up. In addition, caused a decrease in DBP during the first week of monitoring, but that effect was not continuous, and no significant decrease in DBP was observed during follow-up (P 0.0662)

Discussion and сonclusions

We recommend that a minimum restriction to 5g/day would be ideal in this population group.

Keywords

Hypertension • Sodium chloride • Blood pressure • Diet • Sodium dietary

Imprint

Francisco Jose Chacon-Lozsan, Juan Sebastian Peinado-Acevedo. Effects of total table salt restriction on blood pressure; Cardiometry; No.6; May 2015; p.96-103; doi: 10.12710/cardiometry.2015.6.96103 Available from: www.cardiometry.net/no6-may-2015/total-table-salt-restriction

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Introduction The cardiovascular diseases are the main cause of death worldwide; the risk of developing cardiovascular diseases is significantly higher in patients with hypertension (HT), and getting it increases the number of adverse outcomes including mortality [1,2]. Similarly, there is a direct relationship between salt intake, elevated blood pressure and cardiovascular outcomes [3,4]. There is evidence that reducing dietary salt intake lowers blood pressure (BP), therefore, a reduction in salt intake would decrease the BP and cardiovascular risk [5,6].

As estimated for 2010, 1 in 10 cardiovascular deaths were attributable to the consumption of more than 2 g/day sodium, the majority secondary coronary heart disease and stroke; also the 40% of those deaths were recorded in people younger than 70 years [7]. HT is diagnosed more often in regions with average sodium intakes greater than 2.3g/day (100 mEq); however, it is less common in regions with an average sodium intake of less than 1.2g/day (50 mEq) [8]. For this reason various organizations worldwide including the United Nations Organization, the United States Department of Health and Human Services, the World Health Organization and Centers for Disease Control and Prevention, emphasize the reduction of daily salt consumption for all adults [9-12]. European Guidelines on cardiovascular disease prevention and management of hypertension currently recommend the restriction of salt intake of 5-6g/day, with a level of evidence and grade of recommendation 1-A, respectively [13,14].

The mechanisms that explain the relationship between salt intake and HT are unclear, it is known that not only sodium, if not also the chlorine, which is the companion anion in salt (NaCl), play an important role in the increased intravascular volume by their osmotic activity [15]. In addition, some individuals are more sensitive to salt (BP changes to salt intake), as by various mechanisms such as: the higher retention and absorption of sodium, abnormal vascular tone with endothelial damage (higher tendency to vasoconstriction and alteration in normal vasodilation), and others are still not well understood, are more likely to develop HT [16-19].

Recent studies worldwide [20-22] and meta-analysis [3] have been conducted to evaluate the effect of reduced salt intake on BP, their results support the efforts of doctors and patients to reduce sodium intake due their beneficial effects. Therefore it is important to conduct further studies in diverse populations in order to generalize and generate recommendations. The aim of the study was to evaluate the effect of total omission of dietary salt intake on BP.

Materials and methods Patients The effects of total omission on the consumption of dietary salt on the BP were evaluated for the study in a group of 30 hypertensive patients between 40 and 60 years old, over two years of diagnosis, uncontrolled, with monotherapy with angiotensin converting enzyme inhibitors (ACEi) or angiotensin II receptor antagonists (ARBs). The 50% were men, and the rest of the patients were women. All patients had mild exercise habits related to moderate daily work activities. No patients were included pregnant, diabetic, with neoplastic, neurological or immunological diseases. The daily consumption of salt pre-study was 15-20g (See Table 1).

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Table 1. Population characteristics Characteristic

n

%

15 15

50 50

13 17

43 57

12 2 4 12

40 7 13 40

Mean

Std. deviation

158,3 79,6

10,3 9,2

Gender Male Female Age 40-50 51-60 Antihypertensive agents Enalapril Lisinopril Losartan Olmersatan Baseline systolic blood pressure Baseline diastolic blood pressure

Design The study protocol was approved by the Ethics Committee of Centroccidental University Lisandro Alvarado. All patients got their written informed consent before entering in the study. BP was recorded over three days at the same time (15:00 hours), three hours postprandial; according to the guidelines of the American Heart Association for correct BP measurement in humans [23]. The average of the three registers measurement was taken as baseline for comparison of the data. The only intervention was the total restriction of table salt and sauces with salt. Neither other changes in the lifestyle or adjustments to the antihypertensive treatment were recorded. The patients were followed monthly during the first five months by recording BP under the same conditions that basal measurement, after that, indicated was to all the patients the consumption of salt 5g/day (provided by the researchers), and they were followed for another five months under the same measurement conditions as above.

Statistical analysis The data were collected in EXCEL spreadsheet firsthand and processed in GraphPAD PRISM 5.0 for Windows. The data were analyzed with ANOVA, comparing each month tracking your basal previous month and the results are presented in graphs with the average +/- standard deviation taking significant difference as a value of P <0.05.

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Results Changes in systolic blood pressure (SBP) Restriction total of consumption of dietary salt caused highly significant reduction (P <0.0001) of SBP, which was progressive and was evident from the first week of follow up. However, after the start use of the salt administered by the researchers, the SBP increased progressively during follow up to 5 months without significant statistical difference when compared with restart the fifth month of salt intake with the value of the fifth month of salt restricted without reaching its basal level of BP (see Fig. 1).

Figure 1. Effects of salt consumption on Systolic Blood Pressure Changes in diastolic blood pressure (DBP) Restriction total of consumption of dietary salt caused a decrease in DBP during the first week of monitoring, but this effect was not continuous and no significant decrease in DBP was observed during follow-up (P 0.0662), after the first use of the salt administered by the researchers, the DBP was increased up to similar to the baseline measurement values (Fig 2).

Figure 2. Effects of salt consumption on Dyastolic Blood Pressure

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Discussion and сonclusions The present study shows that the total omission of salt intake causes a significant immediate and progressive decrease in SBP, and the effect was not observed for the DBP. The decrease in SBP in following for five months was greater than 20 mmHg, and it might deduce that patients who were out of targets (>140 or 150 mmHg) reached goals only with that simple, economic and accessible intervention to all hypertensive patients. The mechanism that could intervene in the marked and immediate decrease in SBP may be mediated by a decrease in the concentration of sodium in the blood; eating a meal that containing salt raises the levels of serum sodium at 120 minutes, while a food without salt decreases concentration and in its turn the osmolality, this phenomenon decreases significantly the SBP, but the same effect for DBP is not observed. The high concentration of sodium in plasma, and therefore osmolality causes three responses that seek to increase blood volume: 1.

Movement of fluid from the intracellular to the extracellular space; 2. It stimulates thirst, and 3. It increases secretion of antidiuretic hormone, which is evidenced clinically with an increase of 1.91mmHg in SBP with increasing the concentration of serum sodium in 1 mmol/L [28,29]. In addition, the patients that are more sensitive to salt, with the salt intake may have a greater increase in SBP and proteinuria, this may be due to an alteration in renal hemodynamics in this patients group [30].

The absence of significant reduction in DBP may be due to the hypertensive mechanism inducing by the salt is mainly mediated by changes in blood volume rather than changes at peripheral vascular resistance, which is the main modulator of PAD. In addition, vascular resistance also can be increased in response to the decrease in blood volume induced by low sodium intake. An increased activity of aldosterone renin-angiotensin-axis with the less consumption of salt has been already described.

This may increase vascular resistance; activation axis in response to the absence of salt intake is not evident in black, elderly and / or chronic renal failure patients. It explains a greater reduction in BP with this intervention in this group of patients [31,32]. This divergence between the reduction in SBP and DBP had already been demonstrated in other studies [21,29]. This is an important finding since it is proven that the PAS is more associated with cardiovascular disease and predicts risk more accurately than the PAD [30-32].

The subsequent progressive increase of SBP with the consumption of salt administered by the researchers, which did not exceed the 10 mmHg, may be due to basal consumption levels in patients on average were 15-20g/day compared with 5g/day given by the researchers, this SBP would be within the targets set for hypertensive patients, so it would appear that a minimum restriction to 5g/day would be ideal in this population group.

List of abbreviations HT − hypertension BP − blood pressure ACEi − angiotensin converting enzyme inhibitors ARBs − angiotensin II receptor antagonists SBP − systolic blood pressure DBP − diastolic blood pressure

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Statement on ethical issues Research involving people and/or animals is in full compliance with current national and international ethical standards.

Conflict of interest None declared.

Author contributions All authors coordinated and helped to draft the manuscript. All authors read and approved the final manuscript.

References 1. Global status report on noncommunicable diseases 2010. Geneva, World Health Organization, 2011.

2. Rapsomaniki E1, Timmis A, George J, Pujades-Rodriguez M, Shah AD, Denaxas S, et al. Blood pressure and incidence of twelve cardiovascular diseases: lifetime risks, healthy life-years lost, and age-specific associations in 1â&#x20AC;˘25 million people. Lancet. 2014 May 31;383(9932):1899-911.

3. He FJ, Li J, MacGregor GA. Effect of longer-term modest salt reduction on blood pressure. Cochrane Database of Systematic Reviews 2013, Issue 4. Art. No.: CD004937. DOI: 10.1002/14651858.CD004937.pub2.

4. Qin Y, Li T, Lou P, Chang G, Zhang P, Chen P. Salt intake, knowledge of salt intake, and blood pressure control in Chinese hypertensive patients. J Am Soc Hypertens. 2014 Dec;8(12):909-14. doi:10.1016/j.jash.2014.09.018.

Epub 2014 Sep 28. http://www.ncbi.nlm.nih.gov/pubmed/25492834 5. He FJ, MacGregor GA. Salt reduction lowers cardiovascular risk: meta-analysis of outcome trials.

Lancet.

2011 Jul 30;378(9789):380-2. doi: 10.1016/S0140-6736(11)61174-4. http://www.ncbi.nlm.nih.gov/pubmed/21803192 6. Graudal NA, Hubeck-Graudal T, Jurgens G. Effects of low sodium diet versus high sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterol, and triglyceride. Cochrane Database Syst Rev. 2011 Nov 9;(11):CD004022. doi: 10.1002/14651858.CD004022.pub3. http://www.ncbi.nlm.nih.gov/pubmed/22071811 7. Mozaffarian D1, Fahimi S, Singh GM, Micha R, Khatibzadeh S, Engell RE, et al. Global sodium consumption and death from cardiovascular causes. N Engl J Med. 2014 Aug 14;371(7):624-34. doi: 10.1056/NEJMoa1304127.

8. AdroguĂŠ HJ, Madias NE. Sodium and potassium in the pathogenesis of hypertension. N Engl J Med. 2007 May 10;356(19):1966-78.

9. WHO guideline: sodium intake for adults and children. Geneva: World Health Organization, 2012.

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10. General Assembly of the United Nations. High-level meeting on non-communicable diseases, September 19â&#x20AC;&#x201C;20, 2011 11. Food and Nutrition Board, Institute of Medicine. Strategies to reduce sodium intake in the United States. Washington, DC: National Academies Press, 2010.

12. US Dept of Agriculture and US Dept Health and Human Services. Dietary Guidelines for Americans 2010. US Govt Printing Office; US Dept of Agriculture and US Dept Health and Human Services, Washington, DC, 2010.

13. Perk J, De Backer G, Gohlke H, Graham I, Reiner Z, Verschuren M, et al. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Eur Heart J. 2012 Jul;33(13):1635-701. doi: 10.1093/eurheartj/ehs092. Epub 2012 May 3.

14. Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, BĂśhm M, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2013 Jul;34(28):2159-219. doi: 10.1093/eurheartj/eht151. Epub 2013 Jun 14.

15. Kurtz TW, Al-Bander HA, Morris RC Jr. "Salt-sensitive" essential hypertension in men. Is the sodium ion alone important? N Engl J Med 1987; 317:1043.

16. Barba G, Galletti F, Cappuccio FP, Siani A, Venezia A, Versiero M, et al. Incidence of hypertension in individuals with different blood pressure salt-sensitivity: results of a 15-year follow-up study. J Hypertens. 2007 Jul;25(7):1465-71.

17. Capasso G, Cantone A, Evangelista C, Zacchia M, Trepiccione F, Acone D, et al. Channels, carriers, and pumps in the pathogenesis of sodium-sensitive hypertension. Semin Nephrol. 2005 Nov;25(6):419-24.

18. Schmidlin O, Sebastian AF, Morris RC Jr. What initiates the pressor effect of salt in salt-sensitive humans? Observations in normotensive blacks. Hypertension 2007; 49:1032.

19. Forman JP, Scheven L, de Jong PE, Bakker SJ, Curhan GC, Gansevoort RT. Association between sodium intake and change in uric acid, urine albumin excretion, and the risk of developing hypertension.

Circulation.

2012 Jun 26;125(25):3108-16. doi: 10.1161/CIRCULATIONAHA.112.096115. Epub 2012 Jun 18.

20. Mente A, O'Donnell MJ, Rangarajan S, McQueen MJ, Poirier P, Wielgosz A, et al. Association of urinary sodium and potassium excretion with blood pressure. N Engl J Med. 2014 Aug 14;371(7):601-11. doi: 10.1056/NEJMoa1311989 21. Cook NR, Cutler JA, Obarzanek E, Buring JE, Rexrode KM, Kumanyika SK, et al. Long term effects of dietary sodium reduction on cardiovascular disease outcomes: observational follow-up of the trials of hypertension prevention (TOHP). BMJ. 2007 Apr 28;334(7599):885-8. Epub 2007 Apr 20.

22. Slagman MC, Waanders F, Hemmelder MH, Woittiez AJ, Janssen WM, Lambers Heerspink HJ, et al.

Moderate dietary sodium restriction added to angiotensin converting enzyme inhibition compared

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with dual blockade in lowering proteinuria and blood pressure: randomised controlled trial. BMJ. 2011 Jul 26;343:d4366. doi: 10.1136/bmj.d4366.

23. Pickering TH, Hall JE, Appel LJ, Falkner BE, Graves J, Hill MN, et al. Recommendations for blood pressure measurement in humans and experimental animals: part 1: blood pressure measurement in humans: a statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research.

Hypertension. 2005;45:142-161 24. De Wardener HE, He FJ, MacGregor GA. Plasma sodium and hypertension. Kidney Int. 2004 Dec;66(6):2454-66.

25. Suckling RJ, He FJ, Markandu ND, MacGregor GA. Dietary salt influences postprandial plasma sodium concentration and systolic blood pressure. Kidney Int. 2012 Feb;81(4):407-11. doi: 10.1038/ki.2011.369. Epub 2011 Nov 2.

26. Weir MR, Dengel DR, Behrens MT, Goldberg AP. Salt-induced increases in systolic blood pressure affect renal hemodynamics and proteinuria. Hypertension. 1995 Jun;25(6):1339-44.

27. Turner ST, Schwartz GL, Chapman AB, Boerwinkle E. WNK1 kinase polymorphism and blood pressure response to a thiazide diuretic. Hypertension 2005; 46:758.

28. Siffert W, Düsing R. Sodium-proton exchange and primary hypertension. An update. Hypertension 1995; 26:649 29. Pimenta E, Gaddam KK, Oparil S, Aban I, Husain S, Dell'Italia LJ, et al. Effects of dietary sodium reduction on blood pressure in subjects with resistant hypertension: results from a randomized trial.

Hypertension. 2009 Sep;54(3):475-81. doi: 10.1161/HYPERTENSIONAHA.109.131235. Epub 2009 Jul 20.

30. Franklin SS, Larson MG, Khan SA, Wong ND, Leip EP, Kannel WB, Levy D. Does the relation of blood pressure to coronary heart disease risk change with aging? The Framingham Heart Study.

Circulation. 2001; 103: 1245–1249.

31. Kannel WB. Elevated systolic blood pressure as a cardiovascular risk factor. Am J Cardiol. 2000; 85: 251–255.

32. He FJ, Markandu ND, MacGregor GA. Modest salt reduction lowers blood pressure in isolated systolic hypertension and combined hypertension. Hypertension. 2005 Jul;46(1):66-70. Epub 2005 Jun 13.

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Cardiometry practice Phase of atrial systole Pн-Pк and phase of closing atrioventricular valves Рк−Q Significance It provides the closure of atrioventricular valves.

At point Q the atrioventricular valves are completely closed, and pressure applied by blood to the AV node reaches a pre-specified level to generate pulses (the AV node is considered as a baroreceptor which is firing upon a pre-specified blood pressure loading).

Diagnostics Attention! A diagnosis made with the use of the CARDIOCODE device may differ from that established by the conventional multi-lead system electrocardiographic equipment. Therefore, the CARDIOCODE

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diagnosis should prevail, and the treatment guidelines given below are based on the CARDIOCODE diagnostics results only.

Ref. Manifestations & Physiology (cause) No. markers on ECG

1.

SA node atherosclerosis

No heart muscle relaxation is available. Muscle contracture

Considerable drop in elasticity of heart muscle.

Immediately after the Uwave, the blood pressure level at the SA node remains the same, and generation of the P-wave occurs. Otherwise the valve fails to close, and no pulse generation by the AV node occurs.

Calcium pump is out of operation due to ATP energy deficit in heart muscle cells

Critical anatomical area between the IVS and the valves where deposits if pathogenic bacteria and viruses delivered with circulating blood can be found. Alteration of quality of the IVS muscle performance

Inflammation in IVS tissue caused by pathogenic bacteria or viruses available in ventricular space between the IVS and the valves

No-Р-wave-effect

Anatomical change in the shape of the pulmonary valve

Blood leakage through the valve

X

P-wave migration

Anatomical change in the shape of the tricuspid valve

Blood leakage through the valve

X

Prolonged duration of phase Рк – Q

Multiple P-waves

3.

Endocarditis: Change in 1. No symptoms amplitude of available; phase Pк – Q 2. Blood leakage referred to through IVS with isoelectric line heart muscle during orthostatic contractions. Mixing testing of venous and artery blood flows.

5.

Biochemistry

Prolonged time and increase in volume of blood High cholesterol in applied to SA node blood (baroreceptor) to generate pulses

2.

4.

Biophysics

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6.

P-wave bifurcation

Synchronization imbalance between greater and lesser circulation

Difference in resistance to blood flow between greater Х and lesser circulation

Hemodynamic data The criterion of assessment of the atrial performance is hemodynamic parameter PV2 which represents a volume of blood entering the left ventricle in the atrial systole phase and which is measured in ml.

If during the early diastole phase the heart muscle fails to relax, the PV2 value increases. It takes place because the resistance of the load on the atria increases with extension of the “rigid” muscles of the ventricles during blood filling. A deviation of this hemodynamic parameter from the norm exceeding 30% should be treated as an intensive care case.

Secondary manifestations & markers on ECG & RHEO Ref. No.2: Decrease in blood supply to coronary arteries that is found on RHEO in phase Тк – Uн as a horizontal line segment.

Ref. No.5: An early blood pressure rise which begins in phase Q – R on RHEO. It might be accompanied by high diastolic pressure.

Symptoms Ref. No.2 Weakness, dyspnea.

Ref. No.3 а) In case of blood leaking through the IVS a short-time dizziness is observed. b) Weakness, dyspnea.

Ref. No.5 Weakness, dyspnea.

Ref. No.6 Feeling of heaviness in chest within the heart area.

Treatment Acupuncture combined with other therapy methods and means should be administered in all cases.

Acupuncture specifications (Very important! Efficiency properly tested and proven) Point Neiguan (MC6) in pericardium meridian; Point Gongsun (RP4) in spleen meridian; Point Zusanli (Е36) in stomach meridian; Point Sunyinjiao (RP 6) in order to intensify serotonin synthesis.

In some complicated cases Phenobarbital + Ethylbromisovalerinate + Menthae piperitae oleum + Humuli lupuli oleum (Valocordinum) should be administered.

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Ref. No.1 а) Nutrition should be normalized. No meals after 18: 00. b) Phytotherapy aimed at blood vessel cleaning (the following herbal agents should be used: Styphnolobium japonicum, Trifolium pratense, Aesculus hippocastanum etc. upon consultation by phytotherapy practitioner) c) A special breathing training device (for example, Samozdrav) should be used to normalize breathing and blood pressure. d) Ethylmethylhydroxypyridine succinate (Mexicor) should be administered e) L–carnitine should be administered (ELCAR). f) Acupuncture procedure.

Ref. No. 2 а) Ethylmethylhydroxypyridine succinate (Mexicor) should be administered. b) L–carnitine should be administered (ELCAR). c) Acupuncture procedure.

Ref. No.3 а) Phytotherapy to eliminate pathogenic bacteria and viruses (the following herbal agents should be used: Folium Juglandis, Silybum marianum (as hepatoprotector) etc. upon consultation by phytotherapy practitioner) b) Ethylmethylhydroxypyridine succinate (Mexicor) should be administered. c) A special breathing training device (for example, Samozdrav) should be used to normalize breathing and blood pressure.

Ref. No.4 а) Acupuncture procedure b) Vitamins (complex).

Ref. No.5 а) Acupuncture procedure b) Vitamins (complex).

Ref. No.6 а) Ethylmethylhydroxypyridine succinate (Mexicor) should be administered. b) L–carnitine should be administered (ELCAR).. c) A special breathing training device (for example, Samozdrav) should be used to normalize breathing and blood pressure. d) Regular physical exercises

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Phase of IVS contraction Qâ&#x20AC;&#x201C;R Significance The phase provides the contraction of the intraventricular septum (IVS). It depends on aerobic processes.

Diagnostics Attention! A diagnosis made with the use of the CARDIOCODE device may differ from that established by the conventional multi-lead system electrocardiographic equipment. Therefore, the CARDIOCODE diagnosis should prevail, and the treatment guidelines given below are based on the CARDIOCODE diagnostics results only.

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Ref. Manifestations & markers Physiology (cause) Biophysics No. on ECG

Biochemistry

Deficit of agents responsible for Alteration in water oxygen exchange between transportation to inside and the outside of mitochondria muscle cells 1. L-carnitine deficit AND/OR 2. Serotonin deficit

1.

Decrease in amplitude of Mitochondrial the R-wave (in orthostatic cardiomyopathy testing)

2.

Effect of altered IVS muscle contractility Alteration in the IVS performance on Bifurcation of the R-wave muscle contractility X relaxation and reverse performance restoration (reversed motion).

3.

At the beginning of R-wave elevation there is a sharp significant depressed X segment below the isoelectric line available.

4.

Physiological From point Q amplitude alterations decreasing below the interventricular isoelectric line valve

Effect of altered IVS muscle contractility performance on X relaxation and reverse restoration (reversed motion).

in

X

X

Hemodynamic data The hemodynamic data in this phase are not evaluated since there is no blood circulation in this period of time, and all the processes occur with heart valves closed.

Secondary manifestations & markers on ECG & RHEO They might be found in some rare cases because they are associated with the IVS contractility processes.

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Symptoms Ref. No.3 Feeling of heaviness in left side caused by myocardial muscles touching body muscles during the IVS reversed motion.

Ref. No.4 Complex manifestation of various symptoms Treatment Acupuncture combined with other therapy methods and means should be administered in all cases.

Acupuncture specifications (Very important! Efficiency properly tested and proven) Point Neiguan (MC6) in pericardium meridian.

Point Gongsun (RP4) in spleen meridian.

Point Zusanli (Е36) in stomach meridian.

Point Sunyinjiao (RP 6) in order to intensify serotonin synthesis.

In all cases: а) Ethylmethylhydroxypyridine succinate (Mexicor) should be administered b) L–carnitine should be administered (ELCAR). c) A special breathing training device (for example, Samozdrav) should be used to normalize breathing and blood pressure d) Vitamins (complex) should be taken In case of Ref. No. 4 the symptoms should be carefully analyzed, and an adequate well-balanced life style regime should be kept.

Myocardial contraction phase R-S Significance The phase is responsible for the myocardial contraction with the valves closed, upon completion of the IVS contraction. It depends on aerobic processes.

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Diagnostics Attention! A diagnosis made with the use of the device CARDIOCODE may differ from that established by the conventional multi-lead system electrocardiographic equipment. Therefore, the CARDIOCODE diagnosis should prevail, and the treatment guidelines given below are based on the CARDIOCODE diagnostics results only.

Ref. Manifestations & Physiology No. markers on ECG (cause)

Biophysics Changes in heart positioning due to diaphragm moving up

Biochemistry

1.

Small amplitude of R-wave

2.

Deficit of agents responsible for Changes in oxygen Alteration in water exchange amplitude of S- Mitochondrial transportation to between inside and the outside of wave in orthostatic cardiomyopathy mitochondrial muscle cells testing 1. L-carnitine deficit AND/OR Serotonin deficit

3.

Bifurcated amplitude wave

of

S-

X

X

Forced start of flow blood in ventricles with the heart valves closed in order to provide the required energy quantity for the blood flow during the opening of the aortic valve (the pulmonary valve)

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X

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Hemodynamic data The hemodynamic data in this phase are not evaluated since there is no blood circulation in this period of time, and all the processes occur with heart valves closed.

Secondary manifestations & markers on ECG & RHEO As a rule, manifestations & markers are not found on ECG & RHEO. Symptoms No strongly pronounced symptoms are available.

Treatment Acupuncture combined with other therapy methods and means should be administered in all cases.

Acupuncture specifications (Very important! Efficiency properly tested and proven): Point Neiguan (MC6) in pericardium meridian.

Point Gongsun (RP4) in spleen meridian.

Point Zusanli (Е36) in stomach meridian.

Point Sunyinjiao (RP 6) in order to intensify serotonin synthesis.

In some complicated cases Phenobarbital + Ethylbromisovalerinate + Menthae piperitae oleum + Humuli lupuli oleum (Valocordinum).

Ref.No.2 a) Ethylmethylhydroxypyridine succinate (Mexicor) should be administered b) L–сarnitine should be administered (ELCAR). c) Regular physical exercises

Myocardial and septal preloading phase S-L The phase S – L is shaped as the QRS complex against the background of the permanent tension in the cardiac muscle. The phase amplitude is smaller, and the shape of the phase is smoother due to the remaining permanent tension of the muscle fibers that was established after the QRS complex.

The S – L phase is also generated by the AV node which fires an extra action pulse with the valves closed. The phase can be given the name “the next QRS”.

Significance 1. The phase is responsible for building-up of the required pressure level in the ventricles that should be higher than that in the aorta (the pulmonary artery) to provide blood ejection from the ventricles.

2. This phase is responsible for regulation of diastolic pressure in the aorta (the pulmonary artery).

If there are some extra blood volumes in the ventricles available, they are displaced via the closed aortic valve (the pulmonary valve) into the aorta (the pulmonary artery).

3. It depends on anaerobic processes.

4. This phase is an indicator of lactate concentration in IVS and myocardium tissues.

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Diagnostics Attention! A diagnosis made with the use of the CARDIOCODE device may differ from that established by the conventional multi-lead system electrocardiographic equipment. Therefore, the CARDIOCODE diagnosis should prevail, and the treatment guidelines given below are based on the CARDIOCODE diagnostics results only.

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Manifestations Ref. & markers on Physiology (cause) No. ECG 1.

Elevated segment of constant component above the isoelectric line

2.

Increased Marker of normal physiology amplitude of the S-L wave

3.

S-L wave smoothing

4.

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Decreased amplitude of the S-L wave below isoelectric line

1.Small amplitude of muscle contraction in phase QRS caused by mitochondrial cardiomyopathy or endocarditis 2. Changes in coronary flow

Biophysics

Biochemistry

1.Compensatory mechanism 2.

Permanent tension of heart muscle fibers is available that compensates for muscle weakness due to oxygen deficit.

1. Reduction in energy of IVS muscle contraction that is caused as a rule by Lcarnitine deficit.

2. IVS muscle cell swelling due to pathogenic viruses deposited under the atrioventricular valve.

Lactate concentration increase in heart muscle cells

Compensatory Lactate concentration mechanism to increase in heart provide the same muscle cells intensity of muscle fiber contractility against the background of the permanent muscle fiber tension

X

X

Considerable loss in muscle contractility and the ability to relax. As a rule, it may occur under following conditions: 1. before Sudden Cardiac Death when under large amplitude of contraction the IVS is â&#x20AC;&#x153;lockedâ&#x20AC;?.

2. post-myocardial infarction coronary flow distortion.

3. age-related alterations in muscle fiber structure. As a rule, it does not impose considerable limits on physical abilities and the life resources during a long-term period.

Oxygen concentration decrease in heart muscle cells

Overtension of IVS Lactate concentration muscle fibers, that increase in heart causes loss of muscle cells myocardial contraction in this phase

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Hemodynamic data The hemodynamic data in this phase are not evaluated since there is no blood circulation in this period of time, and all the processes occur with heart valves closed.

Ref. No.1 Elevated segment of constant component above the isoelectric line 1. Small amplitude of the R wave or its alteration in orthostatic testing 2. Decreased amplitude of the R wave Ref. No.4 Decreased amplitude of the S-L wave below isoelectric line 1. A considerable increase in amplitude (greater by severalfold) of the R wave (extrasystole) 2. Bifurcation of the R wave 3. Multiple changes in the ECG shape Symptoms Ref. No.1 Elevated segment of the constant component above the isoelectric line 1. Rapid onset of fatigue after active physical exercise 2. In case of endocarditis: considering the degree in disease progression, a short-time dizziness affecting motor coordination 3. Pain in chest area Ref. No.4.

Decreased amplitude of the S-L wave below isoelectric line 1. Temporary loss of consciousness 2. Discomfort feeling in chest area3. Rapid onset of fatigue after active physical exercise and extrasystole Treatment Acupuncture combined with other therapy methods and means should be administered in all cases.

Acupuncture specifications (Very important! Efficiency properly tested and proven) Point Neiguan (MC6) in pericardium meridian Point Gongsun (RP4) in spleen meridian Point Zusanli (Đ&#x2022;36) in stomach meridian Point Sunyinjiao (RP 6) in order to intensify serotonin synthesis

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In some complicated cases Phenobarbital + Ethylbromisovalerinate + Menthae piperitae oleum + Humuli lupuli oleum (Valocordinum) should be administered.

Ref. No.1 Elevated segment of the constant component above the isoelectric line 1 а) Ethylmethylhydroxypyridine succinate (Mexicor) should be administered. b) L–carnitine should be administered (ELCAR). c) A special breathing training device (for example, Samozdrav) should be used to normalize breathing and blood pressure. d) Phytotherapy to eliminate pathogenic bacteria and viruses (the following herbal agents should be used: Folium Juglandis, Silybum marianum (as hepatoprotector) etc. upon consultation by phytotherapy practitioner) Ref. No.1 Elevated segment of the constant component above the isoelectric line 2. а) Ethylmethylhydroxypyridine succinate (Mexicor) should be administered. b) L–carnitine should be administered (ELCAR) c) Acupuncture procedure d) Phytotherapy aimed at blood vessel cleaning (the following herbal agents should be used: Styphnolobium japonicum, Trifolium pratense, Aesculus hippocastanum etc. upon consultation by phytotherapy practitioner) Ref. No.4.

Decreased amplitude of the S-L wave below isoelectric line а) Phytotherapy aimed at blood vessel cleaning (the following herbal agents should be used: Styphnolobium japonicum, Trifolium pratense, Aesculus hippocastanum etc. upon consultation by phytotherapy practitioner) b) L–carnitine should be administered (ELCAR). c) Ethylmethylhydroxypyridine succinate (Mexicor) should be administered. d) A special breathing training device (for example, Samozdrav) should be used to normalize breathing and blood pressure. e) Acupuncture procedure f) Vitamins (complex)

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Phase of rapid ejection L-j The L – j phase is shaped as another QRS complex which appears after the S – L phase against the remaining permanent tension of the cardiac muscle fibers. The amplitude of this phase is smaller, and its shape is smoother due to the remaining tension of the muscle fibers created after the QRS complex as well as due to a lesser blood pressure applied to the muscle fibers of the ventricles since blood enters the aorta. The L – j phase is also generated by the AV node analogously to the previous phase. It can be denoted “the second QRS”.

Significance The phase is responsible for opening the aortic valve (the pulmonary valve) and enabling blood to enter the aorta (the pulmonary artery). It is just the phase that generates the specific blood flow structure known as elevated fluidity regime. The phase depends on anaerobic processes. It is an indicator of actual creatine phosphate concentration in IVS and myocardial muscle tissue cells.

Diagnostics Attention! A diagnosis made with the use of the CARDIOCODE device may differ from that established by the conventional multi-lead system electrocardiographic equipment. Therefore, the CARDIOCODE diagnosis should prevail, and the treatment guidelines given below are based on the CARDIOCODE diagnostics results only.

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Ref. Manifestations & Physiology No. markers on ECG (cause)

Biophysics

Biochemistry

1.

Increase in Incomplete blood amplitude of the volume is ejected L-j wave in rapid ejection phase.

Effect of loading of the The muscle contractility is remaining ventricular provided by creatine blood volume on phosphate reactions. muscle fibers.

2.

Increased number It occurs under Use of physiological Compensatory mechanism of L-j waves heavy physical resources to generate to provide the proper heart exercise ATP energy performance through creatine phosphate reactions

Hemodynamic data PV3 (ml) is a volume of blood ejected by the left ventricle in the rapid ejection phase.

Secondary manifestations & markers on ECG & RHEO Ref. No. 1 Increase in amplitude of the L-j wave Change in RHEO slope angle inclination in this phase Ref. No.2 Increased number of L-j waves Reduction in duration of early diastole phase, decrease in amplitude of the R wave, increase in amplitude of the T wave. Parameter PV3 is significantly high.

Symptoms Ref. No.2 Increased number of L-j waves Symptoms may appear only under physical exercise for a short period of time since all energetic resources are utilized.

Treatment Acupuncture combined with other therapy methods and means should be administered in all cases.

Acupuncture specifications (Very important! Efficiency properly tested and proven) Point Neiguan (MC6) in pericardium meridian.

Point Gongsun (RP4) in spleen meridian.

Point Zusanli (Đ&#x2022;36) in stomach meridian.

Point Sunyinjiao (RP 6) in order to intensify serotonin synthesis.

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In some complicated cases Phenobarbital + Ethylbromisovalerinate + Menthae piperitae oleum + Humuli lupuli oleum (Valocordinum).

Phase of slow ejection j-Тн Significance This phase also enables blood to enter the aorta (the pulmonary artery) till the pressure in the aorta reaches a specified level required to fire the baroreceptors in the aorta (the pulmonary artery) and the aorta is beginning to expand in order to maintain the specific blood flow structure and provide the proper transportation of blood via blood vessels.

Diagnostics Attention! A diagnosis made with the use of the CARDIOCODE device may differ from that established by the conventional multi-lead system electrocardiographic equipment. Therefore, the CARDIOCODE diagnosis should prevail, and the treatment guidelines given below are based on the CARDIOCODE diagnostics results only.

Manifestations Ref. Physiology & markers on No. (cause) ECG 1.

Biophysics

Biochemistry

Prolonged phase Loss of Required is more time to distribute Aortic duration elasticity of stroke volume of blood within the atherosclerosis aorta ascending aorta till the blood pressure (pulmonary reaches a specified level required to fire artery) the baroreceptors in the aorta and generate the T-waves for maintenance of the specific blood flow structure

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Hemodynamic data PV4 (ml) is a volume of blood ejected by the left ventricle in the slow ejection phase.

Secondary manifestations & markers on ECG & RHEO Not available.

Symptoms No evident symptoms available.

Treatment а) Phytotherapy aimed at blood vessel cleaning (the following herbal agents should be used: Styphnolobium japonicum, Trifolium pratense, Aesculus hippocastanum etc. upon consultation by phytotherapy practitioner) b) A special breathing training device (for example, Samozdrav) should be used to normalize breathing and blood pressure. c) L–carnitine should be administered (ELCAR). d) Ethylmethylhydroxypyridine succinate (Mexicor) should be administered. e) Regular physical exercises Acupuncture specifications (Very important! Efficiency properly tested and proven) Point Neiguan (MC6) in pericardium meridian.

Point Gongsun (RP4) in spleen meridian.

Point Zusanli (Е36) in stomach meridian.

Point Sunyinjiao (RP 6) in order to intensify serotonin synthesis In some complicated cases Phenobarbital + Ethylbromisovalerinate + Menthae piperitae oleum + Humuli lupuli oleum (Valocordinum).

Phase of systolic pressure building-up Тн-Тк Significance This phase starts with the generation of a nervous impulse by the baroreceptors in the aorta (the pulmonary artery) to initiate an adequate expansion of the aorta (the pulmonary artery) required for maintenance of the specific blood flow structure generated by the ascending aorta (the pulmonary artery) at the time of opening of the aortic valve (the pulmonary valve). The phase is immediately connected with the performance of the central nervous system. It is not associated with the operation of the heart baroreceptors.

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Diagnostics Attention! A diagnosis made with the use of the CARDIOCODE device may differ from that established by the conventional multi-lead system electrocardiographic equipment. Therefore, the CARDIOCODE diagnosis should prevail, and the treatment guidelines given below are based on the CARDIOCODE diagnostics results only.

Ref. Manifestations No. markers on ECG 1.

&

Physiology (cause)

Biophysics

Increase in amplitude Small amplitudes of Reduction of the Т wave IVS and myocardial resistance contraction flow

Biochemistry

to

in blood X

2.

Decrease in Increased tonus of Loss of expandability amplitude of the Т the aorta of the aorta X wave

3.

The leading edge of Increased tonus of Loss of expandability the Т wave is below the aorta of the aorta X isolectric line

4.

Depression on ECG and no-T-wave-effect at high constant component of the S – L phase

Alteration in the performance of the blood vessel baroreceptors. Cold hands syndrome

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The required transportation of the structured blood flow is not maintained with the no-T-wave-effect.

Diminished pulse generation by the baroreceptors due to anti-androgen drug medication

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Hemodynamic data PV5 (ml) is a volume of blood pumped by the ascending aorta.

Secondary manifestations & markers on ECG & RHEO Special attention should be paid to the RHEO curve segment pertaining to the slow ejection phase. In orthostatic testing, the segment inclination angle may change.

Symptoms Ref. No. 2 Decrease in amplitude of the Т wave. Clod hands syndrome may be reported.

Treatment Acupuncture combined with other therapy methods and means should be administered in all cases.

Acupuncture specifications (Very important! Efficiency properly tested and proven) Point Neiguan (MC6) in pericardium meridian.

Point Gongsun (RP4) in spleen meridian.

Point Zusanli (Е36) in stomach meridian.

Point Sunyinjiao (RP 6) in order to intensify serotonin synthesis.

In some complicated cases Phenobarbital + Ethylbromisovalerinate + Menthae piperitae oleum + Humuli lupuli oleum (Valocordinum).

Ref. No. 1. а) Regular physical exercises b) L–carnitine should be administered (ELCAR). c) A special breathing training device (for example, Samozdrav) should be used to normalize breathing and blood pressure d) Acupuncture procedure. e) Vitamins (complex).

Ref. No. 4.

Depression on ECG and no-T-wave-effect at high constant component of the S – L phase a) Anti-androgenic drug medication should be discontinued.

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Early diastole phase Тк-Рн Significance 1. The phase provides filling of ventricles with blood when they are relaxed and expanded.

2. It is responsible for filling of coronary vessels with blood.

3. It provides closure of the aortic valve (the pulmonary valve).

Ref. Manifestations No. markers on ECG

& Physiology (cause) Closing procedure by aortic valve (pulmonary valve).

Biophysics

Biochemistry

The coronary artery ostia are opened, and the coronary artery filling is initiated owing to the fact that the heart is relaxed and expanded.

Oxygen & lactate concentration indices should be within the norm

1.

RHEO changing and biochemistry data in interval Т-U are significant markers

2.

Prolongation of the Bradycardia phase

1. It may depend on the Low magnesium central nervous system level in blood condition.

2. It may depend on cardiac muscle tissue biochemistry.

3. It may depend on atherosclerosis.

3.

Decreased duration Tachycardia of the phase

It should be attributed to an Oxygen deficit in increased oxygen demand in muscle tissues in the body the body

4.

Extraordinary appearance of QRS-complex.

Extrasystole the

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Diagnostics Attention! A diagnosis made with the use of the CARDIOCODE device may differ from that established by the conventional multi-lead system electrocardiographic equipment. Therefore, the CARDIOCODE diagnosis should prevail, and the treatment guidelines given below are based on the CARDIOCODE diagnostics results only.Hemodynamic data PV1 (ml) is a volume of blood which enters the left ventricle in the early diastole phase.

Secondary manifestations & markers on ECG & RHEO Ref. No.1 RHEO shape changing and biochemistry data in interval Т-U are significant markers.

The normal procedure of filling of the coronary arteries is reflected in the depression of this segment on the RHEO curve. Other shapes of this RHEO segment will show that there is a problem in filling of coronary arteries.

The performance of the coronary flow is assessed as oxygen concentration index (in relative units) indicated on diagrams. Another performance assessing is high lactate concentration index. Both parameters are related to each other.

Ref. No.4 Extraordinary appearance of the QRS-complex 1. The R wave amplitude is an informative marker. In case when the amplitude is greater by three fold than the normal amplitude level, it might be considered to be a risk factor of sudden cardiac death.

2. Other amplitudes of the R waves should be treated to be not critical.

Symptoms Ref. No.1 RHEO changing and biochemistry data in interval Т-U are significant markers Ref. No.2 Prolongation of the phase Loss of consciousness at a heart rate under 40 bpm may occur.

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Ref. No. 3 Decreased duration of the phase Physiological and psychological excitement may be observed.

Ref. No. 4 Extraordinary appearance of the QRS-complex Under greater amplitudes of the R wave, temporary loss consciousness might occur.

The case when the amplitude is greater by three fold than the normal amplitude level might be considered to be a risk factor of sudden cardiac death.

Treatment Acupuncture combined with other therapy methods and means should be administered in all cases.

Acupuncture specifications (Very important! Efficiency properly tested and proven) Point Neiguan (MC6) in pericardium meridian.

Point Gongsun (RP4) in spleen meridian.

Point Zusanli (Е36) in stomach meridian.

Point Sunyinjiao (RP 6) in order to intensify serotonin synthesis.

In some complicated cases Phenobarbital + Ethylbromisovalerinate + Menthae piperitae oleum + Humuli lupuli oleum (Valocordinum) should be administered.

Ref. No.1 RHEO changing and biochemistry data in interval Т-U are significant markers а) Phytotherapy aimed at blood vessel cleaning (the following herbal agents should be used: Styphnolobium japonicum, Trifolium pratense, Aesculus hippocastanum etc. upon consultation by phytotherapy practitioner). b) L–carnitine should be administered (ELCAR). c) A special breathing training device (for example, Samozdrav) should be used to normalize breathing and blood pressure. d) Ethylmethylhydroxypyridine succinate (Mexicor) should be administered. e) Acupuncture procedure.

Ref. No.2 Prolongation of the phase а) Atropa belladonna preparations. Zelenin herbal drops b) L–carnitine should be administered (ELCAR) c) Acupuncture procedure d) Magnesium + Vitamin В6 e) Ethylmethylhydroxypyridine succinate (Mexicor) should be administered.

Ref. No. 4 Extraordinary appearance of the QRS-complex а) Acupuncture procedure

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b) L窶田arnitine should be administered (ELCAR). c) A special breathing training device (for example, Samozdrav) should be used to normalize breathing and blood pressure. d) Ethylmethylhydroxypyridine succinate (Mexicor) should be administered. e) Vitamins (complex) f) Regular physical exercise

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