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13ЖКТ являются частью более сложной комплексной оздоровительной системы (КОС), предназначенной для предотвращения широкого ряда хронических заболеваний ЖКТ (подробное описание системы -www.healthsys.ru). Кроме того, некоторые хронические заболевания, такие как гастрит и язвенный колит, считаются предраковыми состояниями. Таким образом, КОС имеет и определённую противораковую эффективность.
Результаты наших исследований позволяют рекомендовать больным хроническими заболеваниями ЖКТ в качестве лечебно-профилактического средства методы коррекции состояния позвоночника, а именно, специальную гимнастику для позвоночника на основе китайской гимнастики цигун и массаж мышц позвоночника - миофасциальный релизинг для устранения спастических состояний в мышцах позвоночника.
Выводы.
1. У лиц, страдающих хроническими заболеваниями ЖКТ, включая язвенную болезнь желудка и двенадцатиперстной кишки, имеются спастические состояния в межпозвонковых мышцах в области шестого - восьмого грудных позвонков -ТЪ6-1Ъ8 - области симпатической иннервации желудка и других органов ЖКТ.
2. Устранение спастических состояний в межпозвонковых мышцах в области симпатической иннервации желудка и других органов ЖКТ приводит к исцелению от многолетних хронических заболеваний ЖКТ, включая гастрит и язвенную болезнь желудка.
Заключение. Авторы считают, что в данной работе новыми являются следующие положения и
результаты: Хронические заболевания ЖКТ в значительной степени имеют нервное происхождение и вызваны компрессией или раздражением симпатических нервов в составе спиномозговых нервов, выходящих из межпозвонковых отверстий. Устранение спастических состояний межпозвонковых мышц является основой немедикаментозного устранения этих заболеваний.
Список литературы
1. Ажипа Я.И., Трофическая функция нервной системы. - М.: «Наука», 1990. - 672 с.
2. Жулев Н.М., Бардзгарадзе Ю.Н., Остеохондроз позвоночника. Руководство для врачей. СПб. Лань. 1999.
3. Попелянский Я.Ю. Болезни периферической нервной системы. М.: Издательство Медицина, 1989.
4. Черкасов А.Д., Кузьмина М.М. Поиск методов объективного контроля вертеброгенных изменений при некоторых хронических заболеваниях. Х Юбилейная международная конференция и дискуссионный научный клуб. Новые информационные технологии в медицине и экологии. ГГ+МК2002. Труды. Украина. Крым. Ялта-Гурзуф, 2002. - С. 385-387.
5. Черкасов А.Д. Пути предотвращения остеохондроза позвоночника. Часть 1. Локализация дегенеративно-дистрофических изменений в позвоночнике. Ж. Фундаментальные исследования. 2008. № 7. - С. 41-44.
6. Черкасов А.Д. Пути предотвращения остеохондроза позвоночника. Часть 2. Характеристики мышечных блоков в позвоночнике. Ж. Фундаментальные исследования. 2008. № 7. - С. 45-49.
РЕГЕНЕРАЦ1Я К1СТКОВО1 ТКАНИНИ АУТОТРАНСПЛАНТАНТ1В Р1ЗНОГО ПОХОДЖЕННЯ П1СЛЯ Л1КВ1ДАЩ1 ДЕФЕКТУ АЛЬВЕОЛЯРНОГО В1ДРОСТКА ВЕРХНЬО1 ЩЕЛЕПИ У
ЩУР1В
Яковенко Л.М.
д.м.н., професор, завгдувач кафедрою х1рург1чно1 стоматологИ та щелепно-лицевог хгрургИ дитячого в1ку Нацюнальний медичний утверситет 1мет О.О.Богомольця
Кулинич М.О.
аспгрант кафедри х1рург1чно1 стоматологи та щелепно-лицевог хгрургИ дитячого в1ку
Нацюнальний медичний утверситет 1мет О.О.Богомольця
Савицька 1.М. к.м.н., старший науковий ствробтник Нацюнальний тститут хгрургИ та трансплантологи Iм. О.О.Шал1мова
BONE TISSUE REGENERATION OF AUTOGRAFTS OF DIFFERENT ORIGIN AFTER DEFECT CORRECTION OF ALVEOLAR PROCESS OF MAXILLARY IN RATS
Yakovenko L.
PhD in Medicine, Professor Head of the surgical dentistry and children maxillofacial surgery Department
Bogomolets National Medical University
Kulynych M.
Assistant at the surgical dentistry and children maxillofacial surgery Department
Bogomolets National Medical University
Savytska I.
PhD Candidate in Medicine, Seniour researcher of the Shalimov National Institute of Surgery and Transplantology
Анотащя
В статп представлен результати вивчення репаративно! регенераци та перебиу остеогенезу в ауто-трансплантатах рiзного походження та шстщ альвеолярного вщростка верхньо! щелепи у 75 щурiв шсля лкшдаци його дефекту. В 2018-2019 роках на територп Експериментально-бюлопчно! клшки Нацюналь-ного медичного унiверситету iM. О.О. Богомольця Укра!на, м. Ки!в, групою вчених: проф. Яковенко Л.М., астрант Кулинич М.О., лiкар-iнтерн Кулинич О.О. будо проведено експериментальне дослiдження на 75 бших щурах, гiстологiя та морфометрiя проводилась на базi ДУ «Нацюнальний iнститут хiрургil та трансплантологи iM. О.О. Шалiмова» НАМН Укра!ни к.м.н, гiстолог Савицька 1.М.. Тварини були роздiленi на 3 групи по 25 тварин у кожнш, яким дефект альвеолярного вщростку замiщували аутотрансплантатами рiзного походження: контрольна - загоення пiд згустком (ЗПЗ), друга група - трансплантат з велико! гомш-ково! кiстки (ТГК), третя група - трансплантант з нижньо! щелепи (ТНЩ). З експерименту тварин виво-дили на 14,30,60,90 i 120 добу пiсля операци. Результати дослiдження сввдчать про те, що регенерацiя шстково! тканини аутотрансплантанта та змiни навколо нього визначаються його походженням. В групi ТНЩ на 120 добу вщбулося повне шсткове зрощення трансплантата та новоутворено! шстково! тканини, з к1стковою тканиною альвеолярного вщростка, що навколо дефекту, що шдтверджено гiстологiчно та зпдно обрахунк1в морфометри становила 98%, ввд загально! площi дефекту, вона найбшьша за рахунок максимального збереження трансплантата порiвняно з групою ТГК - 50%, ЗПЗ- 15%.
Abstract
The results of the research of reparative regeneration and course of osteogenesis in autografts of different origin and bone of the alveolar process of the maxillary in 75 rats after its defect are presented. In 2018-2019 at the territory of the Experimental Biological Clinic of the Bogomolets National Medical University, Ukraine, Kyiv, group of scientists: professor Yakovenko L.M., graduate student Kulynych M.O., intern Kulynych O.O., experimental research on 75 white rats was conducted, histology and morphometry were performed on the basis of State Institution "A.A. Shalimov National Institute of Surgery and Transplantology" National Academy of Medical Sciences of Ukraine, I. Savytska, Candidate of Science, histologist. Animals were divided into 3 groups of 25 animals, each with alveolar process defect replaced by autografts of different origin: control group - clot healing, second group - shinbone graft, third group - maxillary graft. From the experiment, the animals were removed on 14, 30, 60, 90 and 120 days after surgery. The results of the research indicate that the bone tissue regeneration of the autograft and changes around it are determined by its origin. In the maxillary graft group for 120 days there was complete bone grafting of the graft and the newly formed bone tissue, with bone tissue of the alveolar process, which around 98% of the defect was confirmed histologically and according to the morphometry calculations, which is the largest due to the maximum transplant preservation with shinbone graft group - 50%, clot healing -15%.
Ключов1 слова: репаративна регенеращя, трансплантат, шсткова тканина, щури.
Keywords: reparative regeneration, transplant, bone tissue, rats.
Introduction
The standard of bone grafting of the alveolar process in lip and palate schistasis is an autogenous bone that has ectomesenchymal (enchondral type) (shinbone and iliac crest), or mesenchymal (intra-membrane type) origin (all skull bones)
[1,4,11,12,13,14,19,20,21,22,23,24,25,26,27]. Autograft regeneration occurs as a result of remodeling and resorption processes, which are accompanied by some reduction in bone volume. The rate and amount of resorption depends on many factors: the size and quality of the bone graft, implant site, the biomechanical qualities of the bone around the graft, and the fixation of the
graft to the surrounding bone [2,9,10]. Many domestic and foreign researchers have used experimental models of the study of bone regeneration of the alveolar process and it has been shown that bone blocks from the intraoral region (intra-membrane type), unlike the extraoral (endochondral origin), have a lower resorption rate, are more likely to revascularize and regenerate in the recipient site [2,5,6,7,8,15,16,17,18].
But today, the questions regarding the stages of reparative regeneration and the course of osteoreparative process in autograft remain relevant.
The aim of this research was to study reparative regeneration and osteogenesis in autografts of different
origin and bone of the alveolar process of the maxillary of rats after its defect was corrected.
Materials and methods
In 2018-2019 at the territory of the Experimental Biological Clinic of the Bogomolets National Medical University, Ukraine, Kyiv, group of scientists, namely, professor Yakovenko L.M., graduate student Kulynych M.O., intern Kulynych O.O. carried out an experimental research on 75 white rats (from 200g body weight), aged from 5 to 6 months, histology and morphometry was performed at the A.A. Shalimov National Institute of Surgery and Transplantation» NAMS of Ukraine, Candidate of Sciences, histologist Savytska I.M. When working with laboratory animals, the requirements of the Scientific and Practical Recommendations for the Maintenance of Laboratory Animals and Working with them were observed by the State Pharmacological Center of the Ministry of Health of Ukraine (Protocol No. 8 from 06/22/2012) and the standards for the Guide for the Core and Use of Laboratory Animals (National Academy Press, Revised, 1996) and the American Heart Association's "Guidelines for the Use of Animal in Research." Animals were divided into 3 groups of 25 animals, each with alveolar process defect replaced by autografts of different origin: control group - clot healing, second group -shinbone graft, third group - maxillary graft. Pain treatment in white rats during surgery was performed by in-traperitoneal injection of 0.2 ml of 5% sodium thiopental solution and 0.4 ml of 1% propofol solution. From the experiment, the animals were removed by overdose of 10% sodium thiopental solution intraperitoneally at 14, 30, 60, 90 and 120 days after surgery. With anesthesia and infiltration anesthesia was performed incision and detachment of the mucoperiosteal flap of the alveolar process of the maxillary from the vestibular side in the area of the central incisors, departing 1cm distally from them. A drill hole with a boron diameter of 3 mm, with permanent irrigation of the wound with saline, was applied with the help of a borer. The resulting 14.1mm hole was filled: in the first group (control) - with a blood clot, in the second group - with osteoplastic material taken from the shinbone, and in the third group - with osteoplastic material taken from the mandible. For histological examination, the area of the maxillary in the autograft area was excised. The resulting material was fixed in a formaldehyde solution with a volume fraction of 10%, then decalcified for 5-6 days in a 0.5% solution of formic acid. After washing, the material was sealed in paraffin according to the conventional scheme. Serial sections with a thickness of 7 ^m were stained with hematoxylin and eosin, van Gizon's picrofuxin, a periodic acid Schiff reaction was performed according to McManus [7]. Photographic documentation of histological specimens was performed using an ICC50 HD digital camera Leica DM 500 optical microscope. Morphometric studies (measurements of the area of newly formed bone and connective tissue) were performed in 6-8 fields of view using a Leica DM 500 optical microscope at magnification of approx. 10 vol. 4 using the Paradise image analysis program devel-
oped by Eva, Ukraine. The results were statistically analyzed using the Kruskal - Wallis one-way analysis of variance, and the Dunne's criterion was used to make a posteriori comparisons.
Results and discussions
Histological analysis
While studying the sections of bone tissue of animals of the control group (clot healing) for 14 days -
in the area of the bone defect, which was previously filled with a blood clot, formed a granulation tissue with expressed signs of inflammation, small cells lym-phocytic, lymphocytic to form thick tufts of collagen fibers forming cells of fibrous tissue, the area of which was equal to 56700 ± 8100 (p <0.05), with the connective tissue located around the fibrous small area -1355900 ± 192300 (p <0.05) (Fig. 1, 2). The bone tissue of the alveolar process around the bone defect also had signs of inflammation. On the 30th day, a newly formed bone tissue was observed inside the bone defect, on the periphery of which there was an inflammatory process, small cells of lymphocytic infiltration, and a considerable number of neutrophilic granulocytes was also observed. The area of newly formed bone tissue was 29800 ± 3900 (p <0.05) and the connective tissue was 656600 ± 53700. There are signs of inflammation in the surrounding bone tissue of the alveolar process around the bone defect. On the 60th day - a small amount of newly formed bone tissue was observed inside the bone defect, which had signs of demineraliza-tion, cartilaginous tissue with dystrophic manifestations was placed around it (the chondromatrix is enlightened, its number was reduced, the chondrocyte capsules were enlarged). The area of the newly formed bone tissue of the bone defect is 51600 ± 11100 (p <0.05), and the connective tissue is 466800 ± 22400. Compared to the previous day, there is an increase of bone tissue area by 2 times and a decrease in connective tissue - 1.5 times. Bone tissue of the alveolar process around the bone defect with signs of inflammation. On the 90th day in the middle of a bone defect there was observed a necrosis of the newly formed bone tissue, it is delimited by a connective tissue capsule which is infiltrated by lymphocytes and neutrophilic granulocytes. The area of bone newly formed tissue in the area of bone defect, compared with the previous day, decreased by 7 times and amounted to 7200 ± 1400 (p <0.05), and the connective tissue - increased by 1.5 times and amounted to 670800 ± 57900. The bone of the alveolar process around the bone defect is poorly mineralized, with signs of inflammation around it. On the 120th day - in the central zone of the bone defect there was an inflammation center, in which lymphocytes predominated, a considerable number of neutro-philic granulocytes, fragments of the newly formed bone tissue, surrounded by connective tissue was also noticeable. The area of bone tissue formed in the area of bone defect became 13 times larger than in the previous day, amounted to 93900 ± 8000 (p <0.05), and the connective tissue increased 2 times, from the previous day and had dimensions of 1104600 ± 42200 (Fig. 1, 2). No signs of bone inflammation around the defect were detected.
Fig. 1. Dynamics of change of bone area in bone defect (clot healing), mean value and 95% of confidence interval.
Fig. 2. Dynamics of change in connective tissue area in bone defect (clot healing) mean and 95% of confidence interval.
In the second group (shinbone graft), the bone graft had signs of moderate diffuse demoralization on the 14th day. A small amount of connective tissue was formed around the graft. The bone tissue area was 24800 ± 3200 (p <0.05) and the connective tissue was -149500 ± 11600 (p <0.05) (Fig. 3, 4). Inflammation signs in the surrounding bone tissue around the bone defect were poorly expressed. On the 30th day, the graft was surrounded by many newly formed bone and dense connective tissue; the signs of demineralization were more expressed than in the previous term, but the area of bone graft and the newly formed bone around it increased by 30 times from the previous day and amounted to 719400 ± 49400 (p<0.05), and the connective tissue decreased 1.5 times and amounted to 93000 ± 7900. The bone tissue of the alveolar process around the bone defect had no inflammation signs. On the 60th day, the graft was fused with the surrounding tissues, its matrix partially demineralized, there are visible signs of resorption on the periphery in some of its areas. Autograft osteocytes are marked by expressed signs of dystrophic changes. The graft bone area and the newly formed bone tissue around it in comparison with the previous day decreased by 8 times and amounted to 89200 ± 15200 (p <0.05), and the connective tissue increased by 5 times - 446100 ± 62600. Surrounding
graft bone tissue around a bone defect has no inflammation signs. On the 90th day the graft was mostly preserved in the area of the bone defect, surrounded by newly formed bone tissue, fused with the surrounding tissues, its matrix underwent moderate demoralization, and there were visible signs of resorption in the periphery in some areas. Autograft osteocytes had marked dystrophic changes. The graft bone area and the newly formed bone tissue around it decreased by 1.5 times to 85200 ± 18200, and increased by 2 times -827800 ± 48000 compared to the previous day. Bone tissue of the alveolar process around the bone defect had no inflammation signs. On the 120th day there is bone graft in the area of bone defect, without mineralization observed in it, a newly formed bone tissue is formed on the periphery, whose matrix is less structured than in intact bone, the lines of cementation are well expressed. The graft bone area and the newly formed bone tissue around it from the previous day increased by 8.5 times and amounted to 717600 ± 79400 (p <0.05) and the connective tissue decreased 1.5 times - 587200 ± 119300 (Fig. 3, 4). The bone tissue of the alveolar process around the bone defect has not inflammation signs, and mineralization is characteristic of intact areas.
Fig. 3. Dynamics of change of bone area in bone defect (shinbone graft group), depending on the time,
mean value and 95% of confidence interval.
Fig. 4. Dynamics of change of connective tissue area in bone defect (shinbone graft), depending on time,
mean value and 95% of confidence interval.
In the third (maxillary graft) group the autograft is well preserved on the 14th day, its demoralization is poorly expressed, and a small amount of connective tissue is formed around it. The bone tissue area was 143400 ± 45500 (p <0.05) and the connective tissue was 139500 ± 12700. The bone tissue of the alveolar process around the bone defect had no signs of expressed inflammation. There was no expressed demin-eralization of a bone defect filled with a autograft in which all cellular elements are preserved on the 30th day. The autograft was surrounded by a small amount of newly formed bone and vascularized connective tissue. The graft bone area and the newly formed bone tissue around it increased by 5 times compared to the previous day and amounted to 672900 ± 87600 (p <0.05) and the connective tissue decreased by 2 times - 81500 ± 14800. There are slight inflammation signs in the bone tissue around the bone defect of the alveolar process. On the 60th day there is a graft in the bone defect surrounded by newly formed bone tissue; the lines of cementation between them are well contrasted. No inflammation signs were found in the autograft itself and the surrounding bone tissue. The area of bone of the graft and the newly formed bone tissue around it increased by 3 times in comparison with the previous day
and reached 2062000 ± 137200 (p <0.05), and the connective tissue decreased by 3 times - 26300 ± 1200. There were no inflammation signs of the bone tissue of the alveolar process around the bone defect. On the 90th day inside the bone defect is bone tissue of the graft, which is surrounded by a newly formed bone tissue, no signs of inflammation were detected. The graft bone area and the newly formed bone tissue around it decreased by 2.5 times compared to the previous day, amounted to 803900 ± 106200 (p <0.05), and the connective tissue also decreased by 1.3 times - 20500 ± 1300. There were no inflammation signs of the bone tissue of the alveolar process around the bone defect. On the 120th day the graft bone tissue in the area of bone defect surrounded by newly formed bone tissue is more mature and formed unlike on the 90th day. Signs of inflammation in the graft and surrounding bone tissue of the alveolar process are not detected. The graft bone area and the newly formed bone tissue around it decreased by 1.1 times compared to the previous day and amounted to 740200 ± 48000 (p <0.05) and the connective tissue also decreased by 1.1 times -19100 ± 1900 (Fig. 5, 6).
Fig. 5. Dynamics of change in bone area in bone defect (maxillary graft group), depending on time,
mean and 95% of confidence interval.
Fig. 6. Dynamics of change in connective tissue area in bone defect (maxillary graft group), depending on time,
mean value and 95% of confidence interval.
The analysis of the results of an experimental research of bone regeneration in groups with autografts of different origins showed significant restructuring of the latter during the research period. An indicator of these alterations is the total area of bone tissue, which simultaneously characterizes changes, both in the auto-graft and in the newly formed bone tissue defect. Thus, the total bone tissue area at 14 days in the maxillary graft group was 6 times higher than that in the shinbone graft group and 2.5 times in the clot healing group. The 30th day was characterized by an increase in the total bone tissue area, due to the newly formed bone around the graft: the maxillary graft group is 5 times higher, the shinbone graft group is 30 times higher, and compared to the previous day. The clot healing group has decreased on the contrary, because it was "sealed". On the 60th day only in the maxillary graft group there is an increase in the area of bone tissue by 3 times, preservation of the graft and immature newly formed bone tissue around it. Day 60 for the shinbone graft group is the peak in terms of bone area reduction. During this period, due to the resorption of the autograft on the periphery, the total bone tissue area decreases 8 times unlike the previous day.
The total bone area in all three groups decreases on the 90th day, but in the maxillary graft group it happens thanks to maturation of the bone tissue around the graft; in the shinbone graft group it happens due to resorption of the graft at the periphery; the clot healing group is due to resorption of the newly formed peripheral tissue.
The 120th day is characterized by partial termination of the osteoreparative process in the shinbone graft group (there is no transplantation of bone tissue within
the defect; its demineralization is not observed; a newly formed bone tissue is formed at the periphery, the matrix of which is less structured than in intact bone, and it has well-defined lines). In the clot healing group, the osteoreparative process completion rates were the worst (there was an inflammation in the central area of the bone defect, dominated by lymphocytes; there were also observed a considerable number of neutrophilic granulocytes, fragments of newly formed bone tissue surrounded by connective tissue). In the maxillary graft group, the osteoreparative process was completed with complete growth of the graft with surrounding bone tissue.
Changes in the area of connective tissue in groups using grafts indicate that it has been reduced since 60th day. Most in the shinbone graft group - 5 times, maxillary graft group - 3 times. In the future, a gradual decrease is observed throughout the research period in the maxillary graft group, indicating the end of the osteore-parative process. In the shinbone graft group, a wavy process was observed, namely: it decreased on 60th day, then from 90th day it increased twice, but by day 120 it tended to decrease. That is, the area of connective tissue was equal to the value that was on the 60th day. In the clot healing group, the connective tissue area was the largest compared to maxillary graft group and shinbone graft group and tended to increase.
The area of the formed connective tissue inside the defect depends directly on the total area of the bone tissue, which consists of the area of the graft and the newly formed bone tissue around it. The increase in its periphery in the later stages of the study indicates the resorption of the graft and as a consequence of the decrease in the total bone area.
Signs of an inflammatory process in the middle of the defect (graft, newly formed bone tissue, connective tissue) were observed in the research groups throughout the experiment, but they were most expressed in the clot healing and shinbone graft groups than in the maxillary graft group. Up to day 60 in the clot cloating group, there were lymphocytic infiltration around the newly formed fibrous tissue determined in the defect. In the shinbone graft group there was diffuse demoralization of the bone tissue of the graft, and in the maxillary graft group only along its periphery.
On the 90th day, the inflammatory response within the defect is present in the shinbone graft and clot healing groups, but in the clot healing group it is more expressed as evidenced by lymphocytic infiltration and neutrophil granulocyte cells, it is absent in the maxillary graft group.
The 120th day is characterized only in the group of clot healing preservation of inflammation signs in the newly formed bone tissue, connective tissue in the defect.
Conclusion
The bone tissue regeneration of the autograft and changes around it are determined by its origin. The bone graft changes to permanent bone tissue through the process of demineralization and the formation of new bone tissue around it. The total area of bone in the defect is directly proportional to the area of the graft. The connective tissue that forms around the graft indirectly reflects the process where the mineralization in the graft, namely its area is diminished with the restructuring and maximum preservation of the graft. In the maxillary graft group for 120 days there was complete bone grafting of the graft and the newly formed bone tissue, with bone tissue of the alveolar process, which around 98% of the defect was confirmed histologically and according to the morphometry calculations, which is the largest due to the maximum transplantation with shinbone graft group - 50%, clot healing - 15%.
The process of bone regeneration in the maxillary graft group occurs under the most favorable conditions, as evidenced by the inflammatory reaction, which lasted only up to 60 days, and no abrupt changes in connective tissue area were observed, as in the shinbone graft and clot healing groups.
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