32 IN T E R N A L m E d Ic IN E ISSN 2413-6077. IJmmR 2019 Vol. 5 Issue 2 dOI 10.11603/IJMMR.2413-6077.2019.2.10671 CONNECTIVE TISSUE DISEASES: FOCUS ON MICROCIRCULATORY BED *O.I. Zarudna, I.K. Venher, A.V. Dovbush I. HORBACHEVSKY TERNOPIL NATIONAL MEDICAL UNIVERSITY, TERNOPIL, UKRAINE Background. A microcirculatory bloodstream is a target, source and reason of the pathological process in patients with systemic connective tissue diseases. Objectives. This study is focused on meta-analyses of biopsy material of skin flaps harvested from patients’ fingers to identify specific morphological changes. Methods. A retrospective analysis of the medical records of 39 examinees with systemic sclerosis (SSc), 45 with Systemic Lupus Erythematosus (SLE), and 45 with rheumatoid arthritis (RA) was performed. The condition of peripheral hemodynamics was examined with longitudinal rheovasography of arms and legs. Endothelin-1 (ЕТ1) concentration was evaluated by immunoenzymatic method. We assessed other results of clinical and laboratory tests to compare them with morphological changes of the microcirculatory bed. Results. Most patients involved suffered from abnormal peripheral hemodynamics. It was revealed that kidneys, lungs or heart were damaged more frequently in the patients with peripheral blood circulation disorders, which were the most significant in the patients with SSc (p<0.05). Disorders of peripheral blood flow were exacerbated in case of lengthening of the disease course. Concentration of ЕТ1 was relevantly higher in the patients with peripheral blood flow disorders. Number of pathologic capillaries was the highest in the SSc patients. Conclusions. In terms of integral estimation, extremely significant changes of microcirculatory bloodstream were evidenced in the patients with SSc. However, some morphometric peculiarities were revealed in the patients without peripheral blood flow disorders. Thus, normal rheovasography did not exclude any microcirculation disorders. KEY WORDS: microcirculation; systemic lupus erythematosus (SLE); systemic sclerosis (SSc); rheumatoid arthritis (RA); biopsy; rheovasography. *Corresponding author: Olga Zarudna, Department of Clinical Immunology, Allergology and General Patients’ Care, I. Hor- bachevsky Ternopil National Medical University, 1 Maidan Voli, Ternopil, 46001. E-mail: zarudna@tdmu.edu.ua. Introduction Manifestations of systemic connective tissue diseases are very diverse. However, one thing they all have in common is vasculitis/ vasculopathy that results in systematicity and development of permanent malfunctioning of body organs and systems. Several studies show that patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and rheumatoid arthritis (RA) experience such symptoms as Raynaud syndrome, livedo reticularis, recurrent thrombophlebitis, digital vasculitis, capillaritis of palms and soles, etc. Among the manifes- tations listed above the most common sign is Raynaud syndrome that is characterized by cascade disruption of microcirculation: destruc­ tion of vascular endothelium, capillary basement membrane reduplication, intimal proliferation of smooth muscle cells with collagen hyperpro- duction and predisposition to vasoconstriction, vascular wall thickening with luminal occlusion, which is manifested by generalized clinical symptoms. Meanwhile, endothelium is a target, source and reason of the pathological process. It becomes a receptive field for binding of circulating immunoglobulins, immune comp- lexes, a complement and attacks of sensitized T-lymphocytes. It itself produces vascular endothelial growth factor, endothelin 1, etc. Similar findings are presented in the literature [1, 2, 3, 4]. Numerous studies have been conducted in order to identify noninvasive methods of studying microcirculatory bloodstream and detect specific pathological characteristics in favour of one or another connective tissue di- sease to help confirm a diagnosis. Consequently, the method of nailfold videocapillaroscopy is relevant [5, 6, 7]. Moreover, the results of nail- fold videocapillaroscopic examination are included into diagnostic classification by EULAR criteria of systemic sclerosis [5], indicating their high specificity and sensitivity. For an overall assessment of capillaroscopic pattern, the following indicators are used: capillary length, intercapillary distance, loop diameter, internal diameter, capillary width, International Journal of Medicine and Medical Research 2019, Volume 5, Issue 2, p. 32-39 copyright © 2019, TNMU, All Rights Reserved O.I. Zarudna et al. 33 IN T E R N A L m E d Ic IN E ISSN 2413-6077. IJmmR 2019 Vol. 5 Issue 2 apex width, venous limb, arterial limb [7]. Data analysis shows typical changes, for example, SSc: giant capillaries, loss of capillaries with areas of avascularisation, ramified capillaries with pathological neoangiogenesis and severe derangement of capillary structure [5]. Nailfold capillaroscopic form changes are less sympto- matic in cases of other diseases, for example in SLE. According to the literature concerning the above-mentioned pathology, they are present in 30-75% of cases. SSc (in contrast to SLE) characteristically reveals these changes that occur in 99% of cases at various stages [5, 6]. The most frequent alterations in the patients with SLE include increased tortuosity, elongated loops, and meandering bizarre loops [5]. The patients with RA are reported to have increased capillary tortuosity and prominent, clearly visible subpapillary venous plexus [5]. At the same time, according to the study of auto im- mune processes, in some pathological con di- tions, correlation between the rate of biolo gi- cally active substances and results of capilla- roscopy was revealed. For example, in cases of SLE a relation between concentration of endo- thelin­1 (ЕТ­1) and angioscopic characteristics of microcirculatory bloodstream (MCB) was found [8]. Meanwhile, increase in anti-endo- thelial antibody titre in cases of SSc was present in 22-86% of cases and combined primarily with lung damage and peripheral vascular bed [4]. A few researches describe the results of immune histochemical tests that allows estab- lishing that CD20+, B-lymphocytes, macropha- gocytes and dendritic cells, Ig G, A, M, and a complement in the form of deposits along elastic membrane of a vascular wall prevail among the cells that infiltrate a vessel wall [9]. The revealed morphological abnormalities and immunological disorders in systemic di- seases of connective tissue combined with endothelial dysfunction and coagulation sys- tem disorders create favourable conditions for development of severe systemic complications. The research is aimed at a retrospective study of morphological condition of a peripheral vascular bed in the patients with SLE, SSc, and RA to compare morphological changes with clinical and laboratory data. Methods Retrospective analysis of the medical re cords of 129 patients with rheumatic diseases was performed: 39 were diagnosed with SSc, 45 – with SLE, and 45 – with RA (all were the patients of Ternopil University Hospital, Depart ment of Rheumatology, 2001-2004). The statistical analysis revealed a typical situation for this category of diseases – predominance of women (86.05%) of fertile age. The average duration of the disease was 8.14±0.53 years. The archive of biopsy material of skin flaps harvested from patients’ fingers was reviewed that allowed morphometric analysis. The de cision for biopsy was made by a rheumatologist during the treatment at the Department of Rheumatology. For histological studies, pieces of skin were fixed in 10% neutral formalin solution. Subsequent processing of the material followed by embed- ment in paraffin blocks was carried out by a conventional technique. The sections obtained by a sliding microtome were stained with hematoxylin-eosin. The histological specimens were studied using the optical microscope SEO SCAN and images were made with the Vision CCD Camera with a histological image display system. The condition of peri pheral hemody- namics was examined by longi tudinal rheovaso- graphy of forearm and legs by means of soft- ware-hard ware complex of automated analysis USRH­1 (“УСРГ­01”). In the process of rheovaso­ graphic analysis the following medical parame- ters were estimated: the regularity of pulse waves, their appearance – upward and downward gradients, the type of a top (apex), extent of incisura, presence of additional waves, their localization on the de scending part of a curve. The following measu rements were analysed: As – percussion systolic wave amplitude of a rheogram, Ohm; RІ – rheographic index, that measures a magnitude of pulse volume, in other words a systolic flow; that is a correlation of a variable and a constant dimensions of impedance of the researched area, namely, a percussion wave of a rheogram and calibration impulse magnitude, relative units (RU); Ai – interval between the isoline and incisu- res on the descending part of a curve, Ohm; DI – dicrotic index, which reflects the con­ dition of the tone of arteries and precapillary vessels, %. The main indicator that was used for analysis was a rheographic index that measured the magnitude of pulse volume that was a systolic flow defined by a ratio of a percussion wave of a rheogram and calibration impulse magnitude, relative units (RU). The condition of endothelium was examined in terms of one of the main integral indicators of its functional capacity, i.e. ЕТ1. The contents of ЕТ1 were determined using an immuno­ O.I. Zarudna et al. 34 IN T E R N A L m E d Ic IN E ISSN 2413-6077. IJmmR 2019 Vol. 5 Issue 2 enzymatic method, which was based on the principle of competitive immunoenzymatic analysis, involving a reagent kit Peninsula Laboratories Inc. (USA). The severity of inflammation was deter­ mined by erythrocyte sedimentation rate (degree 1 – ESR <20 mm/hr, degree 2 – ESR 20-40 mm/hr, degree 3 – ESR >40 mm/hr). All case histories contained informed con- sents for the research. The study was conducted in accordance with the Declaration of Helsinki. The Protocol was approved by the Committee on Bioethics of I. Horbachevsky Ternopil National Medical University. Statistical processing of the research results was performed by parametric analysis and non- parametric analysis using the Student’s t-test and Mann-Whitney U-test by means of software package Microsoft EXCEL 5.0 and Statistica 10 (StatSoft). p values lower than 0.05 were con- sidered to be statistically significant. Results All cases were divided into two groups according to the state of peripheral hemo- dynamics, which was examined using longi- tudinal rheovasography of forearm and legs. The majority of patients, the model par- ticipants of the research, had abnormal peri- pheral hemodynamics (group 2). The ratio of the above-mentioned patients to the patients with normal peripheral hemodynamic para- meters (group 1) was 5.1:1.0. Clinical assessment of the involved patients is presented in Table 1. Assessment of peripheral hemodynamics allowed revealing significant changes in indices of longitudinal rheovasography of forearms and legs (Table 2). Morphometric analysis of skin biopsy was conducted in 26 model patients (Table 3, Table 4). Biopsy results of the patients with different nosology and peripheral blood circulation disorders are presented at Figures 1, 2, and 3. Notably, microscopic examination revealed that general architectonics of vessel walls was not damaged. Visible hyperplasia of endo the liocytes in all categories of patients was also evidenced, which may be treated as an adaptive mechanism in cases of blood circulation dis orders. The results of patients’ blood tests for con- centration of ЕТ1 (Table 5) pointed to its extre­ mely high content in the patients with peripheral blood circulation disorders in contrast to donors’ indices. Table 1. Clinical Assessment of the Patients with/without peripheral blood circulation disorders Indicant Patients with normal peripheral hemodynamic parameters (1st group) with abnormal peripheral hemodynamics (2nd group) Absolute numbers % Absolute numbers % Age (years): under 20 20-44 45-59 60 and above 3 9 5 4 2.3 6.9 3.9 3.1 4 53 38 13 3.1 41.1 29.5 10.1 Males Females 6 15 4.7 11.6 12 96 9.3 74.4 SLE SSc RA 9 1 11 6.9 0.8 8.5 36 38 34 27.9 29.5 26.4 Activity of the 1st degree Activity of the 2nd degree Activity of the 3rd degree 2 15 4 1.6 11.6 3.1 52 41 15 40.3 31.8 11.6 Duration of a disease < 1 yr Duration of a disease 1-5 yrs Duration of a disease 5-10 yrs Duration of a disease >10 yrs 3 6 5 7 2.3 4.7 3.9 5.4 10 38 30 30 7.8 29.5 23.2 23.2 Kidney damage No kidney damage 6 15 4.7 11.6 28 80 21.7 62.0 Cardiac involvement No cardiac involvement 7 14 5.4 10.9 37 71 28.7 55.0 Lung damage No lung damage 5 16 3.9 12.4 23 85 17.8 65.9 O.I. Zarudna et al. 35 IN T E R N A L m E d Ic IN E ISSN 2413-6077. IJmmR 2019 Vol. 5 Issue 2 At the same time, concentration of ET-1 in the patients without vessel disorders is not substantially different from normal range. Discussion Among the examinees, the detection rate of peripheral hemodynamic disorders in the Table 2. Indices of peripheral blood circulation in the patients of group 2 (with peripheral hemodynamic disorders) Indices Forearms Lower legs As, Ohm RІ, RU Ai, Ohm DI, % As, Ohm RІ, RU Ai, Ohm DI, % Duration of disease < 1 yr, n=10 0.123± 0.002* 1.23± 0.02* 0.090± 0.002* 73.41± 0.08* 0.147± 0.003* 1.47± 0.03* 0.105± 0.002 71.58± 0.08* >1-5 yrs, n=38 0.091± 0.002* 0.91± 0.02* 0.075± 0.002 82.24± 0.06* 0.145± 0.002* 1.45± 0.02* 0.116± 0.002* 80.24± 0.03* >5-10 yrs, n=30 0.087± 0.003* 0.87± 0.03* 0.074± 0.002 84.98± 0.08* 0.127± 0.003* 1.27± 0.03* 0.106± 0.003* 83.49± 0.04* >10 yrs, n=30 0.085± 0.002* 0.85± 0.02* 0.074± 0.001 87.18± 0.05* 0.114± 0.003* 1.14± 0.03* 0.096± 0.002 86.26± 0.04* Disease SLE, n=37 0.109± 0.002* 1.09± 0.02* 0.083± 0.002* 75.79± 0.05* 0.130± 0.002* 1.30± 0.02* 0.108± 0.008* 83.39± 0.04* SSc, n=37 0.082± 0.002* 0.84± 0.02* 0.072± 0.002 85.73± 0.08* 0.113± 0.004* 1.13± 0.04* 0.095± 0.003 84.41± 0.06* RA, n=34 0.089± 0.002* 0.89± 0.02* 0.070± 0.002 79.06± 0.06* 0.122± 0.003* 1.22± 0.03* 0.099± 0.003 81.11± 0.03* Activity of the inflam­ matory process 1st degree, n=52 0.095± 0.002* 0.95± 0.02* 0.080± 0.002* 84.15± 0.05* 0.121± 0.004* 1.21± 0.04* 0.099± 0.002 81.60± 0.09* 2nd degree, n=41 0.095± 0.003* 0.95± 0.03* 0.080± 0.002* 84.17± 0.05* 0.113± 0.002* 1.13 0.02* 0.095± 0.002 84.15± 0.04* 3rd degree, n=15 0.105± 0.005* 1.05± 0.05* 0.080± 0.004 75.52± 0.07* 0.138± 0.002* 1.13± 0.02* 0.111± 0.002* 80.44± 0.06* Follow-up control 0.152± 0.008 1.52± 0.08 0.069± 0.005 45.43± 0.04 0.181± 0.012 1.81± 0.12 0.088± 0.008 78.53± 0.07* Notes. * – р<0.05 – statistically significant difference between the indices in apparently healthy people of the control group and other studied patients. RA – rheumatoid arthritis; SSc – systemic sclerosis; SLE – systemic lupus erythematosus. Table 3. Average density of skin hemocapillaries of the patients per 1mm² Groups No peripheral blood circulation disorders (group1, n=11) Peripheral blood circulation disorders (group 2, n=15) Normal range 43.0±1.9 – Rheumatoid arthritis, n=8 40.0±1.8 p1>0.05 37.0±1.6 p1>0.05 р2>0.05 Systemic sclerosis, n=8 38.0±1.7 p1>0.05 21.0±1.0 p1<0.01 p2<0.01 Systemic lupus erythematosus, n=10 41.0±1.9 p1>0.05 36.0±1.7 p1<0.05 р2>0.05 Notes: p1 – statistically significant difference between the normal range and average density of hemocapillaries per unit area in patients of both groups; р2 – statistically significant difference between the indices in patients of the groups 1 and 2. O.I. Zarudna et al. 36 IN T E R N A L m E d Ic IN E ISSN 2413-6077. IJmmR 2019 Vol. 5 Issue 2 patients with RA was 75.6 %, which is slightly higher than the established results of statistical researches. Peripheral blood circulation disor- ders were diagnosed in the patients with SLE in 80 % of cases, in the patients with SSc – in 97.4 % of cases, which is consistent with lite- rature [10, 11]. Despite nearly equal distribution of patients in every group by age, duration of a disease, activity of the inflammatory process, it has been revealed that a kidney, lung or heart are da- maged more frequently in the patients with peripheral blood circulation disorders. Such results are probably associated with the de- velopment of systematicity, which is caused by peripheral blood flow and microcirculation disorders. Table 4. Distribution of skin hemocapillaries of the patients over the duct width Disease No peripheral blood circulation disorders (group 1, n=11) Peripheral blood circulation disorders (group 2, n=15) The number of hemocapillaries and their diameter The number of hemocapillaries and their diameter 8­12 μm 15­25 μm above25 μm 8­12 μm 15­25 μm above 25 μm Normal range 100 – – 100 – – Rheumatoid arthritis, n=8 80.6±3.6 р1<0.01 12.1±0.6 7.3±0.3 31.3±1.5 р1<0.01 р2<0.01 46.6±2.2 22.1±1.0 Systemic sclerosis, n=8 71.7±3.3 р1<0.01 24.5±1.1 3.82±0.17 8.0±0.3 р1<0.01 р2<0.01 58.9±2.8 33.1±1.5 Systemic lupus erythematosus, n=10 69.2±3.3 р1<0.01 29.7±1.4 1.13±0.04 7.5±0.3 р1<0.01 р2<0.01 43.2±2.0 49.3±2.4 Notes: p1 – statistically significant difference between the normal range and the number of normal-sized capillaries (8-12 μm) in the patients of both groups; p2 – statistically significant difference between the number of capillaries 8-12 μm in diameter in the patients of the groups1 and 2. Figure 1. Biopsy material of skin flaps harvested from the finger of the patient F. with rheumatoid arthritis, medical record of the in-patient patient No. 01/10064. Staining H&E. ×600 Figure 2. Biopsy material of skin flaps harvested from the finger of the patient Sh. with systemic lupus erythematosus, medical record of the in-patient patient No. 01/00920. Staining H&E. ×600 Figure 3. Biopsy material of skin flaps harvested from the finger of the patient Kh. with systemic sclerosis, medical record of the in-patient patient No. 01/07587. Staining H&E. ×600 O.I. Zarudna et al. 37 IN T E R N A L m E d Ic IN E ISSN 2413-6077. IJmmR 2019 Vol. 5 Issue 2 In the rheograms of the patients with peri- pheral blood circulation disorders the height of percussion wave and RI decrease is related to the increase in duration of the disease. Thus, RI in the forearms of the patients, who suffer from the disease for a period of less than 1 year, decreased by 19.07%. At the same time, the systolic blood flow in the forearms of the pa­ tients, who suffer for 10 or more years, de- creased by 44.08%. Meanwhile, DI value points to hypertonia of precapillary vessels in all investigated groups, but this indice is statistically lower (p<0,001) among the patients, who suffer for a period of less than 1 year, and increases if the duration of the disease is longer. In the patients divided by the nosological units, the lowest rates of systolic flow were observed in patients with SSc, meanwhile, RI decreased by 46.05%; the patients with RA and a deficit in RI, representing 41.45 %, were the second; consequently, the smallest changes in RI were found in the patients with SLE, whose systolic blood flow in forearms decreased by 28.29 %. The tonus of precapillary vessels, which was significantly higher in the patients with SSc (p<0.001), was changed compare to the above- mentioned data. Analysis of rheovasography indices in terms of the degrees of inflammatory process acti­ vity (which was determined by the erythro- cyte sedimentation rate) revealed no statistically significant difference. However, at the highest degree of the inflammatory process activity DI was of the smallest value and significantly different (p<0.001) from the indices at the 1st and 2nd degrees of activity. Thus, the most significant peripheral blood circulation disorders were found in the patients with SSc (p<0.05); disorders of peripheral blood flow were exacerbated in case of lengthening of disease course. Hypertonia of peripheral vessels and decrease in systolic blood flow were reflected in flattening of a rheographic curve and rheographic index decrease. Hypertonia of arterioles and precapillary vessels was evident by high location of incisures in relation to the apex of the rheographic curve and a high DI value. The analysis of morphometric data revealed that the average density of capillaries per unit area statistically decreased only in the patients with peripheral blood flow disorders in cases of SLE and SSc. Along with the decrease in the number of normal-sized capillaries, dilated and mega ca- pillaries were present. Meanwhile, their number was small in the patients without peripheral blood flow disorders and statistically significant in the patients with hemodynamic disorders. In terms of relative values, the number of pathologic capillaries was 66.7% in cases of RA, 92.0% in cases of SSc and 91.5% in cases of SLE. The concentration of ЕТ­1 was significantly higher in the patients with peripheral blood flow disorders. To examine the changes in concentration of ET-1 in detail, all the patients with the signs of vascular bed damage were divided into three groups by the degree of the inflammatory process activity. The revealed changes were reflected in gradual increase in concentration of ЕТ­1 in case of a higher degree of inflammatory process activity, though there was no statistically significant difference between the indices. According to the results of our study it has been established that microcirculatory bed changes in the patient with SSc and SLE com- plied with other literature regarding investi- gation of non-invasive methods of studying of microcirculatory bloodstream such as nailfold videocapillaroscopy [5, 6, 7]. Minimal changes have been revealed in the patients with RA [5]. Conclusions It should be noted that peripheral hemo- dynamic disorders are followed by significant microcirculatory bloodstream disorders such as decrease in average density of hemocapillaries per unit area, decrease in the number of nor- Table 5. Concentration of ЕТ1 in the patients with rheumatic diseases with/without peripheral blood circulation disorders Group of patients ЕТ1, pkg/ml Donors, n=10 1.8±0.7 Group 1, n=5 1.9±0.5 p1>0.05 Group 2 SLE, n=10 19.0±1.4 p1<0.001 p2<0.001 SSc, n=10 23.1±1.5 p1<0.001 p2<0.001 RA, n=10 18.9±1.4 p1<0.001 p2<0.001 Notes: p1 – statistically significant difference between indices in pa- tients and donors; p2 – statistically significant difference between indices in pa- tients of the groups 1 and 2. RA – rheumatoid arthritis; SSc – systemic sclerosis; SLE – sys- temic lupus erythematosus. O.I. Zarudna et al. 38 IN T E R N A L m E d Ic IN E ISSN 2413-6077. IJmmR 2019 Vol. 5 Issue 2 mal-sized capillaries, and increase in the number of dilated and megacapillaries. Mor- pho metric changes are accompanied by endo- thelial dysfunction with a high concentration of ЕТ­1. In terms of integral estimation extremely high level of changes is evidenced in the patients with SSc which complies with current understanding of this disease. However, some morphometric peculiarities were revealed in the patients without peripheral blood flow disorders: in cases of adequate density of hemocapillaries per unit area, there was a decrease in the number of normal-sized capillaries and presence of dilated and mega- capillaries. The above-mentioned changes were not followed by endothelial dysfunction in relation to ЕТ1 indicator. Thus, normal rheova­ sography did not preclude the presence of microcirculation disorders since biopsy revealed deeper changes in microcirculatory bed. The further research should be focused on the search for non-invasive methods of stu- dying microcirculatory bloodstream in the patients with rheumatic diseases, which is the main cause of the development of systematicity. Acknowledgements: The authors are gratefully acknowledged to Mariana Karanevych (PhD in Philology, Associate Professor) with the help in translation of this article. Funding This research received no external funding. Conflict of Interests The authors declare no conflict of interest. Author Contributions Zarudna O.I. – conceptualization, data cu- ration, formal analysis, investigation, writing – original draft and review & editing; Venher I.K. – conceptualization, data curation, validation, methodology; Dovbush A.V. – formal analysis, investigation, visualization, software. системні захВорюВання сполучноЇ тканини: Фокус на мікроциркуляторне русло О.І. Зарудна, І.К. Венгер, А.В. Довбуш ТЕРНОПІЛЬСЬКИЙ НАЦІОНАЛЬНИЙ МЕДИЧНИЙ УНІВЕРСИТЕТ ІМЕНІ І.Я. ГОРБАЧЕВСЬКОГО, ТЕРНОПІЛЬ, УКРАЇНА Вступ. Прояви системних захворювань є надзвичайно різноманітними. Їх об’єднує наявність васкуліту/васкулопатії, що й зумовлює системність і приводить до розвитку стійких порушень функції органів і систем. При цьому мішенню, джерелом та причиною патологічного процесу є ендотелій. Мета. Провести комплексне вивчення стану мікроциркуляторного русла у хворих на системний червоний вовчак (СЧВ), системну склеродермію (ССД) та ревматоїдний артрит (РА). Методи. Для досягнення мети проведено ретроспективний аналіз архівних історій хвороби 129 хворих на ревматичні захворювання, з них 39 – з верифікованим діагнозом ССД, 54 – СЧВ та 45 – РА. Переглянуто архів біоптатів шкірного клаптя пальця пацієнтів, на основі чого проведено морфометричний аналіз. Стан периферичної гемодинаміки вивчали за результатами поздовжньої реовазографії передпліч та гомілок. Вміст ЕТ - 1 визначено за імуноферментною методикою, яка ґрунтується на принципі конкурентного імуноферментного аналізу. Клінічні та лабораторні дані співставлень з результатами морфологічного дослідження біоптатів. Результати. У переважної більшості пацієнтів виявлено розлади периферичної гемодинаміки. Встановлено, що ураження нирок, легень, серця частіше спостерігається у хворих з розладами периферичного кровоплину, проте найглибші порушення виявлено у хворих на системну склеродермію (p<0,05). Порушення периферичної гемодинаміки супроводжуються підвищенням концентрації ендотеліну-1 та поглиблюються за умови зростання тривалості хвороби. Кількість патологічних капілярів найвища у хворих на системну склеродермію. Висновки. Крайній ступінь розладів мікроциркуляторного русла за інтегральною оцінкою клініко- лабораторних та морфометричних досліджень виявлено у пацієнтів на ССД. Однак знайдено деякі морфологічні особливості у пацієнтів без розладів периферичного кровоплину. Отже відсутність патологічних відхилень за результатами реовазографії не виключає розладів на мікроциркуляторному рівні. КЛЮЧОВІ СЛОВА: мікроциркуляція; системний червоний вовчак (СЧВ), системна склеродермія (ССД), ревматоїдний артрит (РА); біопсія; реовазографія. O.I. Zarudna et al. 39 IN T E R N A L m E d Ic IN E ISSN 2413-6077. IJmmR 2019 Vol. 5 Issue 2 Інформація про авторів Зарудна Ольга Ігорівна – канд. мед. наук, доцент кафедри клінічної імунології, алергології та загального догляду за хворими, Тернопільський національний медичний університет імені І.Я. Гор­ бачевського. Венгер Ігор Касянович – доктор медичних наук, професор, завідувач кафедри хірургії №2, Тернопільський національний медичний університет імені І.Я. Горбачевського. Довбуш Андрій Васильович – канд. біол. наук, доцент кафедри гістології та ембріології, Тернопільський національний медичний університет імені І.Я. Горбачевського. Information about the authors Olga I. Zarudna – MD, Ph.D., Associate Professor, Department of Clinical Immunology, Allergology and General Patients′ Care, I. Horbachevsky Ternopil National Medical University. ORCID 0000­0002­9374­3991, e­mail: zarudna@tdmu.edu.ua Ihor K. Venher – MD, Ph.D., DSc, Professor, Head of the Department of Surgery No. 2, I. 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