REVIEWS
The review considers the involvement of the endothelium and endothelial glycocalyx in the systemic inflammatory response. The role of the endothelium in the inflammation is ambivalent and depends on the nature of the inflammatory process. The physiological response of endothelial cells to local inflammation is necessary to successful eliminate the pathogen and restore the tissue homeostasis. In systemic inflammation, the endothelium is the most «suffering» structure of the body. However, endothelial cells can be a source of systemic inflammatory mediators, supporting the pathological inflammatory process. The problem of generalization of inflammation is discussed where endotheliopathy develops and closes the vicious circle, being both a consequence of systemic inflammation and the cause of its prolongation and intensification. In the pathogenesis of a new coronavirus infection the relationship between endotheliopathy and systemic inflammation was most clearly manifested. Preceding endothelial dysfunction causes a severe course of COVID-19 with a «cytokine storm» and coagulopathy that can lead to the death. SARS-CoV-2 infection induces long-term endothelial dysfunction, which is recorded even after the virus elimination. The early detection of blood level of endothelial glycocalyx damage markers (i. e. syndecan-1, glycosaminoglycans like heparan sulfate and hyaluronic acid) may seem to be an effective approach to the prevention of severe forms of COVID-19. Endothelial-protective drugs can reduce the risk of severe new coronavirus infection and eliminate the manifestations of long-COVID.
ORIGINAL ARTICLES (CLINICAL INVESTIGATIONS)
Introduction. The great importance of risk factors, such as arterial hypertension (AH) and low-density lipoprotein cholesterol (LDL-H), for development of cardiovascular diseases, makes highly relevant to obtain the data of the nature of microcirculation (MC) changes that are a key link of maintaining homeostasis under their concomitant influence.
Aim – to evaluate functional state of skin microvascular bed using laser Doppler flowmetry in patients with arterial hypertension (AH) and combined with hypercholesterolemia.
Materials and Methods. The study involved 37 practically healthy volunteers and 94 patients with 2–3 stage of AH, which were divided into 2 groups: Gr.1 with LDL-CH level ≤3.5 mmol/l (n = 35) and Gr.2 with LDL-H level >3.5 mmol/l (n = 59). MC of the forearm skin was assessed by laser Doppler flowmetry. Parameters of basal blood flow, the amplitude-frequency spectrum of its fluctuations, nutritional MC, and parameters of occlusion test were evaluated.
Results. Analyzing rhythm structure of blood flow fluctuations, statistically significant decrease in standardized parameters of their amplitude in endothelial and myogenic frequency ranges was revealed in patients with elevated LDL-CH levels compared to patients of Gr.1 by 19.7 % and 9.7 % (р = 0.045), respectively, which indicated weakening of endothelial function and constriction of precapillary segment of MC. These changes were accompanied by decrease in reserve of microvascular blood flow by 9.1 % in Gr.2 of patients (p = 0.044) with pronounced trend towards reduction of capillary perfusion and activation of blood flow through arteriolovenular shunts.
Conclusion. More pronounced functional disorders of MC, characterized by endothelial dysfunction, constriction of precapillary segment, and decrease in reserve potential of tissue hemoperfusion were revealed in AH patients with atherogenic hyperlipidemia vs AH patients.
Introduction. Sonography of lower extremity veins is advised to be used for evaluation VTE in patients with stroke, however, the timing of the evaluation remains uncertain, therefore the prevalence of VTE and associated factors in different time intervals of hospitalization is necessary to be studied.
Aim – to investigate the prevalence of lower extremity veins thrombosis by sonography compared with the prevalence of associated factors (D-dimer level in the blood, the risk of VTE by Padua score system) in patients with stroke in the first 3 days of hospitalization.
Materials and methods. The study enroled 50 patients hospitalized in the Botkin State Clinical Hospital of Moscow with stroke. Sonography of lower extremity veins was performed, the level of D-dimer in the blood was determined, the risk of VTE by Padua score system was assessed in the first 3 days of hospitalization. The prevalence of these indicators has been studied.
Results. Increased D-dimer level was detected in the majority of patients: 84 % of all patients (42 of 50), 85 % of patients with ischemic stroke (34 of 40), 78 % with hemorrhagic stroke (7 of 9) and in a single patient with TIA. 30 % of all patients (15 of 50), 32.5 % of patients with ischemic stroke (13 of 40), 22 % of patients with hemorrhagic stroke (2 of 9) had high risk of VTE according to Padua (≥ 4 points). The prevalence of lower extremity veins thrombosis according the sonography results was 6 % (3 of 50), that is 14 times less than the prevalence of increased D-dimer level and 5 times less than the prevalence of high risk of VTE by Padua score system. About 66 % of mpatients having thrombosis (2 of 3) were suffering from active cancer.
Conclusion. Patients with stroke in the first 3 days of hospitalization has significant prevalence of lower extremity deep vein thrombosis according to sonography, but factors that distinguish these patients need to be clarified. Lower prevalence of increased D-dimer level and the high risk of VTE by Padua in post-stroke patients during this period of hospitalization seem to be doubtful criteria compared with prevalence of lower extremity deep vein thrombosis for selection to sonography. The distinguishing risk factor for VTE by Padua in 66 % of patients with evaluated deep vein thrombosis in the first 3 days of hospitalization with stroke was an active cancer.
Introduction. The results of studies devoted to the influence of biological sex on microhemodynamic parameters are ambiguous. Today no studies of sex-specific microhemodynamics evaluated by the new incoherent optical fluctuation flowmetry method (IOFF) have been reported.
Objective – to investigate the sex-specific differences of microhemodynamics assessed by the IOFF method in healthy volunteers.
Materials and Methods. 27 healthy volunteers (10 men and 17 women) were included in the study. The groups were comparable by sex, age, and main clinical parameters. Perfusion was measured by the IOFF method. Parameters were evaluated while performing an occlusion test on the hand and a local heating test on the dorsum of the foot and the toe. Microcirculation reactivity was calculated as a relative increase of perfusion response to the vasodilation stimulus.
Results. Women had significantly lower median baseline perfusion than men on the hand and on the dorsum of the foot (hand: 10 [6; 13] PU vs. 15 [10; 19] PU, p = 0.035; foot: 0.78 [0.68; 0.97] PU vs. 1.13 [0.99; 1.29] PU, p = 0.003). Women were demonstrated to have significantly higher reactivity response to thermal and occlusive stimuli than men (p < 0.05). Thus, at the third minute of heating, women had perfusion increased 5.39 [4.32; 6.64] times and men had 3.47 [3.13; 4.65] times (p = 0.018); after the release of the occlusion women had perfusion increased 1.93 [1.37; 3.02] times and men had 1.14 [1.01; 1.74] times (p = 0.011).
Conclusion. Healthy women had been shown to have higher reactivity of microhemodynamics than men. A lower cardiovascular risk women have compared to men could be caused by sex-specific features of endothelium function.
CLINICAL ANALYSIS
Article presents a clinical case report of late aortic coarctation (CoA) diagnosis of a 39-year-old woman. Considering that CoA is a rare congenital pathology, diagnosed and corrected mainly in childhood, physicians supervising patients over 18 years of age often exclude this disease from their diagnostic search. Meanwhile, the reported clinical case demonstrates specific
complaints and features of the anamnesis, if were analyzed carefully would allow to establish a diagnosis much earlier.
The main purpose of the publication is to remind primary care physicians about measuring blood pressure in the upper and lower extremities of young patients with arterial hypertension, without a history of aggravated cardiovascular diseases, and also to have the most common causes of secondary hypertension to be excluded: the endocrine system, kidneys and their vessels pathologies.
In addition, the authors raise a number of interesting practical questions arising from the presented clinical case and give detailed answers in the discussion part of the article.
Clinical case of an 85-year-old patient with Heid’s syndrome is being reported: recurrent gastrointestinal bleeding due to angiodysplasia of the stomach and intestines in combination with acquired destruction of large von Willebrand factor multimers in severe aortic stenosis. Actually it remains difficult to make a diagnosis in these patients and perform timely surgical intervention. Considering the age of the patient, severity of manifestations of heart failure and high risk of surgical complications, transcatheter aortic valve implantation (TAVI) was the method of choice. Surgical correction of heart disease in this case is aimed not only at treating its clinical manifestations, but also at eliminating the cause of recurrent gastrointestinal bleeding in Hyde’s syndrome.
ORIGINAL ARTICLES (EXPERIMENTAL INVESTIGATIONS)
Introduction. In the development of systemic microcirculation disorders, gender is known to have a certain significance. However, the features of the microvessels reactivity and their functional reserve have not been sufficiently studied.
Purpose – to study the gender specificity of the microvessels reactivity of rat skin according to LDF data in the conditions of functional tests.
Materials and methods. The study was carried out on male and female Wistar rats. Females with a stable 4-day estrous cycle according to colpocytogram data were selected for the experiment. The LDF method was used to evaluate the initial skin perfusion and its dynamics under the conditions of a test with local contact hypothermia induced by a thermoelement. The distribution of temperature fields was evaluated using a FLIR ONE Pro thermal imaging camera.
Results. While contact cooling of the skin, microvessels developed a reaction having phase pattern. Immediately after exposure, local contact hypothermia was accompanied by a significant decrease in skin temperature and tissue perfusion (in the area of laser flowmetry). At the same time, males had higher percentage of reduction in skin blood flow (Q %) than females and amounted to 54 % of the initial values. The maximum perfusion after the restoration of blood flow was noted at the 5th minute in males, at the 3rd minute in females and amounted to 147 % and 149.9 %, respectively. The initial blood flow in the skin microvessels in different phases of the estrous cycle in females did not differ significantly. However, when conducting a functional test in the proestrus stage, characterized by the maximum secretion of estrogens by the ovaries, vasoconstriction was less pronounced than in other phases of the cycle.
Conclusion. The revealed features of blood flow reduction followed by «cold vasodilation» under conditions of local contact hypothermia tests indicate a greater functional reserve of microvessels and a more effective mechanism of autoregulation of the microcirculation system in female rats.
Introduction. Age-related changes of blood flow parameters and hepatic portal vein wall morphometry are one of the topical and insufficiently investigated issues of liver hemodynamics.
The aim was to study changes of portal hemodynamics and to analyze the portal vein wall morphometry of rats at different age periods.
Materials and methods. 60 mongrel rats of both sexes weighing 120–350 g were divided into three age groups. The first group included 20 rats aged 1 month, the second – 20 rats aged 6–12 months and the third – 20 rats aged more than 18–24 months. The qualitative and quantitative portal vein hemodynamics parameters were obtained by ultrasound scanners under zoletil-xylazine anesthesia. Morphometric examination of the portal vein was performed. Digital data were processed by methods of variational statistics.
Results. The diameter of the portal vein in groups II and III was greater than the corresponding parameter in group I (R = – 0.40 and R = 0.64, respectively). The time-averaged average blood flow rate in the II age group increased by 9.11 % compared to the I group, decreased by 10.43 % in the III group (the differences are statistically unreliable). The volumetric blood flow rate increased moderately in age groups II and III compared to group I (by 13.07 and 11.13 %, respectively; the difference is statistically unreliable). The ratio of the volumetric blood flow rate to the weight of the animal in the II age group increased by 3.85 % compared to the I group, decreased by 11.54 % in the III group (the differences are statistically unreliable). Since the mass of animals significantly increased with age, the portal vein volumetric blood flow of old animals is likely to be decreased. Mature and old rats demonstrated significant decrease of the muscle membrane thickness, the Kernogan index and the width of the collagen layer.
Conclusion. Age-related changes of rats portal hemodynamics resulted in a slight reliable increase of portal vein diameter and its cross-sectional area. Linear and volumetric parameters of blood flow were found not to have statistically reliable dependence on the age and weight of animals. Morphometric parameters of the rats portal vein wall were revealed to have pronounced changes in different age groups. The aging of the portal vein wall of elder rats consisted in a significant decrease of the muscle membrane thickness, the Kernogan index and the width of the collagen layer.
Introduction. Cell damage is not the only important mechanism of high-intensity focused ultrasound (HIFU) for cancer therapy; concomitant microcirculation disorders having alterations patterns not studied enough also have high significance.
The aim of the study was to analyze perfusion along the tumor perimeter depending on the HIFU exposure.
Materials and methods. We used a stand for HIFU therapy (MTL LLC). Mode: 8.2 kW/cm2 intensity at 0.6 mm focal spot at 1.4 MHz, exposure time: 150, 200, 250 and 500 ms.
The object of the study is the vascular bed of Pliss lymphosarcoma. Tumor tissue temperature was monitored by a T-8 thermograph (Russia), blood flow was measured by the BLF21 laser Doppler recorder (USA).
Results. After HIFU exposure time from 150–250 ms, perfusion was noted to have decreased to 1.06 perfusion units (pf.u) in the central zone (p<0.01) compared to the control, but by the 30 min perfusion has increased to 1.22 pf.un. No signs of perfusion improvement were found in exposure time of 500 ms. In the peripheral zone, against the background of a decrease in blood flow to 3.6 pf. u. (p < 0.05) by 30 min of the experiment, hyperperfusion was restored to 5.86 pf. u. in all exposure time. In the central zone, a sharp decrease in microcirculation was observed, probably caused by damage of blood vessels; in the periphery of the tumor, perfusion changes had a phasic and reversible pattern.
Conclusion. An increase of HIFU exposure correlates with an increase of temperature of Pliss lymphosarcoma tissue near the focus of exposure. Specific perfusion changes are recorded in the central and peripheral zones of the tumor when single exposed to HIFU with different time exposure; the severity of changes depends on ultrasound exposure-time and is characterized by a zonal pattern of blood flow distribution due to the formation of zones of irreversible and reversible damage to microcirculation.
LECTURES
The article is devoted to the correct use of modern statistical methods in data analysis. Considering the complexity of choosing and implementation of statistical method for data analysis and correct interpretation of the results we emphasize the importance of interaction between a medical scientist (biologist) and biostatistician. The article in a clear way emphasizes the correct
presentation of the results as a table and graphic form, recalls the differences between normal and other types of distribution of quantitative characteristics in the aggregate. Examples of using the multivariate methods are given in detail: discriminant analysis and logistic regression. The results of the original bulbar conjunctiva microcirculation study by the biomicroscopy were provided an example of the potential of these complex and infrequently used statistical methods. The conclusions emphasize the need for cooperation between a medical researcher (biologist) and biomedical statistician for the correct application of statistical methods, the maximum extraction of useful information from the primary data, as well as assistance in interpreting the results obtained. The authors provide an extensive list of statistical literature that studying can help medical scientists understand this complex science.
CLINICAL CASE
Introduction. Cerebral microangiopathy is the leading cause of vascular cognitive disorders accompined by dementia in the final stages of the disease.
Purpose – to study the spectrum of lacunar syndromes in patients with acute cerebrovascular accidents based on our own observations and provide a description of rare clinical variants of the didorders.
Materials and methods. We examined 18 patients (10 men and 8 women) aged 33 to 66 years (mean age 52.33 years) in the acute period of lacunar strokes (LS). We studied the neurological status, the data of laboratory-instrumental, speech therapy and neuropsychological testing. The diagnosis of LS was verified using magnetic resonance imaging.
Results. Lacunar strokes were more common in patients of mature age (72.22 %) suffering from arterial hypertension (88.89 %) in combination with obesity (44.44 %); patients with atherosclerosis of the coronary and cerebral arteries (27.78 %), type 2 diabetes mellitus (22.22 %) found to have lacunar stroke less often. The sensorimotor hemisyndrome was found to be prevailed (44.44 %). Other classical lacunar syndromes were detected less frequently: with the same frequency (16.67 %) – isolated hemihypesthesia and «hemiballism / hemichorea», as well as «dysarthria – clumsy hand» (11.11 %). The predominant localization of the lesion is the right hemisphere (88.89 %), the internal capsule (66.67 %), rarely the thalamus (27.78 %). Multiple LS were registered in 27.78 % of cases, including the patients with tandem atherostenosis of the cerebral arteries. Descriptions of two clinical cases of LS are presented.
Conclusion. Sensorimotor hemisyndrome dominated in clinical scenario. We also observed more rare disorders – bulbar syndrome with anarthria with bilateral damage to the knee of the internal capsule and hyperkinetic syndrome with myoclonus of the respiratory, vocal and articular apparatus. The right-hemispheric lesion predominated with the localization of foci in the internal capsule, the thalamus suffered rarely. Multiple LS were registered in 27.78 % of cases. LSs have unfavorable prognosis for patients with uncontrolled arterial hypertension combined with tandem stenoses of extra- and intracerebral arteries with cognitive disorders that made it difficult to manage patients. The relevance of LS neuroimaging in overweight patients was noted.
ЮБИЛЕЙ
ISSN 2712-9756 (Online)