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Regional blood circulation and microcirculation

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Vol 24, No 4 (2025)
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REVIEWS

4-11 8
Abstract

This brief review presents data from the past 25 years on the clinical effectiveness of interval normobaric hypoxic training (IHT) in patients with cardiovascular diseases (arterial hypertension, coronary heart disease, chronic heart failure, cerebrovascular disease), respiratory diseases (chronic obstructive pulmonary disease, bronchial asthma), and type 2 diabetes mellitus. It has been shown that IHT courses lead to systemic positive effects at the cellular, organ and systemic levels in all age groups with the widest range of diseases. IHT, as an alternative treatment and rehabilitation method for patients with chronic noninfectious diseases, is very promising and requires further development.

12-20 9
Abstract

The literature review presents scientific materials on the computational modelling of hemoand hydrodynamics of blood flow in cases of pathologically tortuosity of carotid arteries, as well as in atherosclerotic and aneurysmal damage of the artery wall. A literature review of different articles about methods of computed modelling of the blood flow is conducted. Following a systematic analysis of scientific articles by Russian and foreign authors, key parameters can be identified for use in computed modelling of blood flow in patients with pathological tortuosity of the internal carotid arteries. The leading numerical indicator of wall shear stress (WSS) and blood flow velocity metrics are assessed and used for further modelling, prognosis and determination of indications for surgical treatment, tactics of the operating surgeon, likelihood of relapses and, frequency of complications.

21-31 9
Abstract

The article presents an analysis of obesity as a multifactorial pathology associated with impaired hemostatic balance and an increased thrombotic risk. Based on current data, key pathogenetic mechanisms are examined, including chronic subclinical inflammation, insulin resistance, and oxidative stress, which lead to adipokine profile imbalance and the loss of vasoprotective properties of perivascular adipose tissue. Particular attention is given to glycocalyx degradation, decreased thrombomodulin expression and protein C system activity, elevated von Willebrand factor levels, increased expression of intercellular adhesion molecules, and suppressed fibrinolytic activity due to PAI-1 overexpression. The role of exosomes and microRNAs in the regulation of adipocyte-endothelial interactions is also discussed. Potential approaches to targeted modulation of adipokine pathways and personalized antithrombotic prophylaxis are summarized.

32-39 10
Abstract

Purpose – to conduct a comparative analysis of the parameters of post-occlusion reactive hyperemia development in apparently healthy individuals and patients with arterial hypertension, using a portable dual-channel laser blood microcirculation analyzer. Materials and methods. Two observation groups were formed: patients with arterial hypertension (AH group, n=39) and healthy individuals (control group, n=32). Microcirculation parameters were determined during the occlusion test using laser Doppler flowmetry. The fluorescence amplitude of the coenzyme – reduced nicotinamide adenine dinucleotide (NADH) – was determined using laser fluorescence spectroscopy. The content of nitrates and nitrites (NOx) in the subjects’ blood serum was determined and the deformability of erythrocytes after their incubation with the NO donor – sodium nitroprusside – was assessed. Results. The initial indicator of microvascular perfusion in the observation groups did not differ statistically significantly. In the AH group, the maximum perfusion value (MPmax) achieved during the development of reactive post-occlusive hyperemia was 20% lower (p<0.01), the time to reach MPmax was increased by 46% (p<0.01), and the perfusion half-recovery time was reduced by 42% (p<0.01), compared with the control group. The amplitude of myogenic and neurogenic factors modulating blood flow in the AH group was reduced by 39% and 41%, respectively (p<0.05). The increase in erythrocyte deformability in response to the NO donor was 37% lower (p<0.01), and the NOx content in the blood serum was increased by 32% (p<0.01). The amplitude of NADH fluorescence was 49% (p<0.01) higher in the AG group than in the control group. Conclusion. The obtained results demonstrate a slowdown in flow-dependent vasodilation and a reduction in the post-occlusion hyperemic period in individuals with hypertension compared to healthy subjects. These changes were linked to a decrease in the activity of local mechanisms modulating microcirculation, impaired NO-dependent regulatory processes, and a slowdown in oxidative metabolism in individuals with hypertension.

40-47 8
Abstract

Introduction. Glaucoma is a neurodegenerative disease characterized by the gradual loss of retinal ganglion cells and their axons through apoptosis. Vascular disturbances play a significant role as an underlying cause. Objective. To evaluate the mechanisms of blood oxygen transport and gasotransmitters system in primary open-angle glaucoma (POAG). Materials and Methods. The study included 130 subjects: 100 patients diagnosed with POAG stages I–IV and 30 relatively healthy individuals without glaucoma. Ultrasound examination of the eye and orbit was performed using color Doppler imaging and pulse Doppler velocimetry to assess blood flow parameters in vessels supplying the optic nerve and retina. Choroid thickness was measured by optical coherence tomography. Levels of gasotransmitters (nitric oxide and hydrogen sulfide) and blood oxygen transport function indicators were also determined. Results. Significant reductions in maximum systolic blood flow velocity were observed in POAG: by 26.1% in the ophthalmic artery (p=0.012), 13.3% in the central retinal artery (p=0.047), and 21.7% in the short posterior ciliary arteries (p=0.032). The end-diastolic velocity also decreased, especially in the ophthalmic artery, by 42.9% (p<0.001). The resistive index increased by 7.6% in the ophthalmic artery (p=0.022), and by 4.3% in the central retinal artery and short posterior ciliary arteries (p=0.040 and p=0.048, respectively). Choroid thickness decreased by 14.1% (p<0.001). Gasotransmitter production was disturbed: nitric oxide levels increased by 47.1% (p<0.001) and hydrogen sulfide decreased by 28.0% (p<0.001). Hemoglobin’s affinity for oxygen increased, with the real p50 decreasing by 5.8% (p=0.003) and the standard p50 by 7.9% (p<0.001). Conclusion: Changes in vascular oxygen transport mechanisms, gasotransmitter levels, and blood oxygen-binding properties contribute to ischemic damage of the optic nerve and glaucoma progression.

ORIGINAL ARTICLES (EXPERIMENTAL INVESTIGATIONS)

48-58 9
Abstract

Introduction. Chronic kidney disease–mineral and bone disorder (CKD-MBD) plays a significant role in causing cardiovascular morbidity and mortality related to CKD. CKD-MBD has been studied during advanced stages when changes in inorganic phosphate (Pi) and its hormonal regulation are obvious. The initial phases of myocardial remodeling (MR) in early CKD-MBD remain poorly understood. Aim. To investigate the molecular and structural alterations in the myocardium and intramyocardial arteries in early-stage CKD-MBD model. Materials and methods. CKD-MBD was modeled using 3/4 nephrectomy in spontaneously hypertensive rats (SHR). Sham-operated rats served as a control. After 2 or 6 months, we assessed renal function, inorganic phosphate (Pi) metabolism, bone, myocardial and vascular histology and histomorphometry and gene profiles for Pi-dependent, pro-hypertrophic and pro-fibrotic signaling pathways in the myocardium. Results. The chronic kidney injury in the applied models corresponded to human CKD grade 1–2 and was accompanied by lower bone turnover with no increase in fibroblast growth factor 23 and parathyroid hormone levels. Myocardial remodeling was characterized by interstitial and perivascular fibrosis, thickening of the intramyocardial artery media, cardiomyocyte hypertrophy and tissue retention of phosphorus. The differences in the expression profiles included genes related to cell differentiation (Lgr4, Dkk1, Sfrp2), vascularization (Jag1, Fzd2, Ptch1, Bmp4) and fibrosis (Hes1, Jag1, Mapk1/3, Ctnnb1), hypertrophy (Mapk1/3, Hes1, Jag1, Ctnnb1, Ppp3ca) and Pi balance (Ankh, Mapk1/3, Ppp3ca). Conclusion. The early stages of myocardial and vascular remodeling in CKD-MBD are associated with lower bone turnover and myocardial phosphorus accumulation concurrently with altered myocardial gene expression of pathways related to Pi metabolism, vascularization, fibrosis and hypertrophy.

59-66 8
Abstract

Introduction. Microcirculation disorders accompanying the inflammatory response to periodontopathogenic microflora are a key element in the pathogenesis of periodontitis. The complex therapy of periodontitis includes the administration of antibacterial and anti-inflammatory drugs, which can be optimized through modern microencapsulation technologies that allow creating dosage forms combining different classes of drugs. In this regard, optimization of the ratio of antibacterial and antiinflammatory agents in multi-target drugs is of not only scientific but also practical interest. The aim of the study was to investigate the effect of a range of experimental gel samples with different ratios of microcapsules containing anti-inflammatory and antibacterial substances on the state of the gingival microcirculatory bed in animals with experimental periodontitis. Materials and methods. The studies were carried out on 50 white rats. The experimental design involved dividing all animals into several groups: control (rats with intact gingiva); comparison group (animals with experimental periodontitis); experimental groups № 1, № 2, № 3 (rats with experimental periodontitis treated with a gel containing microcapsules with AgNPs loaded with an equal ratio of tannic acid and metronidazole (1:1), a predominance of capsules with tannic acid (2:1) and a predominance of metronidazole capsules (1:2), respectively). Periodontitis was modeled using the ligature method by suturing a polyfilament non-absorbable thread into the gums in the area of the lower jaw incisors. The state of the microcirculation in all presented groups was assessed using laser Doppler flowmetry after removal of the ligature on the 21st day of the experiment. Results. It has been established that gel applications containing an equal amount of active substances effectively reduce the increased perfusion rate by 30% and partially correct the parameters of active and passive blood flow modulation in rats with experimental periodontitis. A gel with a predominance of antibacterial components reduces the perfusion index by 23%, but does not ensure the restoration of active and passive modulation of gingival blood flow in white rats with experimental periodontitis. The use of the gel, in which the anti-inflammatory component predominates ensures complete restoration of gingival microcirculation in animals with periodontitis. The gel with a predominance of anti-inflammatory components exceeds the analogue with an equal ratio of capsules with active substances in the correction of cardiac oscillations by 39%, as well as the analogue with a predominance of antibacterial components in the effectiveness of perfusion correction by 4%, myogenic by 38%, neurogenic by 27%, respiratory by 1.3 times and cardiac oscillations by 1.4 times. Conclusions. Gels containing microcapsules with tannic acid and metronidazole significantly correct gingival perfusion disorders and its modulation mechanisms in rats with experimental periodontitis. The efficiency of correction of microcirculatory disorders in animals with periodontitis depends on the ratio of antibacterial and anti-inflammatory components in the gel. The use of a gel sample containing capsules with tannic acid and metronidazole in a ratio of 2:1 in rats with experimental periodontitis ensures complete restoration of gingival microcirculation.

67-72 8
Abstract

Objective. To study the biocompatibility, ease of implantation, and mechanical properties of polyimide vascular grafts under experimental conditions on Wistar rats. Materials and methods. We performed nine experiments. Polyimide vascular grafts obtained using electroforming were implanted into the abdominal aorta of rats. Postoperatively, motor activity, temperature, and skin color of the hind limbs of the experimental animals were assessed. After one, three, and six months, the animals were removed from the experiment. A macroscopic assessment of the implantation site was performed to assess capsule formation and expansion at the graft site. A morphological examination of the conduit was then performed, assessing connective tissue capsule growth, neointimal formation, and the severity of the inflammatory response. Results. During surgery, the graft proved easy to suture (no cutting through, optimal suture tightening), and the anastomoses were leak-tight. In all nine cases, motor activity, temperature, and skin color of the lower limbs of the experimental animals were consistent with those of healthy rats. Morphological examination revealed neointimal formation in all cases. The implanted grafts remained patent throughout the observation period, and no aneurysmal dilation was observed. One animal, withdrawn after one month, and two animals, withdrawn after three months, showed the appearance of calcifications at the border of the prosthesis and neointima, which may indicate a low rate of native aortic tissue ingrowth into the graft wall. A moderate immune reaction to implantation was observed. A connective tissue capsule consisting of collagen fibers formed outside the graft, within which blood vessels were visible. Conclusion. Polyimide grafts appear promising and warrant further investigation.

73-81 9
Abstract

Introduction. The histological structure of the small terminal venous vessels in the cranial and caudal segments of the left lung and their innervation remain poorly studied. The aim of this study was to investigate the histological and immunohistochemical structure of the pulmonary vein wall in rats. Materials and Methods. The object of the study was the left lung (LL) of Wistar rats weighing 200–250 g (n=10). The pulmonary vein (PV) of Wistar rats was examined, from its distal sections to its entry into the left atrium. The material was fixed in zinc-ethanol-formaldehyde solution and embedded in paraffin. Paraffin sections (5 μm) were made using a rotary microtome. After deparaffinization, immunohistochemical (IHC) reactions were performed on the sections to detect neural markers: synaptophysin, tyrosine hydroxylase, and PGP 9.5 protein. An IHC reaction for sarcomeric actin was used to identify muscle cells. Results. The rat PV media was shown to contain two types of muscle tissue: cardiac muscle and a thinned subendothelial layer of smooth muscle cells (SMCs). In the caudal part of the LL, most lateral branches of the PV have a muscular wall consisting of an uneven thin layer of smooth muscle fibers. This work describes the cytoarchitecture of venous capillaries located in the parenchyma of the respiratory region. The structure and topography of smooth muscle sphincters characteristic of branches of thin-walled pulmonary veins with a lumen diameter from 25 to 50 μm were studied. A predominance of parasympathetic innervation in the cranial segment of the cardiac muscle of the vessel wall was noted. Sympathetic innervation of the PV is carried out by a thin plexus of catecholaminergic postganglionic terminal varicose axons localized between the myocardial “sheath” and the thinned smooth muscle layer of the vascular intima. The caudal extent of this layer is limited by the boundaries of the sheath itself. A lack of neural structures was noted around thinwalled venous capillaries equipped with smooth muscle sphincters, as well as in septa and acini. Conclusion. IHC reaction for sarcomeric actin allows the study of both cardiomyocytes and smooth muscle cells in the lung. Structural features of the venous wall in the cranial and caudal regions of the rat left lung and differences in their innervation are described. The results are summarized in a diagram and may be of interest to physiologists, surgeons, and clinicians studying cardiopulmonary pathology.



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ISSN 1682-6655 (Print)
ISSN 2712-9756 (Online)