Hemodynamic Disturbances Research Articles

Bicuspid Aortic Valve: Morphology, Clinic, Diagnosis, Complications

Bicuspid aortic valve refers to common (0.5-2% of the population) congenital heart defects that are asymptomatic throughout life, with valve dysfunction and/or aortopathy (pathia- from Greek pathos disease), manifested by expansion, aneurysm or dissection of the vessel. The pathogenesis of the formation of a bicuspid valve is unknown, a genetic component is noted, since the defect develops as sporadic, familial, in combination with other congenital heart defects and with hereditary connective tissue disorders. Morphogenetic studies suggest that different phenotypes of bicuspid aortic valve can be considered as etiologically different diseases, with valve dysfunction or valve dysfunction and aortopathy. Aortic lesion is characterized by phenotypic heterogeneity due to genetic or hemodynamic features. Researchers are discussing the relationship between the phenotype of the bicuspid aortic valve and aortopathy to predict the course of the disease and select the optimal surgical treatment technique. Diagnosis of heart disease is based on the results of an echocardiographic study, magnetic resonance imaging. Surgical treatment is performed for significant hemodynamic disturbances resulting from insufficiency or stenosis of the aortic valve, in cases of infective endocarditis, the risk of which is high, with aneurysm or aortic dissection.

The state of the cardiovascular system in occupational bronchitis and chronic obstructive pulmonary disease, not associated with the impact of harmful industrial factors

The formation and progression of chronic dust bronchitis and chronic bronchitis of toxic-chemical etiology, chronic obstructive pulmonary disease is accompanied by an increase in the degree of ventilation disorders, echocardiographic signs of hypertrophy and dilatation of the right ventricle are formed, typical for chronic pulmonary heart disease. The progression of disturbances in the function of external respiration in dusty lung diseases leads to a decrease in myocardial contractility. The detection of hemodynamic disturbances at the early stages of the development of occupational lung diseases indicates the need for individual monitoring of the functional state of the cardiovascular system in the process of contact with industrial aerosols, especially in groups of workers with long-term exposure.

The baroreflex in aquatic and amphibious teleosts: Does terrestriality represent a significant driving force for the evolution of a more effective baroreflex in vertebrates?

All vertebrates have baroreflexes that provide fast regulation of arterial blood pressure (PA) to maintain adequate tissue perfusion and avoid vascular lesions from excessive pressures. The baroreflex is a negative feedback loop, where altered PA results in reciprocal changes in heart rate (fH) and systemic vascular conductance to restore pressure. In terrestrial environments, gravity usually leads to blood pooling in the lower body reducing venous return, cardiac filling, cardiac output and PA. Conversely, in aquatic environments, the hydrostatic pressure of surrounding water mitigates blood pooling and prevents vascular distensions. In this context, we aimed to test the hypothesis that vertebrate species that were exposed to gravity-induced hemodynamic disturbances throughout their evolutionary histories have a more effective barostatic reflex than those that were not. We examined the cardiac baroreflex of fish that perform (Clarias gariepinus and Hoplerythrinus unitaeniatus) and do not perform (Hoplias malabaricus and Oreochromis niloticus) voluntary terrestrial sojourns, using pharmacological manipulations of PA to characterize reflex changes in fH using a four-variable sigmoidal logistic function (i.e. the “Oxford technique”). Our results revealed that amphibious fish exhibit higher baroreflex gain and responsiveness to hypotension than strictly aquatic fish, suggesting that terrestriality and the gravitational circulatory stresses constitute a relevant driving force for the evolution of a more effective baroreflex in vertebrates. We also demonstrate that strictly aquatic teleosts have considerable baroreflex gain, supporting the view that the baroreflex is an ancient cardiovascular trait that appeared before vertebrates colonized the gravity-dominated realm of land.

Non-Selective Cation Currents Mediated by Cx43 Hemichannel-P2X4 Receptor Signaling Pathway in Rat Atrial Myocytes under Shear Stress

Cardiac myocytes are exposed to shear stress under physiological conditions and hemodynamic disturbances. Shear stress has been thought to trigger two distinct global Ca2+ waves in atrial myocytes through autocrine activation of P2X4 receptor (P2X4R) and P2Y1-receptor (P2Y1R) via connexin 43 (Cx43)-mediated ATP release. In this study, we examined whether such shear stress-triggered Cx43-ATP-P2 receptor signaling generates depolarizing currents in atrial myocytes. Whole-cell patch clamp and dye-flux assays were used with genetic and pharmacological interventions in rat atrial myocytes and HL-1 cells. We found that shear stress activated a non-selective inward cation (Cs+) current (IS,Cs) at resting potential which was eliminated by Cx43 blockade using siRNA, antibodies, carbenoxolone or La3+. IS,Cs was enhanced by removal of external Ca2+, whereas internal Ca2+ buffering suppressed IS,Cs. Hemichannel-mediated dye (calcein red-orange) flux was induced by shear stress. This response was augmented by removing external Ca2+ but was not affected by pannexin blocker (probenecid). The shear-activated current was significantly reduced when Cs+ was replaced with NMDG+, and this was enhanced by quinine and suppressed by La3+. P2X4R antagonists (5-BDBD and PSB-12054), P2XR-blocker (iso-PPADS) and anti-P2X4R antibodies each blocked IS,Cs by approximately 50%. About 25% of IS,Cs was suppressed by P2Y1R inhibitor (MRS2179) and/or transient receptor potential melastatin 4 blocker (9-phenanthrol). P2X4R, but not P2X5R, was co-localized with Cx43 at the cell ends. P2X4R-dependent IS,Cs was augmented in atrial myocytes from hypertrophied rat hearts by short-term aortic constriction. Our data suggest that shear stress triggers Cx43 hemichannels to gate P2X4Rs in their vicinity. This shear stress signaling may play an important role in membrane depolarization at negative potentials and in atrial remodeling under increased afterload.

Computational Modeling of Blood Flow Hemodynamics for Biomechanical Investigation of Cardiac Development and Disease.

The heart is the first functional organ in a developing embryo. Cardiac development continues throughout developmental stages while the heart goes through a serious of drastic morphological changes. Previous animal experiments as well as clinical observations showed that disturbed hemodynamics interfere with the development of the heart and leads to the formation of a variety of defects in heart valves, heart chambers, and blood vessels, suggesting that hemodynamics is a governing factor for cardiogenesis, and disturbed hemodynamics is an important source of congenital heart defects. Therefore, there is an interest to image and quantify the flowing blood through a developing heart. Flow measurement in embryonic fetal heart can be performed using advanced techniques such as magnetic resonance imaging (MRI) or echocardiography. Computational fluid dynamics (CFD) modeling is another approach especially useful when the other imaging modalities are not available and in-depth flow assessment is needed. The approach is based on numerically solving relevant physical equations to approximate the flow hemodynamics and tissue behavior. This approach is becoming widely adapted to simulate cardiac flows during the embryonic development. While there are few studies for human fetal cardiac flows, many groups used zebrafish and chicken embryos as useful models for elucidating normal and diseased cardiogenesis. In this paper, we explain the major steps to generate CFD models for simulating cardiac hemodynamics in vivo and summarize the latest findings on chicken and zebrafish embryos as well as human fetal hearts.

Effect of left atrial ligation-driven altered inflow hemodynamics on embryonic heart development: clues for prenatal progression of hypoplastic left heart syndrome

Congenital heart defects (CHDs) are abnormalities in the heart structure present at birth. One important condition is hypoplastic left heart syndrome (HLHS) where severely underdeveloped left ventricle (LV) cannot support systemic circulation. HLHS usually initiates as localized tissue malformations with no underlying genetic cause, suggesting that disturbed hemodynamics contribute to the embryonic development of these defects. Left atrial ligation (LAL) is a surgical procedure on embryonic chick resulting in a phenotype resembling clinical HLHS. In this study, we investigated disturbed hemodynamics and deteriorated cardiac growth following LAL to investigate possible mechanobiological mechanisms for the embryonic development of HLHS. We integrated techniques such as echocardiography, micro-CT and computational fluid dynamics (CFD) for these analyses. Specifically, LAL procedure causes an immediate flow disturbance over atrioventricular (AV) cushions. At later stages after the heart septation, it causes hemodynamic disturbances in LV. As a consequence of the LAL procedure, the left-AV canal and LV volume decrease in size, and in the opposite way, the right-AV canal and right ventricle volume increase. According to our CFD analysis, LAL results in an immediate decrease in the left AV canal WSS levels for 3.5-day (HH21) pre-septated hearts. For 7-day post-septated hearts (HH30), LAL leads to further reduction in WSS levels in the left AV canal, and relatively increased WSS levels in the right AV canal. This study demonstrates the critical importance of the disturbed hemodynamics during the heart valve and ventricle development.

Hemodynamic disturbances and oliguria during continuous kidney replacement therapy in critically ill children.

About 1.5% of patients admitted to the Pediatric Intensive Care Unit (PICU) will require continuous kidney replacement therapy (CKRT)/renal replacement therapy (CRRT). Mortality of these patients ranges from 30 to 60%. CKRT-related hypotension (CKRT-RHI) can occur in 19-45% of patients. Oliguria after onset of CKRT is also common, but to date has not been addressed directly in the scientific literature. A prospective observational study was conducted to define factors involved in the hemodynamic changes that take place during the first hours of CKRT, and their relationship with urinary output. Twenty-five patients who were admitted to a single-center PICU requiring CKRT between January 1, 2014, and December 31, 2018, were included, of whom 56.3% developed CKRT-RHI. This drop in blood pressure was transient and rapidly restored to baseline, and significantly improved after the third hour of CKRT, as core temperature and heart rate decreased. Urine output significantly decreased after starting CKRT, and 72% of patients were oliguric after 6h of therapy. Duration of CKRT was significantly longer in patients presenting with oliguria than in non-oliguric patients (28.7 vs. 7.9days, p = 0.013). The initiation of CKRT caused hemodynamic instability immediately after initial connection in most patients, but had a beneficial effect on the patient's hemodynamic status after 3h of therapy, presumably owing to decreases in body temperature and heart rate. Urine output significantly decreased in all patients and was not related to negative fluid balance, patient's hemodynamic status, CKRT settings, or kidney function parameters.

Middle cerebral artery pressure laterality in patients with symptomatic ICA stenosis.

An internal carotid artery (ICA) stenosis can potentially decrease the perfusion pressure to the brain. In this study, computational fluid dynamics (CFD) was used to study if there was a hemispheric pressure laterality between the contra- and ipsilateral middle cerebral artery (MCA) in patients with a symptomatic ICA stenosis. We further investigated if this MCA pressure laterality (ΔPMCA) was related to the hemispheric flow laterality (ΔQ) in the anterior circulation, i.e., ICA, proximal MCA and the proximal anterior cerebral artery (ACA). Twenty-eight patients (73±6 years, range 59–80 years, 21 men) with symptomatic ICA stenosis were included. Flow rates were measured using 4D flow MRI data (PC-VIPR) and vessel geometries were obtained from computed tomography angiography. The ΔPMCA was calculated from CFD, where patient-specific flow rates were applied at all input- and output boundaries. The ΔPMCA between the contra- and ipsilateral side was 6.4±8.3 mmHg (p<0.001) (median 3.9 mmHg, range -1.3 to 31.9 mmHg). There was a linear correlation between the ΔPMCA and ΔQICA (r = 0.85, p<0.001) and ΔQACA (r = 0.71, p<0.001), respectively. The correlation to ΔQMCA was weaker (r = 0.47, p = 0.011). In conclusion, the MCA pressure laterality obtained with CFD, is a promising physiological biomarker that can grade the hemodynamic disturbance in patients with a symptomatic ICA stenosis.

Prediction of reactivity during tracheal intubation by pre-laryngoscopy tetanus-induced ANI variation.

The ANI is a nociception monitor based on the high frequency parts of heart rate variability. Tracheal intubation may induce potentially deleterious hemodynamic disturbances or motor reactions if analgesia is inadequate. We investigated whether ANI modification generated by a standardized moderate short tetanic stimulation performed before laryngoscopy could predict hemodynamic or somatic reactions to subsequent intubation. We designed a prospective, interventional, monocentric, pilot study. Regional ethics board approved the study, written informed consent was obtained from each participant. Before laryngoscopy, under steady-state total intravenous anaesthesia with propofol and remifentanil, the ulnar nerve was stimulated with a 5s tetanus (70mA, 50Hz). After another steady-state period, orotracheal intubation was performed. ANI variation, hemodynamic parameters and somatic reactions associated with tetanus and intubation were collected. To assess the predictability of hemodynamic or somatic reaction during laryngoscopy by tetanus-induced ANI variation, we calculated the area under the corresponding Receiver Operating Characteristic curve (AUCROC) and the 95% confidence intervals. Thirty-five patients were analyzed. ANI decreased by 21 ± 17 after tetanus. Regarding the ability of tetanus-induced ANI variation to predict hemodynamic or somatic reactions during subsequent intubation, the AUCROCs [95% CI] were 0.61 [0.41-0.81] and 0.52 [0.31-0.72] respectively. ANI varied after a short moderate tetanic stimulation performed before laryngoscopy but this variation was not predictive of a hemodynamic or somatic reaction during intubation.Trial registration NCT04354311, April 20th 2020, retrospectively registered.

MORPHOLOGICAL JUSTIFICATION OF THE SALIVARY GLAND TISSUE RESECTION BOUNDARIES DURING SURGICAL TREATMENT OF PATIENTS WITH PLEOMORPHIC ADENOMAS

The aim is to substantiate morphologically the resection boundaries of the salivary gland tissue in the surgical treatment of patients with pleomorphic adenoma of different histological variants. Materials and methods: The study used autopsy, surgical and biopsy material, divided into 2 groups. Group 1 included autopsy material (n=6), represented by tissue fragments of the parotid salivary gland, in which macroscopic and microscopic examination did not reveal any general pathological processes. Group 2 included surgical and biopsy material from 30 patients, represented by pleomorphic adenomas with adjacent tissue of the salivary gland at a distance of 0.5 cm and 1.0 cm. Histological, morphometric and statistical research methods were used. Results: The morphological features of the salivary gland tissue which was adjacent to the pleomorphic adenoma at a distance of 1.0 cm, practically corresponded to the physiological norm. However, the tissue of the salivary gland, bordering the tumor at a distance of 0.5 cm, was characterized by pronounced changes. These changes were: violation of the ratio of the specific volumes of the parenchyma and stroma; atrophy of the terminal sections and ducts with cystic expansion of some ducts; thickening of the secretion and formation of calculi in the lumen of some ducts; atrophic and alterative changes in the epithelial lining the terminal sections and ducts; sclerosis and lipomatosis, areas with hyalinosis and dystrophic calcification in the stroma; hemodynamic disturbances in the stroma with a decrease in the number of vessels; pronounced focal or diffuse immune infiltration in the stroma in some areas with the lymphoid follicles formation. Conclusion: The comprehensive study has confirmed that removal of the tumor with the adjacent tissue of the salivary gland at a distance of 1.0 cm in patients with pleomorphic adenoma of various histological variants is the most justified from the morphological point of view.

Snake Bite Presenting as Haemolytic Uremic Syndrome: A Rare Case Report

Snake bite is predominantly an occupational hazard and causes severe health issues. Snake poisoning in India is a significant and prevalent cause of Acute Kidney Injury (AKI). In India, the occurrence of AKI after snake bite is 13-32%. All over the world every year, 1,50,000 people die as a result of it. Multiple mechanisms such as haemodynamic disturbances, direct tubular toxicity, coagulopathy, haemoglobinuria, and myoglobinuria can cause AKI after bites by snakes belonging to the Elapidae, Viperidae, and Colubridae families. Renal pathologic findings include acute tubular necrosis, cortical necrosis, interstitial nephritis, glomerulonephritis, and vasculitis. Thrombotic Microangiopathy (TMA) as a cause of snakebite-induced AKI is rarely reported in literature. Fewer details are known about the clinical course, optimal management, and overall prognosis of this entity. Haemolytic Uremic Syndrome (HUS) is a clinical disease that includes TMA, thrombocytopenia, and AKI as a triad. The HUS is a heterogeneity of illnesses with diverse aetiology which results in presentation, therapy and outcomes variance. Hereby, authors report a case of a 55-year-old female who was bitten by Russell’s viper and developed HUS. Patient eventually progressed to end stage renal disease and was advised lifelong haemodialysis. TMA should be taken into account as a probable cause of AKI following a snake bite. Plasma exchanges have yet to be determined in snake bite TMA.

Safety of Conscious Sedation/Analgesia for Dentistry; A Comparison of Midazolam/Fentanyl Vs Promazine/Meperidine

The anesthesia charts of adult patients undergoing dental surgery lasting >1 h (sinus lift, multiple implants, multiple wisdom teeth extractions) were retrospectively analyzed comparing meperidine/promazine (MEPPROM, 93 cases, 2018-20) to midazolam/fentanyl (MIDFENT, 415 cases, 2011-2020). Patients signed an informed consent, completed a health questionnaire; afer diazepam premedication and full monitoring sedation started with midazolam 1-2 mg: the group MEPPROM received the mixture according to weight, the group MIDFENT received additional midazolam and fentanyl 25-50 microgr. Midazolam for sedation or fentanyl for analgesia was allowed in both groups on demand, aiming at Ramsay score 2-3. Dental anesthesia (articaine or mepivacaine + epinephrine) followed, repeated as needed. The study variables were collected every 5 minutes on specially designed sheets:oxygen desaturation (<90%), brady/tachycardia (<50, >120 bpm), hyper/hypotension (>180, <90 mmHg systolic or >30% difference versus basal), sleep (Ramsay score 4), hypercapnia (etCO2> 40 mmg), nausea, vasovagal reactions, arrhythmias. Age (59), weight (KG 70), height (cm 167). ASA class (1-3), sex were equally distributed between the 2 groups; surgery was longer in the MEPPROM group (148 min vs 118) (averages). Hypertension incidence was similar, but 40 MIDFENT patients received clonidine vs 1 in the MEPPROM. Frequence (%) of hypotension (20 vs 2), tachycardia (15 vs 1), bradycardia (11 vs 4) were always greater in the group MEPPROM. Incidence of desaturation, hypercapnia, excessive sedation were similar. Side effects did not differ:nausea (2 MEPPROM, 4 MIDFENT but with frequent use of haloperidol), vasovagal syndromes (2 MEPPROM, 5 MIDFENT). All patients were discharged within 1 hr after surgery. Under careful titration MEPPROM offer clinical conditions similar to the established MIDFENT routine; however haemodynamic disturbances are more frequent and call for expert vigilance and continuous monitoring of vital signs.

Analgesic Efficacy of Perioperative Esmolol as an Adjunct to Morphine in Mastectomy- A Prospective Observational Study

Introduction: Multimodal analgesia with opioids as the prime component is the mainstay of postoperative analgesia for mastectomy, which can lead to many opioid related unwanted side-effects. Esmolol infusion has been found as a useful adjunct in reducing opioid requirements. Aim: To find the effect of perioperative esmolol infusion on postoperative pain and opioid requirements. Materials and Methods: This prospective observational study was done in 140 American Society of Anaesthesiologists (ASA) physical status l and ll patients, between 20-65 years of age posted for mastectomy under general anaesthesia. Esmolol group (group E) received 0.25 mg/kg of esmolol bolus ten minutes before induction followed by continuous infusion 5 μg/kg/min till end of surgery while control group (group C) received equivalent volumes of saline. Primary outcome measures were Numerical Rating Scale (NRS) for pain, total postoperative opioid consumption and time to first rescue analgesic dosage till 24 hours. Intraoperative haemodynamics and other side-effects were secondary outcomes. Descriptive statistics of numerical rating scores and analgesic requirements were analysed in terms of mean and standard deviation. Independent t-test was used to compare numerical rating scores and analgesic requirement of the two groups. A p-value of &lt;0.05 was considered statistically significant. Results: The mean numerical pain scores were significantly lower in the esmolol group for the first 24 hour. The mean time to first rescue analgesic was 17.59±5.012 hour in the esmolol group and 8.21±2.22 hour in the control group which was statistically significant (p&lt;0.001). The total tramadol consumption was also significantly lesser in the esmolol group (42.14±29.03 mg), compared to control group (102.86±22.3 mg), (p=0.0001). Mean heart rate was statistically lower in the esmolol group, but there was no incidence of bradycardia requiring treatment. Mean Arterial Pressures (MAP) were comparable. Conclusion: Perioperative esmolol infusion when used as an adjunct to morphine decreased postoperative pain and analgesic requirements for the first 24 hours without any haemodynamic disturbances.

Genetic Factors as the Basis of Sex Differences in Damage to Lung Endothelium and Regulation of Angiogenesis Cells in Modeling Pulmonary Emphysema in C57BL/6 Mice with Dyslipidemia and Hyperglycemia.

We studied the formation of injuries in lung endothelium and the response of angiogenesis cells during modeling of pulmonary emphysema in male and female C57BL/6 mice with metabolic disorders. Hemodynamic disturbances and reduction in the area of the microvasculature caused by combined pathology in male mice were more pronounced than in females. Mobilization and migration of angiogenic precursors were impaired in both male and female mice. In males, activity of recruiting endothelial progenitor cells, vascular smooth muscle cells, luminal cells of nascent vessels and pericytes into the lungs was additionally reduced. In females, accumulation of endothelial progenitor cells (CD45-CD31+CD34+), vascular smooth muscle cells, and pericytes in the lungs was observed, which indicated activation of endothelial regeneration. Sex differences in the reaction of the lung endothelium and angiogenesis cells can be explained by genetic factors of lipid and glucose metabolism.

The role of the muscular system in the pathogenesis of thrombotic complications of the lower extremities in cancer patients

Introduction. Thrombosis occurs in 15 % of cancer patients, most of these thrombosis is localized in the venous system of the lower extremities. In addition to biological and chemical factors that increase thrombosis, changes in the muscles of the lower extremities play an important role. Disorders of hemodynamic and metabolic processes in the muscles of the lower extremities lead to morphological changes and increase the risk of thrombosis in cancer patients. The aim of the study. Investigate morphological changes in the muscles of the lower extremities and evaluate their role in the formation of thrombosis in cancer patients. Materials and methods. Histological examination of 90 patients, which were divided into four groups depending on the location of the cancer process and the cause of death. The first group A – 34 patients with colon cancer, the second group B – 20 patients with pancreatic cancer, patients from these groups died as a result of thromboembolism. Group B – 19 patients, and group G – 17 patients - people whose cause of death was not thromboembolism. The analysis of biomaterial by means of histological and polarization methods of research is carried out. Additionally, electron microscopy of the obtained biopsy materials was performed. The number of citrate blood endothelial cells was determined in all subjects according to the method of J. Hladovez. Research results and their discussion. The study revealed a large number of morphological changes in blood vessels and muscle fibers. The data obtained indicate that patients with cancer of the pancreas and colon have significant changes in the endothelial lining of the venules and areterioles. All cells have signs of interstitial edema, changes in organelles and signs of hemodynamic disturbances. In some areas, there were complete atrophy of some muscle fibers and compensatory hypertrophy of others. Studies have shown areas of sarcoplasmic homogenization and myocytolysis. Conclusions. In the case of cancer of the pancreas or/and colon, there is significant damage to the endothelium of the vessels of the lower extremities, there are dystrophic-atrophic changes in the muscles with impaired function. Cells suffer from interstitial and perivascular edema, there are contractures of change, myocytolysis. Morphological changes lead to disruption of their function of damage, myocytolysis and remodeling of muscle fibers. The result is an increased risk of thrombosis with subsequent thrombus consideration and a possible risk of pulmonary embolism.

TREATMENT OF MYASTHENIA GRAVIS PATIENTS WITH COVID-19: REVIEW OF THE LITERATURE.

SUMMARYCoronavirus disease 2019 (COVID-19), caused by the late 2019 outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causes a respiratory disease which could put myasthenia gravis (MG) patients at a greater risk of developing severe disease course, since infections and some drugs are a well-recognized trigger of symptom exacerbation in MG patients. Out of ten most commonly used past and present drugs used in COVID-19 treatment, two (quinolone derivatives and azithromycin) are known to worsen MG symptoms, whereas another two (tocilizumab and eculizumab) might have positive effect on MG symptoms. Colchicine, remdesivir, lopinavir, ritonavir and favipiravir seem to be safe to use, while data are insufficient for bamlanivimab, although it is also probably safe to use. Considering MG treatment options in patients infected with SARS-CoV-2, acetylcholine esterase inhibitors are generally safe to use with some preliminary studies even demonstrating therapeutic properties in regard to COVID-19. Corticosteroids are in general safe to use, even recommended in specific circumstances, whereas other immunosuppressive medications (mycophenolate mofetil, azathioprine, cyclosporine, methotrexate) are probably safe to use. The only exception is rituximab since the resulting B cell depletion can lead to more severe COVID-19 disease. Concerning plasmapheresis and intravenous immunoglobulins, both can be used in COVID-19 while taking into consideration thromboembolic properties of the former and hemodynamic disturbances of the latter. As current data suggest, all known COVID-19 vaccines are safe to use in MG patients.

The Nature of Changes in the Hemostatic System in Liver Cirrhosis

The nature of violations of the hemostatic system in liver cirrhosis is complex, often unpredictable and concerns all its links – vascular-platelet, coagulation and fibrinolysis. It is now well established that patients with cirrhosis may experience both bleeding and thrombosis. The mechanisms of blood clotting disorders in this case are very complex, since defects simultaneously occur both in the procoagulant system and in the anticoagulation system. Aim to study the factors and mechanism of the development of hemostasis imbalance in patients with liver cirrhosis based on the analysis of scientific literature, to determine the information content of existing laboratory tests for the study of hemostasis and the features of correction of hemostasis disorders depending on hyper- or hypocoagulation. It is generally accepted that cirrhosis results in a state of hypocoagulation with an increased tendency to bleeding. However, a number of publications do not support this opinion, and the interpretation of laboratory parameters is explained by the standard methodology, where the procoagulant and antifibrinolytic systems of hemostasis are insufficiently studied. Many researchers have established a state of hypercoagulability in liver cirrhosis, leading to intra- and extrahepatic thrombosis. The cause of bleeding, primarily from varicose veins of the esophagus and stomach, is not hypocoagulation as such, but rupture of varices due to hemodynamic disturbances with increased portal pressure, one of which is thrombosis. Accordingly, therapeutic tactics should be aimed, first of all, not at normalizing laboratory tests, but at eliminating the pathogenetic mechanisms of hemostatic imbalance that occur in liver cirrhosis. At the same time, drug correction should be directed not at individual links of the hemostasis system - pro or anticoagulant, but at the correction of hemostatic imbalance as a whole. Conclusions. To date questions about the nature of changes in the hemostasis system in liver cirrhosis, their relationship with hemorrhagic complications or thrombosis, the principles of drug correction remain open, requiring further research in this direction.

Autoimune component in the development of celebrovascular insufficiency in children with bronchial asthma

Bronchial asthma (BA) remains one of the most serious diseases of our time. A number of studies have shown that this disease in a number of cases, especially with the threat of termination of pregnancy, acute and chronic diseases of mothers, accompanied by fetal hypoxia, originates in the ante- and postnatal period. In general, taking into account the peculiarities of the cellular tissue organization of the brain and cerebrovascular blood supply, prolonged hypoxic lesions increase the activity of the hypothalamic-diencephalic structures and the cerebral cortex. The existing respiratory disorders lead to hemodynamic and metabolic disorders of cerebral structures, emotional sphere and autonomic regulation. However, this issue in childhood requires further study. The aim is to study autoimmune processes in the pathogenesis of cerebrovascular insufficiency in children with BA. Materials and methods. We examined 121 patients with asthma aged 5 to 15 years in the period of exacerbation. To study the role of the autoimmune component in the development of cerebrovascular insufficiency and its relationship with the autoimmune process in the bronchopulmonary system in AD in children, we used a method for the quantitative determination of autoantibodies to lipopolysaccharide antigens (LA) of cerebral vessels and topographic structures of the brain, as well as to homologous LA bronchi and lung tissue. The results of the studies have shown that the first signs of cerebral hemodynamic disturbance are recorded already in patients with mild disease and are aggravated depending on the severity of BA. Conclusions. The most characteristic changes are an increase in the tone of small and medium vessels and impaired cerebral venous circulation. It was also found that the levels of autoantibodies to lipopolysaccharide antigens of cerebral vessels and cellular tissue structures of the brain correlate with an increase in the level of autoantibodies to lipopolysaccharide antigens of the trachea, bronchi and lung tissue and reflect the severity of AD in children.

Mechanical forces and metabolic changes cooperate to drive cellular memory and endothelial phenotypes.

Endothelial cells line the innermost layer of arterial, venous, and lymphatic vascular tree and accordingly are subject to hemodynamic, stretch, and stiffness mechanical forces. Normally quiescent, endothelial cells have a hemodynamic set point and become "activated" in response to disturbed hemodynamics, which may signal impending nutrient or gas depletion. Endothelial cells in the majority of tissue beds are normally inactivated and maintain vessel barrier functions, are anti-inflammatory, anti-coagulant, and anti-thrombotic. However, under aberrant mechanical forces, endothelial signaling transforms in response, resulting cellular changes that herald pathological diseases. Endothelial cell metabolism is now recognized as the primary intermediate pathway that undergirds cellular transformation. In this review, we discuss the various mechanical forces endothelial cells sense in the large vessels, microvasculature, and lymphatics, and how changes in environmental mechanical forces result in changes in metabolism, which ultimately influence cell physiology, cellular memory, and ultimately disease initiation and progression.

Prognostic value of computed tomographic perfusion in the diagnosis of liver fibrosis and cirrhosis. Pilot study

Relevance: Most diffuse liver diseases lead to fibrosis over time with the risk of cirrhosis. With progressive fibrosis and cirrhosis of the liver both physical properties of the hepatic parenchyma and its hemodynamics change. The only reliable method for determining the stage of the disease is puncture biopsy and subsequent histological examination, but this method is invasive and associated with complications. Currently, the determination of the severity of cirrhosis is based on clinical data (the Child-Pugh scale) and elastography is considered to be the main non-invasive instrumental method. It lets reliably differentiate the initial fibrosis and cirrhosis of the liver, while the F2 and F3 stages according to the conventional METAVIR scale remain a "gray zone", as well as the differentiation of degrees of the severity of cirrhosis. In addition elastography has a number of limitations. The main ones of which are operator dependence, apparatus dependence and the inability to determine functional changes in the liver. With the use of perfusion computed tomography (CT perfusion) it is possible to assess the functionality of the liver by quantifying changes in hemodynamics. The method applied measures the characteristics of blood flow in the tissue at a given scanning level by computed-tomographic data on the dynamics of the distribution of the contrast agent in the area of interest is collected, besides the type of liver perfusion is determined. This parameter is needed to assess the dynamics of treatment against the background of drug therapy.Objective: To identify statistically significant parameters of CT perfusion to determine the severity of hemodynamic disturbances in patients with various stages of liver fibrosis and cirrhosis and to compare the values of parameters of liver CT perfusion with fibrosis according to the METAVIR conditional scale determined using elastography.Materials and methods: 18 patients were included in this parallel pilot study. On the basis of clinical and laboratory data and the results of elastography, 10 of them were diagnosed with fibrosis and cirrhosis. The stages of fibrosis F1, F2 were determined in 3 patients; stages F3, F4 – in 7. In the group of patients with F3, F4, according to the METAVIR conditional scale, subgroups were distinguished depending on the severity of cirrhosis: compensated – 3 patients, subcompensated – 2, decompensated – 2. The control group consisted of 8 patients with organ diseases abdominal cavity not associated with liver damage. All patients underwent CT perfusion of the liver on a Philips iCT 256 using the following scan parameters: 80 KVp, 120 mAc, total scan time 56 s, and slice thickness 5.0 mm. Intravenously, bolus was administered to all patients with 50 ml of ioversol 350 mg/ml, the rate of administration was 3.8–4.0 ml/s, the time from the moment of administration of the contrast medium to the start of scanning was 6 s. After receiving a series of images, the data was processed on a Philips workstation. Quantitative analysis was carried out according to the following indicators: TTP (time to peak, s), BV (blood volume, ml/100 g), AP (arterial perfusion, ml/min/100 ml), PP (portal perfusion, ml/min/100 ml), TP (total perfusion, ml/min/100 ml) and HPI (hepatic perfusion index, %).Results: In the control group of 8 patients, the perfusion values were: TTP 37.4±5.2 s, BV 16.1±5.0 ml/100 g, AP 25.0±7.5 ml/min/100 ml, PP 44.5±14.5 ml/min/100 ml, TP 70.1±14.9 ml/min/100 ml, HPI 70.1±14.9%. In 3 patients with F1, F2, according to the METAVIR conditional scale, the following statistically significant values (p&lt;0.039) of perfusion indices were determined: BV 27.2±8.6 ml/100 g, AP 20.0±3.8 ml/min/100 ml; with compensated liver cirrhosis (n=3): TTP 46.2±1.7 s, BV 12.4±1.9 ml/100 g, AP 10.7±2.8 ml/min/100 ml, PP 37.3±5.2 ml/min/100 ml, TP 48.1±3.5 ml/min/100 ml, HPI 22.4±5.5%; subcompensated (n=2): TTP 43.0±3.2 s, BV 8.9±2.6 ml/100 g, AP 12.8±3.0 ml/min/100 ml, PP 27.7±9.0 ml/min/100 ml, TP 40.5±7.3 ml/min/100 ml; decompensated (n=2): BV 30.5±1.8 ml/100 g, PP 8.5±1.5 ml/min/100 ml, HPI 81.3±1.8%.Conclusion: The preliminary results obtained confirm that CT perfusion can be used to predict and assess the severity of hemodynamic disturbances in patients with varying degrees of severity of cirrhosis and supplements clinical, laboratory and elastography data.