This study aims to determine the effectiveness of administering 80 ppm nitric oxide in reducing kidney injury, mitochondrial dysfunction and regulated cell death in kidneys during experimental perfusion. Twenty-four sheep were randomized into four groups: two groups received 80 ppm NO conditioning with 90 min of cardiopulmonary bypass (CPB + NO) or 90 min of CPB and hypothermic circulatory arrest (CPB + CA + NO), while two groups received sham protocols (CPB and CPB + CA). Kidney injury was assessed using laboratory (neutrophil gelatinase-associated lipocalin, an acute kidney injury biomarker) and morphological methods (morphometric histological changes in kidney biopsy specimens). A kidney biopsy was performed 60 min after weaning from mechanical perfusion. NO did not increase the concentrations of inhaled NO₂ and methemoglobin significantly. The NO-conditioning groups showed less severe kidney injury and mitochondrial dysfunction, with statistical significance in the CPB + NO group and reduced tumor necrosis factor-α expression as a trigger of apoptosis and necroptosis in renal tissue in the CPB + CA + NO group compared to the CPB + CA group. The severity of mitochondrial dysfunction in renal tissue was insignificantly lower in the NO-conditioning groups. We conclude that NO administration is safe and effective at reducing kidney injury, mitochondrial dysfunction and regulated cell death in kidneys during experimental CPB.

The changes of epicardial adipose tissue’s (EAT) morphofunctional characteristics represent an important factor of cardiometabolic impairments development. However, factor data determining the severity of EAT adipocytes’ hypertrophy in patients with coronary atherosclerosis are absent in literature.Aim: To compare the size of the EAT adipocyte and the percentage of hypertrophied adipocytes with the parameters of glucose/insulin metabolism, blood lipid transport function, adipokines’ profile and serum levels of high sensitive C-reactive protein (hsCRP) in patients with chronic coronary artery disease (CAD) undergoing coronary artery bypass grafting (CABG); to establish statistically significant determinants of a pronou ced degree of EAT adipocytes’ hypertrophy.Material and Methods. The study included 42 patients (m/f 28/14) aged 53–72 y.o. with CAD, who underwent CABG. The material for the study was EAT adipocytes obtained by the enzymatic method from intraoperative explants. The basal blood levels of glycemia, insulinemia, C-peptide, blood lipid transport function, adipokines and hsCRP were determined. The median indicators of the size of EAT adipocytes and the proportion of EAT adipocytes over 100 μm were 87.32 μm and 14.64%, respectively. The total sample of patients was divided into two groups: gr. 1 with an average size of EAT adipocytes less than or equal to 87.32 μm and gr. 2 with an average size of EAT adipocytes more than 87.32 μm. Gr. 2 had higher body mass index, waist and hip circumferences, triglycerides, hsCRP, and lower adiponectin levels, while the median proportion of hypertrophied adipocytes was three times higher than in group 1. A model of multiple logistic regression was constructed, according to which statistically significant determinants of the pronounced EAT adipocytes’ hypertrophy are represented by the decreased level of adiponectin, and increased concentrations of hsCRP and C-peptide, which reflects the biosynthesis and secretion of insulin. The predictive accuracy of the model was 82%, sensitivity 85%, specificity 79%, AUC = 0.89.Conclusion. Our results indicate a close correlation between the development of EAT adipocytes hypertrophy, impaired production of adiponectin, insulin, and inflammation processes. Concentrations of adiponectin, hsCRP, and basal C-peptide in the blood are biomarkers that accurately determine the presence of EAT adipocyte hypertrophy.

Aim. To study the relationship between the epicardial fat thickness (EFT), biomarkers of inflammation and metabolic dysfunction in patients with coronary artery disease (CAD) and various severity of coronary atherosclerosis.Material and methods. The study consisted of 89 patients (47 men and 42 women) with stable CAD at the age of 62,2±6,5 years, who assessed the presence and severity of coronary atherosclerosis according to angiography with the calculation of the Gensini Score (GS). We conducted an ultrasonic evaluation of the EFT. We determined the content of glucose, lipid fractions, apoproteins, pro-inflammatory cytokines and adipokines, C-reactive protein by a highly sensitive method (hsCRP).Results. In the total sample of patients, the median GS index was 13,5 (3,5; 43) points, the median EFT was 4,93 (3,95; 6,0) mm, the median hsCRP was 2,1 (1,02; 3,65) mg/l. There were no correlation relationships between the GS index and the body mass index, waist circumference, EFT, hsCRP, lipid and carbohydrate metabolism in the general group of patients. In the course of linear regression analysis, an independent contribution of hsCRP >2,1 mg/l to the formation of the first two tertiles of a sample of GS values was established (0≤ GS ≤28, paired linear regression hsCRP at GS β=0,55, p=0,0221), whereas in patients with GS values from the third tertile (GS >28 points), the growth of this parameter had an independent association with an increase in the EFT (estimation of the coefficient of paired linear regression of the EFT on GS β=0,56, p=0,0015). The range of hsCRP changes did not affect the value of the β coefficient in paired linear regression models in patients with GS >28 points (n=29) and in the subgroup of patients with GS >28 and hsCRP >2,1 mg/l (n=18).Conclusion. The absence of an independent association between EFT and minor or moderate severity of atherosclerotic lesions of the coronary arteries (for GS ≤28 points) in patients with CAD, while an independent marker of GS index increase is higher than 2,1 mg/l. An independent contribution to the formation of a severe coronary atherosclerosis (with a GS value of >28 points) is equally made by thickening of EFT, and a moderately elevated level of hsCRP.

Aim . To assess the role of clinical indicators and parameters of stress echocardiography performed according to an extended protocol as predictors for the occurrence of a composite cardiovascular endpoint (CCVEP) in IHD. Material and methods . The study included 186 patients (60.2% men, mean age 60.6±9.9 years) with an established (n=73; 39.2%) and suspected (60.8%) diagnosis of IHD. Stress EchoCG with adenosine triphosphate (38.2%), transesophageal pacing (15.1%), dobutamine (2.6%), and bicycle ergometry on a recumbent ergometer (44.1%) was performed. The stress EchoCG protocol included assessment of regional wall motion abnormalities (WMA), B-lines, LV contractile reserve (CTR), coronary reserve (CR), and heart rate reserve. The median follow-up period was 13 [9; 20] months. The composite CCVEP included death from cardiovascular diseases and their complications, acute coronary syndrome, and revascularization and was defined at the first of these events. Statistical analysis was performed with the Statistica 16.0 and SPSS Statistics 23.0 software packages. Differences were considered statistically significant at p<0.05. Results . Invasive or noninvasive coronary angiography was performed in 90.3% of patients; obstructive coronary disease (stenosis ≥50%) was detected in 67.9% of cases. During the follow-up period, 58 (31.2%) patients had cardiovascular complications. The risk of developing CCVEP was associated with the pretest probability (PTP) of ischemic heart disease (odds ratio, OR, 1.05; 95% confidence interval, CI, 1.02-1.08), dyslipidemia (DLP) (OR 0.40; 95% CI 0.20-0.82), carotid atherosclerosis (OR 0.39; 95% CI 0.18-0.86), LV ejection fraction (OR 0.96; 95% CI 0.93-0.99), appearance at peak stress of new significant (2 LV segments or more) regional WMAs (OR 0.32; 95% CI 0.18-6.55), decreased LV CTR (OR 0.46; 95% CI 0.27-0.79) and CR (OR 0.33; 95% CI 0.18-0.61); p<0.05 for all. In a multivariate analysis with Cox regression, the model with clinical indicators included PTP of IHD (OR 1.04; 95% CI 1.01-1.07; p=0.01) and DLP (OR 0.14; 95% CI 0.02-1.01; p=0.05) as predictors. The model with stress EchoCG parameters included the appearance of new significant WMAs (OR 0.33, 95% CI 0.16-0.65; p=0.001) and reduced <2.0 CR (OR 0.44; 95% CI 0.24-0.82; p=0.01). A comparative analysis of Kaplan-Meier curves confirmed statistically significant differences in the dynamics of the CCVEP occurrence depending on the absence or presence of hemodynamically significant WMAs and/or reduced CR during stress EchoCG (p<0.01). Conclusion . Reduced LV CR and WMA during stress EchoCG in patients with suspected or confirmed IHD are significant independent predictors for the CCVEP occurrence. Among clinical indicators, PTP of IHD and DLP are of the greatest importance for prognosis.

Aim In a prospective observational study of risk stratification in patients with ischemic heart disease (IHD) using stress echocardiography (Stress ECHO), to evaluate the significance of left ventricular (LV) global longitudinal strain (GLS) as an independent prognostic marker or as an adjunct to the existing markers. Material and methods This study included 273 patients (60.4% men, mean age 60.9±9.5 years) with known (n=109; 39.9%) or suspected (n=164; 60.1%; IHD pretest probability (PT): 17 [11-26]% (interquartile ranges: Me [Q1; Q3])) IHD. All patients underwent Stress ECHO with physical exercise (PE) on a recumbent bicycle ergometer (n=165; 60.4%), vasodilator (adenosine triphosphate (ATP), n=74; 27.1%), and other stress tests (n=34; 12.5%). The Stress ECHO protocol included assessment of local contractile disorders (LCD), B-lines, LV contractile reserve (CR), and heart rate reserve. Additionally, LV GLS was assessed at rest and at the test peak, and GLS reserve and GLS change (ΔGLS) were calculated. The prospective follow-up period was 20 [13-25] months. The composite cardiovascular end point (CVE) included death from cardiovascular causes, acute coronary syndrome, revascularization, and stroke/transient ischemic attack, and was calculated until the first event. Results            Prognostic values were obtained for 272 (99.6%) patients. During the follow-up period, 114 cardiovascular complications (CVC) occurred in 87 (31.9%) patients (1 to 3 in each patient). According to the multivariate regression analysis of the Stress ECHO results, the independent predictors for the CVE were the emergence of new LCDs at the peak of stress testing (odds ratio (OR) 2.95; 95% confidence interval (CI): 1.51-5.76; p=0.02) and ΔGLS (OR 0.90; 95% CI: 0.81-0.99; p=0.039). With the use of ATP, the risk of developing CVC was described by a similar model, that had an even higher level of significance (OR for LCD 36.21; 95% CI: 3.09-424.09; p=0.004; OR for ΔGLS 0.48; 95% CI: 0.25-0.94; p=0.032). In PE Stress ECHO, the GLS index added to the LCD did not demonstrate an independent prognostic value. The ROC analysis identified a threshold value for ΔGLS as a predictor of unfavorable prognosis. The threshold absolute value was 1.2 in the entire group and 0.2 in the ATP Stress ECHO subgroup. In case of difficulties in assessing the LCD at the testing peak, an alternative model was used with evaluation of the IHD PT (OR 1.09; 95% CI: 1.04-1.14; p<0.001), emergence of angina at the testing peak (OR 5.07; 95% CI: 1.81-14.26; p=0.002), reduced LV CR (OR 2.18; 95% CI 0.73-6.53; p=0.162), and ΔGLS (OR 0.83; 95% CI 0.72-0.95; p=0.008). Conclusion In Stress ECHO performed for risk stratification in IHD, the ΔGLS value, regardless of and in addition to LCDs, is a predictor of CVC. The absolute value of ΔGLS <1.2 in the entire group and ΔGLS <0.2 in the ATP subgroup indicates an unfavorable prognosis for the next 1.5 years.

Aim . To assess markers of chronic kidney disease (CKD) in patients with medically-controlled hypertension (HTN) (<140/90 mm Hg), as well as to analyze potential association of decreased glomerular filtration rate (GFR) <60 ml/min/1,73 m2 with clinical data and therapy; to establish significant determinants of GFR decrease in this category of patients. Material and methods . The study included 70 patients with HTN and office blood pressure (BP) <140/90 mm Hg aged 64 (57; 68) years (men, 48,6%), of whom 40 patients were examined within the Russian multicenter CHRONOGRAPH program. Office BP was 130 (120; 140)/80 (72; 82) mm Hg. GFR and albuminuria were assessed. Twenty-four-hour BP monitoring and Doppler ultrasound of renal blood flow with estimation of resistance indices (RI) were performed. The content of highsensitivity C-reactive protein (hsCRP), interleukins (IL) 1β, 6, 10 and lipid transport function parameters was determined. Results . CKD markers were detected in 31,4% of patients (in 27,1% — a decrease in GFR <60 ml/min/1,73 m ² ; in 12,9% — pathological albuminuria). Patients with CKD markers were older, had higher office systolic BP and nocturnal pulse pressure, higher blood hsCRP and RI levels throughout the renal flow, and lower high-density lipoprotein cholesterol levels. In the presence of CKD markers, calcium channel blockers, aldosterone receptor antagonists and statins were used more often. The results of correlation analysis were used to determine the determinants of GFR decline. In the general group, GFR values had inverse correlations with age (Rs=-0,58, p<0,0001), segmental intrarenal artery RI (Rs= -0,4232, p=0,0005), blood hsCRP (Rs=-0,3998, p=0,0007), IL-1β (Rs=-0,3139, p=0,0086), office BP and some 24-hour BP parameters. In the presence of CKD markers, a direct association of GFR and IL-10 was determined (Rs=0,4293, p=0,046). In the absence of such markers, GFR had an inverse correlation with IL-1β content (Rs=-0,3110, p=0,0333). A multiple linear regression model included following independent determinants of GFR: age, blood hsCRP and RI in the segmental intrarenal arteries. Conclusion . Among patients with medically-controlled HTN of high cardiovascular risk, a high prevalence of CKD markers was revealed (31,4%). Compared with patients with preserved renal function, in the presence of CKD markers, there were higher levels of office systolic BP, nocturnal pulse pressure, blood hsCRP, and intrarenal artery RI. Associations were established between GFR and the levels of hsCRP, IL-1β and IL-10, which confirms the pathological role of inflammatory biomarkers in developing renal dysfunction in high-risk HTN. Age, elevated blood hsCRP levels, and intrarenal artery RI are independent determinants of decreased GFR in patients with medically-controlled HTN of high and very high cardiovascular risk. The data obtained shows the need for early prescription of combination antihypertensive therapy with nephro- and vasoprotective effects in this category of patients, as well as with an ability to depress the chronic subclinical inflammation.