Estimation of Renal Clearance in Hypertensive Rats According to fMRI Data.

Renal clearance in Wistar rats with multifactorial cardiovasorenal model of arterial hypertension was assessed by fMRI using (EPI_Diffusion_map) protocol after injection of extracellular contrast agent gadolinium Gd-DTPA. Linear regression analysis was used to assess local concentrations of the contrast agent in the abdominal aorta, kidney compartments, pelvis, and bladder areas. Detection of marker clearance in order to verify the glomerular filtration rate was performed by the RPP (Rutland-Patlak plot) method. In 3 months after hypertension modeling, glomerular filtration rate decreased by 2 times in comparison with the control (31.2±0.44 and 62.3±1.31 µl/min/100 g, respectively; p<0.001). Our findings can indicate the formation of hypertensive nephroangiosclerosis in rats with experimental arterial hypertension. It was found that kidney damage in hypertensive rats is associated with hypofiltration.

Structural and Functional Changes of the Thoracic Aorta in Experimental Arterial Hypertension.

The functional characteristics of the thoracic aorta in Wistar rat with experimental arterial hypertension were studied using MRI. The intravital images of the aorta were obtained using a synchronizer of cardiac and respiratory cycles. The pulse-gradient Turbo-spin-echo sequence and the BODY CARDIAC movie 10 mode were used. The unfavorable factor of increased BP initiated structural and functional changes in the thoracic aorta. At the initial stages, they manifested by an increase of the lumen and a decrease in endothelium-dependent vasodilation. Progression of arterial hypertension (3-6 months) was associated with narrowing of the lumen of both ascending and descending parts of the aorta. Deformation of the aortic arch due to increased density of the vascular wall was observed by the sixth month of the development of arterial hypertension.

Estimation of the Morphofunctional Status of the Brain in Hypertensive Wistar Rats Using Diffusion-Weighted MRI.

Morphofunctional changes of the brain tissues of Wistar rats were studied based on the development of a multifactor cardiovasorenal model of arterial hypertension using MRI. An increase of the signal on the diffusion brain maps was recorded in 3 months, which indicated fluid accumulation in the intra- and extracellular space of the brain tissue. The data characterize the development of the pathogenetic mechanism of the hypervolemic variant of experimental arterial hypertension. The development of endothelial dysfunction in the brain vessels was manifested by predominance of abnormal constrictor reactions. In 6 months after arterial hypertension simulation, structural changes in the brain developed, such as leukoareosis, cystic encephalomalacia with dilated cerebrospinal fluid spaces and limited blood supply to brain tissue in the basins of the large cerebral arteries.

[Machine Learning Methods for Prediction of Hospital Mortality in Patients with Coronary Heart Disease after Coronary Artery Bypass Grafting].

Aim      To compare the accuracy of predicting an in-hospital fatal outcome for models based on current machine-learning technologies in patients with ischemic heart disease (IHD) after coronary bypass (CB) surgery.Material and methods  A retrospective analysis of 866 electronic medical records was performed for patients (685 men and 181 women) who have had a CB surgery for IHD in 2008-2018. Results of clinical, laboratory, and instrumental evaluations obtained prior to the CB surgery were analyzed. Patients were divided into two groups: group 1 included 35 (4 %) patients who died within the first 20 days of CB, and group 2 consisted of 831 (96 %) patients with a beneficial outcome of the surgery. Predictors of the in-hospital fatal outcome were identified by a multistep selection procedure with analysis of statistical hypotheses and calculation of weight coefficients. For construction of models and verification of predictors, machine-learning methods were used, including the multifactorial logistic regression (LR), random forest (RF), and artificial neural networks (ANN). Model accuracy was evaluated by three metrics: area under the ROC curve (AUC), sensitivity, and specificity. Cross validation of the models was performed on test samples, and the control validation was performed on a cohort of patients with IHD after CB, whose data were not used in development of the models.Results The following 7 risk factors for in-hospital fatal outcome with the greatest predictive potential were isolated from the EuroSCORE II scale: ejection fraction (EF) <30 %, EF 30-50 %, age of patients with recent MI, damage of peripheral arterial circulation, urgency of CB, functional class III-IV chronic heart failure, and 5 additional predictors, including heart rate, systolic blood pressure, presence of aortic stenosis, posterior left ventricular (LV) wall relative thickness index (RTI), and LV relative mass index (LVRMI). The models developed by the authors using LR, RF and ANN methods had higher AUC values and sensitivity compared to the classical EuroSCORE II scale. The ANN models including the RTI and LVRMI predictors demonstrated a maximum level of prognostic accuracy, which was illustrated by values of the quality metrics, AUC 93 %, sensitivity 90 %, and specificity 96 %. The predictive robustness of the models was confirmed by results of the control validation.Conclusion      The use of current machine-learning technologies allowed developing a novel algorithm for selection of predictors and highly accurate models for predicting an in-hospital fatal outcome after CB.

Peculiarities of Autonomic Regulation of the Heart in Experimental Normobaric Hypoxia of Different Genesis.

We compared autonomic regulation of the heart in Wistar rats with acute exogenous hypoxic and chronic normobaric hypoxia against the background of experimental chronic obstructive pulmonary disease. In animals subjected to normobaric hypoxia, dysfunction of the autonomic regulation of the heart developed; it manifested in a significant limitation of the effects of the parasympathetic and sympathetic nervous systems on the pacemaker activity of the sinoatrial node. Disturbances in autonomic regulation of the heart in acute exogenous hypoxic normobaric hypoxia were characterized by "rigid" heart rhythm and bradycardia in the presence of systolic-diastolic arterial hypotension. Centralization of heart rhythm control did not provide compensation for hemodynamic disturbances. In case of chronic normobaric hypoxia, an increase in arterial hypoxemia was associated with protective "denervation" of the heart against the background of increased activity of the humoral regulation, which manifested in tachycardia, isolated systolic arterial hypertension, and overstrain of regulatory systems.

[Machine Learning Methods in Assessing the Risks of Target Organ Damage in Masked Hypertension].

Aim To develop models for predicting the risk of target organs damage (TOD) in different phenotypes of "masked" arterial hypertension (MAH) based on methods of machine learning (ML).Material and methods A retrospective cohort analysis was performed for 284 clinical records of patients (261 males, 23 females; median age, 38 years). Group 1 included 125 patients with grade 1-2 arterial hypertension (AH) and low or moderate risk; group 2 included 159 subjects with normal "office" blood pressure (BP) exposed to chronic professional stress. The 24-h BP monitoring (24-h BPM) and ultrasound examination of the heart and carotid arteries were performed; glomerular filtration rate (GFR) was estimated using the СКD-EPI formula. MAH was phenotyped by clustering 24-h BPM data, and the risk of TOD was predicted by analysis of odd ratios (OR) and with the ML methods, random forest (RF) and artificial neural networks (ANN). Data were analyzed using the R language in the RStudio environment.Results According to results of the 24-h BPM and cluster analysis, 121 (76.1 %) subjects of group 2 had MAH. The MAH phenotypes were identified as follows: systolic-diastolic (SDMAH) (43.8 %); isolated systolic (ISMAH) (35.5 %), and isolated diastolic (IDMAH) (20.7%). As compared to stable AH, subjects with different MAH phenotypes showed both increases and decreases in individual 24-h BPM indexes. Thus, in subjects with IDMAH, mean 24-h values of systolic and diastolic BP were significantly lower than with AH while in SDMAH, they were considerably higher. The OR analysis demonstrated that odds of differently located TOD were associated with definite MAH phenotypes. With that, ISMAH was associated with the highest risk of glomerular hyperfiltration; IDMAH was associated with reduced GFR and vascular remodeling; and SDMAH was associated with left ventricular myocardial hypertrophy. The developed models for predicting the risk of TOD based on the RF and ANN methods showed a high accuracy, which was provided by multistep procedures of selecting the predictors and cross-validation.Conclusion Modern ML technologies enhance the risk stratification of patients with different clinical variants of AH.

[Comparative analysis of the strength of the respiratory muscles in community-acquired pneumonia with different severity of endogenous intoxication].

AIM: To assess the strength of the respiratory muscles in patients with community-acquired pneumonia (CAP) with varying severity of endogenous intoxication. MATERIALS AND METHODS: In the hospital, 78 men aged 1826 years with CAP were examined. СAP was diagnosed in 56 (72%) patients, severe CAP in 22 (28%). The severity of endogenous intoxication was verified using intoxication indices: hematological index of intoxication (HII), leukocyte index of intoxication (LII), nuclear index of intoxication (NII) and Krebs index. Middleweight molecules (MWM) was determined by spectrophotometry in the serum and the concentration of interleukin (IL)-10 and tumor necrosis factor  (TNF-) by ELISA. The strength of the respiratory muscles was measured on the device Micro RPM (Care Fusion, Great Britain). The maximum expiratory pressure (МЕР), inspiratory pressure (MIP) in the oral cavity, the Maximal Rate of Pressure Development (MRPD) during inhalation (MRPDin) and exhalation (MRPDex), and intranasal test (SNIP) were determined. Statistical processing was performed using descriptive statistics, MannWhitney test, correlation and cluster analysis. RESULTS: Three clusters of endogenous intoxication corresponding to mild, moderate and severe degree were identified. The first cluster was represented only by patients with mild CAP, the second-mild CAP and severe CAP, and the third severe CAP. Dysfunction of the expiratory respiratory muscles prevailed during the height of the disease in patients with the first cluster, and in the second and third inspiratory, including the diaphragm. The level of actually measured values of MIP and SNIP was 68% and 58% of those due to severe endogenous intoxication. Significant negative correlations were established LII, HII, MWM, TNF-, IL-10 с MEP, MRPDex, MIP и SNIP. Respiratory muscle dysfunction remained only expiratory respiratory muscles in convalescents of the first cluster, and expiratory and inspiratory muscles of the second and third cluster. CONCLUSION: The development of respiratory muscle dysfunction in CAP is associated with the influence of endogenous intoxication factors. The results can be used in personalized programs of rehabilitation.

[The behavioral status of rats with experimental comorbidity of chronic obstructive pulmonarydisease and acute cerebral ischemia]. / Povedencheskii status krys pri éksperimental'noi komorbidnosti khronicheskoi obstruktivnoi bolezni legkikh i ostroi ishemii golovnogo mozga.

AIM: To compare behavioral patterns of rats with experimental chronic obstructive pulmonary disease (ECOPD), acute cerebral ischemia (ACI) and a combination of these pathologies. MATERIAL AND METHODS: The study included 70 male Wistar rats (weight 250-300 g) divided into 5 groups. ECOPD was modeled by a combination of inducers (purified papain and bacterial lipopolysaccharide), and ACI by a single-stage bilateral occlusion of common carotid arteries. The neurological status was assessed with NSS, and the behavioral status was assessed using the battery of tests including 'open field', 'radial eight-arm labyrinth', 'O-shaped elevated labyrinth'. RESULTS AND CONCLUSION: With the combination of ECOPD and ACI, a minimal (20%) survival rate of animals and the maximum severity of neurological and behavioral disorders, were recorded. The latter were characterized by a sharp restriction of locomotor and research activity, spatial memory, high anxiety and increasing autonomic imbalance. Survival rate of rats with isolated ACI was 35%, and disturbances of their neurological and behavioral status were moderately expressed. In rats with isolated ECOPD, the neurological deficit was mild. Behavioral disorders were manifested by a moderate limitation of locomotor function, a slight increase in anxiety with preserved research activity and spatial memory. The results of the study indicate the relevance of the respiratory and cerebrovascular comorbidity model for assessing changes in physiological functions and their subsequent correction.

Chronic obstructive pulmonary disease and cerebrovascular diseases: functional and clinical aspect of comorbidity.

Literature data of chronic obstructive pulmonary disease (COPD) and cerebrovascular diseases (CVD) comorbidity are represented in this review. Key aspects of this interaction and its importance for clinical medicine have been considered. CVD and COPD are the main mortality factors in adults, which contribute to great economic wastes. The incidence of chronic cerebral ischemia for COPD patients is almost three times as high as for general population. The incidence of ischemic stroke for COPD patients is 1,2 times higher than in general population. For hemorrhagic stroke and subarachnoid haemorrhages, this figures are 1,3 and 1,46 respectively. Chronic systemic inflammation, tissue hypoxia and oxidative stress play the crucial role in respiratory and cerebrovascular comorbidity. Metabolites of these processes (especially proinflammatory cytokines, reactive oxygen species, C-reactive protein and some neurotrophins) increase the permeability of blood-brain barrier, destroy brain cells and activate atherogenesis in pre- and intracerebral arteries. Endothelial dysfunction affects autoregulation of cerebral circulation. Systemic symptoms of COPD are closely associated with different structural-functional disorders of the brain such as reduction in white matter integrity, grey matter volume reduction and cerebral microbleeds. Also, venous encephalopathy is developed as a result of intrathoracic pressure elevation and stasis in superior vena cava system. These processes result in neurological symptomatology. The intensity of symptoms depends on COPD severity. The occurrence of cognitive impairment, psychic tension, depression, panic disorders also increases. However COPD and CVD comorbidity is an important problem of modern medicine, pathophysiologic mechanisms and clinic aspects of this problem remain unresolved. Understanding of their role opens perspectives for rational pharmacotherapy.

Endothelial dysfunction of cerebral and major arteries during chronic obstructive disease.

Vasomotor activity of the major and cerebral arteries was studied in mice with chronic obstructive pulmonary disease. Regional differences were revealed in the endothelium-dependent response of arteries. The development of chronic obstructive pulmonary disease was associated with a paradoxical response of the dilatational component of vasoregulation against the background of increased constrictive influences of the vascular endothelium in the major and cerebral vessels.