[Gut microbiota and systemic inflammation in patients with chronic heart failure].

Aim To study the interrelationship between intensity of chronic systemic inflammation (CSI) with severity of the condition and intestinal microbiocenosis parameters in patients with chronic heart failure (CHF).Material and methods 47 hospitalized patients with symptomatic CHF were evaluated. The following parameters were determined: clinical condition; N-terminal pro-B-type natriuretic peptide (NT-proBNP). C-reactive protein (CRP); serum interleukins (IL) 6 and 10; and intestinal microbiocenosis composition by mass-spectrometry of microbial markers in whole blood. Microbiocenosis indexes were compared in the main group and in 38 outpatient patients with arterial hypertension and ischemic heart disease without CHF.Results Direct, medium-power correlations were found between CRP and IL-6 concentrations and severity of clinical condition (NT-proBNP, ХСН stage, and edema severity) in patients with CHF. Most patients with CHF had lower numbers of bifido-, lacto-, propionic-, and eubacteria, and Clostridium (С.) ramosum and higher numbers of aspergillus. Among CHF patients, the highest indexes of endotoxemia, gram (-) bacteria, cocci, actinomycetes, and microfungi were observed in the group with NT-proBNP from 400 to 2000 pg/ml. Direct correlations were observed for amounts of C. hystolyticum, Pseudonocardia spp., and Aspergillus spp. with IL-6 and IL-10 and unidirectional inverse correlation were observed for these cytokines with Propionibacterium acnes and jensenii, Streptomyces spp., and Nocardia asteroides. In addition, IL-6 concentration was negatively correlated with contents of Staphylococcus aureus, C. difficile, C. ramosum, Eggerthella lenta, and Corynebacterium spp. and was positively correlated with C. propionicum, Moraxella spp. and Flavobacterium spp. Concentration of IL-6 directly correlated with the number of Eubacterium spp. and inversely correlated with numbers of Ruminicoccus spp. and Streptomyces farmamarensis. The amount of Streptomyces farmamarensis negatively correlated with CRP concentrations.Conclusion The study results evidence the significance of intestinal microbial-tissue complex in the pathogenesis of CSI in CHF and allow suggesting this complex as a promising target for therapy.

Effect of Prebiotic Complex on Gut Microbiota and Endotoxemia in Female Rats with Modeled Heart Failure.

We studied the levels endotoxin and microbial markers in the blood of female rats with experimental heart failure and the effects of preliminary treatment with a prebiotic complex based on fermented wheat bran and inactivated Saccharomyces cerevisiae culture on these parameters. The concentrations of endotoxin, markers of lactobacilli, and opportunistic microorganisms were found to increase in rats with experimental heart failure and significantly decreased against the background of treatment with prebiotic complex. The dynamics of markers of bifidobacteria, eubacteria, and propionibacteria were reciprocal. The observed effect of the prebiotic complex effect on gut microbiota in rats with experimental heart failure suggests that this complex can be used for the correction of intestinal dysbiosis and endotoxemia in this clinical condition.

[The role of telocytes in myocardial remodeling and the development of cardiovascular complications in patients with chronic heart failure after coronary artery bypass grafting].

Аim of the study. A study of the role of cardiac telocytes (Tc) in myocardial remodeling and the effect of changes in their morphology on the clinical outcome of coronary bypass (CABG) in patients with chronic heart failure (CHF). MATERIALS AND METHODS: The perioperative period was analyzed in 83 patients (43 men and 40 women) with CHF I, IIA and IIB, NYHA functional class I-III undergoing CABG. Myocardial biopsy of the right atrial appendage (RAA), obtained during the CABG, was studied using histological, immunohistochemical (expression of CD-34/vimentin, MMP-2, TIMP-1, caspase-3, bcl-2) and morphometric methods. RESULTS: In the analysis of the myocardium of RAA of a group of patients with cardiovascular complications (CVC) after CABG, a significant decrease in the diameter of cardiomyocytes (CMCs) of their nuclei, bulk density (BD) of CMC, a significant decrease in BD Tc, trophic index; an increase in CMC with signs of apoptosis, BD of stroma, a violation of the ratio of MMP-2/TIMP-1. CONCLUSIONS: The intercellular network Tc with secreted regulatory factors and microvesicles is an important structural and functional link of the myocardium. The decrease in BD Tc has a significant effect on the remodeling and regenerative potential of the myocardium, leading to the development of CVC in patients with CHF.

[Prognostic Value of Melatonin Level, Structural and Functional Changes of the Myocardium in the Development of Complications in Patients With Heart Failure who Underwent Coronary Artery Bypass Grafting: the Possibilities of Pharmacological Cardioprotection].

OBJECTIVE: To assess the significance of melatonin, NT-proBNP and morphological markers of myocardial remodeling for predicting the risk of complications after coronary artery bypass grafting (CABG) in patients with ischemic heart disease and chronic heart failure (CHF). MATERIALS AND METHODS: We included in this study 83 patients who underwent CABG in the period from September 2013 to October 2014. All patients before CABG underwent standard laboratory and instrumental examination. Concentrations of melatonin and NT-proBNP were measured in 2 days before and after surgery. The evaluation of morphological markers of myocardial remodeling (expression of MT2 melatonin receptors [MTR2], caspase-3, bcl-2) was carried out in tissue samples taken at biopsies of the right atrial appendage during CABG. RESULTS: Analysis of groups of patients with favorable and unfavorable hospital outcomes revealed no significant differences in serum levels of NT-proBNP. There was a significant decrease in the level of melatonin in the subgroup of patients with unfavorable outcome of CABG in combination with high comorbid load and high degree of apoptosis of cardiomyocytes at the background of moderate and high MTR2 expression. Comparative assessment of pharmacotherapy prior to CABG revealed favorable effect on myocardial remodeling of a combination of perindopril and amlodipine. CONCLUSION: Preoperative evaluation of the level of melatonin sulfate, apoptosis markers, and comorbid load can serve as prognostic factors of complicated course of the postoperative period after CABG in patients with CHF. The combination of perindopril and amlodipine in patients with heart failure with preserved ejection fraction exerted a significant cardioprotective effect on the myocardium, contributing to a decrease of the apoptotic dominant.

[Role of telocytes in the heart in health and diseases]. / Rol' telotsitov v serdtse v norme i pri patologii.

This review summarizes the data available in the literature on the development, structure, and function of telocytes (TCs) and their role in the heart in health and diseases. At the present time, TCs have been found in many organs of mammals and humans. TC is a small oval cell that contains a nucleus surrounded by small amounts of cytoplasm, with extremely long and thin processes named telopodias. TCs have unique ultrastructural and immunohistochemical features; double positive labeling for CD34/PDGFR-ß and CD34/vimentin is suitable for their identification. The role of TCs in the heart at different study stages is the subject of debate. There are currently available data on a decline in the number of cardiac TCs in patients with various heart diseases. Relying on a number of investigations showing that TCs are present in the subepicardial stem cell niches, the authors consider a hypothesis for the key role of cardiac TCs in the regeneration and reparation of the heart.

[Extracellular matrix remodeling myocardium of the left ventricle rats with experimental heart failure after perindopril and melatonin administration].

The aim of the study was to examine the reorganization of extracellular matrix left ventricular myocardium (LVM) rats (n = 38) with experimental heart failure (EHF) as affected by perindopril and melatonin administration. Rats LVM was studied using the methods of light microscopy, immunocytochemistry and morphometry. At day 14 of EHF, marked mosaic staining cardiomyocytes acid dyes, manifest hemodynamic disturbances: venous and capillary congestion, lymphostasis, perivascular and interstitial edema, there was a increase the volume density (OD) stroma, high activity of MMP-1 and TIMP-1. After modeling the EHF to 28 days in LVM, a further increase of hemodynamic met, cardiosclerosis areas and perivascular sclerosis, a significant increase OD stroma, observed decrease in the expression of MMP-1 and TIMP-1. In rats given perindopril and melatonin for 14 days, there was a regression of pathological changes in the balance was maintained MMP-1/TIMP-1 ratio close to the group of intact rats. Cardioprotective effects of perindopril and melatonin on extracellular matrix LVM of rats with EHF is discussed.

[Structural reorganization of the myocardium in ovariectomized rats with experimental heart failure after melatonin administration].

The aim of the study was to examine the reorganization of left ventricular myocardium (LVM) in ovariectomized rats with experimental heart failure (EHF) as affected by melatonin administration. Rat LVM was studied using the methods of light microscopy, immunocytochemistry and morphometry. At day 14 of EHF, marked heteromorphism of contractile cardiomyocytes (CMC), signs of dystrophy, overcontraction and damage of muscle fibers, karyopyknosis, paranuclear edema, local sarcoplasm destruction were detected together with CMC showing signs of apoptosis. At day 28 after EHF modeling, a further increase in the number of CMC with significant changes in the morphological and tinctorial properties was found as well as the cells with signs of apoptosis. In rats given melatonin for 14 days, there was a regression of pathological changes, with the decrease in the hypertrophy of CMC and their nuclei, reduction of the number of CMC with the signs of apoptosis. Cardioprotective effect of melatonin on LVM of ovariectomized rats with EHF is discussed.

[The role of structural changes of the endothelium and myocardium in the development of experimental heart failure].

The aim of the investigation was to study the role of structural myocardial and endothelial reorganization during the experimental heart failure (doxorubicin model). Rat endocardial and aortal endothelium as well as left ventricular myocardium, were studied using the methods of light and electron microscopy and immunocytochemistry (TUNEL-assay). The major regularities of structural and functional myocardial and endothelial reorganization were determined in rats with an experimental heart failure. The pronounced cardiomyocyte (CMC) heteromorphism was found. CMCs with the signs of hypertrophy and hyperplasia were identified together with the CMCs showing discomplexation of sarcomeres and fragmentation of myofibrils, CMCs with the numerous caveolae, liposomes, autophagosomes and myelin-like bodies. The peculiarities of the ultrastructural changes were established in the endocardial and aortal endothelium. The increase in CMC and endothelial cell number showing the signs of apoptosis, was demonstrated. The role of structural and functional myocardial and endothelial reorganization during experimental heart failure is discussed.

[Ultrastructural characteristic of reactively modified myocardium cultured in vitro]. / Ul'trastrukturnaia kharakteristika reaktivno izmenennogo miokarda pri kul'tivirovanii in vitro.

The aim of the present investigation was to study the structure of reactively modified rat myocardium (experimental heart failure model) during in vitro organotypical culture, including the direct effect of some hypothalamic nonapeptides (oxytocin) and monoamines (dopamine, noradrenalin). Light and electron microscopic methods were used. The major regularities of structural and functional reorganization of myocardium were determined. Multidirectional nature of ultrastructural changes of cardiomyocytes and of cardiac non-muscular cells was found to depend on direct effect of hypothalamic nonapeptides and monoamines upon myocardium. Adaptogenic role of oxytocin in provision of cardiac muscle protection and vitality is discussed.

[Morphological aspects of heart remodeling in chronic heart failure]. / Morfologicheskie aspekty remodelirovaniia serdtsa pri khronicheskoi serdechnoi nedostatochnosti.

Intraoperative biopsy specimens of the right atrium auricula from patients at different stages of chronic heart failure (CHF) were studied using the methods of light and electron microscopy. Marked heteromorphism of cardiomyocytes (CMC) was demonstrated which was found to be correlated to CHF progression. CMC showing the signs of hypertrophy and organelle hyperplasia, sarcomere discomplexation, myofibril fragmentation were identified, as well as CMC containing numerous pinocytotic vesicles, caveolae, distended T-system tubules. Apoptotic CMC and interstitial cells were also shown. No significant correlation between the myocardial cell apoptosis and CHF stage was established.