Molecular effects of cardiac contractility modulation in patients with heart failure of ischemic aetiology uncovered by transcriptome analysis.

Cardiac contractility modulation (CCM) is based on electrical stimulation of the heart without alteration of action potential and mechanical activation, the data on its fundamental molecular mechanisms are limited. Here we demonstrate clinical and physiological effect of 12 months CCM in 29 patients along with transcriptomic molecular data. Based on the CCM effect the patients were divided into two groups: responders (n = 13) and non-responders (n = 16). RNA-seq data were collected for 6 patients before and after CCM including 3 responders and 3 non-responders. The overall effect of CCM on gene expression was mainly provided by samples from the responder group and included the upregulation of the genes involved in the maintenance of proteostasis and mitochondrial structure and function. Using pathway enrichment analysis, we found that baseline myocardial tissue samples from responder group were characterized by upregulation of mitochondrial matrix-related genes, Z disc-protein encoding genes and muscle contraction-related genes. In summary, twelve months of ССM led to changes in signaling pathways associated with cellular respiration, apoptosis, and autophagy. The pattern of myocardial remodeling after CCM is associated with initial expression level of myocardial contractile proteins, adaptation reserves associated with mitochondria and low expression level of inflammatory molecules.

Skeletal Muscle Resident Progenitor Cells Coexpress Mesenchymal and Myogenic Markers and Are Not Affected by Chronic Heart Failure-Induced Dysregulations.

BACKGROUND AND PURPOSE: In heart failure (HF), metabolic alterations induce skeletal muscle wasting and decrease of exercise capacity and quality of life. The activation of skeletal muscle regeneration potential is a prospective strategy to reduce muscle wasting; therefore, the aim of this project was to determine if functional properties of skeletal muscle mesenchymal progenitor cells (SM-MPC) were affected by HF-induced functional and metabolic dysregulations. METHODS: Gastrocnemius muscle biopsy samples were obtained from 3 healthy donors (HD) and 12 HF patients to purify mRNA for further analysis and to isolate SM-MPC. Cells were expanded in vitro and characterized by immunocytochemistry and flow cytometry for expression of mesenchymal (CD105/CD73/CD166/CD146/CD140b/CD140a/VIM) and myogenic (Myf5/CD56/MyoG) markers. Cells were induced to differentiate and were then analyzed by immunostaining and Q-PCR to verify the efficiency of differentiation. The expression of genes that control muscle metabolism and development was compared for HD/HF patients in both muscle biopsy and in vitro-differentiated myotubes. RESULTS: The upregulation of MYH3/MYH8/Myf6 detected in HF skeletal muscle along with metabolic alterations indicates chronic pathological activation of the muscle developmental program. SM-MPC isolated from HD and HF patients represented a mixed population that coexpresses both mesenchymal and myogenic markers and differs from AD-MMSC, BM-MMSC, and IMF-MSC. The functional properties of SM-MPC did not differ between HD and HF patients. CONCLUSION: In the present work, we demonstrate that the metabolic and functional alterations we detected in skeletal muscle from HF patients do not dramatically affect the functional properties of purified and expanded in vitro SM-MPC. We speculate that skeletal muscle progenitor cells are protected by their niche and under beneficial circumstances could contribute to muscle restoration and prevention and treatment of muscle wasting. The potential new therapeutic strategies of HF-induced skeletal muscle wasting should be targeted on both activation of SM-MPC regeneration potential and improvement of skeletal muscle metabolic status to provide a favorable environment for SM-MPC-driven muscle restoration.

[Results of 3 years work of the Russian hospital register of chronic heart failure (RUssian hoSpital Heart Failure Registry - RUS-HFR): relationship between management and outcomes in patients with chronic heart failure].

AIM: To analyze management and outcomes in patients with CHF managed by specialists in heart failure (HF) or general cardiologists/physicians in real-life clinical practice. MATERIALS AND METHODS: Survival rate, rehospitalization rate, general health condition, and the administered therapy were evaluated for HF patients with reduced LV ejection fraction at three years of discharge from cardiological hospitals. These patients had been included in a prospective, multicenter, observational study, "The Russian Hospital HF Registry" (RUS-HFR). The first group consisted of patients who were managed at a specialized HF department of the Federal Center and followed up at the outpatient stage by a cardiologist specializing in HF (Group 1, St.­Petersburg; n =74). The other two groups (Group 2 and Group 3) included patients who were managed at other cardiological departments of the Federal Center (n=186) or the Regional Center (n=130) and subsequently followed up at the place of residence. RESULTS: After the discharge from the hospital, 58-95 and 12-19% of RUS-HFR patients were followed up by a cardiologist or a physician, respectively, on an outpatient basis while 5-23% of patients did not visit a doctor at all. In three years, the survival rate of Group 1, 2, and 3 patients was 80 vs. 78 (р>0.05) vs. 52% (р0.05) vs. 100% (p1,2.

[Response predictors for physical training HFrEF patients].

PURPOSE: To identify different types and possible predictors of physical rehabilitation (PR) response in reduced ejection fraction heart failure (HFrEF) patients, selected on the basis of achievement the lactate threshold during cardiopulmonary exercising test (CPET). METHODS: 64 patients, chronic heart failure (CHF) NYHA II-III functional class were included in our study. Mean age 54±12,5 years, body mass index (BMI) 26,5±6,4 kg/m2, ejection fraction (EF) 26,4±1,4 %, NYHA II: III (67 %: 33 % patients). The original estimated results of physical examination, laboratory parameters, CPET, quality of life (QOL), exercise tolerance (ET) and echocardiography (EchoCG). Physical rehabilitation (PR) efficiency was estimated on the basis of peak oxygen uptake (VO2peak), QOL and ET dynamics after 1,3 and 6 months; EF dynamics was estimated after 6 months. Data were statistically processed using software package "Statistika, 9.0". RESULTS: After 6 months PR EF increased by 7,5±0,5 %, QOL - 17.5±8 points, ET - 9.5±1 points and VO2 peak - 4.4 ml/min/kg, end-diastolic volume decreased by 6±2.0 ml from baseline (p1,2,3,4, respectively). Echocardiography, CPET, QOL and ET improvement revealed a significant number of patients (EF - 48 %, VO2 peak - 64 %, QOL - 64 %, ET - 67 % of patients, respectively). Revealed a strong positive correlation between the initial values of VO2 peak and EF (rEF=0,4, p), and between baseline levels of sodium, haemoglobin and the of PR efficiency (rNa= 0,41, p,0,05; rHb = 0,45, p.

[Morphologic changes in the dental and periodontal tissues of rats exposed to autonomotropic preparations]. / Morfologicheskie izmeneniia tkanei zuba i parodonta u krys pod vozdeistviem vegetotropnykh preparatov.

Autonomotropic [correction of Vegetotropic] drugs were injected to 40 rats for 10 days in order to detect changes in incisor growth rate and the morphologic changes in dental and periodontal tissues related with this changed rate. Adrenalin-enhanced eruption is associated with enhanced dentinogenesis and osteogenesis with increased salt deposition. Atropine, a cholinolytic, sharply inhibits incisor growth, this being parallelled with congestion in the pulpal and periodontal vessels and emergence of alveolar process bone tissue resolution. These findings have lead the authors to a conclusion that teeth eruption involved active plastic processes in dental pulp and periodontium tissues.

[Determination of diffusion coefficients in a solution by the transport of a solute through porous membranes]. / Opredelenie koéffitsientov diffuzii v rastvore po perenosu veshchestva cherez poristuiu membranu.

The possibility of determining the coefficients of diffusion in solution by the transport of solutes through porous polymeric membrane was studied. Reliable and reproducible results can be obtained by using nucleoporous filters with cylindrical pores. The method enables the selective determining of the diffusion coefficients of solutes being in complex mixtures, which is of special interest for biochemical research. The possibilities of the method are illustrated on the pattern of some globular proteins, polyethylene glycols and proteolytic enzymes.