[The Prognostic Role of Biomarkers in Patients With Chronic Heart Failure].

Objective Investigate the role of biomarkers in the prognosis of the clinical course of the disease in patients with chronic heart failure (CHF) of different NYHA functional classes (FC).Material and Methods The study included 132 patients with CHF: Group 1 was composed of 70 patients with NYHA FC II CHF, and Group 2 included 62 patients with FC III-IV CHF. The patients underwent clinical, instrumental, functional, and laboratory measurements, which included serum concentrations of NT-proBNP, ST-2, galectin-3, and C-reactive protein. Patients were examined at baseline and at 3, 6, and 12 mos of follow-up. The following cardiac complications were used as endpoints: urgent hospitalization due to decompensated CHF, heart transplantation, cardiovascular death. Endpoints were registered during the 12-mo follow-up period.Results Endpoints were recorded for 58 patients (44%) of the total sample of patients with CHF: 38 patients were urgently hospitalized, 10 patients underwent heart transplantation, 10 patients died. Cardiac complications were recorded at a higher rate in patients with FC III-IV CHF (63% vs. 27% of patients with FC II; p<0.001). In FC II CHF patients, the incidence of cardiac complications was significantly correlated with NT-proBNP blood concentrations (Rpb=0.53; p=0.023), left ventricular end-diastolic volume (LVEDV) (Rpb=0.50; p=0.044), and mitral regurgitation (Rpb=0.53; p=0.038). Cardiac complications in patients with FC III-IV CHF were associated with ST-2 (Rpb=0.52; p=0.004) and galectin-3 (Rpb=0.46; p=0.009) blood concentrations, and with systolic pulmonary artery pressure (PAP) (Rpb=0.41; p=0.014). Unlike other laboratory measurements, galectin-3 concentrations were significantly correlated with type 2 diabetes mellitus (DM2) (Rpb=0.40; p=0.003). In this study, correlation analysis and evidence of significant differences in the concentrations of biomarkers provided a rationale for identifying potential predictors of severe cardiac complications during medium- and long-term follow-up periods in patients with CHF of different severity: NT-proBNP concentrations in FC II patients; ST-2 and galectin-3 serum concentrations in FC III-IV patients; galectin-3 concentrations in patients with CHF and DM2.Conclusion NT-proBNP blood concentrations are associated with CHF severity and serious cardiac complications in patients with FC II CHF within the following 12 mos. The poor prognosis of FC III-IV CHF is associated with the concentration of the ST-2 biomarker. The blood concentration of galectin-3 is a significant predictor of poor prognosis in patients with CHF and DM2. Predictors of the adverse course of CHF of varying severity were differentiated. For FC II CHF, NT-proBNP > 1723 pg/ml or, if NT-proBNP < 1723 pg/mL, then EDV > 311 ml. For FC III-IV CHF, ST-2 > 67 ng/mL or, if ST-2 < 67 ng/mL, then PAP > 61 mm Hg. Galectin-3 has a prognostic value for the clinical course of the disease at different follow-up periods in patients with CHF and DM2: galectin-3 concentrations > 16 ng/mL and 13-16 ng/mL are risk factors for mid- and long-term cardiac complications, respectively.

[Progression of Chronic Heart Failure: Prognostic Criteria and Non-Drug Prevention].

PURPOSE: to study frequency of progression of chronic heart failure (CHF), to develop multifactorial models for evaluation of risk of progression, and measures of non-drug secondary prevention of CHF. MATERIALS AND METHODS: We included in this study 531 patients with functional class (FC) I-III CHF (FC I - n=254, FC II - n=255, FC III - n=22). Examination included clinical-instrumental, clinical-functional, and laboratory (with determination of NT-proBNP concentration) investigations, use of the AUDIT and Morisky Green questionnaires. RESULTS: Rate of CHF progression for 24 months was 11.7 % (FC I - 16.1, FC II - 7.8, FC III - 4.5 %). Irrespective of FC significant factors of CHF progression were history of myocardial infarction, and low adherence to treatment. Additional prognostic criteria of increase of CHF FC I to FC II were age >74 years, excessive body mass, disturbance of carbohydrate metabolism, arterial hypertension, and frequent intake of alcohol. FC II CHF progression was associated with such factors as type 2 diabetes, 3­degree arterial hypertension, permanent atrial fibrillation, and smoking. Using these prognostic criteria, we developed multifactor models, based on which scales for assessing the risk of FC I and II CHF progression were created. These models demonstrated high accuracy of prognosis and good reproducibility (on independent test samples of patients with CHF FC I and FC II prognostic accuracy was 86.3 и 85.5 %, respectively). We also developed a program of secondary non-drug prevention of CHF progression,  with inclusion of structured dynamic education of patients with organization of control and self-control of knowledge quality. After this therapeutic education progression CHF in high risk patients was 2.2 %. CONCLUSION: Complex application of scores for evaluation of risk of FC I-II CHF progression and the program of secondary non-drug prevention determined lowering of frequency of increases of class of CHF severity from 11.7 to 2.2 %.

[Arterial Hypertension and Methylenetetrahydrofolate Reductase C677T Gene Polymorphism].

OBJECTIVE: to determine the association of polymorphisms of C677T methylenetetrahydrofolate reductase (MTHFR) gene with essential arterial hypertension (EH) in the group of patients of Belarusian ethnicity. METHODS: The clinical examination and molecular genetic study of the polymorphism C677T of MTHFR gene by polymerase chain reaction and restriction fragment length polymorphism analysis were performed in 423 people, including 315 patients with EH and 108 healthy individuals. RESULTS: The distribution of C and T alleles of polymorphism C677T of the MTHFR gene in hypertensive patients was 67.8 and 32.2%, in normotensive individuals - 71.8 and 28.2%, respectively. In the group of hypertensive patients, the prevalence of the TT (C677T) genotype of the MTHFR gene was 10.8%, in the healthy group - 5.5%. The TT genotype of the C677T MTHFR gene was more common in hypertensive patients with obesity in comparison with hypertensive patients with body mass index < 29.9 kg/m2 (61.8 vs 38.2%, respectively; p.

[CARDIOPROTRECTIVE EFFECT OF REMOTE POSTCONDITIONING: MECHANISMS AND POSSIBILITIES OF CLINICAL APPLICATION].

Experimental data indicate that postconditioning at a distance is an effective method for cardiac protection against reperfusion injury. Remote postconditioning prevents reperfusion necrosis and apoptosis of cardiomyocytes, decreases a probability of postinfarction remodeling of the heart. Cardioprotective effect of remote postconditioning depends on the release of tissue factor(s) increasing cardiac tolerance to long-term ischemia-reperfusion after transient ischemia. Clinical investigations show that postconditioning at a distance is an effective method for the prevention of reperfusion injury of the heart during coronary artery bypass surgery.

[Neuroprotective and nephroprotective effects of remote postconditioning: Prospects for clinical use]. / Neiroprotektornyi i nefroprotektornyi éffekty distantnogo prekonditsionirovaniia. Perspektivy klinicheskogo primeneniia.

The results of experimental and clinical studies strongly suggest that remote ischemic preconditioning (RIP) has no neuroprotective effect during cardiac surgery performed under extracorporeal circulation. Remote preconditioning (RP) has no neuroprotective effect in hemorrhagic stroke. A randomized multicenter study is needed to evaluate the efficiency RIP in patients with ischemic stroke. RP reduces the severity of ischemia/reperfusion kidney injury during transplantation. RIP has been established to prevent contrast-induced nephropathy. There is a need for a multicenter trial to evaluate the efficiency of RIP in patients with abdominal aortic aneurysm repair. Analysis of the presented data indicates that RIP fails to prevent cardiorenal syndrome in infants and children during cardiac surgery. The data available in the literature on the capacity of RIP to provide nephroprotective effect in patients after coronary artery bypass surgery are discordant and indicative of the advisability of a multicenter study.

[Remote preconditioning phenomenon. prospects for use in pathology of lung and gastrointestinal tract].

The literature data on the effectiveness of remote ischemic preconditioning (RIP) in the prevention of lung injury are contradictory. Authors of some works argue that RIP prevents lung damage during surgical interventions, the authors of other publications claim that the RIP does not protect lung against pathological processes. It is obvious that there is an urgent need for multicenter, randomized trials aimed at studying RIP protective effects against pathological processes in lung. Also required is clinical evaluation of the effectiveness of RIP in the thromboembolism of pulmonary arteries, the transplantation of the lungs and intestinal infarction. Remote preconditioning prevents the intestine injury associated with abdominal aortic aneurysm repair. Experimental data indicate that RIP has the hepatoprotective effect during ischemia and reperfusion injury of liver, septic or haemorrhagic shock. The question of whether the DIP has a protective effect during ischemia-reperfusion of the pancreas remains open.

[Antioxidant status and glutathione redox potential of erythrocytes in patients with acute coronary syndrome].

Indicators of oxidative stress (OS), systemic inflammation, metabolism and redox status of glutathione (GSH) were investigated and compared in patients with ST-segment elevation myocardial infarction on electrocardiograms (STEMI), and patients with unstable angina (UA). The elevated and decreased myeloperoxidase level, superoxide dismutase activity, and moderate increased plasma levels of interleukin-6, while maintaining the antioxidant potential, were found in Group 1. Disorders in pro-/antioxidant balance and systemic inflammatory response were manifested in UA. Increased GSH concentration (and total GSH) in erythrocytes has been established for STEMI patients and the decreased GSH for UA patients. Thus, a significant shift of erythrocytes redox to oxidization and increase (unlike STEMI patients) of glutathione peroxidase activity were recorded. Mechanisms of the pro- and antioxidant functions of red blood cells in acute coronary syndrome are considered. The role of red blood cell glutathione to provide more oxidized intravascular environment for S-glutathionylation and optimization of redox signaling in target cells is pronounced.

[Opioids--triggers of adaptive phenomenon of ischemic preconditioning of heart].

It was established that short-term ischemia/reperfusion evokes an increase in myocardial tissue of enkephalin levels. A blockade of delta-opioid receptors abolishes the cardioprotective effect of ischemic preconditioning both in vivo and in vitro. An inhibition of kappa-opioid receptors abolishes the cardioprotective effect of ischemic preconditioning only in vitro. Agonists of mu-, delta1- delta- and kappa1-opioid receptors mimic the cardioprotective effect of preconditioning. Consequently, it can be argued that endogenous opioid peptides are triggers of ischemic preconditioning.

[Perspective of use of agonists of adenosine and opioid receptors for prevention of reperfusion damages of heart. Analysis of experimental and clinical data].

In Russia inhospital lethality after acute myocardial infarction is 16.5-16.7%. The part of patients perishes even after recanalisation of infarct-related coronary artery as a result of reperfusion cardiac injury. Experimental data indicate that adenosine receptor agonists and opioids can prevent reperfusion damages of heart that is mimic postconditioning phenomena. Data of clinical observation show that adenosine during intravenous infusion or intracoronary administration during thrombolysis or percutaneous coronary intervention exert infarct reducing effect and eliminate manifestation of of "no-reflow" phenomenon. Clinical data indicate that morphine is able to prevent cardiac reperfusion injury in human. Thus, analysis of published data testifies that adenosine and opioid receptor agonists can be prototype for development of drugs for prophylaxis of reperfusion heart injury.

[Cardioprotective effect of remote postconditioning: mechanisms and possibility of clinical application].

Experimental data indicate that postconditioning at distance is an effective method of cardiac protection against reperfusion injury. Remote postconditioning prevents reperfusion necrosis and apoptosis of cardiomyocytes, decreases probability of postinfarction remodeling of the heart. Cardioprotective effect of remote postconditioning is depended on release from tissues after transient ischemia of humoral factor(s) increasing cardiac tolerance to long-term ischemia-reperfusion. Clinical studies show that postconditioning at distance is an effective method of prevention of reperfusion injury of the heart during coronary artery bypass surgery.

[Protein kinases role in adaptive phenomenon of heart ischemic postconditioning development].

Authors submitted an analysis of papers given up an involvement of protein kinases in heart ischemic postconditioning. This analysis of literature source allowed to authors affirms that signaling system of postconditioning can involve kinases: PKC, PI3K, Akt, MEKl/2, ERK1/2, MTOR, p70s6K, GSK3b, PKG and also eNOS, NO, GC, motoKATP channel, ROS, MPT pore. At the same time it is unclear a real contributions of kinases mTOR, p70s6, AMPK and GSK3b in the mechanism of infarct limiting impact of postconditioning. It is required a further study of the chain of signaling events following JAK2 and p38 kinase activation. The knowledge of Ras and Raf-1 role in postconditioning has hypothetical character. The tyrosine kinase significance in postcondi-tioning is unclear, particular Src kinase, which plays an important role in the regulation of cardiac tolerance to an impact of ischemia and reperfusion.

[Adaptive phenomenon of ischemic postconditioning of the heart. Perspectives of clinical use].

Analysis of experimental data indicates that aging, metabolic syndrome may be serious obstacle against realization of cardioprotective effect of postconditioning. The moderate hypercholesterolemia, postinfarction cardiosclerosis and cardiac hypertrophy do not abolish protective effect of postconditioning in experimental animals. The issue whether diabetes mellitus and arterial hypertension affect an efficacy of postconditioning is a subject of discussion. Clinical investigations testify on cardioprotective impact of postconditioning in patients with acute myocardial infarction and cardiosurgery patients. At the same time, it is remained unclear when after coronary artery occlusion postconditioning exhibits cardioprotective effect. It is remained unknown how do affect aging, diabetes mellitus, metabolic syndrome, arterial hypertension, myocardial hypertrophy, cardiac postinfarction remodeling and efficacy postconditioning in clinical praxis. It is required a further clinical investigations turning the development pharmacological approaches to prophylaxis of reperfusion injury of the heart.

[Phenomenon of heart ischemic postconditioning].

Authors of review analyzed papers on problem of heart ischemic postconditioning. In the review, it was demonstrated that postconditioning decreased an infarct size, prevented cardiomyocytes apoptosis, improved cardiac contractility in reperfusion period, augmented cardiac tolerance to arrhythmogenic impact ofreperfusion, prevented neutrophil invasion into the reperfused heart, abolished reperfusion endothelial dysfunction and suppressed reperfusion oxidative stress in myocardium.

[Trigger mechanism of adaptive phenomenon of ischemic heart postconditioning].

Analysis of published data indicates on trigger role of protons, adenosine, opioids, bradykinin, calcitonin gene-related peptide, nitric oxide, epoxyeicosatrienoic acid, reactive oxygen species, hydrogen sulfide in ischemic heart postconditioning. It is shown that B-type natriuretic peptide, transforming growth factor-beta1, cardiotrophin-1, urocortin, acetylcholine, insulin and carbon monoxide can mimic postconditioning phenomenon.

[The use of beta-adrenoblockers in the treatment of arterial hypertension in pregnant women].

We reviewed literature on the application of beta-adrenoblockers for the treatment of arterial hypertension during pregnancy. Decisions concerning administration of various preparations from this group in pregnant women should be taken with consideration of efficacy in correction of hypertension and safety for fetus and neonate. The review contains discussion of advantages and drawbacks of the use of beta-adrenoblockers for the treatment of hypertension in pregnancy in comparison with other antihypertensive drugs.

Polydisulfides of substituted phenols as effective protectors of peroxidase against inactivation by ultrasonic cavitation.

Kinetics of inactivation of horseradish peroxidase (HP) induced by low-frequency ultrasonic (US) treatment (27 kHz) with the specific power of 60 W/cm2 were studied in phosphate (pH 7.4) and acetate (pH 5.2) buffers within the temperature range of 36.0 to 50.0 degrees C and characterized by effective first-order rate constants of US inactivation k(in)(us) in min(-1). Values of k(in)(us) depend on the specific ultrasonic power within the range of 20-60 W/cm2, on the concentration of HP, and on pH and temperature of the solutions. The activation energy of US inactivation of HP is 9.4 kcal/mole. Scavengers of HO* radicals, mannitol and dimethylformamide, significantly inhibit the US inactivation of HP at 36.0 degrees C, whereas micromolar concentrations of polydisulfide of gallic acid (poly(DSG)) and of poly(2-aminodisulfide-4-nitrophenol) (poly(ADSNP)) virtually completely suppress the US inactivation of peroxidase at the ultrasonic power of 60 W/cm2 on the sonication of the enzyme solutions for more than 1 h at pH 5.2. Various complexes of poly(DSG) with human serum albumin effectively protect HP against the US inactivation in phosphate buffer (pH 7.4). The findings unambiguously confirm a free radical mechanism of the US inactivation of HP in aqueous solutions. Polydisulfides of substituted phenols are very effective protectors of peroxidase against inactivation caused by US cavitation.

Ultrasound fibrin clot destruction in vitro in the presence of fibrinolytic agent.

Ultrasound fibrin clot destruction was investigated in vitro using electron microscopy and by monitoring the changes in the light transmission of clot debris suspension. It has been established that in the course of a combined action of ultrasound and fibrinolytic agent at high ultrasound intensities and short sonification periods, fibrin clot is disrupted mainly due to sonomechanical treatment, while fermentative lysis takes place in parallel and at a significantly lower rate. However, the streptokinase action prevails after ultrasound switching off and results in the prevention of clot debris conglomeration.

Platelet aggregation and change in intracellular Ca(2+) induced by low frequency ultrasound in vitro.

Treatment of platelet-rich plasma and washed platelets with low frequency ultrasound (US, 22 kHz) at intensity range of 1.0-8.8 W/cm(2) resulted in intensity- and time-dependent platelet aggregation. The effect was absent in calcium-free medium and was initiated by adding supernatant from sonicated suspension (16 W/cm(2), 2 min) to non-treated platelets. A marked decrease in the rate of US-induced aggregation was observed in the presence of specific inhibitors of platelet activation dipyridamole, pentoxifillin, aspirin and verapamil. Concentration of intracellular calcium in washed platelets evaluated with fluorescent probe quin-2 acetoxymethyl ester (quin-2) increased upon sonication in both the calcium containing and calcium free media. It is suggested that US increase of [Ca(2+)](i) is involved in platelet aggregation induced by low frequency US.

[Comprehensive evaluations of the action of galvanic current dosages used in physiotherapy on the intact myocardium in an experiment]. / Kompleksnaia otsenka deistviia ispol'zuemykh v fizioterapii dozirovok gal'vanicheskogo toka na intaktnyi miokard v éksperimente.

The most common physiotherapeutically used intensity (2.4 and 8.0 mA) and duration (15, 30, and 45 min) of galvanic current were examined for their effects on the intact myocardium in laboratory rats. These effects were found to be alterative (damaging) and directly proportional to the dosage: the greater the current intensity and duration were, the higher myocytic lesion is. However, these changes were transient and myocardial microstructural normalization was observed 24 hours later.