[Immunomodulating, metabolic and cardioprotective effects of AT1-angiotensin receptors blocker losartan in patients with coronary heart disease and type 2 diabetes mellitus].

AIM: To evaluate effects of 6-month therapy with losartan in combination with indapamide on a clinical course, immunological, metabolic parameters, left ventricular function, exercise tolerance and quality of life in patients with coronary heart disease (CHD) associated with metabolic syndrome (MS). MATERIAL AND METHODS: Forty six CHD patients with postinfarction cardiac dysfunction in MS were randomized into two groups. Group 1 consisted of 22 patients with impaired glucose tolerance, group 2--of 24 type 2 diabetics. Treatment included combination of losartan (50 mg/day) with indapamide (1.5 mg/day), on demand nitrates, nebivolol. Basic therapy in diabetes included sugar-reducing drugs. Clinical condition, findings of echocardiography, parameters of lipid and carbohydrate metabolisms, immunoglobulins, circulating immune complexes, autoantibodies to cardiolipin (AB to CL), spectrum of proinflammatory cytokines were studied before and 3 months after course treatment. RESULTS: Overactivation of cytokines (primarily IL-2, IL-1, TNF alpha) with high expression of IgA, IgG, CIC, AB to CL was found in CHD patients with type 2 diabetes mellitus and less evident in impaired glucose tolerance. Losartan in both groups had an antihypertensive effect, stabilized LV hypertrophy, improved clinical symptoms leading to cytokines expression decline: TNF alpha by 9.8%, IL-1--by 6.1%, IL-6--by 6.7%. Losartan was well tolerated, caused no negative metabolic effects. CONCLUSION: New original facts of cytokine overactivation and humoral immunity disturbances were discovered which play an essential role in pathogenesis of postinfarction dysfunction and LV remodeling developing in type 2 diabetes mellitus. Losartan 6-month treatment in the fixed combination has a positive effect on clinicohemodynamic and immunometabolic indices. This gives grounds for wider use of losartan in CHD combined with type 2 diabetes mellitus.

[Suppressive effect of recombinant immunomodulator ronkoleukin on the blood level of antiinflammatory cytokines, anticardiolipin autoantibodies and heart failure].

AIM: To elucidate clinical efficacy and immunocorrecting properties of recombinant immunomodulator ronkoleukin in patients with postinfarction cardiac dysfunction with NYHA FC II-III CHF. MATERIAL AND METHODS: In a 6-months prospective comparative clinically controlled study we observed 33 survivors of myocardial infarction divided into 2 groups according to FC of chronic heart failure (CHF): group I (n=17) with FC II CHF with LVEF > 45% (mean age 52 +/- 2.9 years) and group II (n=16) with FC III CHF and lowered ( 40%) LVEF (mean age 53.7 +/- 3.3 years). Comparison group comprised practically healthy subjects. Clinico-laboratory and functional assessment of state of patients was carried out before initiation of therapy with ronkoleukin and in 2 - 3 days after completion of 2 courses of therapy with 3 months interval. Immunological study included determination of subpopulation content of peripheral blood lymphocytes, blood plasma immunoglobulins, antiinflammatory cytokines Il-1a, Il-1b, Il-2, Il-6, Il-8, TNFa and AB to Cl. RESULTS: It was found that ronkoleukin is an effective immunocorrector producing no adverse effects in patients with FC II-III CHF. Most pronounced effect ronkoleukin manifested in relation to humoral immunity lowering dysimmunoglobulinemia, blood levels of IgA, IgG, CIC and antibodies to cardiolipin, inhibiting excessive cytokine activation in dependence on degree of severity of CHF. CONCLUSION: Administration of ronkoleukin to patients with postinfarction dysfunction of the heart with FC II-III CHF for correction of secondary immunodeficient state in addition to basic therapy provides positive changes of hematological, immunological parameters, intracardiac hemodynamics, facilitates regression of symptoms of CHF and improves quality of life.

[Clinico-immunological disorders in patients with ischemic heart disease combined with metabolic syndrome and modulating effect of nebivolol for their correction].

AIM: To evaluate clinico-immunological disorders in patients with ischemic heart disease (IHD) and metabolic syndrome (MS), to study an immunocorrective action of nebivolol during 6-month treatment. MATERIAL AND METHODS: A total of 54 patients with postinfarction left ventricular dysfunction and chronic cardiac failure of NYHA functional class II-III were divided into two groups: group 1 (n=24) comprised patients with effort angina FC II-III and impaired glucose tolerance, group 2 (n=30) consisted of anginal patients associated with type 2 diabetes mellitus (DM). Clinical, laboratory and functional indices were registered before therapy with nebivolol and 6 months after it. Immunological control included determination of the subpopulation composition of lymphocytes, immunoglobulins, circulating immune complexes (CIC), antibodies to cardiolipin (CL), proinflammatory cytokines: IL-1alpha, IL-2, IL-6, IL-8, alpha-interferon, tumor necrosis factor alpha (TNFalpha). RESULTS: Nebivolol demonstrated good antihypertensive and anti-ischemic cardioprotective efficacy in IHD patients with MS, it did not deteriorate atherogenic dyslipidemia and impaired carbohydrate metabolism. As a good immunocorrector, nebivolol significantly inhibited cytokine overactivation, had a weak effect on dysimmunoglobulinemia, CIC level and expression to CL antibodies. Side effects were not recorded. CONCLUSION: IHD patients with MS (especially patients with type 2 DM) have manifest immune disorders presenting with overactivation of proinflammatory cytokines with high levels of IgA, IgG, CIC and antibodies to CL in the presence of low immunoregulatory index. Nebivolol provided good control of arterial hypertension, myocardial ischemia, positive changes in immunological indices, improved intracardiac hemodynamics.

[Clinicoimmunological disorders in patients with postinfarction left ventricular remodeling and chronic cardiac failure].

AIM: To characterize clinical and immune disorders in patients with ischemic heart disease (IHD), postinfarction left ventricular remodeling (PLVR), clinical manifestations of chronic cardiac failure (CCF). MATERIAL AND METHODS: A comparative clinical controlled trial of immune system was made. The immune system was assessed by diagnostic and prognostic significance of changes in population composition of T- and B-lymphocytes, by activation of proinflammatory cytokines (IL-1alpha, IL-2, IL-6, IL-8, Inf-alpha, TNF-alpha); high expression of circulating immune complexes (CIC), autoimmune complexes to cardiolipin (CL) in 94 CCF patients with PLVR. The patients were divided into 3 groups according to severity of CCF. Group 1 consisted of 32 patients with CCF (FCII by NYHA) and normal ejection fraction (EF) of the left ventricle (52.0 +/- 2.8%). Group 2--31 CCF (FCIII) patients with decreased EF (by 43.8%) (36 +/- 4.3%). Group 3--31 CCF (FCIV) patients with low (25 +/- 3.8%) EF of the left ventricle. The protocol required conduction of echocardiographic parameters, paired bicycle exercise tests, 6-min walk tests, 24-h ECG monitoring, population cell composition of T- and B-lymphocytes, concentrations of cytokines, IgG and IgG autoantibodies to CL. RESULTS: A dominating hyperactivation of cytokines TNFalpha, IL-1alpha, IL-2, IL-6 with high expression of CIC and autoAB to CL was associated with moderate or severe CCF (FCII-IV by NYHA), declined inotropic function of the left ventricle (EF 38-23%), low exercise tolerance and remodeling of the left ventricle. CONCLUSION: Immune disorders in the form of hyperactivation of proinflammatory cytokines (most of all TNFalpha, IL-1alpha, IL-2, IL-6), enhanced expression of CIC and autoAB to CL growing with severity of CCF and abnormal heart pump function play an important role in CCF pathogenesis in IHD patients with LCPR and can be markers of the disease progression.

[The long-term results of coronary artery bypass grafting in patients with type II diabetes].

A three-year follow-up of patients with coronary heart disease (CHD) and type II diabetes after coronary artery bypass grafting, shows that the following pathologic conditions are significantly more frequent: arterial hypertension, visceral obesity, marked disturbances of blood lipid spectrum, an increases CHD duration, and an increased rate of myocardial reinfarction and revascularizations. The study shows that the presence of diabetes mellitus in CHD patients undergoing coronary artery bypass grafting, is associated with pronounced disturbances in blood lipid spectrum, and is an important risk factor of coronary event progression.

[Antiischemic and metabolic effects of nebivolol and metaprolol CR/XL (betalok ZOK) in patients with postinfarction heart dysfunction].

The purpose of the study was to evaluate anti-ischemic and metabolic effects of the cardioselective beta-adrenoblockers nebivolol and retarded metoprolol-metaprolol CR/XL (betalok ZOK) in patients with postinfarction heart dysfunction, associated with type II diabetes mellitus (DM). 40 patients with coronary heart disease (CHD), functional class (FC) II-III exertional angina, postinfarction left ventricular (LV) dysfunction, and NYHA FC II heart failure, associated with type II DM, were randomized into 2 groups. The 20 patients of the 1st group were administered nebivolol in a dose of 1.25 to 5 mg per day, the 20 patients of the 2nd group - betalok ZOK in a dose of 12.5 to 100 mg per day. The course therapy lasted 8 weeks. The effects of the treatment were evaluated using paired veloergometry, echoCG, and lipid spectrum analysis. The study found that nebivolol in a mean dose of 4.2 +/- 0.3 mg per day and betalok ZOK in a dose of 46.5 +/- 6.2 mg per day reduced the frequency and severety of angina attacks (by 73.8% and 67.8%, respectively) and daily nitroglycerine uptake (by 78.6% and 69.1%, respectively), and increased activity tolerance (by 7.9% and 25.3%, respectively). None of the preparations displayed any adverse effects on carbohydrate exchange and blood lipid spectrum. Nebivolol, unlike betalok ZOK, significantly (p = 0.02) reduced triglyceride blood level by 29%. Thus, the new generation cardioselective beta1-adrenoblockers nebivolol and metoprolol CR/XL (betalok ZOK) provide anti-ischemic and metabolic effects in patients with CHD and postinfarction LV dysfunction, associated with type 2 diabetes mellitus. Nebivolol is preferable as far as blood lipid spectrum is concerned.

[Effect of carvedilol on blood levels of cytokines and symptoms of heart failure in patients with postinfarction cardiac dysfunction.]. / Moduliruiushchee vliianie karvedilola na aktivatsiiu tsitokinov i regress serdechnoi nedostatochnosti u bol'nykh s postinfarktnoi disfunktsiei serdtsa.

Effect of 6 months treatment with carvedilol (25 mg/day) on blood levels of cytokines (interleukins 1alpha, 2, 6, 8, tumor necrosis factor alpha) and clinical symptoms of heart failure was studied in patients with cardiac dysfunction after myocardial infarction. Patients with NYHA class II heart failure, ejection fraction 50% and moderately lowered tolerance to physical exercise (n=21) initially had enhanced cytokine expression: blood content of interleukin (IL) 2 was 2.8 times, tumor necrosis factor (TNFalpha) 78%, IL-1alpha 60% above normal level. Therapy with carvedilol in this group was associated with decreases of Il-2 (-23.8%), TNFalpha (-16.7%), IL-1alpha (-12.5%) (p<0.05-0.01). This was accompanied by alleviation of clinical symptoms and improved exercise tolerance. Patients with NYHA class III heart failure (n=16) with low left ventricular ejection fraction (30+/-2.7%) and low exercise tolerance had high levels of all studied cytokines. Levels of IL-2, TNFalpha and IL-1alpha were most elevated (3.1, 2.8 and 2 times higher than normal values, respectively). Therapy with carvedilol was associated with improvement of clinical symptoms and exercise tolerance (+35%, p<0.05)), increase of ejection fraction (+15%, p<0.05), decrease of left ventricular end systolic volume (-17.5%, p<0.05), and lowering of blood levels of TNFalpha (-31%), IL-2 (-17.4%), IL-1alpha (-15.6%). However cytokine levels remained substantially elevated compared with normal values. Carvedilol was well tolerated, and did not cause negative metabolic effects or other complications.

[A role of activation of proinflammatory cytokines and production of autoimmune complexes in the pathogenesis of chronic heart failure in patients with postinfarct cardiac dysfunction]. / Rol' aktivatsii provospalitel'nykh tsitokinov i produktsii autoimmunnykh kompleksov v patogeneze serdechnoi nedostatochnosti u bol'nykh s postinfarktnoi disfunktsiei serdtsa.

A comparative randomized clinical study was conducted to evaluate the diagnostic and prognostic value of the activation of proinflammatory cytokines [tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1alpha, IL-2, IL-6, IL-8)] and the increased production of autoimmune complexes in the pathogenesis of chronic heart failure (CHF) in patients with coronary heart disease (CHD). The study included 47 patients with CHD who had a more than 6-month history of Q-forming myocardial infarction. The patients were randomized into 3 groups: 1) 21 patients with NYHA Functional Class (FC) II heart failure (HF); 2) 16 patients with FC III HF; and 3) 10 with FC IV HF. Basic therapy involved angiotensin-converting enzyme (ACE) inhibitors, nitrates, diuretics, beta-adrenoblockers; 27.6% received digoxin, disaggregatory agents. A study protocol involved the estimation of the parameters of EchCG, paired bicycle ergometric tests, 6-min walking test, ECG daily monitoring, the levels of proinflammatory cytokines in the serum and IgG autoantibodies to cardiolipin. The findings suggest that with the higher expression of autoimmune complexes, the activation of cytokines (primarily TNF-alpha, IL-1alpha, IL-2) plays an important role in the pathogenesis of CHF in patients with postinfarct cardiac dysfunction: the high activation of cytokines and the elevated level of autoimmune complexes are associated with moderate or severe NYHA FC II-IV HF, depressed left ventricular contractility (ejection fraction, 23-38%), low exercise tolerance, and cardiac remodeling.

[Use of a multivariate analysis method for determining the interconnection of genetic markers with gene clusters and solution of taxonomy problems for the recombinant influenza A virus model]. / Primenenie metodov mnogofaktornogo analiza dlia opredeleniia vzaimosviazi geneticheskikh markerov s konstelliatsiei genov i resheniia zadach taksonomii na modeli rekominantov virusa grippa A.

The collection of influenza A viral recombinants has been studied for determining interconnection of the definite genetical marker (pneumovirulence for mice) with genes constellation by the technique of image identification. Pneumovirulence is found to be defined by correlation of polymerase complex M-, NS- and NA-genes. The data on NA influence on pneumovirulence were obtained for the first time, the phenomenon being found only with the use of image identification technique. The used methods of image identification (the method of correlation plaiads and cluster analysis) are recommended for use in studying the specificity of the gene control for different genetical features.