[Structural and Functional Remodeling of Vascular Wall in Persons With Family History of Hypertension].

Aim of investigation - to study parameters of structural and functional remodeling of vascular wall in persons with family history of hypertension (with burdened or positive hypertensive heredity). We examined 95 persons (aged 17 - 28 years) with family history of hypertension (positive hypertensive heredity) and divided them into 3 groups: group 1 - patients with arterial hypertension (AH), group 2 - patients with high normal blood pressure (BP), group 3 - persons with normal BP). Control (C) group comprised 24 subjects with normal BP without family history of AH. Examination included ultrasound investigation of brachial artery (BA) and common carotid artery, assessment of endothelial-dependent flow-mediated dilatation (EDFMD) of BA, calculation of parameters of distensibility coefficient of vascular wall. EDFMD in groups 1 and 2 was lower than in controls, and corresponded to values of carotid intima-media thickness (CIMT) (p<0.001). Mean values of arterial wall distensibility coefficient in persons with family history of AH were smaller than in control group (p=0.0001 - p <0.005). Lowest mean values of common carotid artery elasticity coefficient as well as highest pulse wave propagation velocity along elastic type vessels was observed in group 1. Thus patients with family history of AH even at early stages had signs of endothelial dysfunction: lowered EDFMD of BA, increased CIMT, lowered elastic properties and increased stiffness of carotid artery wall.

[Pharmacogenomic control of angiotensin converting enzyme gene I/D polymorphism predominant risk factor of development of chronic heart failure and target of enalapril treatment].

Aim of investigation - to study effect of angiotensin-converting enzyme (ACE) gene polymorphism as a dominant risk factor of development of chronic heart failure (CHF) and target for effective therapy with ACE inhibitor enalapril in patients with ischemic heart disease. We followed 226 patients with CHF on stable permanent basic therapy comprising -adrenoblocker, diuretic, aldosterone antagonist, digoxin, and ACE inhibitor. Seventy eight patients received enalapril (starting dose 2.5 mg twice daily with subsequent titration up to 10-20 mg twice daily). Control group comprised 136 patients without cardiovascular abnormalities. Allele D of polymorphic locus I/D of ACE gene in homozygous state was associated with high risk of development and severity of clinical manifestations of CHF. In patients with D/D genotype of ACE gene at the background of therapy with enelapril we noted more pronounced lowering of CHF functional class and augmentation of left ventricular ejection fraction compared with patients having I/I and I/D genotypes. We revealed associative interrelationships of ACE gene polymorphism (polymorphic locus I/D) with development and severity of CHF as well as effectiveness of therapy with an ACE inhibitor enalapril.

[Impact of angiotensionogen and angiotensin II receptor type 1 gene polymorphisms on the development and course of chronic heart failure].

AIM: To study the impact of angiotensinogen (AGT) and angiotensin II receptor type 1 (AGTR1) gene polymorphisms on the development and course of chronic heart failure (CHF) in patients with coronary heart disease (CHD). SUBJECTS AND METHODS: Two hundred and twenty-six patients (149 men and 77 women; mean age 55.9 +/- 5.8 years) with CHF were examined. Genotypes were identified by the restriction fragment length polymorphism analysis of polymerase chain reaction products. A control group comprised 136 subjects (63 men and 73 women; mean age 53.6 +/- 4.8 years) without signs of cardiovascular diseases, as evidenced by the examination. RESULTS: The T allele of the M235T polymorphism in the AGT gene was found to be associated with the development and unfavorable course of CHF in patients with CHD. At the same time, carriage of the M allele of the M235T polymorphism in the AGT gene reflected the favorable course of this disease. That of the C allele and A/C genotype of the A1166C polymorphism in the AGTR1 gene was associated with the development of CHF and the A allele and A/A genotype manifested themselves as protective factors. According to the severity of CHF and the nature of its course, the distribution of frequencies of the genotypes and alleles of the A1166C polymorphism in the AGTR1 gene showed no significant differences between the patient groups. CONCLUSION: There were associations of the polymorphisms of the AGT gene (the M235T polymorphic marker) and the AGTR1 gene (the A1166C polymorphic marker) with the development of CHF in patients with CHD.

[Rational minimally invasive nature in surgical reconstructions of the abdominal aorta].

Based on a meta-analysis of the literature and own experience in a total of 490 reconstructions of the aortofemoral segment using a miniapproach, the authors carried out a comparative analysis of the main minimally invasive methods employed for treatment of the pathology concerned.

[Outcomes of using autologous peripheral-blood stem cells in patients with chronic lower arterial insufficiency].

Presented herein are the outcomes of using autologous peripheral blood stem cells (SCs) in patients with stage II В lower limb chronic obliterating diseases (according to A.V. Pokrovsky's classification). Autologous SCs had previously been stimulated by means of the recombinant granulocytic colony stimulating factor (G-CSF) for five days. On day six, we performed mobilization of the peripheral blood stem cells on the MSC+ unit by means of leukopheresis followed by intramuscular administration of half of the obtained dose into the affected extremity. The mean number of the transplanted mononuclears amounted to 6.73 ± 2.2 x 10(9) cells, with the number of CD34+ cells averaging 2.94 ± 2.312 x 10(7). Assessing the therapeutic outcomes at 3 and 6 months of follow-up showed a statistically significant increase in the ankle-brachial pressure index (ABPI) [being at baseline 0.59 ± 0.04, at 3 months - 0.66 ± 0.04 (P=0.001), and after 6 months - 0.73 ± .08 (P=0.035)], accompanied and followed by improved measures of the treadmill test, with the pain-free walking distance at baseline equalling 102.2 ± 11.55 m, after 3 months - 129 ± 11.13 m (P<0.001), and after 6 months - 140 ± 13.11 m=0.021 vs baseline). The findings of the immunohistochemical study confirmed the development of neoangiogenesis in the skeletal muscle and a 25 percent increase in the capillary-network density following administration of autologous stem cells into the muscle. The method of transplanting peripheral-blood autologous stem cells for treatment of patients presenting with distal forms of chronic obliterating insufficiency of the lower limbs proved safe and efficient. The findings obtained during this study made it possible to recommend extending the indications for its application at the expense of patients with critical ischaemia.

[Polymorphism of eNOS and iNOS Genes and Chronic Heart Failure in Patients With Ischemic Heart Disease].

UNLABELLED: URGENCY: Despite substantial progress in the treatment of coronary heart disease (CHD) and chronic heart failure (CHF) prognosis in these conditions remains extremely serious. This warrants their timely prevention and early detection. Aim. To study influence of inducible NO synthase (iNOS) (CCTTT)n, Glu298Asp and diallel polymorphism in the fourth intron (4a/4b polymorphism) of endothelial NO synthase gene (eNOS gene) on the state of endothelial function and risk of development of CHF in patients with CHD. MATERIALS AND METHODS: 165 patients with CHD were studied (121 male and 44 female, mean age 56.7 + or - 5.3 years). Vasomotor endothelial function was evaluated using ultrasound method in the reactive hyperemia and trinitroglycerol tests. Genotypes were identified using RFLP analysis of PCR products. Control group consisted of 114 persons (54 male and 60 female, mean age 53.2 + or - 4.9 years). RESULTS: It was determined that the number of repeats of polymorphic locus (CCTTT)n of the iNOS gene and Glu allele of the polymorphic locus Glu298Asp of eNOS gene in the homozygous state were associated with the risk of development of CHD and class of severity of CHF clinical manifestation. In addition Glu allele of the polymorphic locus Glu298Asp of eNOS gene in the homozygous state was associated with the severity and unfavorable development of CHF. The endothelial-dependent dysfunction was more severe in homozygotes of Glu allele of the polymorphic locus Glu298Asp of eNOS gene than in carrier of allele 298Asp. Associations between polymorphic variant of VNTR intron 4 gene eNOS and CHF with the risk of development and endothelial dysfunction were not found. CONCLUSION: An association between polymorphism of iNOS gene (CCTTT)n, eNOS gene (Glu298Asp) with development of CHD and severity of CHF was shown. The polymorphism of eNOS gene (Glu298Asp) was associated with endothelial dysfunction.

[Impact of Gly389Arg beta1-adrenoceptor polymorphism on the risk of chronic heart failure, the nature of its course, and on the efficiency of its treatment with carvedilol].

AIM: To study beta1-adrenoceptor gene (ADRB1) polymorphism on the development and course of chronic heart failure (CHF) and on the efficiency of its treatment with the beta-adrenoblocker carvedilol in patients with coronary heart failure. SUBJECTS AND METHODS: Two hundred and twenty-six patients (149 males and 77 females; mean age 55.9 +/- 5.8 years) with CHF, who received continuous basic therapy: angiotensin-converting enzyme inhibitors, a diuretic, an aldosterone antagonist, digoxin, and a beta-adrenoblocker, were examined; 68 patients were given for 24 weeks carvedilol (its starting dose was 3.125 mg twice daily with its further adjustment until an individually tolerable dose was achieved). Genotypes were identified by the restriction fragment length polymorphism analysis of polymerase chain reaction products. A control group comprised 136 subjects (63 males and 73 females; mean age 55.9 +/- 5.8 years) without signs of cardiovascular disorders, as evidenced by the examination. RESULTS: In patients with CHF, the Gly allele of the Gly389Arg polymorphic locus of the ADRB1 gene in homozygous state was associated with the high individual risk for CHF, the severity of its clinical manifestations and the nature of its course while carriage of the Arg allele of the Gly39Arg polymorphic locus manifested itself as a protective factor. During long-term carvedilol therapy, CHF patients with the Arg/Arg genotype of the ADRB1 gene were observed to have a more pronounced decrease in the functional class of heart failure, a significant increase in left ventricular ejection, and a decrease in left ventricular end-systolic and end-diastolic sizes as compared with patients with the Gly/Arg genotype. CONCLUSION: There were associations of the polymorphism of ADRB1 gene (the Gly39Arg polymorphic locus) with the development and severity of CHF and with the efficacy of therapy with beta-adrenoblocker carvedilol.

[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.

[Characteristics of systemic inflammatory reaction in elderly patients of different age with the chronic heart failure].

The peculiarities of development systemic inflammatory reactions during the chronic heart failure were studied in the research. The patients with different severity of the chronic heart failure and different clinical course were examined at the beginning and in the dynamics of the clinical observation. The functional activity of neutrophils, pro- and antioxidant activity of serum were estimated in these patients. It was found that the functional activity of neutrophils in the course of systemic inflammatory reactions during the chronic heart failure decreased against the misbalances between pro- and antioxidative

[Use of zeolite-containing biologically active food supplement in patients with burn trauma]. / Primenenie tseolitsoderzhashchei biologicheski aktivnoi dobavki k pishche u patsientov s ozhogovoi travmoi.

The content of cationic protein in blood neutrophils, the serum activity of lysosomal enzymes, the intensity of peroxide lipid oxidation, the antioxidant serum activity and the blood concentration of trace elements were assessed in patients with burn injury. Some patients as addition to the main therapy got zeolyt-containing biological active addition to food (BAAF) "Lytovit" with its ability for sorption and selective ion exchange. Before the beginning of the treatment in all patients high value of the cationic protein degranulation, decrease of neutrophils biocidity, and increase of lipid peroxidation against a background of antioxidant activity were found. In patients, who had got zeolyt containing BAAF, the normalization of trace elements blood concentration and indices of neutrophils functional activity began earlier, then in patients without zeolyt containing biological active addition treatment. "Lytovit" promoted the more early regress of the clinic manifestations: the body temperature normalization, wounds self-cleaning from purulent discharge, diminishing of frequency and area of the grafts lysis.

[The determination of the leukocyte-modulating activity of the blood serum in an acute coronary syndrome]. / Opredelenie leikotsitmoduliruiushchei aktivnosti syvorotki krovi pri ostrom koronarnom sindrome.

A method for evaluating the serum leukocyte-modulating activity (LMA) in patients with unstable angina pectoris (UAP) and acute myocardial infarction (AMI) is proposed. The method consists in measuring the total phlogogenic potential of the blood serum from increase or decrease in the chemiluminescence of donor leukocyte suspension after its incubation with patient's serum. LMA sufficiently accurately reflects the imbalance between the pro- and anti-inflammatory activities of the serum in patients with UAP and AMI. Predominance of the stimulating components in the serum predicts a more acute course and rapid development of AMI with complications. Inhibition of the leukocyte activity by patient's serum predicts a torpid protracted course of the acute coronary syndrome, indicative of an extremely low phlogogenic potential of the serum. The course of the acute coronary syndrome is complicated in both cases, requiring additional correction with anti-inflammatory drugs.

[Trimetazidine effects on exercise tolerance and left ventricular diastolic function in patients with coronary heart disease]. / Vliianie terapii trimetazidinom na tolerantnost' k fizicheskoi nagruzke i diastolicheskuiu funktsiia levogo zheludochka serdtsa u bol'nykh ishemicheskoi bolezn'iu serdtsa.

AIM: Trial of trimetasidine effects on exercise tolerance (ET) and left ventricular diastolic function (LVDF) in patients with coronary heart disease (CHD). MATERIALS AND METHODS: The study group included 40 CHD patients. Of them 10, 18 and 12 had myocardial infarction, unstable angina pectoris and stable angina, respectively. 38 CHD patients of the control group had these disorders, respectively, in 5, 15 and 18 cases. 2-3-month therapy with nitrates, beta-blockers (BB) and inhibitors of angiotensin-converting enzyme (ACE) was given to both groups with adjuvant trimetasidine (60 mg/d) given to patients of the study group. The effects were judged by the results of cycle exercise tests and echo-CG including the loading one. RESULTS: Adjuvant use of trimetasidine improved exercise tolerance, mean threshold capacity, LVDF. When added to BB treatment, trimetasidine reduced damage to LVDF under dipiridamol test. CONCLUSION: Trimetasidine addition to combined treatment of CHD raises exercise tolerance and improves LVDF.

[The diagnostic and prognostic assessment of the changes in lysosomal enzymatic activity in the blood of patients with acute myocardial infarct and unstable stenocardia]. / Diagnosticheskaia i prognosticheskaia otsenka izmeneii aktivnosti lizosomal'nykh fermentov v krovi u bol'nykh ostrym infarktom miokarda i nestabol'noi stenokardiei.

Serum activity of five lysosomal marker enzymes was measured in patients with acute myocardial infarction (AMI) and unstable angina pectoris (UAP) with consideration of the disease severity. A significant increase of enzyme activity was found both in patients with UAP and AMI on the first day of hospitalization. The enzymes activity was higher in patients with more severe form of AMI. Lysosomal enzyme activity was closely related to severity of the disease: clinical improvement occurred in patients with decreased activity (on day 7-10), while in aggravation of the disease lysosomal hyperenzymemia stayed high up to the end of the observation period (on day 30). The above findings demonstrate feasibility of using lysosomal enzymes test both for differentiation between AMI and UAP and for predicting the disease recurrences.

[Various mechanisms of lysosome involvement in the process of tissue injury]. / Nekotorye mekhanizmy vovlecheniia lizosom v protsessy tkanevogo povrezhdeniia.

Impairments in structural integrity of liver, heart and skeletal muscle lysosomes followed by necrotic and necrobiotic alterations in the tissues and secretion of active hydrolases in blood were detected under conditions of exhaustive physical exercises in rats when dose-dependent physical loading was studied. At the same time, in patients with hypertrophic cardiomyopathy physical loading, carried out as stepwise spiroveloergometry up to the submaximal heart rate, led to release of lysosomal enzymes into blood, which was not observed in healthy persons under similar conditions. The higher level of enzymes was found in circulation of the patients with most severe forms of the disease.