[DEPENDENCE OF LEVEL OF MYELOPEROXIDASE OF PLASMA OF BLOOD ON FUNCTIONAL STATE OF NEUTROPHILS AT ACUTE INFARCT OF MYOCARDIUM.]

The purpose of this work was to define dependence of maintenance of myeloperoxidase (MPO) in plasma of blood of patients by the acute infarct of myocardium from the state of oxygen metabolism of neutrophils, which was estimated on activity of myeloperoxidases, superoxid-anion and catalase in cells and on maintenance by peroxigens. 19 is inspected practically healthy volunteers and 56 patients with the the acute infarct of myocardium. The got results testify that maintenance of MPO in plasma of blood of patients with acute infarct of myocardium depends on the functional state of neutrophils, which, in its turn, is related to the clinical features of patients. Low maintenance is associated exceptionally with low activity of MPO of neutrophils, and also other oxygen radicals. High maintenance of MPO in plasma accompanied low or high activity of MPO of neutrophils and is pathognomonic for patients with the acute infarct of myocardium.

KORVITIN REDUCES THE HIGH MAINTENANCE OF MYELOPEROXIDASE IN PLASMA OF BLOOD OF PATIENTS WITH THE ACUTE INFARCT OF MYOCARDIUM.

We studied the content of myeloperoxidase in plasma of blood, which is a new additional marker of the metabolic activity of phagocytes and the activity of inflammation in patientes with the acute infarct of myocardium and possibility of its correction of Korvitin. We inspected 15 practically healthy persons in which the content of myeloperoxidase was 74,5±16,3 ng/ml, 13 patients with a stable stenocardia (the conent of myeloperoxidase was 218,4±30,9 ng/ml) and 60 patients with acute infarct of myocardium (the content of myeloperoxidase was 606,0±59,3 ng/ml at the beginning of therapy) in the dynamics of treatment. In patients accepting standard treatment (without application of Korvitin), the content of myeloperoxidase was unchanged during 7 days of treatment. It patients administered korvitin, the action of this preparation depended on the initial level of myeloperoxidase. In Patients with the initial normal plasma content of myeloperoxidase (16,7%), its content insignificantly increased during the time course of the treatment, while in patients with the high initial level of myeloperoxidase (83,3%), its level declined during treatment.

[Impact of renal dysfunction on clinical course of myocardial infarction complicated by acute heart failure in patients with preserved systolic function].

Aiming to assess the relationships between renal function and ST-segment elevation myocardial infarction (MI) clinical course and remote outcomes in patients with preserved systolic left ventricular (LV) function (LV ejection fraction > 40%) estimated glomerular filtration rates (eGFR) were evaluated on 1st and 3rd -10th MI day (n = 491). On 3rd-10th day of MI in patients with acute heart failure (HF) symptoms on admission day (1st group, n = 153) eGFR < 70 ml/min x per body surface unit was independent marker of re-infarction (Hazzard Ratio (HR) with 95% confidence intervals (95% CI) = 4,08 [1,72 -11,73], P < 0,01) and cardiovascular death (CVD) (HR [95% CI] = 3,61 [1,09 - 11,99], P = <0,05) during three years of follow-up. In patient without acute HF (2nd group, n = 338) eGFR < 68 ml/min was predictive of CVD within three years post-MI (HR [95% CI] = 7,13 [2,06 - 24,74], P = 0,002). eGFR did not correlate with myocardial damage markers. In the 1st group eGFR on the 3rd MI day was negatively correlated with tumor-necrosis factor alpha (TNF-alpha) and vascular endothelial growth factor levels. There were no correlation between systemic inflammation activation with eGFR in 2nd study group indicating different mechanisms of renal dysfucntion in patients with and without acute HF and preserved LV function.

[Cytokine profile of mononuclear leukocytes in patients with myocardial infarction complicated by cardiac insufficiency].

Between the pro- and antiinflammatory components of the immune system there is a dynamic balance, violation of which is an important mechanism of development of many pathological states, in particular, cardiac insufficiency. The purpose of the work was a study of secretion of cytokines by mononuclears in patients under myocardial infarction, uncomplicated (1 group) and complicated (2 group) acute cardiac insufficiency, and determination of balance between pro-(TNF-alpha, IL-6, IL-8) and antiinflammatory (1L-10) factors in development of acute cardiac insufficiency in patients with myocardial infarction. The results indicate that in patients of group 1 there is initially a high level of both proinflammatory and antiinflammatory cytokines. After 10 days, we observed a decline in the IL-6 level and an increase in the TNF-alpha and IL-10 levels. In patients of group 2 we observed initially high levels of TNF-alpha and IL-6 and a reduced levels of IL-8 and 1L-10, as compared to patients of group 1. In dynamics of supervision of this group, further increase of all proinflammatory cytokines and a decline of IL-10 was registered. Balance between the pro- and antiinflammatory cytokines reflects the index of inflammatory activity, determined by formula (TNFalpha+IL-6+IL-8)/IL-10 and testifying that in patients of group 1 in the dynamics of treatment there is normalization of cytokin's balance, accompanied by decline of the index, while in patients of group 2 the index rose at 10th day.

[The frequency of allelic polymorphism of matrix Gla-protein gene in acute coronary syndrome patients].

Allelic polymorphisms of matrix Gla protein (MGP) gene were determinated in 115 patients with acute coronary syndrome (ACS) and in 110 practically healthy people. It was shown that interrelation of major homozygotes, heterozygotes and minor homozygotes by T-138-->C MGP promoter polymorphism in patients with ACS were 59.8%, 32.7%, 7.5% and in control 58.7%, 36.7%, 4.6% (P>0.05 by X2-test); by G-7-->A polymorphism: 42.1%, 45.6%, 12.3% and 41.8%, 54.5%, 3.6% correspondingly (P<0.05); and by Thr83Ala exon 4 polymorphism: 42.6%, 43.5%, 13.9% compared to 43.9%, 45.9%, 10.2% in control (P>0.05). The obtained data show that MGP A/A variant of MGP promoter G-7-->A polymorphism is a risk factor of ACS in Ukrainian population. These data indicate also that the intensity of calcification influences atherosclerotic injury of coronary artery.

[Metabolic activity of neutrophilic granulocytes and possible ways of its correction in patients with acute coronary syndrome].

The present study aimed to investigate the metabolic activity of neutrocytes and the action of corvitin on the level of superoxide anion and myeloperoxidases of cells in vitro with the calculation of index of consumption of myeloperoxidase in patients with ST-elevation acute coronary syndrome. Patient were divided into 2 groups according to the level of superoxide anion. Group 1 included the patients (68%) with the initially low level of superoxide anion, and adding of corvitin to the cells of such patients promoted normalization of this index. In this group we observed also neutrocytosis, low index of consumption of myeloperoxidase and a high level of this enzyme in general population of neutrocytes. Group 2 included patients (32%) with initially normal level of superoxide anion. In this group, corvitin did not influence substantially this factor. Such patients had a level ofmyeloperoxidase within control values and the index of consumption of this enzyme was also within control values. The analysis of hospital period showed that the patients of group 1 had a higher frequency of ventricular tachycardia/ventricular fibrillation, paroxysms of atrial fibrillation, bundle-branch blocks and worsening of the kidney function. We suppose that a low level of superoxide anion in neutrocytes play a major role in the development of complications in patients with acute coronary syndrome. An intravenous administration of corvitin was effective in restoring the metabolic activity of neutrocytes.

[Allelic polymorphism of endothelial NO-synthase (T(-786)-->C) promoter gene as risk factor of acute coronary syndrome].

Frequency of promoter endothelial NO-synthase gene allelic polymorphism by using polymerase chain reaction and restriction fragment length polymorphism (RFLP-PCR) was determined in 221 patients with acute coronary syndrome (ACS) and in 83 almost healthy subjects. Data obtained indicate that different promoter allelic variant frequency differs significantly in patients with ACS and in control group. Correlation of normal homozygotes (T/T), heterozygotes (T/C) and pathologic homozygotes (C/C) was 48%, 36% and 16% respectively in patients, and in control it was 48%, 46%, 6% (P<0.05 by c2-test). Thus, in patients with ACS in Ukrainian population pathologic C/C variants of 5'-flanking region of eNOS gene were found 2.7-times more often in ACS patients, than in control. This allows us to suggest, that this allelic polymorphism can be considered as one of genetic risk factors of ACS development.

[Pathophysiologic aspects of endothelial NO-synthase genetic polymorphism]. / Patofiziolohichni aspekty henetychnoho polimorfizmu endotelial'noï NO-syntazy.

Information about fourteen allelic variants of promoter, exons and introns of a gene of endothelial NO-synhase (eNOS) dealing with their role in a susceptibility to cardio-vascular diseases has been reviewed. Data of the populational genetic studies, performed in different regions of the world, were analysed to show the interrelation between an availability of on allele in the genome and a risk of ischemic heart disease. The main attention was focussed on the clarification of a relation between some allelic variants of the gene and functional (biochemical) properties of the protein, encoded by this gene, as well as on two principal mechanisms of realization of the pathological allelic variants in eNOS gene: 1) forming the protein in an insufficient quantity or with an altered activity (an interrupted transcription, and stability of informational RNA, formation of a cathalitically deficient protein); 2) an increased protein degradation (due to an acidic hydrolysis or an enhanced proteasomal proteolysis). In practical aspect, the most important problem, according to the point of view of the authors, is that of searching the pharmaco-therapeutical remedies, able to influence the different stages of the molecular-biological realization of an altered eNOS gene (transcription, translation, posttranslational modifications and degradation). Clarification of the above pathogenetic mechanisms will open broad perspectives in constructing therapeutical schemes for individuals possessing the pathological alleles of this gene.

[Autosensitization to myofibrillar proteins of myocardium in patients with different clinical forms of ischemic heart disease]. / Autosensybilizatsiia do miofibryliarnykh bilkiv miokarda u khvorykh z riznymy klinichnymy formamy ishemichnoi khvoroby sertsia.

An indirect ELISA method has been used to study formation of autoantibodies (AA) to myocardial myofibrillar proteins in patients with different clinical IHD forms. Purified myosin (MS), actin (AC) and tropomyosin (TM) of the intact human myocardium acted as antigens. The highest level of AA to MS and AC was found in patients with AMI (acute myocardial infarct): it exceeded twice that of the norm and 1.5 times that in patients with IAP (instable angina pectoris). Moreover the AA level in IAP patients exceeded that of normal 1.5 times. In PC (postinfactional cardiosclerosis) patients the MS AA and AC AA tend to the norm. The TM AA contents in PC patients is 1.2 times higher than that in AMI and IAP patients, not differing from the norm in all patient groups. The role of autosensibilization to contrectile proteins in progress of IHD and development of AMI is discussed.