Oxidative resistance of the plasma and electrophysiological remodeling of the myocardium in coronary patients.

The diagnostic and prognostic potentialities of the parameters of free-radical processes and high resolution ECG in coronary disease were evaluated. A relationship between oxidative resistance of the plasma (MDA concentration after 24-h copper-induced oxidation) and clinical characteristics of coronary disease (functional class of angina and high-resolution ECG parameters) was detected. Changes in ECG parameters directly correlated with MDA levels, the frequency of their registration reflects the severity of coronary disease. The absolute values of ECG, MDA, and their dynamics correlated with the severity of coronary disease and outcome of acute coronary syndrome, the prognosis was unfavorable for patients with MDA level >100 nmol/ml. The level of MDA increased by days 5-7 of observation in all patients with acute coronary syndrome, indicating exhaustion of the plasma antioxidant system during exacerbation of the coronary syndrome. Hence, evaluation of the plasma oxidative resistance and high resolution ECG can serve as a new diagnostic complex approach for detecting coronary patients with an unfavorable prognosis.

[Correlations between electrophysiological myocardial remodeling and parameters of free radical oxidation in patients with various forms of ischemic heart disease].

AIM: To investigate potentialities of a novel biochemical test assessing oxidative resistance of plasma as a marker of ischemic damage to the myocardium and to study this marker correlation with high-performance ECG parameters reflecting electrophysiological remodeling of the myocardium in patients with ischemic heart disease (IHD). MATERIAL AND METHODS: A total of 145 IHD patients entered the trial: 32 patients free of effort angina, 67patients with stable effort angina of functional class (FC) II-III, 56 patients with acute coronary syndrome (ACS) and 32 healthy controls. ACS patients were examined according to the following protocol: stage 1--6-12 hours since the disease onset, stage 2--at the end of the first 24 hours, stage 3--day 5-7 of the disease. In ACS patients the following outcomes (end points) were evaluated: recurrent myocardial infarction (MI), hospitalization because of exacerbation of IHD, documented potentially harmful arrhythmias and death within 1 year. High-performance ECG and a novel biochemical test of plasma oxidizability were used. The latter was determined by accumulation of malonic dialdehyde after 24 hours of incubation with 20 mcM of copper sulphate. RESULTS: A correlation was found between activity offree radical processes and electrophysiological remodeling of the myocardium by high-performance ECG. Amplitude and temporal characteristics of QRS complex and P wave can be used for follow-up of progression and severity of IHD in addition to standard electrocardiography. CONCLUSION: Unidirectional changes of high-performance ECG, plasma oxidizability and severity of IHD course allow using them as novel diagnostic tests of ischemic lesion and electrophysiological remodeling of the myocardium, for estimation of IHD severity.

[Antioxidant properties of statins].

Statins block expression of protein subunits of Gi-proteins (p22phox and gp91phox) which determine oxidase activity of NADPH oxidases and expression of GTP-ase (NADPH activator). This leads to suppression of activity of prooxidant enzyme systems (NADPH oxidase, xanthine oxidase, oxidase activity of endothelial NO-synthase) and diminishment of production of most aggressive free radicals -- superoxide anion and peroxinitrite. Hyperproduction of these radicals is associated with lowering of nitric oxide (NO) level and augmented NO destruction, the state of oxidative stress and endothelial dysfunction. Statins increase expression of enzymes with antioxidant properties (catalases, paroxonases), augment resistance of low density lipoproteins to oxidation, decrease take up of oxidized low density lipoproteins by monocytes and differentiation of monocytes into macrophages at the account of suppression of cellular scavenger receptor CD36 gene expression. Thus statins are powerful antioxidants.

[Relation between resistance to oxidation and cholesterol acceptance of high density lipoproteins in patients with ischemic heart disease]. / Vzaimosviaz' mezhdu okislitel'noi ustoichivost'iu i kholesterin-aktseptornoi sposobnost'iu lipoproteinov vysokoi plotnosti u bol'nykh ishemicheskoi bolezn'iu serdtsa.

Cholesterol (CH) acceptance ability of high density lipoproteins (HDL) was assessed in 43 ischemic heart disease (IHD) patients, including patients with post-infarction cardiosclerosis and class II-III effort angina. CH acceptance ability of HDL was measured as increment of HDL CH after incubation with artificial CH-containing system. Oxidabilities of HDL and total plasma were estimated by quantitation of lipid peroxidation products (hydroperoxides and thiobarbituric acid-reactive substances - TBARS) after incubation with Cu(2+) ions. HDL fraction (after apo B lipoproteins removal) of IHD patients appeared to include 2 times less additive CH compared with donor's HDL despite lower (-12%) HDL CH level. Negative correlation (r =-0.38, p<0.05) existed between formed TBARS in HDL and HDL CH acceptance. In total plasma of IHD patients elevation of both formed TBARS and particularly hydroperoxides was observed. Parallelism between decrease of CH acceptance by HDL, oxidability of HDL and of total plasma testifies on weakness not only of CH-accepting, but also of antioxidant HDL functions in IHD patients.

[The way of evaluation of cholesterol accepting capacity of plasma high density lipoproteins]. / Sposob otsenki kholestrin-aktseptornoi emkosti lipoproteinov vysokoi plotnosti plazmy krovi.

The simple way of quantitative evaluation of high density lipoproteins (HDL) capacity to absorb additive cholesterol quantity is proposed. It allows to evaluate indirectly intensity of the first, rate limiting stage of reverse cholesterol transport its accepting from the cells by means of HDL. The way includes the usage of stable artificial cholesterol donor--cholesterol covered inert polymer particles, which are than more convenient, than cell culture use. The total HDL rough fraction (i.e. serum after apoB lipoproteins removal) was shown to include more than 50% cholesterol in addition to yet presenting amount. But this ability is sharply reduced, or sometimes even is completely absent, in HDL of 63 coronary heart disease (CHD) patients (as compared with 41 healthy donors). This difference of potential cholesterol accepting capacity is revealed even at the same initial HDL concentrations. The negative correlation (r = - 0.32, p < 0.05) between this HDL property (delta HDL cholesterol) and their oxidability in the ions Cu2+ presence was observed. This underlines atherogenic role of HDL oxidability. The treatment of patients by phospholipids (as Lipostabyl) resulted to recovery of HDL cholesterol accepting capacity. The possible mechanisms of junction of this HDL activity with their oxidability are discussed, as well as necessity of evaluation of HDL properties and reverse cholesterol transport for the choice of care strategy of CHD patients.

[Correlation between severity of angina, its stability, and oxidative modification of lipids in patients with ischemic heart disease]. / Sviaz' mezhdu tiazhest'iu stenokardii, ee stabil'nost'iu i urovnem okislitel'noi modifikatsii lipidov u bol'nykh ishemicheskoi bolezn'iu serdtsa.

AIM: To elucidate the relations between angina severity, stability, concomitant arterial hypertension, diabetes mellitus, plasma oxidation. MATERIAL AND METHODS: The study included 152 patients with stable angina of effort (functional class II-III). Of them, 67 had concomitant arterial hypertension (AH), 20 AH and compensated diabetes mellitus type II, 14 patients with anginal functional class III were admitted to hospital for unstable angina, 11 patients with IHD with unstable angina and 28 healthy donors. The study was made of dynamic features of lipid oxidation using copper-induced plasma oxidation. Lipids were measured with enzyme assays. RESULTS: The degree of LP oxidation increases with aggravation of angina. IHD risk factors activate atherogenic modification of lipids in patients with stable angina. There was no differences between the groups in content of low density lipoproteins cholesterol. CONCLUSION: Plasma resistance to oxidation may serve an additional criterion for assessment of severity and stability of various IHD forms.

Chemiluminescence assay of the antioxidant state in patients with atherosclerosis.

We evaluated antioxidant state of 62 patients with coronary heart disease and 47 patients with obliterating atherosclerosis of lower extremities by peroxide-depend chemiluminescence and inhibition of azo-initiated chemiluminescence and hydrogen peroxide-hemoglobin-luminol chemiluminescence system. The flash amplitude of peroxide-dependent chemiluminescence in the plasma from patients was 32% below the control. Antioxidant activity of the plasma from patients was higher than in healthy individuals by 33 and 27% depending on the type of free radical-generating systems. The increase in antioxidant activity was most pronounced in patients with combined pathology: coronary heart disease complicated by obliterating atherosclerosis. These results explain the decrease in peroxide-dependent chemiluminescence of the plasma and whole blood in patients with atherosclerosis compared to that in healthy individuals.

[Specific features of lipid atherogenic modification in patients with ischemic heart disease and diabetes mellitus]. / Osobennosti aterogennoi modofikatsii lipidov u bol'nykh ishemicheskoi bolezn'iu serdtsa s soputstvuiushchim sakharnym diabetom.

A comparative study of the effect of concomitant compensated diabetes mellitus (DM) on plasma oxidation in patients with ischemic heart disease (IHD) with stable angina of effort (functional class II-III) in 28 anginal patients with IHD, arterial hypertension and DM, 67 anginal patients with IHD and hypertension, 57 anginal patients with IHD and 28 donors. Lipoproteins oxidation was studied by enzymic methods. A significant effect of the type of DM on dynamics of plasma oxidation in IHD patients was found. This may be an additional prognostic criterion of IHD progression in DM patients.

[Effects of clinical indices and anti-angina therapy on the quality of life in patients with stable angina pectoris]. / Vliianie klinicheskikh pokazatelei i antianginal'noi terapii na kachestvo zhizni bol'nykh stabil'noi stenokardiei.

AIM: To determine effects of basic clinical indices and various antianginal drugs on quality of life (QL) assessed with general and special questionnaire before and after selection of antianginal therapy in patients with stable angina pectoris. MATERIAL AND METHODS: The study enrolled 89 patients with stable angina (functional class II-IV). They were examined before and after decision on adequate therapy. QL was assessed with questionnaires Disease Impact Profile and Seatle Angina Questionnaire (SAQ). Factors essential for QL were determined with factor analysis and multiple regression methods. QL correlation with exercise tolerance was examined. RESULTS: SAQ has identified a positive correlation of some parts and total QL with exercise tolerance (p < 0.05). Treatment satisfaction correlated negatively with intensity of threshold load (p < 0.05). Factors affecting QL differed in patients with selected and non-selected therapy. QL was affected by anginal severity and complications, concomitant diseases with chest pain, harmful habits. Intake of non-selected drugs (beta-adrenoblockers, aspirin, ACE inhibitors, saluretics, benzodiazepins) may deteriorate QL. CONCLUSION: It is impossible to describe QL with clinical characteristics alone. This is an independent index which requires a special estimation.

[Validation of methods assessing the quality of life in patients with stable angina pectoris]. / Validizatsiia metodik otsenki kachestva zhizni u bol'nykh stabil'noi stenokardiei.

The aim of the study was evaluation of the validity, reliability and sensitivity of the Seattle Angina Questionnaire (SAQ) and Disease Effect Profile (DEP) translated into Russian by the authors in assessment of life quality (LQ) of patients with stable angina of effort (SAE). The examination of 106 SAE (functional class II-IV) patients demonstrated that LQ by SAQ and DEP correlated with the evidence by the Medico-Social Questionnaire of the Cardiological Research Centre. The constructive validity of SAQ and DEP was examined using factor analysis. All the SAQ sections but one and 7 of 11 sections of DEP were valid. Reproducibility was 0.938 and 0.906, respectively (p < 0.05), Cronbach's alpha was 0.56 and 0.94, respectively. According to SAQ, adequate choice of therapy improves LQ in SAE patients with functional class III but not in functional class II or IV. According to DEP LQ remained unchanged irrespective of the therapy. Thus, Russian translation of SAQ and DEP has proved its internal, external and constructive validity, is integral and reproducible. In addition, SAQ is sensitive to changes in LQ in SAE.

[The antioxidant protection of the heart by coenzyme Q10 in stable stenocardia of effort]. / Antioksidantnaia zashchita serdtsa koénzimom Q10 pri stabil'noi stenokardii napriazheniia.

It was found that patients with angina of effort (functional class II and III) exhibit enhanced generation of active oxygen forms by leukocytes, higher concentration of malonic dialdehyde in plasma and lower antiperoxide resistance of plasma. These changes increase with increasing severity of the disease. Adjuvant use of coenzyme Q10 in combined antianginal therapy suppresses generation of active oxygen forms by leukocytes, lipid peroxidation. Antiperoxide plasma resistance rises. In this way clinical improvement of effort angina is achieved.