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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.

Dynamics of lipoprotein oxidation in blood plasma was studied by Cu-induced plasma oxidation in 114 patients with atherosclerosis of lower extremities of various severity with and without ischemic heart disease. Preparedness of plasma lipoproteins to oxidation in patients was higher than in healthy subjects. Degree of oxidizeability increased with increase of severity and extent of atherosclerosis and was highest in patients with atherosclerosis of lower extremities and ischemic heart disease. There were no significant differences between groups of patients with various severity and extent of atherosclerosis in levels of total cholesterol and triglycerides as well as in other parameters of lipid spectrum. Correlation analysis revealed no relationship between age of patients and degree of plasma oxidizeability.

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 aim of this study was to determine the concentration parameters and time-course of copper-induced oxidation in serum and whole blood plasma. We investigated the oxidizability of undiluted and (2-60-fold) diluted whole plasma (prepared with citrate as an anticoagulant) and serum by monitoring the change in the level of conjugated dienes, ketodienes and malondialdehyde in the samples. The kinetic curves of the accumulation of different lipid peroxidation (LPO) products had similar S-shape, but they differed by a number of quantitative parameters--lag-time, time of improvement and the level of maximal rate of oxidation, as well as time of improvement of the maximal accumulation and maximal amount of LPO products. When the LPO products were formed in undiluted plasma and serum, the lag phase of 2-2.5 h for conjugated dienes and ketodienes, and 11-12 h for malondialdehyde was observed. Oxidation profile showed a negligibly short period of inhibition followed by rapid oxidation for all investigated LPO products when plasma and serum were diluted at least 10-fold. The rate of accumulation and amount of LPO products decreased in the following order: conjugated dienes > ketodienes > malondialdehyde. Choice of blood plasma or serum and a dilution factor strongly influenced intensity of copper-induced LPO. Anticoagulant (sodium citrate), that was used by preparation of plasma, possessed an inhibitory action on LPO, due to formation of copper-citrate chelates. Dilution of plasma and serum increased LPO through lowering of influence of water-soluble antioxidants, but action of fat-soluble antioxidants (dissolved in the lipid phase of lipoprotein particles) by was unchanged. These results indicate that measurement of lipid oxidation induced in vitro in the whole plasma or serum might be more relevant model of the lipoprotein oxidation in the blood than the in vitro oxidation of single isolated lipoproteins.

In patients with coronary heart disease oxidizability of lipids during Cu(2+)-induced oxidation of blood plasma inversely correlated with fibrinogen content. A positive correlation was found between the amount of lipid peroxidation products in the plasma from these patients and fibrinogen content. The increase in fibrinogen content was associated with high levels of total lipids and triglycerides and low concentration of high-density lipoprotein cholesterol. In vitro experiments demonstrated that fibrinogen reduces oxidizability of blood plasma. Our results suggest that the decrease in lipid oxidizability at high concentration of fibrinogen in patients with coronary heart disease is related to predominant oxidation of fibrinogen and its competition with plasma lipids during Cu(2+)-induced oxidation.

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.

Using the RELP analysis we studied the frequency of X2 allele of apoB gene in three groups of patients: 1) men at the age of 20-59 with lipid metabolism disorders revealed in population inspection of Oktyabrsky district in Moscow; 2) men with ischaemic heart disease and 3) healthy men. It was established that in individuals suffering from type IIa hyperlipidemia the frequency of X2 allele was significantly higher than in healthy donors from Moscow population. Homozygotes for X2 allele of XbaI RELP had 7-9% higher serum cholesterol levels, than homozygotes for X1 allele. The study suggests the X2 allele of the apoB gene to be associated with the development of high plasma cholesterol level. No significant difference in X2 allele frequencies was found between patients with ischaemic heart disease and healthy donors. There was also no association found between cholesterol and triglyceride levels and the presence of X2 allele in this group of patients.

The inhabitants of 7 isolated villages (of different nationalities) and of 5 panmictic populations were studied. Populational and segregation analyses of Hb A2 in 3036 normal and 150 heterozygous individuals for beta- and delta beta-thalassemia were carried out. The Hb A2 levels in some populations are established to deviate from the normal distribution. Bimodal dependency of the levels of Hb A2 distribution is demonstrated, which suggests the existance of heterogenous subpopulations by the Hb A2 level. The segregation analysis has revealed distinct genetic determination of Hb A2 levels. There was a good correlation between Hb A2 and Hb F values (r=-0.82).